Enantioselective Addition of Dialkylzinc Reagents to N-(Diphenylphosphinoyl) Imines Promoted by 2-Azanorbornylmethanols

Abstract

A set of new beta-amino alcohols 2, with the 2-azanorbornyl framework, has been prepared and evaluated as promoters for the enantioselective addition of dialkylzinc reagents to N-(diphenylphosphinoyl) imines 1. By variation of the substitution pattern in the ligand, ee's up to 92% could be obtained. Although a stoichiometric amount of the ligand was used, about 90% of it could be recovered during the workup. Amino alcohol 2b, that gave the best enantioselectivities in the stoichiometric reaction, was also applied in a catalytic process, and ee's up to 85% were achieved using 0.25 equiv of the ligand, which is the highest ee obtained so far using that catalytic amount of the ligand. Addition products 3 could be converted into the free amines 4 without racemization by acidic hydrolysis. The utility of ligands 2 as catalysts in the addition of diethylzinc to benzaldehyde has also been investigated, and ee's up to 75% were achieved.

Enantioselective Addition of Dialkylzinc to Aromatic Aldimines Mediated by Camphor‐Derived Chiral β‐Amino Alcohols

“…It had been reported previously that dimethylzinc is much less reactive than diethylzinc 2a. 8a, 13 The addition reaction of dimethylzinc to imine 3 a gave neither the addition product nor the reduction product in the absence of 1 (Table 3, entry 1).…”

“…The exact role of methanol in our catalytic system is not fully understood at this stage 14. 15 However, based on literature reports,2a, b, 8b, 13 the rationale of the stereochemical outcome of the addition reaction is shown in Figure 2. The coordination of imine and chiral aminoalcohol to both zinc atoms would lead to a favored bicyclic transition state A .…”

Reactivity of Oxiranes with Organolithium Reagents

“…Obviously, the configuration of the proline moiety determines the sense of the enantioselection. Indeed, in all cases (S)-proline analogues 53 (Scheme 26) and 55 (entry 2) provide (S)-cyclohexenol, whereas the (R)-analogue 56a, obtained in seven steps from (S)-phenylethylamine 48,59 , gives the opposite enantiomer (entry 3). Interestingly, a reversal of selectivity is observed with HCLA (S)-54 where the lithium amide is located on the extracyclic nitrogen (entry 1).…”

Enantioselective Synthesis of [(1R,3-exo)-2-Benzyl-2-azabicyclo[2.2.1]hept-5-en-3-yl]methanol via Aza-Diels-Alder Reaction

“…heptane and its derivatives are useful as synthetic intermediates in the preparation of a great variety of compounds of chemical, pharmaceutical and/or biological interest. For example, 2-azabicyclo[2.2.1]hept-5-enyl-3-carboxylates 1 are used in the preparation of the corresponding bicyclic derivatives of 2-azabicyclo [2.2.1]hept-5-enyl-3-methanol 2, which have been successfully employed as chiral ligands in asymmetric synthesis/catalysis (carbon-carbon bond formation, 1 asymmetric transfer hydrogenation of ketones 2 ). Carboxylates 1 have also been used in the enantioselective synthesis of lactam 3 and its saturated analogue, 3 key intermediates in the synthesis of several compounds with biological interest; among them are the four stereoisomers of 4-aminocyclopent-2-ene carboxylic acid (4) and the corresponding saturated analogues, 4 which show specific inhibitory activity towards some processes of the action and metabolism of GABA; 5 furthermore, isomer (1R,3S)-3-aminocyclopentane carboxylic acid is the core structure of the antibiotic amidomycin.…”