Direct asymmetric synthesis of quaternary carbon centers by the addition-elimination process: nitroolefination of .alpha.-substituted .delta.-lactones

Abstract

The reactions of chiral nitro enamines 2a-c with zinc enolates 4-6 of a-substituted &lactones afforded a,a-disubstituted &lactones with a high ee through an addition-elimination process. The best results were obtained with the reaction of 2c with 5. Michael-type addition of the enolate onto the nitro enamine is kinetically controlled and decides the absolute stereochemistry of the product. A cyclic transition model is proposed to rationalize the S-selectivity.

Highly Enantioselective Construction of Sterically Hindered α-Allyl-α-Aryl Lactones via Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation

“…In 1989, Fuji reported the diastereoselective nitroolefination of αquaternary δ-lactones via a Michael-type addition followed by elimination of an electron-rich chiral group (eq [1], Scheme 1). 4 This process formed the α,α-dialkyl lactones in high enantioselectivities (56−96% ee).…”

“…8 Further elegant routes for the enantioselective construction of α-acyl-γ-butyrolactones possessing α-quaternary stereocenters followed in reports by Maruoka, Jacobsen, Park, and Cossy. 9,10 In 2008, Fillion used the Cu-catalyzed 1,4addition of diethylzinc to 2-(2,2-dimethyl-4,6-dioxo-1,3dioxan-5-ylidene)aryl acetates as the key enantioselective step to form the precursor to α-ethyl-α-phenyl-γ-butyrolactone in 88% ee (eq [4], Scheme 1). 11 Breit described the regioselective hydroformylation of 3-substituted homoallylic alcohols subsequently to produce α,α-disubstituted γ-butyrolactones and highly substituted tetrahydrofurans.…”

Nitroalkynes: A Unique Class of Energetic Materials

“…6 This assignment is likely incorrect, since the electronegativity of the nitro substituent reduces the coupling constant of trans-nitroenamines to such values. 99,100 In the case of hydrochloride adduct 92, the stereochemistry is tentative. The stereochemistry of 93-100 was ascertained by extensive comparison of their spectral data with those of the (minor) stereoisomers.…”

Asymmetric Syntheses of Oxindole and Indole Spirocyclic Alkaloid Natural Products

“…28 The reaction involved an oxindole enolate attack on the chiral nitroenamine auxiliary 82 through an addition-elimination mechanism. 29 Fuji and co-workers prepared several oxin-dole alkaloids using this methodology, including (-)horsfiline 30 and (-)-spirotryprostatin. 31 In Fuji's synthesis of (-)-horsfiline, the chiral quaternary center that would later be transformed into the spiropyrrolidine was made using a proline-derived nitroolefination chiral auxiliary to give the desired product in 65% yield and >99% ee.…”