Enoates conjugate additions

Conjugate addition reactions of acyclic Midiael acceptors possessing betetoatom-SLibstituted stereogenic centers in tlieir )>-positions may provide usefiil levels of diastereoselectivity. A typical example is given witli tlie y-alkoxy-substituted enoate 49 in Sdieme 6.8 [17]. High levels of diastereoselectivity in favor of tlie anii addition product SO were found in tlie course of dlmediylcuprate addition. 

Conjugate additions of alkylcopper- boron trifluoride to enoates of sulfonamide-shielded alcohols (6 and 7) quite generally proceeded with >99% de and >90% yield30. The following general trend has emerged from the reactions of 6 and 7. 

Entry 6 is an example of application of the chiral diazaborolidine enolate method (see p. 572). Entry 7 involves generation of the silyl ketene acetal by silylation after conjugate addition of the enolate of 3-methylbutanoyloxazolidinone to allyl 3,3,3-trifluoroprop-2-enoate. A palladium catalyst improved the yield in the rearrangement... 

Diastereoselective conjugate addition of nucleophiles to enones, enals, and enoates occurs with high stereocontrol and constitutes a powerful method in stereoselective synthesis.185... 

After their preliminary studies on the conjugate addition of nitromethane to sugar-derived enoates,34 Costa et al. reported more exhaustive studies that include the addition of nitromethane to enoate 33 in the presence of TBAF, to give a mixture of the two adducts 34 and 35 (Scheme 13).35... 

Scheme 3.6. Diastereoselectivity in silylcuprate conjugate addition-alkylation (alkyl halides) or protonation reactions with a,/S-enoates [46],...

High levels of asymmetric induction can be achieved intramolecularly if the substrate functionality and the heteroatom ligand are contained in the same molecule. Chiral amido(a]kyl)cuprates derived from allylic carbamates [(RCH= CHCH20C(0)NR )CuR undergo intramolecular allylic rearrangements with excellent enantioselectivities (R = Me, n-Bu, Ph 82-95% ee) [216]. Similarly, chiral alkoxy(alkyl)cuprates (R OCuRLi) derived from enoates prepared from the unsaturated acids and trans-l,2-cyclohexanediol undergo intramolecular conjugate additions with excellent diasteroselectivities (90% ds) [217]. 

A similar explanation may also hold for the result of conjugate addition to y-phthalimido enoate 80 (Scheme 6.16). Thus, addition of the bulky cyano-Gilman silyl cuprate gave the syn diastereomer 81 (dr = 96 4) [32, 33]. Preference for the sterically least hindered nucleophile trajectory seems to dictate the overall stereochemical outcome (transition state 82). 

Scheme 6.15. Conjugate addition to enoate 75 influence of the nature of the cuprate reagent on diastereoselectivity.

Diastereofacial selection on addition of organocoppper reagents to chiral y-alkyl-substituted Michael acceptors has been investigated less extensively, due to the usually low selectivities generally observed for these systems [38, 39]. This is exemplified by the reaction of E and Z enoates 90 (Scheme 6.19). Thus, either syn-91 or anti-93 is formed upon conjugate addition with BF3-modified reagents, as a function of enoate geometry. The stereochemistry of the reaction is in accordance with the modified Felkin-Anh model [40]. 

Scheme 6.22. Non-stereoselective conjugate addition to the -chiral enoate 102.

High diastereoselectivity upon conjugate addition to -silyl substituted enoates has in some cases been observed A. Baebeeo, D. C. Biakemoee, 1. Fleming, R. N. 

Systematic studies of organocuprate conjugate additions to three pairs of y-epimeric and geometrically isomeric y-chiral acyclic enones and enoates (159a,b) and (160a,b) have allowed one to generalize diastereofacial selectivity of these reactions (Scheme 20). 

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