Science of Synthesis

MacMillan, D. W. C.; Watson, A. J. B., Science of Synthesis: Asymmetric Organocatalysis, (2012) 1, 338.

The asymmetric Michael addition of activated methylene compounds to α,β-unsaturated carbonyl compounds is a powerful and reliable tool for the stereocontrolled formation of C—C bonds.[‌84‌–‌87‌] Under iminium catalysis, 1,3-dicarbonyl derivatives are employed in partnership with a suitable catalyst to provide a range of highly modifiable enantioenriched 1,5-dicarbonyl adducts and derivatives.[‌88‌–‌96‌] While enones were the first substrates to succumb to this process, a key development was the realization that, under specific conditions, enals could be used as the carbonyl component without any deleterious 1,2-addition side reactions (e.g., aldol, Knoevenagel processes).

Mee eeeeeeeee eeeee ee eeeeeeeeee eeee eeee e eeeeeeeee ee eeeeeeee eeeeeeeeeee eeeeeeeeee eeeeee eeeee eeeeeeeeeee, eeeeeeee eeeee eeee ee ee eeeee eeee eeeeeeeeeee ee eeeeeeeeeeeeee/eeeeeeeeeeeeee eee eeeee eee eeeeeeeeeeeee eee eeeeee. Mee eeeeeeeeeeee eeeeeeeeee ee eeeeee eee eeeeee eeeeeeeeeee eeeeeeeee eeee eeeeeee eeeeeeee ee eeeeeeeeeee eeeeeeeeeeee eeeeeee eeee eeee eeeeee, eeeeeeeeeeeeeeeeee (eeeeeeeee), eee eeeeeeeee.

Meeeeeeeee eee eeeeeeeee eeee eeeeee eeee eeeeeeee ee eee eeeeeeee eeeeeeee ee eeeeeeee eeeeeeeeeee eeeee eeeeeeeeeee ee eee eeeeeeee eeeeeee. Mee eeeeeeeeeeeee ee eeeee eeeeeeeee eeeeee ee eeeeeeeee eeeee eeeee eee eeeeeeee eeeeeee eeeeee eeeeeeeee ee eee eeeeeeee eee ee ee eee eeeeeeee eee eeeeeeeeeeee eee eeeeeeeeeee ee ee eeee ee eeeee eeeeeeee (eeeeeee). Meeeeee eeeee eee eeeeeeeeeee eeee eeee eeeee eeeeeeeeeeee eeeeeeeee ee eee eeeeeeee eeeeeeeeeeeeee (‌Meeee 8‌).

Mee eeeeeeee eeeeeeee eee eeeeeeeeee eeeeeee eeeeeeeeeee, e.e. ee eeee ‌88‌ eee ‌88‌, eeeeee eeeeeeeeeeeee ee eee eeeeeeeeeeee eeeeee (‌Meeeee 88‌).

‌Meeee 8‌ Meeeeeeeeeeeeeee 8,8-Meeeeeee ee 8,8-Meeeeeeeee-Meeee Meeeeeeeeeee[‌88‌–‌88‌]

Meeee	Meeeeeee Meeeeeeee		Meeeee	Meeeeeeeee	Meeeeee	ee (%)	Meeee (%)	Mee
	Meeeeeeee	Meeeeeeeee
8			8:8	‌88‌ (8.8 eeeee), MeMM (8.88 M), 8 °M		88e	88	[‌88‌]
8			8:8	‌88‌ (8.8 eeeee), MeMM (8.88 M), 8 °M		88e	88	[‌88‌]
8			8:8	eee-‌88‌ (8.8 eeeee), MeMM (8.8 eeeee), M8M (8 M), 8 °M ee ee		88	88	[‌88‌]
8			8.8:8	‌88‌ (8.8 eeeee), M8M (8.888 M), ee		88e	88	[‌88‌]
8			8.8:8	‌88‌ (8.8 eeeee), MM8Me8 (8.8 M), 88 °M		88	88	[‌88‌]
8			8.8:8	‌88‌ (8.8 eeeee), MM8Me8 (8.8 M), 8 °M		88	88	[‌88‌]
8			8:8	‌88‌ (8.8 eeeee), ee		88	88	[‌88‌]
8			8:8	‌88‌ (8.8 eeeee), ee		88	88	[‌88‌]
8			8:8.8	‌88‌ (8.88 eeeee), eeeeeeeeee (8 eeeee), MMMe8 (8.88 M), ee		88	88	[‌88‌]
88			8:8.8	‌88‌ (8.88 eeeee), eeeeeeeeee (8 eeeee), MMMe8 (8.88 M), ee		88	88	[‌88‌]
88			8:8.88	‌88‌ (8.8 eeeee), MM8Me8 (8.8 M), ee		88	88	[‌88‌]
88			8:8.88	‌88‌ (8.8 eeeee), MM8Me8 (8.8 M), ee		88	88	[‌88‌]
88			8:8.8	‌88‌ (8.88 eeeee), eeeeeeeeee (8 eeeee), MMMe8 (8.88 M), ee		88	88	[‌88‌]

e Meeee (eeeeeeeee/eeeeeeeeee).

e ee ee eeeeeeeeeeeee eeeeee eeeee.

e ee ee eee eeeeeeeeeeeee eeeeeeeeeeeeee eeeeeeeeee; ee ee eee eeeee 8:8 ee 8:8 (eee eeeeeeeee).

‌Meeeee 88‌ Meeeeeeeeeeeee eee Meeeeeeeeeeee ee Meeeeeeeeeee Meeeee[‌88‌,‌88‌]

Meeeeeeeeeee Meeeeeeee

Meeeeeee (M)-[8-(8-Meeeeeeeeee)-8-eeeeeeeee]eeeeeeee (‌Meeee 8‌, Meeee 8); Meeeeee Meeeeeeee:[‌88‌]

Me (M)-8-(8-eeeeeeeeeee)eeeeeeee (888.8 ee, 8.8 eeee, 8 eeeee) ee MeMM (8 eM) ee 8 °M eee eeeee (M)-8-{eee[8,8-eee(eeeeeeeeeeeeeee)eeeeee](eeeeeeeeeeeeeee)eeeeee}eeeeeeeeeee (‌88‌; 88.8 ee, 8.888 eeee, 8.8 eeeee) eee eeeeeeee eeeeeeee (88.8 ee, 8.88 eeee, 8 eeeee). Mee eeeeeeeee eeeeeee eee eeeeeee eee 88 e ee 8 °M eee eeee eeeeeeee eeeeeee e eee ee eeeeee eee (8–8 ee), eeeeeee eeee Me8M eee MM8Me8 (eeeeeee eee eeeeeeee). Mee eeeeeeee eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee ee eeee e eeeeeee, eeeee eee eeeeeeee ee eeeee eeeeee eeeeeeeeeeeeee (Me8M/eeeeeee/MM8Me8 8:88:8.8); eeeee: 88.8 ee (88%). Mee eeeeeeeeeeee eeeeee eee eeeeeeeeee eeeee eeeeeeeee ee eee eeeeeeeeeeeee eeeeee eeeee ‌88‌ ee eeeeeeeee eeeee.

8,8-Meeeeeee 8-Meeeee (M)-8-(8-Meeeeeeeeee)eeeeeee-8,8,8-eeeeeeeeeeeeee (‌88‌):[‌88‌]

MMMMMMM: Meeee(eeeeeeeeeeeeee)eeeeeee eee eee eeeeeeeeee eeeeeeee eee eeee eeeee ee eeeeeeeeee. Mee eeeeeeeeee eeeeee ee eeeeeeeee ee e eeee-eeeeeeeeee eeee eeee eeeee eeeeeeeeeee eeeeee eeeeeeeeeee eee eeeeeeeeee.

Meee: eee eeeeeeeeeeee eee eee eeeeeeeee eeeeeeee ee eeee eeeeeeeeeeeeee eeee eee eeeeeeeee. M eeeeeee ee eeeeeeee (M)-[8-(8-eeeeeeeeeee)-8-eeeeeeeee]eeeeeeee (‌Meeee 8‌, eeeee 8; 88 ee, 8.8 eeee, 8 eeeee) eee 8 M ee MeM8MM8 (8 eM) ee e-MeMM (8 eM) eee eeeeeee eeee 8 M MMeM8 eeee (8 eM). Mee eeeeeee eee eeeeeee eee 8 eee eeeeee eeeeeeee ee eee. ee MeMMM8 (8 eM). Mee eM eee eeee eeeeeeee ee ee. eM 8 eeeee 8 M MMe. Mee eeeeeeeee eeeeeee eee eeeeeeeee eeee MeMMe (8 × 88 eM) eee eee eeeeeeee eeeeeee eeeeeeee eeee eeeeee eeee M8M (88 eM) eee eeeee (88 eM) eee eeeee (MeMM8). Mee eeeeeeeee eeee eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee ee eeee e eeeeeee, eeeee eee eeeeeeeee ee eeeeeee/MeMM (8:8; 8 eM) eee eeeeeee eeee 8 M MMMMMM8 ee eeeeee eeeeeeee eeeee eee eeeeee eeeee eeeeeeeee. Mee eeeeeee eee eeeeeee eee 88 eee eeeeee eeeee eeeeeeee eeee MeMM (8 eeee). Mee eeeeeee eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee ee eeee e eeeeeee, eeeee eee eeeeeeee ee eeeee eeeeee eeeeeeeeeeeeee (Me8M/eeeeeee/MM8Me8 8:88:8.8); eeeee: 88 ee (88%); 88% ee. Mee eeeeeeeeeeee eeeeee eee eeeeeeeeee ee MMMM eeeeeeee [MM eeeeee, eMeMM/eeeeee 8:8, 8 eM · eee−8; eM (eeeee) = 88.8 eee, eM (eeeee) = 88.8 eee].

eeee-Meeee (8M,8M)-8-Meeeee-8-eee-8-eeeeeeeeeeeeeeee (‌Meeee 8‌, Meeee 8); Meeeeee Meeeeeeee:[‌88‌]

Me e eeeeeee ee (M)-8-{eee[8,8-eee(eeeeeeeeeeeeeee)eeeeee](eeeeeeeeeeeeeee)eeeeee}eeeeeeeeeee (‌88‌; 88.8 ee, 8.888 eeee, 8.8 eeeee) eee (M)-8-eeeeeeeeeeeeee (88.8 ee, 8.88 eeee, 8.8 eeeee) ee M8M (8.8 eM) ee ee eee eeeee eeee-eeeee 8-eeeeeeeeeeee (88.8 ee, 8.88 eeee, 8 eeeee). Mee eeeeeeeee eeeeeee eee eeeeeee eee 8 e eeeeee eeeee eeeeeeee eeeeeeee ee eeeee eeeeee eeeeeeeeeeeeee (Me8M/MM8Me8 8:88); eeeee: 88.8 ee (88%). Mee eeeeeeeeeeee eeeeee eee eeeeeeeeee eeeee eeeeeeeeeeeeeee ee eeee eeeeee ‌88‌ ee eeeeeeeee eeeee.

(M)-8-Mee-8-eeeeeeeeeeeee (‌88‌):[‌88‌]

eeee-Meeee (8M,8M)-8-eeeeee-8-eee-8-eeeeeeeeeeeeeeee (88.8 ee, 8.88 eeee, 8 eeeee) eee eeeeeee eeee 88% MMM ee MM8Me8 (8.8 eM). Mee eeeeeeeee eeeeeee eee eeeeeee eee 8 e eeeeee eeeee eeeeeeee eeee M8M eee eeeeeeeee eeee MM8Me8 (eeeeeee eee eeeeeeee). Meeeeeeeee ee eee eeeeeee eeeee eeeeeee e eeeeee eee eee eeeeeeee eee eeeee eeeeeee; eeeee: eee eeeeeeee; 88% ee. Mee eeeeeeeeeeee eeeeee eee eeeeeeeeee ee MM eeeeeeee [M-MM eeeeee, M8 = 88 °M, M8 = 888 °M, 88 °M · eee−8, M8 = 888 °M; eM = 88.8, 88.8 eee].

Meeeeeee (M)-[8-Mee-8-(8-eeeeeee)eeeee]eeeeeeee (‌Meeee 8‌, Meeee 8); Meeeeee Meeeeeeee:[‌88‌]

M eeeeeee ee eeeeeeee eeeeeeee (8.88 e, 8 eeee, 8 eeeee), (M)-8-(8-eeeeeee)eee-8-ee-8-eee (888 ee, 8 eeee, 8 eeeee), eee (8M)-8-eeeeee-8-eeeeeeeeeeeeeeeeeee-8-eeeeeeeeee eeee (‌88‌; 88 ee, 8.8 eeee, 8.8 eeeee) eee eeeeeee eee 888 e ee ee. Mee eeeeeee eee eeee eeeeeeee eeeeeeee ee eeeee eeeeee eeeeeeeeeeeeee (Me8M/eeeeeee); eeeee: 888 ee (88%); 88% ee. Mee eeeeeeeeeeee eeeeee eee eeeeeeeeee ee MMMM eeeeeeee (MM eeeeee, eMeMM/eeeeee 8:8).

Meeeeee (M)-8-(8-Mee-8,8-eeeeeeeeeeeeee)eeeeeeee (‌Meeee 8‌, Meeee 8); Meeeeee Meeeeeeee:[‌88‌]

Me e eeeeeee ee (M)-8,8-eeeeeeeeeeeeeeeee (888.8 ee, 8.8 eeee, 8 eeeee) eee (M)-8-(eeeeeeeeee-8-ee)-8M-eeeeeeeee (‌88‌; 88.8 ee, 8.888 eeee, 8.88 eeeee) ee MMMe8 (8 eM) ee ee eee eeeee eeeeeee eeeeeeee (888.8 ee, 8.88 eeee, 8.8 eeeee) eee eeeeeeeeee (88.8 ee, 8.8 eeee, 8 eeeee). Mee eeeeeeeee eeeeeee eee eeeeeee eee 8 e ee ee eee eeee eeeeeee eeee MM8Me8 (88 eM) eee eeeeee eeee eee. ee MM8Me (88 eM). Mee eeeeeee eeeee eee ee-eeeeeeeee eeee MM8Me8 (8 × 88 eM) eee eee eeeeeeee eeeeeeee eeee eeeee (MeMM8), eeeeeeee, eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee ee eeee e eeeeeee, eeeee eee eeeeeeee ee eeeee eeeeee eeeeeeeeeeeeee [Me8M/eeeeeeeee eeeee (ee 88–88 °M) 8:8]; eeeee: 888.8 ee (88%); 88% ee. Mee eeeeeeeeeeee eeeeee eee eeeeeeeeee ee MMM eeeeeeee [MM-M eeeeee, eMeMM 8:8, 8 eM · eee−8; eM (eeeee) = 88.8 eee, eM (eeeee) = 88.8 eee].

References