1,2-Oxazines were synthesised via a copper-catalysed aerobic acyl nitroso Diels-Alder reaction from 1,4-disubstituted 1,3-dienes and N-Boc-hydroxylamine. From this, 1,2-oxazinanes were received in a novel follow-up reaction path. The stability of several 1,2-oxazines and 1,2-oxazinanes towards organometallic compounds was tested to rate their operability as cyclic chiral Weinreb amide auxiliaries. 3,6-Di-tert-butyl-1,2-oxazinane gave the best results and was introduced as chiral Weinreb amide-type auxiliary to yield chiral α-substituted ketones in a diastereomeric ratio of up to 98:2. The removal of the auxiliary can be performed with BuLi to form unsymmetrical α-chiral ketones. Thereafter, the chiral auxiliary can be re-isolated and purified by sublimation in vacuum.
Herein, we described a new protocol for the asymmetric synthesis of apremilast using tert-butanesulfinamide as a chiral auxiliary. This synthetic route consisted of four steps starting from the commercially available 3-hydroxy-4-methoxybenzaldehyde, and apremilast was accordingly obtained in an overall 56% yield and with 95.5% ee.
Light-driven unidirectional molecular motor has gained enormous attention since the pioneering work by Prof. Ben L. Feringa in 1999 and it holds great promise in next generation smart materials. The intrinsic feature of point chirality and helicity of these motor molecules requires efficient strategies to access their optically pure form especially when chirality-sensitive materials are fabricated. In this short review, we will summarize synthetic strategies to access optically pure first and second generation molecular motors. Generally, three strategies will be discussed including direct asymmetric synthesis, chiral auxiliary method and resolving agent aided chiral separation. We expect this review can ignite the enthusiasm of synthetic chemists to address very fundamental but unavoidable synthetic questions for chiral alkene based molecular motors concerning their large scale applications.