Synlett 2017; 28(04): 433-438
DOI: 10.1055/s-0036-1588368
letter
© Georg Thieme Verlag Stuttgart · New York

Thieme Chemistry Journals Awardees – Where Are They Now?
Phospha-Münchnone 1,3-Dipolar Cycloaddition with Alkenes: A One-Pot Approach to 2-Pyrrolines from Imines, Acid Chlorides and Alkenes

Victoria Jackiewicz, Bruce A. Arndtsen*
  • Department of Chemistry, McGill University, 801 Sherbrooke St. W., Montreal, QC H4X 2E9, Canada   Email: bruce.arndtsen@mcgill.ca
Further Information

Publication History

Received: 03 October 2016

Accepted after revision: 07 November 2016

Publication Date:
02 December 2016 (eFirst)

Abstract

We describe herein studies on the cycloaddition of phospha-Münchnones and alkenes, and the factors that influence selectivity between 2-pyrrolines and bicyclic products. Coupling this cycloaddition with the formation of the dipoles can provide a one-pot route to synthesize 2-pyrrolines in moderate yield from imines, acid chlorides and alkenes.

Supporting Information

 
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  • 21 Typical Experimental Procedure: In a glovebox, p-tolyl(H)C=NEt (59 mg, 0.40 mmol) and p-toluoyl chloride (68 mg, 0.44 mmol) were mixed in CH2Cl2 (1 mL) for 30 min, followed by the addition of PhP(2-catechyl) (95 mg, 0.44 mmol). The reaction mixture was stirred at ambient temperature for 2 h. DBU (152 mg, 1.00 mmol) was added to the solution and the final volume was adjusted to 2 mL. After 15 min, dimethyl furmarate (66 mg, 0.46 mmol) in CH2Cl2 (2 mL) was transferred to a 3-mL syringe and added to the reaction mixture via syringe pump over 6 h. The reaction mixture was allowed to stir for 16 h before the crude solution was concentrated in vacuo. Due to the sensitivity of many of these products, and to more accurately determine product composition, all yields were determined by 1H NMR analysis by filtration of a toluene solution of the product through alumina and 1H NMR analysis relative to an internal hexamethylbenzene standard (70% yield 3a). The product was isolated by flash chromatography on silica using toluene–EtOAc as the eluent to afford 3a in 56% isolated yield as a light yellow solid. 1H NMR (500 MHz, CDCl3): δ = 7.46 (2 H), 7.32 (d, J = 8.1 Hz, 2 H), 7.11 (d, J = 4.9 Hz, 2 H), 7.09 (d, J = 4.9 Hz, 2 H), 5.02 (d, J = 7.7 Hz, 1 H), 4.41 (d, J = 7.7 Hz, 1 H), 3.63 (s, 3 H), 3.46 (s, 3 H), 2.95 (dq, J = 14.5, 7.2 Hz, 1 H), 2.66 (dq, J = 14.5, 7.2 Hz, 1 H), 2.21 (s, 3 H), 2.18 (s, 3 H), 0.73 (t, J = 7.1 Hz, 3 H). 13C NMR (126 MHz, C6D6): δ = 175.51, 165.83, 163.60, 139.94, 139.60, 138.43, 130.50, 130.10, 129.50, 128.91, 128.81, 128.72, 128.53, 128.43, 127.62, 98.87, 69.42, 57.92, 52.43, 50.68, 41.47, 21.91, 21.69, 13.24. HRMS (APCI): m/z calcd for C24H27NO4H+: 394.20128; found: 394.20069.