Science of Synthesis

Terada, M., Science of Synthesis: Stereoselective Synthesis, (2011) 3, 333.

Although the enantioselective intermolecular carbonyl-ene reaction of unactivated alkenes is extremely well studied, the corresponding reaction with an imine, namely the imino-ene reaction, has received relatively limited attention. This is somewhat surprising given that the products of diastereoselective imino-ene reactions are prevalent in the total synthesis of natural products.[‌10‌] The first enantioselective imino-ene reaction was developed independently by two groups using similar chiral copper(I) catalysts.[‌98‌–‌100‌] For example, the chiral copper(I) complex generated in situ from tetrakis(acetonitrile)copper(I) perchlorate and ligand ‌53‌ provides the optimal catalyst for the reaction of ethyl (tosylimino)acetate as an enophile with various 1,1-disubstituted alkenes, to afford the corresponding α-amino acid derivatives ‌54‌ in good yield and with excellent enantioselectivity (‌Scheme 22‌). Interestingly, the use of (trifluoromethyl)benzene as the solvent in conjunction with 2 equivalents of the alkene is critical for achieving high yield and enantioselectivity. Activated ene components, such as vinyl sulfides and enol ethers, also provide the corresponding products in good yield.

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M8	M8	M8	ee (%)	Meeee (%)	Mee
M	Me	M	88	88	[‌88‌,‌88‌]
M	MMe	M	88	88	[‌88‌,‌88‌]
M	8-MeMM8M8	Me	88	88e	[‌88‌]
(MM8)8		M	88	88	[‌88‌,‌88‌]
MMM=MM		M	88	88	[‌88‌]
		M	88	88	[‌88‌,‌88‌]
		M	88	88	[‌88‌,‌88‌]

e ee (eee/eeee) 8:8.

Meeeeeeeeeee Meeeeeeee

Meeee (M)-8-(Meeeeeeeee)-8-eeeeeeeeee-8-eeeeee (‌88‌, M8 = M8 = M; M8 = Me); Meeeeee Meeeeeeee:[‌88‌,‌88‌]

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References