Diastereoselective synthesis of trans-1,2-diamines via sequential opening of cyclohexene oxide and aziridinium ions

Abstract

A synthesis of trans-1,2-diaminocyclohexane derivatives via opening of cyclohexene oxide with secondary amines followed by preparation and opening of the corresponding aziridinium ions in situ by primary and secondary amines is described. Use of chiral α-methylbenzylamine for the opening of aziridinium ions gave a mixure of diastereomers that are readily separated by column chromatography. The C 2 symmetric trans-1,2-bis (N-pyrrolidino)cyclohexane was resolved to obtain nonracemic samples that can be readily enriched by co-crystallization with fumaric acid to obtain enantiomerically pure compounds.

Chiral 1,2-Amino Alcohols and 1,2-Diamines Derived from Cyclohexene Oxide: Recent Applications in Asymmetric Synthesis

“…47 Using the protocol already described, we also reported the synthesis of other cyclic 1,2-diamines derived from cyclopentene oxide, 1,4-cyclohexadiene monoxide, and (S)-1phenylethylamine, affording 1,2-cyclic diamines 111-114 (Scheme 25). 48 A similar methodology was reported almost simultaneously by Periasamy et al, 49 who prepared amino alcohols 115 by refluxing cyclohexene oxide with secondary amines such as pyrrolidine, piperidine and dimethylamine. trans-1,2-Diamines 116 were then prepared via aziridine intermediates (Scheme 26).…”

General Copper-Catalyzed Coupling of Alkyl-, Aryl-, and Alkynylaluminum Reagents with Organohalides

“…Ligands PN-2, PN-6, PN-7, PN-8, PP-1, NN-1, NN-4, NO-1, OO-1, and SIMes·HCl were purchased from commercial sources. Ligands PN-1, PN-3, PN-4, PN-5, PN-9, NN-2, and NN-3 were synthesized following the reported procedures …”

“…90 The title compound 55 was obtained as yellow oil (153 mg, 67% yield) after purification by silica gel column chromatography. 1 (58). 91 The title compound 58 was obtained as yellow oil (185 mg, 71% yield) after purification by silica gel column chromatography.…”

Convenient Methods for the Synthesis of Chiral Amino Alcohols and Amines

“…[35] Earlier, the amine 7b was accessed through N-deallylation using Wilkinson's reaction of d-(-)-camphorquinone (35) with methanolic ammonia followed by reduction with NaBH 4 afforded the amino alcohol 37 as the only product in 85% yield. The d-(-)-camphorquinone imine derivatives 38 and 41 were also readily prepared using ethanol amine and isoboranyl amine (40) and converted to the amino alcohol derivatives 39 and 42 in 75-85% yields by reduction with NaBH 4 in methanol under ambient temperature (Scheme 5).…”

“…Racemic 10 was resolved using chiral dibenzoyl-l-tartaric acid with up to 82% ee and the non-racemic mixture was enriched using fumaric acid to obtain samples with up to 92% ee (Scheme 13). [40] Following a similar protocol, the chiral 1,1'-bi-2-naphthol-derived amino ether 64 was synthesized through opening 63 (Scheme 14). [41] 11.…”