Azaenolates conjugate additions

Tandem processes mediated by triethylborane involving conjugate addition to enones followed by aldol reaction are reported (Scheme 52, Eq. 52a). More recently, a tandem process involving addition of an isopropyl radical to an o ,/3-unsaturated oxime ether afforded an azaenolate intermediate that reacts with benzaldehyde in the presence of trimethylaluminum. The aldol product cyclizes to afford an isopropyl substituted y-bulyroloaclonc in 61% overall yield (Scheme 52) [116]. In these reactions, triethylborane is acting as a chain transfer reagent that delivers a boron enolate or azaenolate necessary for the aldolization process. 

The conjugate addition of unstabilized enolates to various acceptors was conceptually recognized by early researchers however, complications were encountered depending on the enolates and acceptors employed. Reexamination of this strategy was made possible by the development of techniques for kinetic enolate formation. This discussion is divided into three enolate classes (a) aldehyde and ketone enolates, azaenolates or equivalents, (b) ester and amide enolates, dithioenolates and dienolates and (c) a,0-carboxylic dianions and a-nitrile anions, in order to emphasize the differential reactivity of various enolates with various acceptors."7 The a-nitrile anions are included because of their equivalence to the hypothetical a-carboxylic acid anion. 

The introduction of a chiral auxiliary on the nitrogen of an azaenolate offers the capability to perform asymmetric conjugate additions of chiral nucleophiles to achiral acceptors. This is in contrast to the typical asymmetric conjugate addition of achiral nucleophiles to chiral acceptors.137 For example, the con-... 

The authors suggested a stepwise mechanism in which precomplexation of the sulfoxide to the lithium azaenolate would take place, thus allowing conjugate addition to follow. This notion was based on Posner s and Paquette s earlier work on conjugate additions of nucleophiles to 57. As before, thermal elimination of toluene sulfenic acid led to the conjugated products (not shown) in 92-93% yields for R2 = methyl.30 However, for R2 = H thermal elimination of arylsulfenic acid did not afford any dihydropyrrole product but rather led to the formation of pyrroles. Treating 58 or 59 with Raney nickel at low temperature led to the rapid formation of 60 and 61, respectively, in 82-86% yield. 

Chiral Cuprate Reagents. This chiral amine has also found application in asymmetric conjugate addition of copper azaeno-lates to cyclic enones. Lithium azaenolates of optically active acetone imines have been used in the preparation of chiral cuprate reagents. However, the asymmetric induction is low (17-28% ee) when this amine is employed (eq 5). ... 

Reactions of the Bislactim Ether Cuprate. The lithiated bislactim ether can be converted to an azaenolate cuprate by treatment with CuBr SMe2 (see Copper(I) Bromide)fi Conjugate addition of the cuprate to enones (eq 3) and dienones, or alkylation with base labile electrophiles like ethyl 3-bromopropionate, proceeds with high trans diastereoselectivity. Hydrolysis of the Michael... 

The early (1975) contributions from the Meyers laboratory (Scheme 4.13a) paved the way for a number of related methods in subsequent years. Figure 4.24 illustrates a number of conceptually related conjugate additions. In several of these examples, there is a crucial difference from the examples in Scheme 4.13 in all except Figure 4.24e the a-carbon is prochiral, and two stereocenters are formed in the reaction. Fortunately, it is possible to either alkylate or protonate the azaenolate stereoselectively, such that two new stereocenters are produced in a single... 

The term Michael addition has been used to describe 1,4- (conjugate) additions of a variety of nucleophiles including organometallics, heteroatom nucleophiles such as sulfides and amines, enolates, and allylic organometals to so-called Michael acceptors such as a,p-unsaturated aldehydes, ketones, esters, nitriles, sulfoxides, and nitro compounds. Here, the term is restricted to the classical Michael reaction, which employs resonance-stabilized anions such as enolates and azaenolates, but a few examples of enamines are also included because of the close mechanistic similarities. 

The asymmetric a-sulfenylation of ketones is a particularly challenging reaction, as demonstrated by the poor success reported in the stereoselective variants via classical enolate/azaenolate reaction with an electrophilic sulfur reagent [71]. An umpolung approach has been devised by Coltart and co-workers [72] to effect the first asymmetric a-sulfenylation of ketones with arene thiols. Nitroso alkene derivatives, in i/tM-generated under basic conditions from a-chloro oximes, reacted with arene thiols in the presence of cinchona thiourea 27, which promoted the conjugate addition of thiophenol (Scheme 14.25). The chiral nonracemic a-sulfenylated oximes were directly hydrolyzed by IBX to ketones in high yield and good enantioselectivity. 

Yamamoto et al. have described an asymmetric conjugate addition of copper azaenolates such as 56 derived from an acetone imine of optically active erythro-2-... 

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