Synthetic Reagents

Dr.. Bapu Dr Bap u R. Thorat Tho rat Assit. Professor of Chemistry Govt. of Maharash M aharashtra, tra,

Ismail Yusuf Arts, Science and Commerce College, Jogeshwari (E), Maharashtra 400060

Reagent

Reagent & Reaction cond.

Substrate

Product

A group of organic molecules serve as substrates for a particular type of reaction when treated with specific reagent. e. g. Nitration of aromatic compounds by using nitrating mixture ; the aromatic compounds are substrates and nitrating mixture is reagent for nitration reaction.

Types of reactions

1. 2. 3. 4.

Additi Addi tion on rea react ctio ion; n; Elim El imin inat atio ion n rea react ctio ion; n; Subs Su bsti titu tuti tion on rea react ctio ion; n; Rear Re arra rang ngem emen ent; t;

1. Peri Pericy cycl clic ic rea eact ctio ion; n; 2. Ph Phot otoc ochem hemic ical al and an d radical reaction ; 3. Ox Oxiidation; 4. Reduction

free fr

Nitration

Bromination Sulfonation

Carbonylation

Halogination Acylation

Alkylation

Formylation

Oxidation

Oxidation of an organic compound involves one or more of the following changes: (1) an increase in the multiple bond order of the C (2) addition of O to a C (3) replacement replacement of an H on a C by O.

Reduction

Reduction of an organic compound involves one or more of the following changes: (1) an decrease in the multiple bond order of the C (2) addition of H to a C (3) replacement replacement of an O on a C.

Oxidizing agents Cr(V Cr (VII ) Reage Reagents: nts: Sodium or potassium dichromate (Na 2Cr 2O7 or K 2Cr 2O7), or

Jones reagent

chromium trioxide ( CrO3), to aqueous solutions of sulfuric or acetic acid. Modified reagents: PCC (Pyridinium chlorochromate); PDC (Pyridinium dichromate); chromium trioxide pyridine (CeO 3.py2); M n O  2 

K M n O4   

Sodiu odiu m H ypoc ypochl hl ori te (NaOCl) 

O  2 

Peroxycarboxylic acids

sel eni u m di oxi de (SeO  (SeO   )  2 

H 2 O   /N 2  aOH 

Triiosproxide aluminium Oppenauer Oppenauer oxidation Osmium tetroxide (OsO4) Pb(OAc)  4 

DM SO/oxalyl O/oxalyl chlori de: de:

Swern oxidation Ozone (O   )  3  H I O  4  chromyl chlor i de (Cl  (C l 2 Cr O   )  2 

Fremy's Frem y's salt ((KSO ) N-O.)

K [Fe(CN) K  [Fe(CN) ]

Reducing agents Metals used for reduction: Copper (low valent), Chromium (low valent), Fe, Indium (low

valent), Iron, Lithium, Magnesium, Manganese, Neodymium (low valent), Nickel, Niobium (low valent), Potassium, Red-Al, Sodium, Strontium, Stronti um, Titanium Titanium (low valent), Zinc, Samarium. Hydrides: Potassium tetrahydro borate, Potassium borohydride, Sodium borohydride, Sodium

cyanoborohydride, Sodium tetrahydro borate, Sodium triacetoxyborohydride, Decaborane, Diisopropylaminoborane, Dimethylsulfide borane, Di borane, LiTEBH, Nickel borohydride Sodium

bis(2-methoxyethoxy) aluminumhydride,

DIB AL-H,

LAH,

Aluminium

triisopropoxide/isopropanol Tin hydrides, Tributyl tin hydride

Tributylstannane, Trichloro silane, Silanes, Triethyl Triethylsilane, Tris(trimethylsily Tris(trimethylsilyl) l)silane, Diethoxymethyl silane Zirconocene chloride hydride Copper hydride

Hydrogen Formic acid

Hydrazine

Sodium dithionate

Organometallic Organom etallic reagents in organic synthesis Organometallic chemist Organometallic chemistry ry timeline 1827 Zeise's salt is the first platinum-olefin platin um-olefin complex: complex: K[PtCl3(C2H4)]H2O Zeise's salt 1863 C. Friedel & J. Crafts prepare organochlorosilanes 1890 L. Mond discovers Nickel carbonyl 1899 Introduction of Grignard reaction 1900 P. Sabatier works on hydrogenation organic compounds with metal catalysts: Hydrogenation of fats 1909 P. Ehrlich introduces Salvarsan for the treatment of syphilis, an early arsenic based organometallic compound. (As 3Ar 3) [Ar –  [Ar  –  3-amino-4-hydroxypheny]   3-amino-4-hydroxypheny]

1912 Nobel Prize: Victor Grignard and Paul Sabatier 1930 Henry Gilman works on lithium cuprates: RX + 2Li RLi + LiX 1951 Ferrocene is discovered 1963 Nobel prize for K. Ziegler and G. Natta on Ziegler-Natta Ziegler-Natta catalyst 1965 Discovery of cyclobutadieneiron tricarbonyl Ferrocene (C 4 H   )F (C O)  4  e(CO)  3  1968 Heck reaction 1973 Nobel prize G. Wilkinson and E. O. Fischer on sandwich compounds 2005 Nobel prize Y. Chauvin, R. Grubbs, and R Schrock on metal-catalyzed alkene metathesis 2010 Nobel prize Richard F. Heck, Ei-ichi Negishi, Akira Suzuki. "for palladium-catalyzed cross couplings in organic synthesis" 

Organometallic Organom etallic reagents in organic synthesis

Materials which possess direct, more or less polar bonds M+ — C- between metal and carbon atoms. In addition to the traditional metals, lanthanides, actinides, and semimetals,  elements such as boron, silicon, arsenic, and selenium are considered to form organometallic organometallic compounds. e.g. Organoborane compounds such as triethylborane (Et 3B).  Organometallic Organometallic chemistry combines aspects of inorganic chemistry and organic  chemistry. 

Classification of organometallics based on the bond type:

Organometallic Organom etallic reagents in organic synthesis

Covalent, multicenter, multicenter, σ-bonded

Organo borane compounds compounds Organoborane or organoboron compounds are organic derivatives of BH3. Organoboron compounds are important reagents in organic chemistry enabling many chemical transformations, the most important one called hydrobora hydroboration tion. Characteristics: • C-B bond, low polarity (electronegativity C 2.55, B 2.04) • Electron-rich groups  like vinyl or phenyl provide the C-B bond with partial double bond character. Organoboron hydrides R 2BH and RBH2  form dimers which always display hydride bridges rather than alkyl bridges. •

Organo borane compounds compounds Hydroboration: Hydroborat ion: Synthesis Sy nthesis of alkylborane (mono, di, tri-)

Borane (BH3 in dimer form) reacts rapidly to alkenes and alkynes forming alkyl and alkenyl  boranes are called as called hydroboration. This concept was discovered by Herbert Charles Brown at Purdue University with help from George Wittig.  Number of alkenes alkenes of widely different different structures except most hindered alkenes. di -substituted ethylenes) gives trialkylborane.  The simple alkenes gives (mono- and di-substituted  Tri-substituted ethylenes gives dialkylborane, and  Tri-substituted  Tetra-substituted ethylenes forms monoalkylboranes. -alk k ylbor anes ar are e l ess reacti reactive ve and mor e sel ecti ctive ve th than an th the e boran e Th e mono- and di -al

. itself  More substituted C has δ + δ+

Less substituted C has δ-

δ-

Asymmetric alkenes

In case of allyl derivatives and nuclear substituted styrenes, the proportion of product formed by addition of boron to the α-carbon (more substituted carbon) atom increases with the electronegativity of the substituents.

Organo borane compounds compounds CH3(CH2)3CH=CH2 6% 94% CH2=CHCH3 94%

(CH3)2C=CHCH3

CH3CH=CH(CH3)2

2% 98%

58% 42%

CH2=CHCH2OC2H5

CH2=CHCH2Cl

19%

6%

40%

CH3O

82%

Cl 25%

18%

5%

Mechanism Hydroborations take place stereoselective in a syn   mode   mode that is on the same face of the alkene. The reaction proceeds through transition state is represented as a square with the corners occupied by carbon, hydrogen and boron with maximum overlap between the two olefin p-orbitals and the empty boron orbital.

+ H B

solvent

protonolysis H B

H

H

Organo borane compounds compounds Hydroboration: Hydrobora tion: Synthesis of alkylborane (mono, di, tri-) + alkene

H

H

alkylborane

B

H

organoborane

+ alkyne

B

B H

B

H

H3C 2

CH3

B2H6/THF

H

H3C

CH3

H3C

CH3

B

organoborane alkenylborane

e.g. H C 3 1

B

H

Hydride source

[(CH3)2CH-CH(CH3)]2BH disiamylborane

B2H6/THF

[(CH3)2CH-C(CH3)2]BH2 thexylborane

B2H6/THF

B-H

3 B2H6/THF

9-BBN no reaction because of steric hinderence

4

The hydroboration of alkenes and alkynes is highly stereospecific and takes place by addition to the less hindered side of the multiple bond.

Organo borane compounds compounds Hydroboration: Hydrobora tion: Limitations

1. The regio-s regio-selectiv electivity ity in the hydrobora hydroboration tion of terminal terminal alkenes, alkenes, although although high, high, is not not complete and in 1,2-disubstututed alkenes there are little discrimination between the two termini of the double bond. 2. There is little difference in the rate of reaction of borane with differently substituted double bonds, so that it is rearly possible to carry out selective hydroboration of one bond in presence of another . 3. The hydroboration hydroboration of termi termi nal alkyne is diff icul t to contr contr oll ed at the si ngle add addii tion but the desired alkenylborane undergoes second addition of a second molecule of borane to the 1,1-dibora-alkane.

Problems: 1-alkylcycloalkanes 1-alkylcycloalkanes on hydroboration followed by oxidation gives 4-chlorostyrene on hydroboration followed followed by oxidation gives 4-chlorostyrene on hydroboration hydroboration followed by heating and then oxidation gives Hydroboration of 2-pentene gives  –  (i)  (i) on protonolysis (ii) oxidation, (iii) heat and then

Organo borane compounds compounds From Grignard Reagent: Synthesis of alkylborane (tri-)

This method is generally used for the synthesis of trialkylborane such as trimethylborane and triethylborane. 3 RMgX

+

BX3

R3B

+ 3 MgX2

By exchange meth method: od: Synthesis of alkylborane (tri-)

The organoborane exchange exchange their alkyl group with more reactive alkene alkyl. R3B

+ 3 Alkene more reactive

R'3B

+ 3 Alkene' less reactive

Isomerisation: The organoborane compounds undergo isomerisation on heating if and only if α-carbon atom with respect to boron atom bearing atleast one hydrogen atom. Such organoborane compound undergoes isomerisation to stable organoborane compound (to organoborane compound in which boron has less substituents) by addition-elimination mechanism. B H

e.g.

+

BH3

THF

B o

200 C

Organo borane compounds compounds Organo-Borane Reagents used organic synthesis

Many of these reagents, such as thexylborane, disiamylborane, dipinylborane, 9-borabicyclo[3.3.1] nonane, catecholborane, chloroborane etherates, haloborane-dimethyl sulfides, IPCBH2, ICP2BH, RBCl2 and R 2BCl. [(CH3) 2CH-CH(CH3)] 2BH disiamylborane

   

[(CH3) 2CH-C(CH3) 2]BH ]B H2 thexylborane

B-H 9-BBN

O BH O catecholborane

H2BX

[(CH3) 2CH-C(CH3) 2]BHCl

monohaloborane     dihaloborane (X- Cl, Br) BH 2

mono-isopinocampheylborane [ICPBH 2]

HBX2

) BH 2

di-isopinocampheylborane [ICP2BH]

thexylmonochloroborane

Organo borane compounds: compounds: Disiamylborane It is dialkylborane used selectively for the hydrob hydr oborati orati on of C=C bond in such a way that . It is used selectively for boron atom attach to less stericaly hindered carbon  monohydroboration mon ohydroboration of alkynes.

Preparation: H3C H3C

CH3

B2H6/THF

[(CH3)2CH-CH(CH 3)]2BH

H

disiamylborane

2-methyl-2-butene

Steric interactions between between methyl and an d Siamyl group

Examples:

B(C5H11)2 e.g.1.

[(CH3)2CH-CH(CH3)]2BH

+ B(C5H11)2 3% B(C5H11)2

2,

[(CH3)2CH-CH(CH3)]2BH

oxidation

97% OH

Organo borane compounds: compounds: 9-BBN It is more sensitive to the structure of the alkene. Terminal alkenes react more rapidly than the internal alkene and Z-alkene also react more rapidly than the E-isomer. These are also used for monohydroborati on of alkynes . The al kynes whi ch on oxidati on to ketone  ketone  acid catalyzed hydrolysis of terminal alkyne gives methyl ketone while by using disiamylborane or 9-BBN followed by oxidation gives aldehyde. These reagents are used to reduce mono- and di-substituted alkene  preferentially than the tri- and tetra-substituted alkene. The same result is obtained by using catacholborane, dibromoborane or thexylmonochlorborane. B-H BH3/THF

e.g.

e.g.1.

R

H5C2

2. H5C2

 

H

 

H-B

B-H

R'

C2H5

9-BBN THF

9-BBN THF

9-BBN THF H5C2 H

R

R'

H

B

H5C2 H H B

C2H5

protonolysis

oxidation

R

R'

H

H

H5C2

B oxidation

H H5C2 H

C2H5 OH

H H5C2-CH2CHO OH

Organo borane compounds: compounds: Thexylborane It is most radialy available of monoalkylborane. It is useful for cyclic hydroboration of diene. Hydroboration of diene itself by using borane gives polymer  but with thexylborane gives cyclic or bicyclic organoboranes. Thexylborane is also used for the synthesis of trialkylboranes containing three different alkyl groups. This process has limited scope because the  first alkene must be relatively unreactive.. unreactive This difficult can be overcome by using thexylchloroborane The thexylchloroborane react with an alkene  gives an chloroalkylthexylborane  which may be converted to dialkythexylborane by reaction with one equivalent Grignard’s Grignard’s reagent  reagent or an alkyl-lithium or by hydridation with wi th LAH in presence presence of alkene. Dialkylthexylboranes are useful for the synthesis of cyclic or acyclic ketones. H3C H3C

CH3

B2H6/THF

[(CH3)2CH-C(CH3)2]BH2

CH3

thexylborane

2,3-dimethyl-2-butene e.g.1.

Thexylborane THF

1.CO

NaBH4

-

2. H2O/OH

B

O 2.

OH

COOEt Thexylborane THF

COOEt 1.CO

H B

B

COOEt

-

2. H2O/OH

Organo borane compounds: compounds : Optical active reagents (Ipc 2BH and IpcBH2)

Diisopinacamphenylborane (Ipc 2BH) and monopinacamphenylborane (IpcBH 2) are prepared in either form by reaction of borane with (+) or (-)-α (-)-α-pinene under appropriate conditions. These reagents are used for the t he synthesis of optical active alcohols.

H

)

BH3

BH

2

THF (+)-a-pinene

H

)

purification with 15% a-pinene and stand it over night

IPC 2BH 93% ee

H BH

2

BH2

a-pinene TMEDA

IPC BH

 

IPCBH

100%ee

 

100%ee

2

2

The Z-alkene is converted into optical active secondary alcohol of high optical purity by using Ipc2BH followed by oxidation. But with E-substituted alkene best result will obtained by using IpcBH2, the success of reaction is depends on the bulk of the alkyl substituents of the double  bond.

)2BH

)2B

H2O2/NaOH

HO

H BH2

H B

H2O2/NaOH

H (R, 87% optical pure) H HO

H (S, 73% optical pure)

Reactions of organoboranes

Protonolysis Protonolysis of organoborane compounds by using organic acid is the convenient method for the reduction of carbon-carbon multiple bonds. Alkenylborane   are more reactive than the alkylborane. This reaction takes place with retensation of configuration  at the ynes s ar ar e cl cl eanl y carbon atom attach to the boron atom. The alk yne converr te conve ted d into int o Z-al kene kenes  s  . R R B R

O

H

+

O R'

H R + R B O R

R'

R-H

Boiling with propaonic acid At RT with acetic acid

+

R2B(OCOR')

2 R-H +  B(OCOR')3

O

Advantageous - the reduction of the double bond or triple bond in compound containing other reducible functional groups can be easily occurs such as compounds containing ester, sulphide, protected carbonyl group, nitro group, etc 1.

2.

C4H9 CH2

C2H5

BH3/THF

C2H5 (C5H11)2BH Diglyme

(C4H9CH2CH2)3B C2H5 H

C2H5 B

propionic acid reflux CH3COOH o 25 C

C2H5

C4H9CH2CH3 C2H5

91%

Reactions of organoboranes

Protonolysis

Diastereoselective Diastereoselect ive hydration of the double bond of acyclic alkenes. RL

H CH3 RM

1. R2BH 2. H2O2/NaOH

RM

RL H RM H

H3C

H

+ H CH3

major 

RL

minor 

Terminal alkene in which R L  and R M  are stericaly large and medium sized substituent groups respectively. The stereochemistry  of the hydroboration appears to be controlled  primarily by the size of the groups on the nearby chiral carbon. CH3

e.g. H3C

CH3 1. thexylborane

OH

2. H2O2/NaOH H3C

CH3

CH3

CH3

CH3

+

OH

H3C OH

OH (81%, 6:1 selectivity)

Intramolecular hydroboration takes place via boat like transition state rather than the chair. The formation of boat like transition state is preferred  because the boron-hydrogen bond eclipses the πsystem of the double bond but it is not a case in chair form formation. This indicates that intramoleculer hydroboration reaction takes place through planar four

H

H H3C B H boat transition state is preferred.

H3C

B H

chair transition state not prefered.

Reactions of organoboranes

Oxidation Oxidation of organoboranes to alcohol  can be easily carried out by using alkaline hydrogen peroxide. In overall reaction the water molecule can be added (overall is cis-/syn-addition) across the double bond by using anti-Markownikoff rule. This also used to convert alkyne into ketone and aldehyde (by using terminal alkyne) rather than to the methyl ketone. R R B R

-

+O

R

H R R

O

B-

-

R O

OH

B O

OH R

R

R R

-B O

R

H

-

B O R

O R

ROH + ROH

ROH + B(OH)3

H2O2 + NaOH

The reaction path involving intramoleculer transfer of alkyl group from boron to carbon in an intermediate ate compound. CH3 1.

OH 1. (C5H11)2BH  / Diglyme 2. H2O2/NaOH

CH3 CH3 2.

1. (C5H11)2BH  / Diglyme 2. H2O2/NaOH

CH3 CH3 OH CH3 H

OH CH3 H CH3 OH CH3

Reactions of organoboranes

Oxidation The direct oxidation of primary trialkylborane into aldehyde and secondary trialkylborane into ketone, without isolation of the alcohol is possible by using pyridinium chlorochromate (PCC) or aqueous chromic acid.

BSia2

 

PCC or chromic acid

Sia2BH O chromic acid or 

BSia2

PCC H

CHO H

Reactions of organoboranes

Amine formation The trialkylboranes are converted into primary amine  by reaction with hydroxylamine-Osulphonic acid or N-chloroamine.dialkylchloroborane with organic azide gives secondary amine. Only one alkyl group can be migrate towards the nitrogen atom therefore, yield of the  product is less which can be increased by using 9-BBN or Sia2BH.

R3B

+

R

H2N-Cl/H2NOSO4H

R R

B +

Cl

NH2

Cl -

R B + R NH2

R

R-NH2 + R2B-Cl

.dialkylchloro dialkylchloroborane borane with w ith N-chloroamine /organic /organic azide gives secondary amine. R R2B-Cl

+

R'N3

-

B R

Cl + N 2 N

R'

OH

R'

R B Cl

N R

OH2

H R N R'

Reactions of organoboranes

Primary bromide bromide and an d iodide formation Primary bromides and iodides are also obtained by the reaction of trialkylboranes derived form terminal alkenes with bromine and iodine in presence of base such as NaOH, methanoic sodium methoxide, etc. R3B

+

X2 bromine or iodine

organoborane of terminal alkene

MeONa/MeOH

R-X

+

BX3

primary halide

Mechanism R R3B

+

X2

R R

B

+ X X

-

OH

R B R

+ R X

R-X

+

R2BOH

Reactions of organoboranes

Carbonylation The reaction of organoborane with carbon monoxide under appropriate conditions is very important for the synthesis primary alcohol, secondary alcohol and tertiary alcohols, aldehydes and open, cyclic and polycyclic polycy clic ketones.

+

R3B

R 1atm., r.t. R B dry atmosphere R

-

CO

+

O

H2O

R B R

O LiAlH(OMe) 3

R

R

R

R B

R sec-alcohol

NaOH/H2O B H2O2

O

H R aldehyde

R

R

R

R ketone

OH NaOH/H2O

OH

R

NaOH

Bora-ketone

R

O

H2O2

HO

OH R

NaOH

R

R

R B O Bora-epoxide

prim-alcohol

NaOH  presence of small amount of water &  NaOH

polymer 

in presence of some hydride reducing agent

OH

R O B

OH

R NaOH R OH B R OH2 R O R R monomer  tert-alcohol O

R R

OH

R 3B with one mole of CO

Reactions of organoboranes R3B

Synthesis of tertiary alcohol

+

CO

R 1atm., r.t. R B dry atmosphere R

-

+

O

R R B O Bora-epoxide

B R

R Bora-ketone

High temperature 30 alcohol in high yield

 

RCOO COOR' + 2 RMgX

R OH R R tert-alcohol

R

R

O

R

R OH R R tert-alcohol

dehydration   alkene

 

R O B R polymer 

OH OH

O NaOH OH2

R B

O R R monomer 

Low yield

(R is bulky substituent)

The migration of alkyl group from boron to carbon atom intramoleculerly

Synthesis of trialkylmethanols: The trialkylborane react with dichloromethyl methyl ether in  presence of strong hindered hindered base lithium triethylcarboxide.

R3B

- + CH3OCCl2Li THF

R

Cl

B

R R

Li + OMe

R

R

Cl

B R

Cl

CR2Cl

R3C

OMe

Cl

R B

OMe

B OMe [O]

R3C-OH

B OMe [O]

R3C-OH

H3COCHCl2 + Base

..

R3B

H3COCCl THF

R

B

R R

OMe +

R

R B

Cl

R

Cl OMe

CR2Cl

R3C

OMe

Cl

R B

E.g. Carbonilation of equimolar mixture of triethylborane  and tributylborane  gives after oxidation-

Reactions of organoboranes

Synthesis of secondary alcohol

R3B

+

CO

R 1atm., r.t. R B dry atmosphere R

-

+

O

R

O

R

R NaOHR

B

R B O Bora-epoxide

R

R Bora-ketone R

Carbonylation reaction carried in presence of small amount of water which resist migration of third alkyl group.

alkene A

BHR A alkene B

B

R

R sec-alcohol

oxidation

from

thexyl

or R A

B

B

RB

O

R ketone

R A

CO

  H2O2 NaOH

OH

Unsymmetrical ketones by using mixed organoboranes prepared thexylchloroborane (Thexyl (Thexyl group has very low migratory aptitude apti tude value). BH2

OH R

B

HO

NaOH/H2O

alkaline hydrolysis

R A

R

RB

OHOH [O]

O RB

RB

R A O

Dienes similarly used for the synthesis of cyclic ketones. H

O

H B

Thexylborane THF

O

1.CO/H2O /5OoC/70atm 2. H2O2/NaOH

H

H

Thexylborane THF

B

H 1.CO/H2O 2. H2O2/NaOH

O

Reactions of organoboranes

Synthesis of primary alcohol

R3B

+

CO

Carbonylation is carried out in presence of some hydride reducing agent such as lithium trimethoxyaluminium hydride.

R 1atm., 1atm., r.t. r.t . R B dry atmosphere R

-

+

O

R B R

O LiAlH(OMe) 3

R

R

R

R

O

H2O2

B

NaOH OH NaOH/H2O

R H aldehyde R

OH

prim-alcohol

Main disadvantage  of this procedure is that only-one alkyl group of trialkylborane is converted into the required derivative and other two are effectively wasted. This difficulty can be overcome by the hydroboration of alkene by using 9-BBN or disiamylborane.

CH3(CH2)7

B

CO CH3(CH2)7CHOH B LiAlH(OCH3)3

LiAlH4

CH3(CH2)7CH2

H2O2 NaOH

B

CH3(CH2)7CH2OH

CHO ;

H2C=CHCH2CO2Et

 

HOC(CH2)3CO2Et

Reaction of B-alkylboronic ester with methoxy(phenylthio)methyl-lithium  forming mercurous chloride, induces transfer of the alkyl group from intermediate which react with mercurous boron to carbon  and subsequent oxidation by using alkaline hydrogen peroxide gives corresponding aldehyde in good yield. CH3 CH3

CH3 BBr.(CH3)2S

HBBr 2.(CH3)2S CH2Cl2

O B

(CH3)3SiO(CH2)3OSi(CH3)3

O LiCH(OCH3)SPh

CH3

CH3 CHO

H2O2 NaOH

CH3

OMe B

B

B

Alkyl shift

O

-B

Hg2Cl2

O SPh

OMe

Reactions of organoboranes

Cyanation

Trialkylborane treated with sodium cyanide forming trialkylcyanoborate. Addition of one molar equivalent of benzoyl chloride or trifluoroacetic unhydride induces two successive migrations of alkyl groups from boron to the adjacent carbon atom of cyanide group forming the cyclic organoborane intermediate which on oxidation without isolation gives ketone in high yield. In presence of excess anhydride forming trialkylmethanol. Asymmetric Asymmetric ketone can be easily obtained from two different alkene.

R3B

+ CN

B

F3C

R R B R

-

R

R

O

R

O

N

R N CF3

O

R

B

N

O

O

F3C

R

1.CF 1.CF3COOH 2. NaOH/H2O CF3

H2O2

R OH R R tert-alcohol

NaOH R

O

R ketone

R R

B O

R

O F3C

N

O F3C

R

F3C

R O

B

R CR3

O

N

NCOCF 3

B

O CF

F3C

O

H2O2 NaOH

R3COH

Reactions of organoboranes

Ketone and tertiary alcohol can be synthesized by the reaction of trialkylboranes with anion of tri(phenylthio)-methane . Two alkyl groups are migrates from boron to carbon in the initial adduct to give an intermediate which can further oxidized to ketone. A third migration of alkyl group for the synthesis of tertiary alcohol can be induced by the treatment of mercuric ion ; oxidation of the product gives tertiary alcohol. R HO R 2 2 R3COH B R NaOH X SPh

R +R3B + LiC(SPh)3

+ [R B-C(SPh) ]Li 3

3

R

-B

R SPh

R

R SPh 2+ SPh Hg PhS or CH3O2SF

B-SPh R

H2O2

O

NaOH R

R

Reactions of organoboranes Reaction with α-bromoketone α-bromoketone and α-bromoester α-bromoester Organoborane  react radialy with α-bromoketone  and α-bromoester  in presence of potassium t-butoxide or hindered base forming corresponding ketone  and ester respectively. The alk yl or aryl grou group p of organoborane di di splace places s bromi ne atom from its  position. O RCOCH2Br  + t-C4H9OK

R

R'

O

-

B-

BR'3 R

Br 

Br 

R'

R'

O

B R'

R

O R'

t-C4H9OH R

R'

R'

 Nucleophilic substitution Limitationsa) Organoborane having highly branched groups do not react.  b) Only-one of the three alkyl groups in the trialkylborane is used in the reaction and remaining is wasted therefore yield of the reaction is decreased. This difficulties are overcome by using an alkyl derivatives of 9-BBN. This reaction can be extended to dibromoacetates dibromoacetates   and can be controlled at the α-alkyl-alkyl-α α-bromoacetates or dialkylacetates. BH3/THF

B

BrCH2COOEt

CH COOEt

Reactions of organoboranes Reaction with wi th diazo-compounds

It is nucleophilic substitution reaction of organoborane compound. The ketones and esters are synthesized from the diazo-compound and organoborane in presence of base. O

O +

-

R3B + N2-CHCOCH3

R R B R

R +

N2

CH3

CH3 hydrolysis

B R

R

CH3

R O

The mechanism studies have been suggested that the migration of alkyl or aryl group from boron boron to carbon atom is occurring with w ith elimination elimination of nitrogen gas. It is also used for the synthesis of nitrile or cyanide derivative. Yield of the reaction can be increased by using dialkylchloroborane  instead of trialkylborane.

Suggest the mechanism of following:

Reactions of organoboranes

Synthesis of cyclopropane

Cyclopropane or its derivatives are synthesized from dialkylborane such as thexylborane or 9-BBN and allylic chloride in presence of base.

ClCH2CH=CH2 allyl chloride

Sia2BH Cl THF

B

-

OH

Cl

-

HO B

cyclopropane

Reactions of organoboranes

Alkenylborane and trialkylalkynylborates are used for the synthesis of conjugated dienes and diynes, saturated and α,β-unsaturated α,β-unsaturated ketones  by the migration of an alkenyl or alkynyl alkynyl group from boron to carbon instead of alkyl group. R H

Et

)3B

I2,NaOH THF

Et

B

H

H

R R

Et

+

I Et

Et

OH

R

I

R

H

B I

Et

B

Et

Et I

Et

H

I

H

Et I

Et

R

Et

Et

Et

R H

BH2

+

Cl

C6H11

Cl

C6H11

Cl B

H

HC

C4H9

C6H11

B

C6H11 H CH3ONa H H

H

C4H9

H Thexylborane

MeO B H H

C4H9 C2H5COOH

H2O2/NaOH C6H11 C4H9

C6H11

LiC CC6H5 (C4H9)3B +   LiC

THF

C4H9 C4H9 B C4H9

C4H9

C4H9

CC6H5

I2 o -78 C (C H ) B 4 9 2

C6H5 C4H9C CC6H5 I

Reactions of organoboranes Reaction with conjugated Aldehyde and ketones: ketones:

Trialkylboranes reacts with vinyl aldehyde or ketone, forming an ate-complex 1, in which pielectrons move with the migration of R on B to the vinyl carbon to give enolborinate 2, corresponding saturated aldehyde or ketone. ketone. which is then hydrolyzed with w ith water to the corresponding saturated The yields and conditions are changed according to the substitution at α- and β-position. The yield was drastically change with β-substitution.

The conjugated ester and nitriles nitril es undergoes polymerization polymerization with trialkylboranes.

Examples C5H11 CH3CHO

B

1

O

C5H11 carbonylation

C2H5O B H

H

C5H11

)2BH NH2

+

2

H2O2/NaOH

H2N-Cl/THF

H (90%ee)

3

BH2 1. 2.

OH H (92%ee)

(

H2BBr.(CH3)2S

)

 

2

BBr.(CH3)2S

B H CH 3

CH3OH   CH3ONa

)2

(

CH3CHO

C2H5O

+ H CH3

C4H9 O

C5H11 B

B-OCH3

Cl2CHOCH3 (C2H5)3COLi O H9C4

C5H11

4

CH3

H

H

2

H

CH3

1.Cl2CHOCH3/Et3COLi C5H11 2.H2O2/NaOH H3C

H

Exercise

1

2

3

4

5

6

7

6 7

Organocopper reagents Organocopper compounds in organometallic chemistry contain carbon to copper chemical bonds. e.g. R 2CuLi, RCu(CN)Li or R 2Cu(CN)Li 2.   

  

The first organocopper organocopper compound, the explosive dicopper acetylide Cu2C2 was synthesized by Bottger in 1859. Henry Gilman prepared methylcopper in 1936. In 1941 Kharash discovered that reaction of a Grignard’s  Grignard’s  reagent with cyclohexenone in presence of Cu(I) resulted in 1,4-addition  instead of 1,2addition. In 1952 Gilman investigated for the first time dialkylcuprates.

Organocopper reagents

Organocopper Compounds α,β-Unsaturated α,β -Unsaturated carbonyl compounds have two reaction sites: R'' R'-MgX

O

R'''

+ R'''

1,4-addition

R

R''

R''

OMgX

R' R (1,4- addition)

+

R'''

OMgX

R' (1,2- addition)

R

1,2-addition

The composition of the product can be varied with sterric bulk of R’ in the Grignard reagent and R group in the carbonyl compound. Also as size of R’ R’   group of the Grignard reagent increases, the amount of 1,4addition product increases. The 1,4-addition of the Grignard reagent was proceeds though six membered transition state, whereas the 1,2-addition reaction proceeds through four membered transition state. Also if electron withdrawing group attached to alkene moiety, alkene  moiety, increases the yield of 1,4-addition product. What is the major product obtained by the treatment of Grignard reagent on α,β α,β-unsaturated -unsaturated aldehyde?

Organomagnesium Compounds Grignard’s Reagent: Grignard’s  Reagent: Reactivity X R'' R'-MgX

R'

O

+ R'''

R

R'' R'''

Mg R O

H3O+

R''' R''

O R'

R

The cuprous salts (Cu 2X2) was added to the Grignard’s Grignard’s   reagents forming less reactive product such as [ R 2MgCu or RCu) containing copper (I) which forming co-ordinate bond strongly with carbonyl oxygen atom in six membered transition state. Grignard reagent shows 1,4-addition reaction with carbonyl compound except α,β-unsaturated α,β -unsaturated aldehyde.

Organocopper Organocopper reagents: Reactions Substitution reactions: Cuprates R 2CuLi treated with alkyl halides R'-X gives the alkylcopper compound R-Cu, the coupling product R’-R R’-R and the lithium halide. r.d.s I

Nucleophilic attack to R’X

III

Oxidative addition

Reductive elimination

Order of reactivity of electrophiles: acid chlorides > chlorides > aldehydes aldehydes >  > tosylates tosylates ~  ~ epoxides epoxides >  > iodides > bromides  bromides >  > chlorides chlorides >  > ketones ketones >  > esters esters >  > nitriles nitriles >>  >> alkenes alkenes.. Oxidative coupling: coupling of copper acetylides to conjugated alkynes in the Glaser coupling or to aryl halides in the Castro-Stephens Coupling. Reductive coupling: coupling reaction of aryl halides with copper metal: Ullmann reaction. Redox neutral coupling: the coupling of terminal alkynes with halo-alkynes with a copper(I) salt in the Cadiot-Chodkiewicz coupling, Thermal coupling of organocopper compounds. Grignard’s would react in a 1,4-addition. Michael additions to enones where a Grignard’s would Carbocupration is a nucleophilic addition of organocopper reagents (R-Cu) to acetylene or terminal alkynes resulting in an alkenylcopper compound (RC=C-Cu). The presence of magnesium(I) bromide is generally required.

Organocopper reagents: R 2CuLi

Preparation: CH3Li

Two equivalent of lithium compound treated with one equivalent of cuprous iodide in ether ether.. +

2 (CH3)3CLi

CuI

+ 

ether 

CuI.Ph3P

CH3Cu ether   

CH3Li  

Li(CH3)2Cu

Li[(CH3)3C]2Cu.PPh3

The aryl, alkenyl and primary alkyl cuprates are prepared by this route but secondary  and tertiary cuprates are obtained from corresponding lithium derivative and ether soluble derivative of copper (I) iodide such as its complex with tributylphosphine or dimethyl sulphide.

Properties: These reagents are more stable and more reactive than the well known Cu(I) reagents.

Structure : The exact composition of the reagent is not well defined, but the spectroscopic studies and other evidences shows that in ether it exists in dimer form. The organic ligands are bonded to tetrahydral cluster of four metal

Organocopper reagents: R  reagents: R 2CuLi (reactions) Reaction with organic halide and other homologues reactants: reactants: Nucleophilic substitution bromine or iodine from organic halide by alkyl or alkenyl or aryl groups at or below room temperature to gives substituted products. 1. n-C6H13- OTs OH H3C H 2. H Br 

Br 

(C4H9)2CuLi

C10H22

o

ether, -75 C H3C

3.

OH H

Li(CH3)2Cu o ether, -15 C H3C

(sec-C4H9)2Cu(cn)Li2 o

Cl

THF, -78 C

I 4.

H

Cl

Br 

(

) Cu(CN)Li 2 o 2 THF, O C

CH3

It reacts with primary alkyl tosylates, with the secondary the  secondary alkyl halide are not gives product to high yield  by using ordinary organo cuprates such as R 2CuLi, these difficulty can be overcome by using higher order cuprates such as Li2R 2Cu(CN) which is prepared from two equivalent of organo lithium compound and one equivalent of cuprous cyanide.

Organocopper reagents

The important feature of this reagent was that they react with secondary alkyl halide by SN2 mechanism therefore if the starting alkyl halide is optically active then product obtained is having inversion in configuration. e.g. Reaction of lithium diphenylcuprate with (-)-(R)-2-bromobutane takes place forming  predominant _______________ _______________ of configuration. C2H5

CH3

Br 

(C4H9)2CuLi ether-THF, reflux

H

C2H5

CH3

H

C6H5

But iodide gives a racemic product on reaction with lithium diphenylcuprate which indicates that the reaction of cuprates with iodides at any rates takes place by a one electron transfer and not by SN2 reaction. Alkenyl halide reacts with organocuprates with retensation in configuration of the double  bond to give substituted alkene. The alkenylcuprates  react with retensation of geometry of the double bond. C6H5

H

Li(CH3)2Cu

C6H5

H

o

H

Br  (C2H5)2CuLi

ether, 0 C

+

H

2 HC CH

Organocuprates Organocuprates shows syn-addition to acetylenes

C2H5

CH3

)2 CuLi

I HMPA -30 to 25 oC

C2H5

Organocopper reagents: R  reagents: R 2CuLi (reactions) Reaction with acid halide and epoxide

Organocuprates are reacts radialy with acid chloride to give ketone and with epoxide to gives alcohol.

O R

O Li(CH3)2Cu o ether, 0 C

Cl

R

CH3 C3H7

O

Addition elimination OH

(C3H7)2Cu(CN)Li2 o

THF, O C 86%

Less substituted carbon atom

Li(CH3)2Cu O

OH

o

ether, -10 C CH3

Organocopper reagents: R  reagents: R 2CuLi (reactions)

Reaction with allylic halides and acetates Allylic halides and acetates are also react with organocuprates gives either rearranged or unrearranged product  i.e. reaction takes place at the allylic end or the carbon bearing leaving group. C4H9 (C4H9)2CuLi

 AcO

+

H9C4

o

ether, -10 C

(83%) O

CO

  O

(17%)

CO

(C4H9)2CuLi

Br 

ether, -10 oC C4H9

(C4H9)2CuLi O

O

o

ether, -30 C

H9C4

 

COOH

Organocopper reagents: R  reagents: R 2CuLi (reactions) With α,β α,β-Unsaturated -Unsaturated carbonyl compounds:

The R 2CuLi react with α,β-unsaturated α,β-unsaturated ketones β-substituted saturated ketone. ketone. The steric hindrance also affects the yield of r eacti action on i s i ncr eas ase ed by usin g L ewi s acid catalyst  and using higher order cuprates Li 2R 2Cu(CN). such as boron tr i f l uor i de etherate  CH3 OMe

OMe

Li(CH3)2Cu o

ether, -10 C O

O H

O

H

O (

n-C4H9

) Cu(CN)Li 2 2

(n-Bu) 2CuLi, BF3 o Diethyl ether, -70 C

o

ether, -50 C

O

O 53%

Controlling of the stereochemistry  of the addition of organocuprates is difficult. It gives mixture of enantiomers/diastereomers, but one of them is major product formed by approach of the reagent in a direction orthogonal to the plane of the enone system. system.

Organocopper reagents: R  reagents: R 2CuLi (reactions) With α,β α,β-Unsaturated -Unsaturated carbonyl compounds: Mechanism: The transfer of organo groups from organocuprates to the β-position of the conjugated ketones is uncertain (basically intramolecular). Most of evidences show that - initial transfer of one electron from organocopper (I) species to the ketone to give anion radical followed by co coupli upli ng and intr amo amolec lecul ul er transfe transferr of organic gr oup fr om the me metal tal to  β -carbon - carbon ato atom  m  . The  – R groups of the organocuprate, R 2CuLi, are transfer with retention of configuration which ruled out the formation of free radicals, therefore R migrates intramoleculerly from cuprate to enone.

R4Cu2Li2

+

.

R

+ H3CCH-CH=CCH3  + [R2CuLi]2

H3CCH=CHCOCH3

Cu

.

O

O

(CH3)2CuLi o

0C

Li R

Br  CH3

CH3

H3C CH3

R O-

O O-

Br  CH3

CH3

R

Formation of enolate anion confirm by following example

H+

O-

Cu

R

H3C

CH3

Li R

O

CH3

Organocopper reagents: R  reagents: R 2CuLi (reactions) With α,β α,β-Unsaturated -Unsaturated carbonyl compounds: Limitation: Conjugate addition of ordinary organocuprate to α,β α,β-unsaturated -unsaturated aldehydes is not synthetically useful reaction because of the simultaneous the  simultaneous formation of pro products ducts formed by the reaction at the carbonyl group. group. The conjugated addition can be affected by using modified reagent such as Me5Cu3Li2. Me5Cu3Li2 shows negligible attack on the carbonyl group. (CH3)5Cu3Li2 CHO Diethyl ether 

-CO CHO 1,4-addition

Organocuprate also shows conjugate cis-addition into α,β α,β-acetylenic -acetylenic ester to give β,β β,β--Olefinic esters are not react with organocuprates disubstituted acrylic ester at -78oC. α,β -Olefinic under the mild reaction conditions, but conjugate addition can be effected in the presence of boron trifluoride etherate. C7H15

 

COOCH3

C7H15

(CH3)2CuLi o THF, -78 C

H3C O

O

I

R*O H

CH

CuI, BF3, o -10 C

R*O

COOCH3

C7H15

H3O+

H3C

Cu CH3

CH3 Hydrolysis

COOH

COOCH3 H

Organocopper reagents: R  reagents: R 2CuLi (Limitations)

Many cases an - excess of reagent has to be required. Conjugate addition to enones at any rate only one of the two organo-groups in the cuprates take part  in the reaction and other is effectively wasted. This limitation can be overcome by using higher order organocuprates R 2Cu(CN)Li is that only required in small excess. excess . The number of other mixed reagents have been developed R rR tCuLi are used in which R r  is tightly bound to copper and only R t is transferred.

Organocopper reagents: RCu reagents: RCu

Organocopper(I) reagents RCu are less exclusively used in organic synthesis because they are less stable. The more stable organo compounds as RCuMgBr2 or [RCuBr]MgBr are used which is formed from equimolar quantity of copper (I) bromide and Grignard’s Grignard’s reagent  reagent or organocopper in presence of zinc salt . It was added to terminal alkynes to forming synthetically useful 1-alkenyl copper (I) compound. The R-group and Cu is added to the same side of double bond. .RCu.MgBr  2

R'

+

R'

H

H R

H

H

C4H9 H CH

NH4Cl OH2

H

H

H

H

R2CuLi C4H9

R

Cu

H

. H Cu.MgBr  C 4 9 2  + H

H CH CH OH

I2

C4H9

I

Cu CO2

O H C4H9

R'

CH3I

H COOH

H

R R'

H

R

H H

H

C4H9

R

CH3I NH4Cl OH2

CH3

H

H

C4H9

H

Organocopper reagents: Castro-Stephens coupling

The Castro-Stephens Coupling is a cross coupling reaction between a Copper(I) acetylide and an aryl halide forming a disubstituted disubstit uted alkyne. alkyne.

Example

Organocopper reagents: Ullmann or Ullmann coupling Ullmann coupling is a coupling reaction between aryl halides with copper or copper-bronze alloy

The reaction probably involves the formation of an organocopper compound (RCuX) which reacts with the other aryl reactant in a nucleophilic aromatic substitution.

The Ullmann reaction is limited to electron deficient aryl halides and requires harsh reaction conditions. In organic synthesis this reaction is often replaced by palladium coupling reactions such as the Heck reaction, the Hiyama coupling and the Sonogashira coupling.

Organocopper reagents: Ullmann or Ullmann coupling

Mechanism

Organocopper reagents: Named reactions

The Cadiot-Chodkiewicz coupling  is a coupling reaction between a terminal alkyne and a haloalkyne catalyzed by a copper(I) salt such as copper(I) bromide and an amine base.

Eglinton Reaction

Rosenmund-von Braun Reaction

Sonogashira Sonogashira coupling Vinyl/aryl halide

Terminal alkynes The palladium complex activates the organic halides

Complete the following reactions

1

2 7 1. 2. 3.

3

Mg Cu2Br2 Alkyne, 4. 4. NH NH4Cl

4

5

6

1. 2. 3.

1. Lithiation 2. R2CuLi formation 3. React action wi with RX RX

Mg Cu2Br2 Alkyne

Organochromium compounds

The aryl chromium complexes increase the reactivity significantly of the aromatic ring. E.g. Unsaturated chromium complexes, complexes , alkyl chromium species and chromium carbenes. carbenes .

Synthesis:  

Heating the arene with chromium hexacarbonyl, Cr(CO)6. By ligand exchange (naphthalene) with naphthalene chromium tricarbonyl complex. R R

Cr(CO)6/heat CO

Structure

+

3 CO

Cr 

CO CO

Heptacity

The desired arylchromium complex bearing the arene ( η6-species) and three carbon  li gands on the chromium (0) atom (18-electron complex). complex). monoxide ligands

Reactivity The chromium atom exerts electron withdrawing effect on the aromatic ring which allows the nucleohp nucleohpilic ilic attack on the aromatic ring rather than the electrophilic substitution. The electron deficient arene ring can stabilized the negative charge, therefore allowing the metallation (lithium, magnesium, etc) on the ring or at benzylic position. The chromium can be released easily by mild oxidation such as by b y using iodine. The intermediate is converted into cyclohexadiene by protonolysis (by using trifluoroacetic acid).

Mechanism The nucleophilic nucleophilic attack on the arylchromium complex can be occurs from the face opposite to the bulky chromium atom and gives an intermediate η5-cyclohexadiene anion complex. complex . The nucleophilic attack can be takes place on the carbon atom bearing halogen ( ipso substitution ) then subsequent loss of halide anion leads to overall nucleophilic substitution. COOEt

EtOOC

COOEt

F EtOOC CO

COOEt

F

Cr 

CO CO

Ipso position

CO

COOEt

Cr 

CO

CO CO

Cr 

CO CO

In some cases, the addition of nucleophile to arylchromium complex need not takes place at the ipso  position. Using the hard nucleophile (pK a > 20), the attack is irreversible and forming mixture of the products from the attack at the ortho-, meta-, and para-positions . Commonly, the attack of the nucleophile takes place at the meta-position . The regioselectivity of the substitution can be depends on the nature and location of the substituents attached to aromatic ring and on the nucleophile. CH3

F

CH3 CO

Cr 

CO CO

H3C Li

S S

then H +

S

CH3

S H3C CH3

In cyclohexadienyl anion, hydrogen shift and elimination of HX leads the overall substitution (not  by ipso substitution).

Addition of reagents such as n- or s-butyllithium to the arylchromium complex normally results lithiation of the aromatic ring. O

O Li

F nBuLi CO

O

Cr 

CO CO

ortho-to fluorine

F

CO

F O

O

Cr 

CO CO

CO

Cr 

CO CO

O

Nucleophile

Cr(CO)3

Lithiation at benzylic position of arylchromium complexes can be occurs readily using suitable base. Addition of the electrophile  is then takes place at opposite side (less hindered, uncomplexed face) of the bulky chromium metal . CH3 Me3Si MeO

OMe Cr 

CO

Me3Si MeO

nBuLi

Cr 

CH3I

CO CO

OMe

CO CO CO

H

Hindered side

Addition of the nucleophile to the chromium complexed benzylic electrophilic carbon or other electrophilic group occur from the less hindered, uncomplexed uncomplexed faces f aces. CH3 O

OH

CH3Li Cr 

Cr  CO

CO CO

CO

CO CO

Hindered side

Nozaki-H Noz aki-H i yama ama-Ki -Ki shi r eac acti tion  on  The addition of CrCl2 to the unsaturated halide (alkenyl or alkynyl) followed by coupling with aldehyde. OH Br  +

HOC

CO2Me

CO2Me

CrCl2 THF

The chromium(II) species inserts into the unsaturated halide (or sulfonate) to give the corresponding organochromium(III) organochromium(III) reagent. The organochromium compounds have low reactivity  (basicity or nucleophilic character) and tolerate (not reacting) many different functional groups, reacting chemoselectively with ester. aldehyde in presence of ketone or ester. O

O + I

PhCHO

CrCl2 DMF

Ph OH

This insertion can be catalyzed by nickel salts (NiCl2) or manganese powder. In addition to unsaturated halides, gem-dihaloalkanes  reacts with chromium(II) salts resulting organochromium species which reacts with aldehyde forming alkenyl halide, which is typically E-selective (alkenylation). This is called as Takai alkenylation

Iron Pentacarbonyl [Fe(CO) 5] Reaction of pentacarbonyl iron with sodium amalgam (Na-Hg) forming sodium tetracarbonyl ferrate (II) which is a volatile reagent. It is used for the synthesis of aldehyde and ketone from alkyl halide .

Fe(CO)5 RCH2-Br 

+ 

Na(Hg)

THF

1. Na2Fe(CO)4

Na2Fe(CO)4 2. PPh3

3. AcOH

RCH2-CHO

Mechanism: -

CO

CO

CO RCH2-Br  + Na2Fe(CO) 4

+

Na

RCH2

Fe

RCH2CO Fe CO CO R shift from Fe to CO

CO +

Na

RCH2

Fe

CO CO

CO   AcOH 1. PPh3 2 RCH2-CHO +  AcONa + [PPh 3]Fe(CO)3

RCH2COOH

OH2

-

CO

RCH2-CO

RCH2-COX

CO

  acid ROH

R'2NH

RCH2COOR ester  RCH2CONR'2 amide

The reaction of anion [RCH 2Fe(CO)4]- with second molecule of alkyl halide gives neutral product which after rearrangement undergoes reductive reaction or rearrangement in presence of suitable coordinating solvent (solvent containing at least one electron donating atom) forming ketone . -

CO CO +

Na

RCH2

Fe

CO CO

CO

R'CH2X

RCH2

 

R'CH2

CO Fe

CO CO

solvent  

CO

RCH2 Fe

R'CH2CO

CO CO

R'CH2COCH2R + [solvent]Fe(CO) 3

Tetracarbonyl Nickel (0) Ni(CO) 4 It is important regent for the carbonylation reaction in organic synthesis. Tetracarbonyl nickel (0) and organo-lithium compound combine to forming unstable complex which was synthetically important intermediate for the synthesis of aldehyde and ketone. -

O 1. R-Li

  +

Li

Ni(CO)4

O

+ R   Ni(CO)3

O

+ H

R   Ni(CO)3

R   Ni(CO)3 H solvent

O 2. R-Li

  +

Ni(CO)4

Li

-

R-CHO

+ R   Ni(CO)3

+

O O

R'-X R   Ni(CO)3

Ni(CO) 3(Solvent)

R   Ni(CO)3 R' solvent R-CO-R' Ketone

+

Ni(CO) 3(Solvent)

Olefin  undergoes carbonylation reaction  by using Ni(CO)4, CO and water in presence of  proton (acid) Ni(CO)3

Ni(CO)4 +

Ni(CO)3

H

+

+

CO + H2O/CO/H

CO H

+ Ni(CO)3

Ni(CO)2

H

H   COOH

Alkynes react with tetracarbonyl nickel (0) in presence of water  forming α,β-unsaturated carboxylic acid. R

  4 H + Ni(CO)

CO  

RCH=CH-Ni(CO)3

+ R-CH=CH-CO-NI(CO)3 OH2 R-CH=CH-COOH

The tetracarbonyl tetracarbonyl nickel (0) reacts with a lithium compound forming an intermediate complex which shows nucleophilic character of acyl group. O R-Li +  Ni(CO) 4

R   Ni(CO) 3

-

O R  

Ni(CO)3

R-C=O

+

R O

O R

O

Selenium oxide (SeO2) Preparation: It is prepared by heating selenium strongly in air in presence of trace amount of nitrogen peroxide which acts as catalyst.

Se

Nitrogen peroxide

O2

+

SeO2

It is also prepared by passing the vapour of sulphuryl fluoride over selenium and silica contained in a glass vessel 2 SO2F2

+

+

Se

SiO2

SeO2

+

2 SO3

+

SiF4

Uses: Selenium dioxide is used as oxidizing agent; it oxidized active methyl or methylene groups as well as allylic group into carbonyl compound without affecting other functional groups. i)

CH3CHO +

ii)

Ph-CO-CH3

iii)

SeO2

CH3CH2COCH3

 

SeO2

+ +

SeO2

 

OHC-CHO (Glyoxal) Ph-CO-CHO (Phenyl glyoxal) CH3COCOCH3 +

CH3CH2COCHO (major)

iv)

+ N

CH3

SeO2 N

COOH

When the meth methylene ylene group is activated by single C=C bond is oxidized into i nto keto-group keto-group.

SeO2 O (2-Pinene)

(Verbenone) (35%)

Mechanism: The oxidation with selenium dioxide is carried out in presence of acetic acid. The actual reagent taking part in the reaction is a selenious acid. This reaction is proceeds through an enol ester of selenious acid. The formation of selenious acid ester is the rate determining step. OH O R

H2 C R'

HO R

O

H2 SeO3

R'

SeO2 + OH2 +  AcOH

R

Se

O R'

O R

OSe-OH

O

OH

OH2

R

R'

R'

enol ester of selenious acid

O O R

R R' O

H2SeO3 R' H

O

O Se OH

Selenium dioxide in aqueous or alcoholic solution is used in allylic oxidation. During this oxidation, both allylic alcohols are formed. HO

H SeO2 + OH2

or 

+

SeO2 + ROH

HO

The mechanism of this reaction involves selenious acid or equivalent species as a oxidant. The double bond shows nucleophilic attack on the selenious acid forming unsaturated selenious acid monoester . The mechanism of this reaction is shows belowHO HO O Se

H

OH

+

OH O Se

HO Se

OH

OH

OSeOH

O

If the molecule contain primary, secondary and tertiary hydrogen’s, hydrogen’s, the  the order of oxidation isOH -CH2- > -CH3 > -CH-. H3C CHCH3 CH3CH2

SeO2

H3C CHCH3 H3C 34%

OH

CHCH3

+ CH3CH2 01%

When double bond is in a ring, oxidation occurs within the ring and at the α- to the more substituted end of the double bond or chain. CH2CH3

CH2CH3 HO

SeO2

The selenium dioxide is used as dehydrogenating agent. It acts as dehydrogenating agent in α,β-unsaturated ketones, alcohols into acidic or basic medium. It can be converts ketones into α,β-unsaturated ketone/aldehyde, ester into unsaturated ester. ester. Generally, Generally, it dehydrogenates the cyclic ketones, 1,4dicarbonyl systems systems and primary alcohols O

O SeO2

1.

Pyridine

2. 3.

4. 5.

SeO2

CH3COCH2CH2COCH3 EtOOCCH2CH2COOEt

C6H5-CH2OH C H -CH

SeO2

CH3COCH=CHCOCH3 H

COOEt

0

170 C SeO2

at its B.P. SeO2

EtOOC

H

C6H5-CHO C H -CHO

2,3-Dichloro-5,6-dicyano 2,3-Dichloro-5,6-dicy ano quinone It is used as strong dehydrogenating agent or strong oxidizing agent. It remove hydrogen atom from adjacent carbon atom or by rearrangement forming double bond. The reagent first abstract abstract the hydride ion followed by the removal of proton.

DDQ 0

Benzene/80

Mechanism Proton shift

+

H + Cl

H

Cl O

O NC

H

Cl

Cl OH

O

Hydride ion transfer

NC

Cl

CN

+

CN

H

OH

O NC

11. C6 H5-CH=CH-CH3

+ DDQ   Ph-CH=CH-CH 2 C6 H6, reflux

Oxidation allyl methyl/methylene C H -CH=CH-CHO

Cl

CN

DDQ-H C 6 H5-CH=CH-CH2-OAr   ArO

C H -CH=CH-CH(OAr)

DDQ DD Q OH 2

C H -CH=CH-CH(OAr)