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One‐Pot Procedure for the Synthesis of N ‐Substituted 2‐(Arylmethyl)pyrrolidines from 1‐Aryl‐2‐cyclopropylalkynes and Primary Amines by a Hydroamination/Cyclopropylimine Rearrangement/Reduction Sequence
Author(s) -
Gräbe Kerstin,
Zwafelink Björn,
Doye Sven
Publication year - 2009
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200900515
Subject(s) - hydroamination , chemistry , pyrrolidine , amine gas treating , aryl , regioselectivity , medicinal chemistry , catalysis , amination , primary (astronomy) , organic chemistry , combinatorial chemistry , alkyl , physics , astronomy
A one‐pot procedure for the synthesis of N ‐substituted 2‐(arylmethyl)pyrrolidines from 1‐aryl‐2‐cyclopropylalkynes and primary amines is presented. The procedure proceeded first through an [Ind 2 TiMe 2 ]‐catalyzed regioselective hydroamination of a 1‐aryl‐2‐cyclopropylalkyne with a primary amine. The resulting cyclopropylimine, which was not isolated, was then forced to undergo a cyclopropylimine rearrangement in the presence of catalytic amounts of NH 4 Cl at 145 °C to deliver the corresponding 2‐pyrroline. A subsequent reduction performed with NaBH 3 CN and ZnCl 2 finally gave the desired N ‐substituted 2‐(arylmethyl)pyrrolidine.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)