Synlett 2017; 28(13): 1570-1575
DOI: 10.1055/s-0036-1588502
cluster
© Georg Thieme Verlag Stuttgart · New York

Palladium-Catalyzed Aerobic Oxidative Cyclization of Aliphatic Alkenyl Amides for the Construction of Pyrrolizidine and Indolizidine Derivatives

Kai-Yip Lo
Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. of China   Email: yangdan@hku.hk
,
Liu Ye
Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. of China   Email: yangdan@hku.hk
,
Dan Yang*
Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. of China   Email: yangdan@hku.hk
› Author Affiliations
Financial support was provided by the University of Hong Kong and the Hong Kong Research Grants Council (HKU 706109P and HKU 706112P).
Further Information

Publication History

Received: 26 June 2017

Accepted after revision: 27 June 2017

Publication Date:
13 July 2017 (online)


Published as part of the Cluster Catalytic Aerobic Oxidations

Abstract

An efficient palladium-catalyzed aerobic oxidative cyclization has been developed to synthesize a variety of pyrrolizidine and indolizidine derivatives from simple aliphatic alkenyl amides in moderate to good yields. The reaction features the capability of accessing various N-heterocycles and the use of molecular oxygen (1 atm) as the green oxidant.

Supporting Information

 
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  • 13 General Procedure To a well-stirred solution of Pd(TFA)2(33.2 mg, 0.1 mmol) in toluene (5 mL) were added pyridine (32.3 μL, 0.4 mmol) and DABCO (44.9 mg, 0.4 mmol). The mixture was stirred continuously until the solid dissolved. The reaction solution was oxygenated for 15 min, then amide 1a (139.2 mg, 1.0 mmol) and toluene (5 mL) were added. The resulting solution was stirred under an O2 atmosphere for 15 min, then heated at 95 °C with an air condenser under an O2 atmosphere for 21 h. The reaction mixture was filtered through a short pad of Celite, then concentrated in vacuo. The residue was purified by flash column chromatography to afford 2a (101.5 mg, 0.74 mmol, 74% yield) as a yellow oil. 2-Methylenehexahydro-3H-pyrrolizin-3-one (2a) Yellow liquid; analytical TLC (silica gel 60), 50% EtOAc in n-hexane, R f = 0.18. 1H NMR (400 MHz, CDCl3): δ = 5.93 (t, J = 2.7 Hz, 1 H), 5.28 (t, J = 2.2 Hz, 1 H), 3.77 (tt, J = 7.2, 4.9 Hz, 1 H), 3.67 (dt, J = 12.0 Hz, 8.1 Hz, 1 H), 3.21 (ddd, J = 12.3, 9.6, 3.0 Hz, 1 H), 3.00 (ddt , J = 17.0 Hz, 7.4 Hz, 2.1 Hz, 1 H), 2.50 (ddd, J = 17.0 Hz, 7.4 Hz, 3.1 Hz, 1 H), 2.26–1.93 (m, 3 H), 1.30–1.21 (m, 1 H). 13C NMR (100 MHz, CDCl3): δ = 168.3 (C), 143.0 (C), 115.2 (CH2), 58.5 (CH), 41.4 (CH2), 31.9 (CH2), 31.4 (CH2), 25.9 (CH2); IR (CH2Cl2) 3048, 2981, 2888, 1692, 1659, 1445, 1244, 1208, 1156 cm–1. LRMS (EI, 20 eV): m/z = 137 (100) [M+]. HRMS (EI): m/z calcd for C8H11NO [M+]: 137.0841; found: 137.0843.