New phosphine-diamine and phosphine-amino-alcohol tridentate ligands for ruthenium catalysed enantioselective hydrogenation of ketones and a concise lactone synthesis enabled by asymmetric reduction of cyano-ketones

Table 1 Enantioselective hydrogenation of some ketones using Ru catalysts derived from phosphine-amino-alcohols

Entry^[a]	Cat	Ketone	[cat] mol%	[base] mol%	Conversion (yield) [%]^[b]	e.e. [%]^[c]
1	5	9a	0.5	1	99	23 (S)
2	6	9a	0.5	1	99	27 (R)
3	ent-5	9a	0.5	1	99	29 (R)
4	ent-5	9a	0.5	2.5	99	43 (R)
5	ent-5	9a	0.5	5	98	51 (R)
6	4	9a	0.5	2.5	99 (99)	15 (S)
7	5	10a	0.5	1	26	4
8	4	10a	0.5	2.5	99 (99)	74 (S)
9^[d]	4	10a	0.5	2.5	99	79 (S)
10^[e]	4	10a	1	5	98	80 (S)
11	4	10a	0.09	5	45	3 (S)
12	6	11a	0.5	2.5	99 (97)	0

^[a] Unless otherwise indicated, reactions were carried out using 0.33 mmol mL^-1 of ketone at 50°C and 50 bar of hydrogen pressure with a 16 h reaction time using t- BuOK as base. ^[b] Conversions were determined by ¹H NMR analysis of the crude reaction mixtures (all peaks were assigned). Yields are for pure alcohols after short-path silica gel chromatography. ^[c] The e.e. value was determined by chiral HPLC. ^[d] 35°C. ^[e] 3 h.

ISSN: 2661-801X