Oxa- and Azacycle Formation via Migrative Cyclization of Sulfonylalkynol and Sulfonylalkynamide with N-Heterocyclic Carbene

Abstract

An N-heterocyclic carbene promotes cyclization of sulfonylalkynols and sulfonylalkynamides that accompanies 1,2-migration of the sulfonyl groups. This reaction provides a novel access to oxa- and azacycles possessing a pendent vinyl sulfone functionality, which, in turn, is amenable for further transformations.

Mechanistic Support for Intramolecular Migrative Cyclization of Propargyl Sulfones Provided by Catalytic Asymmetric Induction with a Chiral Counter Cation Strategy

“…1‐Tosyl‐2‐(1‐tosylvinyl)pyrrolidine (2 b) and 1‐Tosyl‐6‐(tosylmethyl)‐1,2,3,4‐tetrahydropyridine (3 b) : The typical procedure using G (19.9 mg, 20.0 μmol) and 1 b (40.6 mg, 100 μmol) in place of M and 1 a , and purification by column chromatography (hexane/EtOAc 2 : 1) gave a 96 : 4 mixture of 2 b in 62 : 38 er and 3 b (16.8 mg, 40% and 2%, respectively) as a yellow oil with [α] D 29 −35 ( c 0.46, CHCl 3 ). The spectroscopic data were identical to those reported [2] . The ratio of 2 b and 3 b was determined by the integral area of the 1 H NMR signals at 6.46 and 5.66 ppm.…”

“…Propargyl sulfones 1 a-1 e were prepared in the reported procedures. [2] General Procedure for Chiral Pyridine Mediated Reactions. 1-(1-Tosylvinyl)isochromane (2 c): A 10 mL flame-dried test tube with a magnetic stirring bar was charged with 1 c (31.4 mg, 100 μmol) and D (3.7 mg, 5.0 μmol).…”

“…The spectroscopic data were identical to those reported. [2] The enantiomeric ratio was determined to be 59 : 41 by chiral stationary phase HPLC analysis (CHIRALPAK AD-H, hexane/i-PrOH 10 : 1, 1.1 mL/min, 254 nm, t R = 15.7 min for R and 21.2 min for S). The absolute configuration of the major enantiomer was opposite to that provided by catalysts C and M, and thus tentatively assigned to R by analogy to 2 a.…”

“…As part of our ongoing studies to develop catalytic reactions, [1] we recently reported that an oxa‐ and azacycle‐forming reaction of sulfonylalkynols and sulfonylalkynamides was triggered by nucleophiles, such as an N‐heterocyclic carbene (NHC), [2] 4‐dimethylaminopyridine (DMAP), and phosphines (Scheme 1). [3] In the presence of catalytic amounts of these nucleophiles, bond formation with the internal O‐ or N‐nucleophile occurred at the γ‐position of sulfone with 1,2‐sulfonyl migration [4,5] .…”

“…(3) Conjugate addition of Ts − to I followed by proton transfer provides allylic sulfone IV , whose S N 2′‐type cyclization leads to 2 and regeneration of Ts − . According to the postulated reaction mechanism, [2,3] we envisaged that the cyclization of IV could enantioselectively produce 2 in the presence of chiral cations. We expected that a counter cation of cyclizing alkoxide IV would be cationic co‐product III and that observation of enantioenrichment in 2 with chiral III would strongly support the mechanism.…”