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. Author manuscript; available in PMC: 2018 Nov 8.
Published in final edited form as: J Am Chem Soc. 2017 Oct 24;139(44):15868–15877. doi: 10.1021/jacs.7b08749

Scheme 1. Enantioselective Iodolactonization of Amide Derivatives to Iodo Pyrrolizidinone (+)-21a.

Scheme 1

aReagents and conditions: (a) (±)-29 (1.0 equiv), 34a (1.2 equiv), PivCl (1.05 equiv), LiCl (1.7 equiv), Et3N (2.5 equiv), CH2Cl2, −20 °C, 6 h, 35a+36a (82%, 1:1 dr); (b) (±)-29 (1.0 equiv), 34b (1.2 equiv), PivCl (1.05 equiv), LiCl (1.7 equiv), Et3N (2.5 equiv), CH2Cl2, −20 °C, 6 h, 35b+36b (87%, 1:1 dr); (c) (±)-29 (1.0 equiv), EDCI (1.5 equiv), HOAt (1.0 equiv), 34c (2.0 equiv), i-Pr2NEt (3.0 equiv), CH2Cl2, 0 → 25 °C, 16 h, 35c+36c (68%, 1:1 dr); (d) (±)-29 (1.0 equiv), EDCI (1.5 equiv), HOAt (1.0 equiv), 34d (1.0 equiv), i-Pr2NEt (3.0 equiv), CH2Cl2, 0 → 25 °C, 24 h, 35d (42%); (e) I(sym-collidine)2ClO4 (5.0 equiv), CH2Cl2:MeOH:H2O 1:1:0.05 (v/v/v), 25°C, 7 d, 3%, (98:2 er) from 35b; 72 h, 28% (24:76 er) from 35c+36c; 47%, 73% brsm (>99:1 er) from 35d. PivCl = pivaloyl chloride; EDCI = 3-(ethyliminomethyleneamino)-N,N-dimethylpropan-1-amine, HOAt = 3-hydroxytriazolo[4,5-b]pyridine.