threo-Selective Michael Addition of N,N-Dibenzylglycinate and Alaninate Enolates to α,β-Unsaturated Esters. A Concise and Stereoselective Synthesis of (±)-CCG-II

Abstract

Lithium enolates of N,N-dibenzylglycinate and alaninate added to β-substituted α,β-unsaturated esters, and threo-adducts were obtained in high stereoselectivities. The reaction was employed in a concise and Stereoselective synthesis of (±)-CCG-II.

Enantioselective Synthesis of l-CCG-I

“…The stereochemical outcome can be rationalized by considering participation of the azaallyl anion in the less crowded transition state (Figure ) to give the erythro adduct in the initial conjugate addition. The formation of trans -cyclopropane is in accordance with similar Michael-induced ring closure reaction reported in the literature. , Thus, this route is complementary to the Yamaguchi synthesis, which yields the threo product …”

“…After workup and chromatographic purification the product 3 was obtained in 72% yield and 92% diastereomeric ratio as determined by 1 H NMR (200 MHz) analysis of the methine (C2) proton. It is pertinent to note that this protocol involves conditions for generation of the cyclopropane milder than those used by Yamaguchi (LDA, −78 °C) …”

Synthesis, NMDA Receptor Antagonist Activity, and Anticonvulsant Action of 1-Aminocyclobutanecarboxylic Acid Derivatives

“…After washing and drying, the solution was added with ethereal diazomethane to account for any hydrolized acidic product. Evaporation of the solvent and chromatography (200 g of silica gel; CH2Cl2-ether-EtOAc, 4:2: I) separated 21 (1.14 g) from 22 (0.43 g), with intermediate mixed fractions (0.15 g; total: 1.72 g, 78%). Compound 21: mp 212-213 °C (EtOH); NMR 1.01-1.06, 1.18-1.23, 1.63-1.68, and 1.79-1.84 (four m, 4 H, cyclopropane protons), 1.50-1.56 (br, 6 H), 2.58-2.80 (m, 4 H, cyclobutane protons), 3.39 and 3.52 (br, 4 H), 3.68 and 3.73 (two s, two Me), 7.17 (s, NH), 7.4-7.8 (5 H).…”

Allylic Alkylation versus Michael Induced Ring Closure: Chelated Enolates as Versatile Nucleophiles

“…An interesting sequence giving rise to cyclohexyl amino acid derivatives was reported by Moreno-Manas et al, based on a double Michael addition and subsequent Dieckman condensation . But other nucleophiles such as the enolates of Schöllkopf's bislactim ethers, sarcosinates, or N , N -dibenzylglycinates also can be used.…”