jo4018099_si_003.cif (11.73 kB)
Enantioselective Synthesis of Angularly Substituted 1‑Azabicylic Rings: Coupled Dynamic Kinetic Epimerization and Chirality Transfer
dataset
posted on 2016-02-18, 18:08 authored by Zachary
D. Aron, Tatsuya Ito, Tricia L. May, Larry E. Overman, Jocelyn WangA new
strategy for enantioselective synthesis of azacyclic molecules
in which dynamic kinetic equilibration of diastereomeric iminium ions
precedes a stereochemistry-determining sigmatropic rearrangement is
reported. The method is illustrated by the synthesis, in high enantiomeric
purity (generally 95–99% ee), of a variety of 1-azabicyclic
molecules containing angular allyl or 3-substituted 2-propenyl side
chains adjacent to nitrogen and up to three stereogenic centers. In
these products, the size of the carbocyclic ring is varied widely
(5–12 membered); however, useful yields are obtained in forming
1-azabicyclic products containing only fused pyrrolidine and piperidine
rings. Chirality transfer from substituents at carbons 1 and 2 of
the 3-butenylamine fragment of the starting material is investigated,
with methyl and phenyl substituents at the allylic position shown
to provide exquisite stereocontrol (generally 98–99% chirality
transfer). An attractive feature of the method is the ability to carry
out the key transformation in the absence of solvent. Illustrated
also is the high yielding conversion of four such products to a new
family of bicyclic β-amino acids of high enantiomeric purity.