Microwave-Assisted Solvent-Free Synthesis of Enantiomerically Pure N-(tert-Butylsulfinyl)imines

Abstract

A simple, environmentally friendly, and very efficient procedure for the synthesis of optically pure N-(tert-butylsulfinyl)imines has been developed with microwave-promoted condensation of aldehydes and ketones using (R)-2-methylpropane-2-sulfinamide in the presence of Ti(OEt)(4), under solvent-free conditions. This procedure allows for the preparation of a variety of sulfinyl aldimines with excellent yields and purities in only 10 min, making any further purification of the imines unnecessary. Several sulfinyl ketimines have also been prepared in good yields by extension of the reaction times to 1 h. This methodology has proved to be equally efficient for the synthesis of aromatic, heteroaromatic, and aliphatic N-(tert-butylsulfinyl)imines. Conventional heating has also been shown to be useful to promote these reactions, especially for the synthesis of aldimines.

Synthesis of Highly Enantiomerically Enriched Amines by Asymmetric Transfer Hydrogenation of N-(tert-Butylsulfinyl)Imines

“…10 The N-(tert-butylsulfinyl)imines are prepared by reaction of stoichiometric amounts of the corresponding ketones and 2-methylpropane-2-sulfinamide in the presence of two equivalents of Ti(OEt) 4 under solventfree conditions. 11 The obtained imines 3 are reduced by asymmetric transfer hydrogenation using isopropyl alcohol as hydrogen source and, as a catalyst, a ruthenium complex bearing a commercially available simple achiralaminoalcohol: 2-amino-2-methylpropan-1-ol. This catalyst has been shown to be very versatile, giving good results for the reduction of a variety of aromatic, heteroaromatic and aliphatic sulfinylketimines, including several examples of sterically congested imines.…”

Microwave Reactors: A Brief Review on Its Fundamental Aspects and Applications

“…The reaction has shown to take place in presence of ketone, aldehyde, ester, nitrile, or amide functionalities. September 2014 | Volume 1 | e686 5) Microwave-irradiated condensation of carbonyl compounds with (R)-2-methylpropane-2-sulfinamide under solvent-free conditions in the presence of Ti(OEt) 4 offers a simple, environmentally friendly synthesis of optically pure N-(tert-butylsulfinyl)imines [66]. Sulfinyl aldimines can be prepared with both excellent yields and purities in only 10 min, while the reaction time for the preparation of ketimines has been extended to 1 h. 6) An efficient microwave-assisted metal-free amino benzannulation of aryl(4-aryl-1-(prop-2-ynyl)-1H-imidazol-2-yl)methanone with dialkylamines affords various 2,8-diaryl-6-aminoimidazo[1,2-a]pyridines in good overall yield [67].…”

Synthesis of γ-, δ-, and ε-Lactams by Asymmetric Transfer Hydrogenation of N-(tert-Butylsulfinyl)iminoesters

“…Next, the required iminoesters were prepared by reaction of ketoesters 1 with either (R)-or (S)-2-methylpropane-2-sulfinamide in the presence of titanium tetraethoxide under neat conditions (Scheme 3), according to a procedure recently reported by us. 18 Thus, the expected enantiomerically pure N-(tertbutylsulfinyl)iminoesters with (R) (compounds 2) or (S) (compounds ent-2) absolute configuration were isolated in good yields after column chromatography. [ent-2b (77%)] 2c: R = 4-ClC 6 H 4 (63%)…”

“…N-(tert-Butylsulfinyl)iminoesters 2 and ent-2 were prepared by reaction of (R)-2-methylpropane-2-sulfinamide (for 2) or (S)-2-methylpropane-2-sulfinamide (for ent-2) with the corresponding ketoester according to our recently reported procedure, 18 as follows: the mixture of ketoester 1 (5.0 mmol), (R)-or (S)-t-BuSONH 2 (612 mg, 5.0 mmol) and Ti(OEt) 4 (2.1 mL, 10.0 mmol) was stirred overnight under argon at 72 ºC (oil bath temperature). After cooling to room temperature, the mixture was diluted with ethyl acetate (10 mL) and poured into brine (3 mL) while rapidly stirring.…”