Addition of Grignard Reagents to Chiral 1,2-Bisimines: A Diasteroselective Preparation of Unsymmetrical 1,2-Diamines

Abstract

A diastereoselective synthesis of tert‐butyl‐1,2‐diamines has been developed from the addition of tert‐butylmagnesium chloride to the 1,2‐bisimines derived from glyoxal and chiral amines such as 1‐(S)‐ethylphenylamine, 1‐(S)‐phenylpropylamine or 1‐(S)‐(p‐chlorophenyl)ethylamine. The influence of solvent, temperature and chiral auxiliaries on the chemical reactivity and stereoselectivity has been fully studied. Evidence of a dynamic kinetic resolution during the bis‐addition process of the organometallic, leading to the 1,2‐di‐tert‐butylethanediamine,[1] as a single diastereomer, has been demonstrated. This resolution has been applied with high diastereoselectivities to the synthesis of unsymmetrical disubstituted 1,2‐diamines, by addition of one equivalent of tert‐butylmagnesium chloride, followed by one equivalent of a second Grignard reagent. Several chiral 1‐tert‐butyl‐1,2‐diamines have also been synthesized by monoaddition of tert‐butylmagnesium chloride to the bisimines, followed by hydride reduction of the chiral intermediate imines.

Vicinal Diamino Functionalities as Privileged Structural Elements in Biologically Active Compounds and Exploitation of their Synthetic Chemistry

“…The resulting diamines were obtained with up to 95% dr. The subsequent removal of the chiral auxiliary using Pearlman's catalyst gave the diamines in good yields (49).…”

Stoichiometric asymmetric processes

“…192 An in depth study has been carried out using allylmagnesium and zinc reagents with bisimines 48 bearing the α-methylbenzylamine stereodirecting group (Scheme 32) 193 and independent studies have shown that dynamic kinetic resolution may be observed with Grignard additions to such species. 194 Grignard addition to chiral aza-acetals proceeded with reasonable levels of stereoselectivity dependent upon the Grignard reagent, 357 and reactions with related C 2 symmetric bisoxazolidines have also been investigated. 195 An in depth study of the enantioselectivity of the addition of Grignard reagents to chiral sulfinyl imines has also been carried out.…”

Synthesis and Spectroscopic Studies of Co(II), Ni(II) and Cu(II) Complexes of Bidentate Schiff Base having N and Sulphur Containing Donor Site

“…widely studied are attracting wide range of applications in organic synthesis and metal ion complexation [5][6][7][8][9] . The conventional synthesis of such compounds are still very common along with modern synthetic approaches in continuation of our recent work in synthesizing Schiff bases and their transition metal complexes, we herein report, synthesis and spectroscopic studies of Co(II), Ni(II) and Cu(II) complexes with 2-methyl thioquinazoline -4(3H) semicarbazone.…”