The Wittig and Related Carbonyl Olefination Reactions

SECTION 2.5. THE WITTIG AND RELATED CARBONYL OLEFINATION REACTIONS 

Alkylation of /3-keto sulfoxides gives intermediates which can undergo thermal elimination to form a,/3-unsaturated ketones  

CHAPTER 2 REACTIONS OF CARBON NUCLEOPHILES WITH CARBONYL GROUPS 

Phosphorus ylides are usually stable, albeit highly reactive, compounds and can be represented by two limiting Lewis structures. These are sometimes referred to as the ylide and ylene form. Using (CH3)3PCH2 (trimethylphosphonium methyl-ide) as an example, these two forms can be illustrated as follows  

The stability of phosphorus ylides is ascribed to resonance between the two Lewis structures in which the ylene form implies electron donation into phosphorus 2 d orbitals. Recent careful and P nmr spectroscopic studies of trimethyl- 

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The reactions described in this chapter include some of the most useful and frequently employed synthetic methods for carbon-carbon bond formation aldol and Claisen condensation reactions, the Wittig and related olefination reactions, and the Robinson annulation. All of these processes involve, at some point, the addition of a carbon nucleophile to a carbonyl group. The type of product which is isolated depends on the nature of the substituent (X) on the carbon nucleophile, the substituents (A and B) on the carbonyl group, and the ways in which A, B, and X affect the reaction pathways available to the intermediate formed in the addition step. 

Asymmetric carbonyl olefination methods by routes other than the Wittig and related olefination reactions are available, and some precedents belonging to this... 

This section deals with reactions that correspond to Pathway C, defined earlier (p. 64), that lead to formation of alkenes. The reactions discussed include those of phosphorus-stabilized nucleophiles (Wittig and related reactions), a a-silyl (Peterson reaction) and a-sulfonyl (Julia olefination) with aldehydes and ketones. These important rections can be used to convert a carbonyl group to an alkene by reaction with a carbon nucleophile. In each case, the addition step is followed by an elimination. 

The Peterson olefination reaction involves the addition of an a-silyl substituted anion to an aldehyde or a ketone followed by the elimination of silylcarbinol either under acidic (awP -elimination) or basic (syn-elimination) conditions to furnish olefins178. Thus, Peterson olefination, just like Wittig and related reactions, is a method for regioselective conversion of a carbonyl compound to an olefin. Dienes and polyenes can be generated when the Peterson reaction is conducted using either an ,/l-unsaturated carbonyl compound or unsaturated silyl derivatives as reaction partners (Table 20)179. 

The B-alkyl-9-BBN undergoes an interesting reverse reaction to afford the parent alkene when treated with benzaldehyde. Consequently, the reaction is uniquely employed for the synthesis of exocyclic olefins (Chart 24.3). The hy-droboration of cyclic olefins with an internal double bond, followed by homologation with carbon monoxide in the presence of lithium trimethoxyaluminum hydride afford B-(cycloalkylmethyl)-9-BBN. This intermediate on treatment with benzaldehyde leads to an exocyclic methylene compound (Chart 24.3) [16]. Since the synthesis proceeds from the cycloalkene, thus it provides a valuable alternative to the customary methylenation of carbonyl compounds by Wittig and related procedures. The method also provides a clean synthesis of deuterium-labeled compounds (Eq. 24.10) [16], without positional scrambling or loss of label. Consequently, methylmethylene-d -cyclopentane in 52% isolated yield is obtained. 

Generally, arsonium ylides [62] are more reactive but less accessible than phos-phonium ylides. Recently, the chiral arsonium reagent 30 has appeared, and has been applied in asymmetric Wittig-type carbonyl olefinations. This first chiral arsonium reagent also bears 8-phenylmenthyl as a chiral auxiliary on its carboalkoxy portion [63], and gave moderate chemical yields and diastereoselectivities in the conversion of 4-substituted cyclohexanone derivatives to axially chiral non-racemic alkylidene cyclohexanes under the same reaction conditions as used for the related reactions with phosphorus reagents (Scheme 7.15). On the other hand, the corre-... 

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