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. 2014 Dec 5;16(23):6048-51.
doi: 10.1021/ol502691w. Epub 2014 Nov 13.

Synthesis of bicyclic guanidines via cascade hydroamination/Michael additions of mono-N-acryloylpropargylguanidines

Ki-Hyeok Kwon  1 , Catherine M Serrano  1 , Michael Koch  2 , Louis R Barrows  2 , Ryan E Looper  1
Affiliations

Synthesis of bicyclic guanidines via cascade hydroamination/Michael additions of mono-N-acryloylpropargylguanidines

Ki-Hyeok Kwon et al. Org Lett. .

Abstract

A cascade silver(I)-catalyzed hydroamination/Michael addition sequence has been developed to deliver highly substituted bicyclic guanidines. This transformation gives rise to geometrically and constitutionally stable ene-guanidines and generates a remote stereocenter with moderate to high diastereoselectivity.

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Figures

Scheme 1
Scheme 1. Synthetic Strategy for the Bicyclic Guanidines
Scheme 2
Scheme 2. Synthesis of Bicyclic Guanidines from Propargylguanidines and Confirmation of Their Stereochemistry by X-ray Crystallography
Figure 1
Figure 1
Substrate scope for the cyclization/Michael addition catalyzed by AgNO3 where R4 = aryl. Reaction conditions: substrate (0.3 mmol), AgNO3 (10 mol %), MeCN (0.1 M), 8 h. The diasteromeric ratios were determined by 1H NMR analysis of the crude mixture.
Figure 2
Figure 2
Substrate scope for the cyclization/Michael addition catalyzed by AgNO3 where R4 = alkyl. Reaction conditions: substrate (0.3 mmol), AgNO3 (10 mol %), MeCN (0.1 M), 8 h. The diastereomeric ratios were determined by 1H NMR analysis of the crude mixture.
Figure 3
Figure 3
Substrate scope for the cyclization/Michael addition catalyzed by AgNO3 where R4 = H. Reaction conditions: substrate (0.3 mmol), AgNO3 (10 mol %), MeCN (0.1 M), 8 h. The diastereomeric ratios were determined by 1H NMR analysis of the crude mixture. b Performed on a 2.5 mmol scale.
Scheme 3
Scheme 3. Transformation of the Resultant Bicyclic Guanidines
See this image and copyright information in PMC

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