Synthesis of Enantiomerically Pure <i>N</i>-<i>tert</i>-Butanesulfinyl Imines (<i>tert</i>-Butanesulfinimines) by the Direct Condensation of <i>tert</i>-Butanesulfinamide with Aldehydes and Ketones

TLDR

This work presents the first general one‑step method for synthesizing N‑tert‑butanesulfinyl imines from aldehydes and ketones. The condensation employs Lewis‑acidic dehydrating agents such as MgSO₄, CuSO₄, or Ti(OEt)₄ to drive the reaction of tert‑butanesulfinamide with aldehydes. Using MgSO₄, high yields (84–96 %) are obtained with excess aldehyde; CuSO₄ gives high yields with only 1.1 equiv aldehyde and tolerates sterically demanding and electron‑rich aldehydes (90 % and 81 % respectively); Ti(OEt)₄ and Ti(O‑i‑Pr)₄ enable synthesis from unreactive aldehydes (82 %) and ketones (77–91 %), with E‑selectivity for most ketimines and high E/Z ratios (5:1) for 2‑hexanone.

Abstract

Experimental details for the first general methods for the one-step preparation of N-tert-butanesulfinyl imines (tert-butanesulfinimines) (2) from aldehydes and ketones is described. To effect the condensations of tert-butanesulfinamide (1) with aldehydes, the Lewis acidic dehydrating agents MgSO4, CuSO4, or Ti(OEt)4 are employed. Aldehyde condensations mediated by MgSO4 proceed in high yields (84−96%) when an excess of aldehyde is used. In contrast, only a slight excess of aldehyde (1.1 equiv) relative to tert-butanesulfinamide provides sulfinimines in high yields when the more Lewis acidic dehydrating agent CuSO4 is used. The CuSO4-mediated procedure is effective for a wide range of aldehydes, including sterically demanding aldehydes, such as isobutyraldehyde (90%), and electron-rich aldehydes, such as p-anisaldehyde (81%). The still more Lewis acidic Ti(OEt)4 and Ti(O-i-Pr)4 also afford N-tert-butanesulfinyl aldimines from especially unreactive aldehydes, such as pivaldehyde (82%). In addition, Ti(OEt)4 is effective for the condensation of 1 with ketones to afford a wide range of N-tert-butanesulfinyl ketimines in good yields (77−91%). For sulfinyl ketimines derived from methyl or n-alkyl phenyl ketones and methyl or n-alkyl isopropyl ketones, only the E isomer is detected by 1H and 13C NMR in CDCl3. For those cases where the difference in steric demand about the imine is very small, such as for 2-hexanone, high E/Z ratios are still observed (5:1).