Synthesis of Enantiopure Benzo Fused Cyclic Sulfoximines Through Stereoselective [3+2] Cycloaddition between N‐tert‐Butanesulfinyl [(2‐Pyridyl)sulfonyl]‐difluoromethyl Ketimines and Arynes

Abstract

The previously developed stereoselective [3+2] cycloaddition between N‐tert‐butanesulfinyl ketimines and arynes has been extended to the synthesis of enantiopure [(2‐pyridyl)sulfonyl]difluoromethylated cyclic sulfoximines. The use of 2‐PySO2CF2 as the facilitating group offers new opportunities for the elaboration of the [3+2] cycloaddition products by virtue of the diverse relativity of 2‐pyridyl sulfones.

Recent advances in the synthesis of cyclic sulfinic acid derivatives (sultines and cyclic sulfinamides)

“…Further efforts by the same group resulted in a modular cycloaddition strategy using 2-PySO 2 CF 2 instead of the previous PhSO 2 CF 2 as the facilitating group, affording more possibilities for further transformation of the [3+2] cycloaddition benzo-fused cyclic sulfoximine products. 35…”

Cyclic Sulfinamides

“…The configuration at the sulfur stereogenic center was also retained during the loss of t ‐Bu group (selected examples are depicted in Scheme 43). [77,78] …”

“…There are some other ordinary examples of oxidation of γ‐sultims with m CPBA. Interestingly, while sp 3 ‐enriched γ‐sultims 96 a (prepared via Scheme 40) and 107 d (prepared via Scheme 44) were oxidized at rt, their bezofused congener 104 d (prepared via Scheme 43) required lower (0 °C) temperature (Scheme 92, A , [76] B , [79] and C [78] ). Under these conditions, the pyridine ring of γ‐sultam 228 remained intact.…”

“…The reaction with SelectFluor [154] at rt turned benzofused γ‐sultim 107 d (prepared via Scheme 43) into sulfonimidoyl fluoride 238 formed as a sole diastereoisomer in good yield (Scheme 98). [78] …”

“…In this way, γ‐sultims 107 d (prepared via Scheme 44), 247 (prepared via Scheme 103), and 103 d (prepared via Scheme 43) were alkylated in good yields using either MeI or AllI and NaHMDS or NaH as a base at low temperature (Scheme 106, A [79] and B , C [78] ).…”