Aldol reactions defined

In the text below organocatalytic asymmetric aldol reactions are classified into indirect aldol reactions and direct aldol reactions . Indirect aldol reactions are syntheses which require a modified ketone as a starting material (Scheme 6.9, pathway 1). For example, enolates which are prepared in a previous step starting from the ketone are often used. Syntheses which allow the direct use of a ketone, in a non-activated form, as a nucleophile are defined as direct aldol reaction (Scheme 6.9, pathway 2). 

A directed aldol reaction is a variation of the crossed aldol reaction that clearly defines which carbonyl compound becomes the nucleophilic enolate and which reacts at the electrophilic carbonyl carbon. The strategy of a directed aldol reaction is as follows ... 

The first catalytic, diastereoselective and enantioselective cross-aldol reactions of aldehydes have also been documented. Geometrically defined trichlorosilyl enolate derivatives of aldehydes undergo diastereoselective addition to a wide range of aldehyde acceptors with good enantioselectivity. The use of chiral Lewis base (138) was critical for achieving useful enantioselectivity. ... 

O Scheme 25) [150]. The latter acts as an acceptor only because of its good electrophilic and non-nucleophilic character. The a-thioacetal functionality in this enantioselective crosscoupling allows access to highly oxidized, stereo-defined synthons of broad versatility. Moreover, the observed reactivity profile makes them pre-eminent substrates for highly selective cross-aldol reactions with ketone donors. 

Roush has also completed the synthesis of a C13-C25 fragment of bafilomycin A], now using a methyl ketone aldol reaction between ketone 184 and aldehyde 5 to form the C20-C21 bond (Scheme 9-52) [71], This reaction was only. selective (89% ds) under carefully defined conditions which included choice of metal enolate and, remarkably, the remote C15 oxygen protecting group. Replacing the C15 MOM ether with a silyl ether, as in 185, led to a ca. 1 1 mixture of aldol prod-... 

FORMATION AND ALDOL REACTIONS OF REGIO-DEFINED ENOLATES... 

The great power of the aldol addition reaction lies in the ability to generate and use structurally defined enolates. In this section, the emphasis is on the formation of regio-defmed enolates, and the aldol reactions of these enolates. Stereochemical issues are dealt with in Sections 1.6.2-1.6.4. 

The introduction of the foregoing bases opened the way for the preparation of structurally defined enolates examples are seen in equations (5) to (7). The first examples of the use of these regio-defined enolates in crossed aldol reactions were reported by Stork, Kraus and Garcia in 1974 representative examples are shown in equations (8) and (9). ... 

Masamune and cowoikers designed a set of chiral rra/iy-2,5-dimediylborolane-based reagents diat show remarkable enantioselectivities in hydroboration, ketone reduction and crotyl addition to aldehydes. The chirality transfer also turns out to be highly efficient in the aldol reaction. Initial experiments were aimed at defining the structural parameters which affect the E(0) Z(0) ratios of the enolates prepared from various alkanethioates with 2,5-dimethylborolanyl triflate (90) under standard conditions... 

In 1974, Jeffery et al. reported the first use of well-defined dimeric or trimeric aluminum enolates in the aldol reaction. - Reaction of dimethyl-Z(0)-4,4-dimethylpent-2-en-2-oxyalane (123) with acetaldehyde or benzaldehyde provides the anti aldol products (124) as chelated dimers involving five-coordinate aluminum atoms, as shown in Scheme 51. However, the corresponding (0)-enolate (125) gives dimeric products of syn configuration which undergo isomerization, if not hydrolyzed immediately, to provide the same anti products. This syn-anti isomerization is much more facile with benzaldehyde, and is in sharp contrast to aldol reactions mediated by boron. 

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