. Author manuscript; available in PMC: 2017 Sep 2.

Published in final edited form as: J Org Chem. 2016 Aug 12;81(17):7824–7837. doi: 10.1021/acs.joc.6b01481

Table 1.

Reaction Conditions Optimization in Alkaloid-Catalyzed Heterodimerization of Ketenes.^a

entry	catalyst	addition time of AcCl (h)	solvent	% Yield (conv)	% ee^b
1	TMSQ	1	THF	0	-
2	TMSQ	1	CH₂Cl₂	(40)	nd
3^c	MeQ	1	CH₂Cl₂	(50)	nd
4^d	MeQ	1	CH₂Cl₂	(65)	nd
5	MeQ	8	CH₂Cl₂	65	83^e
6	TMSQ	8	CH₂Cl₂	57	94^e
7	(DHQ)₂PHAL	8	CH₂Cl₂	38	93
8	QT	8	CH₂Cl₂	<5	nd
9	NBzQ	8	CH₂Cl₂	43	13
10	PhQ	8	CH₂Cl₂	39	61
11	BzQ	8	CH₂Cl₂	55	72
12	MeQd	8	CH₂Cl₂	64	98^e
13	MeQd	8	THF	47	91
14	MeQd	8	PhCH₃	35	89
15	MeQd	8	CH₂Cl₂ (−78 °C)	50	91
16	MeQd	8	CH₂Cl₂ (0 °C)	20	36
17	MeQd	8	CH₂Cl₂ (rt)	15	5

Only one heterodimer regioisomer observed by GC-MS and ¹H NMR analysis of crude for entries 5,6 and 12 (Z:E ratio >97:3 as determined by GC-MS and ¹H NMR analysis).

ee determined by chiral HPLC.

entry 1–3: 0.13 M concentration of acceptor ketene in solvent.

entry 4–17: 0.25 M concentration of acceptor ketene in solvent.

MeQ and TMSQ afforded the (R)-enantiomer of 3a, while MeQd provided the (S)-enantiomer of 3a.