Aldehyde homoenolate synthetic equivalents

R2CCH2CH=CHS R2CCH2CH=CHSCH3 5 CH=CHCH=0 [CH3SCH=CHCHSCH3] R X + CH3SCH=CHCHSCH3 -  

For wide-ranging discussions of asymmetric synthesis see the books listed in the general references. 

Morrison and H. W. Mosher, Asymmetric Organic Reactions Prentice-Hall, Englewood Cliffs, New Jersey (1971). 

Diastereoselectivity can be achieved as the result of thermodynamic as well as kinetic factors. If the desired diastereomer is the most stable of the series, then establishment of conditions for equilibration will permit a diastereoselective synthesis. As a general rule, better selectivity is achieved by kinetic methods because the greater sensitivity of the transition state to stabilizing and destabilizing interactions will be reflected in greater preference for one particular product. 

The second broad type of asymmetric syntheses are enantioselective processes which give rise to one of the enantiomers of a pair in excess. Enantioselective syntheses can only be achieved by the participation of optically active starting materials, reagents, or catalysts in the reaction process. There are several ways in which an enantioselective synthesis can be achieved. In principle, the ideal method is to use a single enantiomer of an available chiral substance as a catalyst. The advantage is that, theoretically, an optically active catalyst can generate an unlimited amount of product. A second possible choice is the use of an optically active 

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There are two main synthetic applications where the reaction of an allyl system with electrophiles is accompanied by an allylic rearrangement. One consists of the use of heteroatom-substituted allylic anions as homoenolate anion equivalents and the other represents a synthetically valuable alternative to the aldol reaction by addition of allyl metal compounds to aldehydes. 

The acyl cation 2a or acylium ion 2b is a familiar intermediate in the Friedel-Crafts reaction. It is easy to make (acid chloride + Lewis acid 1) and it can be observed by NMR as it expresses the natural reactivity pattern of the acyl group. The acyl anion by contrast has umpolung or reverse polarity.1 One might imagine making it from an aldehyde by deprotonation 3 and that it would be trigonal 4a or possibly an oxy-carbene 4b. Such species are (probably) unknown and their rarity as well as their potential in synthesis has led to many synthetic equivalents for this elusive synthon. The acyl anion, the d1 synthon, is the parent of all synthons with umpolung2 and should perhaps have been treated before the homoenolates dealt with in the previous chapter. 

A chiral ligand mediated approach to lithiation-substitutions of allylic amines has also been well developed. Weisenburger and Beak demonstrated that lithiation of doubly protected allylic amines 141 in the presence of the chiral ligand (-)-sparteine (5), and substitution with a variety of electrophiles provided highly enantioenriched enecarbamate products 142 (Scheme 44) [100]. The authors demonstrated that the intermediate organolithium could be viewed as either an aldehyde P-homoenolate or y-lithioamine synthetic equivalent by hydrolysis or reduction and deprotection of the enecarbamates, respectively. 

Another group of synthetic equivalents has been developed which correspond to the propanal homoenolate, CH2CH2CH=0. This structure is the umpolung equivalent of an important electrophilic reagent, the a,jS-unsaturated aldehyde... 

The power of NHC catalysts lies in the ability of these heterocycles to promote the transient generation of reactive species, such as acyl anion equivalents or activated carboxylates. Using the mechanistic postulates for these processes, it is possible to predict that the combination of an NHC catalyst and an a,p-unsaturated aldehyde could lead to the generation of a wide variety of cata-lytically generated reactive intermediates (Scheme 14.12). Over the past 5 years, the rapid developments of new catalysts and reaction conditions have made possible the selective generation of eaeh of these classes of reactive species, including the synthetically powerful homoenolate and ester enolate equivalents. 

A-heterocyclic carbenes (NHC) are also efficient organocatalytic tools for generating homoenolate equivalents from a,P-unsaturated aldehydes. These reactive intermediates display a versatile reactivity in a number of catalytic transformations attesting to an important synthetic potential [38]. Recently, Scheldt et al. [39a] accomplished the first enantioselective protonation of a homoenolate species generated by a chiral NHC precursor 93 in the presence of DIE A and an excess of ethanol as the achiral proton source (Scheme 3.46). The suggested mechanism involves an initial addition of NHC 93 to the enal 89 followed by a formal 1,2-proton shift resulting in the formation of the chiral homoenolate equivalent 91. A diastereose-lective P-protonation/tautomerization sequence leads to the acyl triazolinium inter-... 

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