Scope of enantioselective reduction of imines with trichlorosilane.
PhD thesis, University of Glasgow.
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Herein, we report the results of research continuing previous successI in the field of enantioselective organocatalytic reduction of imines with trichlorosilane. Syntheses of various precursors (ketones) and substrates (imines) for the reduction reaction and their reduction following the protocol (Scheme A1) are described in this thesis.
1. Aromatic heterocycles containing nitrogen – good yields of the reduced product (68-85 %), the enantioselectivity depended on steric bulk in proximity to the nitrogen, steric bulk improved the enantioselectivity (up to 78 % ee), probably due to thwarting the coordination of the nitrogen to HSiCl3.
2. Aromatic heterocycles containing sulfur – sulfur in the ring was tolerated well (89 % ee).
3. Aromatic heterocycles containing oxygen – generally good yields (62-90 %), dependence on position isomer was observed: furan-2-yl-derived substrates were reduced in moderate enantioselectivity (45-85 % ee), possibly due to the problem of coordination; in contrast, furan-3-yl derivatives were reduced in good enantioselectivity (77-91 % ee).
4. Non-heterocyclic aromatic or aliphatic – good yields (62-98 %) but varied enantiomeric excess (10-97 %). The high enantioselectivity values (76-97 % ee) were for substrates with significant contrast of the steric hindrance of the groups next to the reaction centre.
Furthermore, an example of practical utilisation of the method is presented. Naturally occurring alkaloid N-acetylcolchinol was synthesised in 9 steps and overall 8 % yield (Scheme A2). The stereogenic centre was introduced using our method and afforded the desired enantioenriched amine in 96 % ee.
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