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Synthesis of BCP Benzylamines From 2‐Azaallyl Anions and [1.1.1]Propellane
Author(s) -
Shelp Russell A.,
Walsh Patrick J.
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201810061
Subject(s) - chemistry , propellane , benzylamine , combinatorial chemistry , reactivity (psychology) , molecule , bicyclic molecule , stereochemistry , organic chemistry , medicine , alternative medicine , pathology
Abstract For bioactive molecules, bicyclo[1.1.1]pentanes (BCPs) are an emerging isostere of rigid spacer groups that have shown potential to improve drug‐like qualities. As BCPs become an increasingly popular motif for evaluation in drug candidates, organic chemists must meet the demand to reliably incorporate them into new targets. To provide access to BCP analogues of diaryl methanamines, a ubiquitous scaffold in medicinal chemistry, we report the synthesis of BCP benzylamines through reactivity of [1.1.1]propellane with 2‐azaallyl anions, which are generated in situ from N ‐benzyl ketimines. The reaction proceeds rapidly at room temperature and tolerates a broad substrate scope, providing straightforward access to 23 new BCP benzylamine derivatives. Initial experiments support the intermediacy of a BCP anion. Additionally, the reaction can be promoted by substoichiometric loadings of base, highlighting an unusual reactivity of both 2‐azaallyls and [1.1.1]propellane.