Michael adducts enantiomers

Similar schemes can be developed easily for analogous reactions of acceptor-substituted polyenes. For example, a triene with an acceptor group in 1-position can form six regioi-someric products of Michael addition and electrophilic capture, and each of these exists as E/Z stereoisomers, diastereomers and/or enantiomers. Thus, reactions of this type are only useful if both the regio- and stereoselectivity can be controlled fortunately, only one isomeric Michael adduct is formed in many cases. This is true in particular for polyunsaturated Michael acceptors which bear at least one triple bond besides one or more double bonds. An additional feature of the latter substrate type is that nucleophilic additions can... 

A highly selective method for the preparation of optically active 3-substituted or 3, y-disubstituted-S-keto esters and related compounds is based on asymmetric Michael additions of chiral hydrazones (156), derived from (5)-l-amino-2-methoxymethylpyrrolidine (SAMP) or its enantiomer (RAMP), to unsaturated esters (154).167-172 Overall, a carbonyl compound (153) is converted to the Michael adduct (155) as outlined in Scheme 55. The actual asymmetric 1,4-addition of the lithiated hydrazone affords the adduct (157) with virtually complete diastereoselection in a variety of cases (Table 3). Some of the products were used for the synthesis of pheromones,169 others were converted to 8-lactones.170 The Michael acceptor (158) also reacts selectively with SAMP hydrazones.171 Tetrahydroquinolindiones of type (159) are prepared from cyclic 1,3-diketones via SAMP derivatives like (160), as indicated in Scheme 56.172... 

The application of the Michael addition of phosphonate esters in the synthesis of coronafacic acid was reported by Shibasaki and coworkers and is outlined in Sch. 61 [89]. The Michael adduct ent-427 was prepared in 94 % ee in the same fashion as its enantiomer 427 (Sch. 59) by employing a catalyst prepared from (5)-BINOL. 

The synthesis of both enantiomers of the antitumor-antibiotic fredericamycin A was achieved in the laboratory of D.L. Boger. The DE ring system of the natural product was assembled via a tandem Michael addition-Dieckmann condensation. The highly substituted 4-methylpyridine precursor was treated with excess LDA followed by the addition of the Michaei acceptor cyciopentenone. The Michael adduct underwent an intramolecular acylation with the ester functionaiity in situ to afford the desired DEF tricycie. 

Using a polymer-supported cinchonidine derivative (105), Hodge and coworkers [58] evaluated the enantioselective Michael addition between methyl 1-oxoindan-2-carboxylate (106) and methyl vinyl ketone (107) to afford the S-enantiomer of the Michael adduct 108 (Scheme 6.28). Employing a glass tube reactor [1.4 cm i.d. x 36 cm (length)], sealed at one end, containing 15 g of PS-cinchonidine 105 (reactor volume = 28.9 ml), the authors introduced solutions of 106 (0.50 M) and 107 (0.53 M) in toluene from separate inlets at a total flow rate of 0.83 pi min ... 

Asymmetric induction in Michael reactions. Wynberg and Helder have reported asymmetric syntheses of Michael adducts from inactive donors and methyl vinyl ketone in the presence of catalytic amounts of quinine and cinchonine. Enantiomeric ratios were affected by the solvent highest inductions were obtained in toluene and tetrachloromethane. Quinine and cinchonine favored different enantiomers of the adduct. The enantiomeric excess was determined in one case from PMR spectroscopy to be 68%. 

Moreover, as is usually found in most of the asymmetric reactions catalyzed by cinchona alkaloid derivatives, the opposite enantiomer of each diaster-eomeric Michael adduct could also be obtained by simply changing the catalyst to the corresponding pseudoenantiomeric quinidine-based compounds of type 83 or 71. Once again, a model was proposed to account for the observed results, involving a conformationally rigid intermediate in which both the pronucleophile and the electrophile were attached to the catalyst by the formation of multiple H-bonds, explaining the reversal of the diastereoselection by the epimeric nature of C-9 in catalyst 71b with respect to 84c. The stereochemical... 

FIG. 4 Self-disproportionation of Michael adduct enantiomers during the purification on achiral HPLC column. 

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