Julia olefination reaction

Chapters 1 and 2 focus on enolates and other carbon nucleophiles in synthesis. Chapter 1 discusses enolate formation and alkylation. Chapter 2 broadens the discussion to other carbon nucleophiles in the context of the generalized aldol reaction, which includes the Wittig, Peterson, and Julia olefination reactions. The chapter and considers the stereochemistry of the aldol reaction in some detail, including the use of chiral auxiliaries and enantioselective catalysts. 

There are several new methodologies based on the Julia olefination reaction. For example, 2-(benzo[t/Jthiazol-2-ylsulfonyl)-j -methoxy-i -methylacetamide 178, prepared in two steps from 2-chloro-iV-methoxy-jV-methylacetamide, reacts with a variety of aldehydes in the presence of sodium hydride to furnish the ajl-unsaturated Weinreb amides 179 <06EJOC2851>. An efficient synthesis of fluorinated olefins 182 features the Julia olefination of aldehydes or ketones with a-fluoro l,3-benzothiazol-2-yl sulfones 181, readily available from l,3-benzothiazol-2-yl sulfones 180 via electrophilic fluorination <06OL1553>. A similar strategy has been applied to the synthesis of a-fluoro acrylates 185 <06OL4457>. 

The S. Julia olefination reaction modified and optimized by P. Kocien-ski [10] became the premiere fragment linkage reaction in construction of functionally complex targets. It has frequently been referred to as the Julia-Kocienski reaction. 

The Wittig, Horner-Wadsworth-Emmons, Peterson, and Julia Olefination Reactions... 

The Julia olefination reaction is highly regioselective and ( )-stereoselective, providing a valuable alternative to the Schlosser reaction for making rrans -disubstituted olefins. The reaction involves condensation of a metalated alkyl phenyl sulfone with an aldehyde to yield a P-hydroxysulfone, which is then subjected to a reductive elimination to produce the alkene. There are limitations to the preparation of tri- and tetra-substituted alkenes via the sulfone route because the P-alkoxy sulfones derived from addition of the sulfone anion to ketones may be difficult to trap and isolate or they may revert back to their ketone and sulfone precursors. 

The removal of the sulfone group can be accomplished under a number of different reductive conditions. Most popular is the concomitant removal of both the sulfone and the derivatized (3-hydroxy group to give an alkene and this is commonly termed the Julia olefination reaction (see Section 2.8). 

Kocienski and his co-workers have described the novel intramolecular Lewis acid catalysed directed aldol reaction of the spiro-cyclic ortholactone (18 ) prepared from the fragments (185) and (186), to set up the spiro-acetal portion (I88). Milbemycin (189) was then secured from (I88) by sequential sulphone-based (Julia) olefination reactions to produce the double bonds at C10-... 

Recently, fluoro-Julia olefination reaction using a-fluorinated heteroaryl sulfone has been actively studied for the synthesis of fluoroaUcene [38]. Fluorinated... 

Scheme 8 Mechanism of fluoro-Julia olefination reaction...

Table 2 Fluoro-Julia olefination reaction using various reagents ...

Tributyltin-1,3-dienes have been synthesized from tributyltin substituted benzothiazolyl sulfones and aldehydes via a Julia olefination reaction. The selectivity of the process proved higher in the presence of KHMDS as base (Scheme 96) [190]. 

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