carbonyl chemistry iiwillson.cm.utexas.edu/teaching/ch391/files/ch391lecture8.pdfchemistry 391...

Carbonyl Chemistry IICarbonyl Chemistry II

++CCOO--

CCOO

Lecture 8Lecture 8Chemistry 391 10/20/02

Chemistry 391 10/23/02

Reaction ThemeReaction ThemeThe most common reaction of a carbonyl group is addition of a nucleophile to form a tetrahedral addition compound

Tetrahedral carbonyl addition compound

+ CR

RO CNu

O -

RR

Nu -

Here it is an acid or electrophile


Carbon Carbon NucleophilesNucleophilesAddition of carbon nucleophiles is one of the most important types of nucleophilic additions to a C=O group; a new carbona new carbon--carbon bondcarbon bond is formed in the process!!!!

We will study the addition of these carbonnucleophiles

A Grignard reagent

An organolithium reagent

An anion of a terminal alkyne

Cyanide ion

RC C - NRMgX RLi - C


See Ashby, E.C., Smith , M.B. J. Chem Soc. 1964, 86 4363 and references thereto…I consider the detailed structure of this reagent to still be a topic of research!


GrignardGrignard ReactionsReactions

Mg+2H3O+

CH3CH2- MgBr+

HC

HO CH3CH2 C

H

H

O- MgBr+CH3CH2 C

H

H

OH +THF dil.

Mg+2H3O+

CH3CH2- MgBr+ C

HO CH3CH2 C

H

O- MgBr+ +THF dil.

CH3CH2 C

H

OH

Mg+2H3O+

CH3CH2- MgBr+ CH3CH2 C O- MgBr+

CH3

CH2

CH2

CH3

+THF dil.

CH3CH2 C OH

CH3

CH2

CH2

CH3

C O

CH3

CH2

CH2

CH3


Grignard Reactions

Mg+2H3O+

CH3CH2- MgBr+ CH3CH2 C O- MgBr+

O

+THF dil.

CH3CH2 C OH

O

C OO

MgBrO

THFO-MgBr+

H3O+

Dilute

OH

These are valuable and important reactions…

Please add to your card stock!

GrignardGrignard reagents react with estersreagents react with esters

––++

RR CC

OO••••

•••• ••••

OCHOCH33••••••••

R'R'

RR

MgXMgX

CC

OO

••••••••

δδ–– δδ++ OCHOCH33••••••••

R'R' diethyldiethyletherether

MgXMgX

but species formed is but species formed is unstable and dissociates unstable and dissociates under the reaction under the reaction conditions to form a ketoneconditions to form a ketone

GrignardGrignard reagents react with estersreagents react with esters

––++

RR CC

OO••••

•••• ••••

diethyldiethyletherether OCHOCH33

••••••••

R'R'

––CHCH33OOMgXMgX

RR

MgXMgX

CC

OO

••••••••

δδ–– δδ++ OCHOCH33••••••••

R'R'

MgXMgX

this ketone then goes this ketone then goes on to react with a on to react with a second mole of thesecond mole of theGrignardGrignard reagent to reagent to give a tertiary alcohol

CC

OO

RR R'R'

••••••••give a tertiary alcohol

ExampleExample

2 CH2 CH33MgBrMgBr ++ (CH(CH33))22CHCCHCOCHOCH33

OO

1. diethyl ether1. diethyl ether

2. H2. H33OO++

Two of the groups Two of the groups attached to the attached to the tertiary carbon tertiary carbon come from thecome from theGrignardGrignard reagent

(CH(CH33))22CHCCHCCHCH33

OHOH

CHCH33reagent

(73%)(73%)


Sorry, but This Does NOT work!!!!

But……


This does!!


HH22CC CHLiCHLi CHCH

OOOrganolithiumOrganolithium ReagentsReagents

++

1. diethyl ether1. diethyl ether

2. H2. H33OO++

CHCH22CHCHCHCH

OHOH(76%)(76%)


Salts of Terminal AlkynesSalts of Terminal AlkynesAddition of an acetylide anion followed by H3O+ gives an α-acetylenic alcohol

Mg+2H3O++

THF dil.C O

CH3

CH2

CH2

CH3

C O- MgBr+

CH3

CH2

CH2

CH3

C OH

CH3

CH2

CH2

CH3

RC C- Na+ RC C RC C


Salts of Terminal Salts of Terminal AlkynesAlkynes

HO C

OCCH3HO

HO CH2 CH

O

H2 SO 4 , HgSO4

H2 O

2 . H 2O2 , NaOH

An α-hydroxyketone

α

β

α

CH

1 B2H6

A β-hydroxyaldehyde

Write the mechanism using the arrow convention


O

HC C1) Na, THF

2) H3O+

CHC

OH1) B2H6, THF

2) H2O2, NaOH

HO CH2CH

O

O

HC C1) Na, THF

2) H3O+

CHC

OH ?????

HO

O

CH3


MECHANISM FOR REACTION OF MECHANISM FOR REACTION OF ALKENES WITH BHALKENES WITH BH33

Step 1:A concerted reaction. The π electrons act as thenucleophile with the electrophilic B and the H is transferred to the C with syn stereochemistry.

Step 2:First step repeats twice more so that all of the B-H bonds react with C=C to produce the trialkylborane


Step 3:Peroxide ion reacts as the nucleophile with theelectrophilic B atom.

Step 4:Migration of C-B bond to form a C-O bond and displace hydroxide. Stereochemistry of C center is retained.

Step 5:Attack of hydroxide as a nucleophile with theelectrophilic B displacing the alkoxide.

Step 6:An acid / base reaction to form the alcohol.


Another variant on the Another variant on the WittigWittig reaction that is much easier and reaction that is much easier and cheaper to carry out is called thecheaper to carry out is called the WittigWittig--Horner reactionHorner reaction. This . This uses auses a phosphitephosphite ester instead of aester instead of a phosphinephosphine::

E/Z is an interesting issue and still not fully clear.Triphenylphosphines tend normally to give the Z- (or cis-) isomer. Trialkylphosphines or the presence of groups thatstabilise the ylide tend to give E- (or trans-) geometry. So take your pick!


Addition of HCNAddition of HCNMechanism of cyanohydrin formation

N C- H3O+

THF dil.C O

CH3

CH2

CH2

CH3

C O-

CH3

CH2

CH2

CH3

N C Mg+2+C OH

CH3

CH2

CH2

CH3

N C


CyanohydrinsCyanohydrinsThe value of cyanohydrins is for the new functional groups into which they can be converted– acid-catalyzed dehydration of the 2° alcohol gives a

valuable monomer

Propenenitrile (Acrylonitrile)

+

acid catalyst

2-Hydroxypropanenitrile (Acetaldehyde cyanohydrin)

CH3 CHC N

OH

NCH2 =CHC H2 O


CyanohydrinsCyanohydrins– acid-catalyzed hydrolysis of the cyano group

gives an α-hydroxycarboxylic acid

acid catalyst

Benzaldehyde cyanohydrin (Mandelonitrile)

2-Hydroxy-2-phenyl- ethanoic acid

(Mandelic acid)

+N

OH

CHC CHCOH

HO OH2 O


CyanohydrinsCyanohydrins– catalytic reduction of the carbon-nitrogen

triple bond converts the cyano group gives a 1° amine

Benzaldehyde cyanohydrin 2-Amino-1-phenylethanol

Ni+CHC

OH

NOH

CHCH2 NH22 H2

LiAlH4 also works well...LiAlH4 also works well...

But…what about Pd/C and H2But…what about Pd/C and H2


WittigWittig ReactionReactionThe Wittig reaction is a very versatile synthetic method for the synthesis of alkenes fromaldehydes and ketones.

Triphenyl- phosphine oxide

Methylene- cyclohexane

A phosphonium ylide

+

+-+

+

O

CH2 Ph 3 P-O -

Ph 3 P-CH 2


Phosphonium YlidesPhosphonium YlidesYlideYlide: a molecule which, when written in a Lewis structure showing all atoms with complete valence shells, has positive and negative charges on adjacent atoms

Phosphonium ylidesPhosphonium ylides are formed in two steps: 1. treatment of triphenylphosphine with a 1° or 2°

alkyl halide to form a phosphonium salt followed by 2. treatment of the phosphonium salt with strong base,

typically butyllithium


Phosphonium YlidesPhosphonium Ylides

An alkyltriphenyl-phosphonium iodide

+Ph 3 P-CH 3 I-S N2

Triphenyl-phosphine

+Ph 3 P CH3 -I

+CH3 CH2 CH2 CH2 Li + + H-CH 2 -PPh 3 I -

Butyllithium

•• +-CH2 -PPh 3 + + Li + I -CH3 CH2 CH2 CH3

A phosphonium ylide

Butane

Ph3P+ CH2-

Ph3P CH2


WittigWittig ReactionReactionPhosphonium ylides react with the C=O group of aldehydes or ketones to give alkenes

Triphenylphosphine oxide

An alkene

+

-••+

An oxaphosphetane

•••• •• ••

-

+•• ••

••

CH2

CR2 O

CH2

CR2

CH2

CR2O

Ph 3 P Ph 3 P

O

Ph 3 P


WittigWittig ReactionReactionexamples

-++

+ 1-Phenyl-2-butene (87% Z isomer; 13% E isomer)

+

O

PhCH 2 CH Ph 3 P-CHCH 3

PhCH 2 CH=CHCH 3 Ph 3 P-O -

What about the E/Z ratio…??What about the E/Z ratio…??


WittigWittig ReactionReactionExamples:

++ -

+2-Methyl-2-heptene

+

O

CH3

CH3 CCH3 Ph 3 P-CH(CH 2 ) 3 CH3

CH3 C=CH(CH2 ) 3 CH3 Ph 3 P-O -


A variant on the Wittig reaction that is much easier and cheaper to carry out is called the Wittig-Horner reaction. This uses a phosphite ester instead of a phosphine:

The Wittig-Horner reaction

The ylide is much more reactive in this case.


TheThe WittigWittig ReactionReaction“ Cis/trans, E/Z etc. Well, that's an interesting issue though still not fully clear.Triphenylphosphines tend normally to give the Z- (or cis-) isomer. Trialkylphosphines or the presence of groups that stabilise the ylide tends to give E- (or trans-) geometry. So take your pick! What makes the Wittig reaction so useful is that it can tolerate all kinds of functionality”.

http://www.sunderland.ac.uk/~hs0bcl/org8.htm


++ -

+

Ethyl (E)-4-phenyl-2-butenoate (only the E isomer is formed)

+

O O

Ph 3 P-O -

PhCH 2 CH Ph 3 P-CHCOCH 2 CH3

H

C CCOCH2 CH3

PhCH 2 H

O

So….this is not so easy!!


Homework: Due Wed 10/29Homework: Due Wed 10/29

Read Chapter 15 and “learn” the reactions on pages 752 –754

Do: 15.27, 15.33, 15.35a,b, 15.39, 15.41, 15.45 and the 10 synthesis problems on the web page!

carbonyl chemistry iiwillson.cm.utexas.edu/teaching/ch391/files/ch391lecture8.pdfchemistry 391...

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