Science of Synthesis

Mase, N., Science of Synthesis: Water in Organic Synthesis, (2012) 1, 176.

LUMO-lowering organocatalysis, generally called iminium catalysis, is a powerful methodology for the asymmetric conjugate addition reaction of active methylene compounds ‌82‌ to enals and enones ‌81‌. (S)-2-{Bis[3,5-bis(trifluoromethyl)phenyl](trimethylsiloxy)methyl}pyrrolidine (‌77‌) is a water-compatible catalyst employed in an asymmetric conjugate addition reaction of the β-keto ester ‌82‌ (R3 = CO2t-Bu; R4 = Ac) to (E)-but-2-enal (‌81‌, R1 = H; R2 = Me) in water (‌Scheme 23‌).[‌73‌] Similarly, the conjugate addition reaction of dibenzyl malonate (‌82‌, R3 = R4 = CO2Bn) to cinnamaldehyde (‌81‌, R1 = H; R2 = Ph) catalyzed by O-(trimethylsilyl)-protected diphenylprolinol (R)-‌78‌ and acetic acid in water occurs at 0 °C to room temperature within 24 h.[‌74‌] Highly efficient prolinol-based catalyst ‌79‌, including a hydrophobic alkyl chain, provides the conjugate addition products ‌83‌ in good yields with excellent stereoselectivities in the presence of a large amount of water.[‌75‌] Quinine-based primary amine ‌80‌ is a powerful organocatalyst for the aqueous conjugate addition reaction of less reactive enones ‌81‌ (R1 = R2 = alkyl).[‌76‌]

‌Meeeee 88‌ Meeeeeee ee Meeeeeee Meeeeeeee ee Meeee ee Meeeee eee Meeeeee Meeeeeeee[‌88‌–‌88‌]

‌Meeeeeeeeee 88‌

e Mee M-eeeeee eee eeeeeeee.

e Meeee eee ee eeee eeeeeeee eeeee MeMM8 eeeeeeeee.

e Meeee eee eeeeeeee eeeee eeeeeeeeee/eeeeeeeeeeeeeee ee eee eeeeeeeeeeeeee eeeee ee eee eeeeeeee eeeeeee (Me8M, MeMM, M8M, 88 °M, 8 e).

Mee eeeeeeeee eeeeeeee eeeeeeee ee eeeeeee eeeeeeeeeeeee (‌88‌) ee eeeeeeeeeeeeee eee eeeeeee eeeeeeeee, eeeeeeee ee eeeeeeeeeeeeeeee eee eeeeeee eeeeeeeee, eee eeee eeeeeeeee ee eee eeeeeeee ee M-(eeeeeeeeeeeeee)eeeeeeeeeeeeee ‌88‌ ee e eeeeeeee. Mee eee ee eeeee ee eeeeeeee eeeeee eee e eeeeeeeeee eeeeeeeeee eeeeee ee eee eeeeeeee, eeeeeeee ee ee ee eeeeeeeee eeeeeee eee eeee ee eeeeeeeeeee 8 eeeeeeeeee ee ee eeeeeeee eeee (‌Meeeee 88‌).[‌88‌]

‌Meeeee 88‌ Meeeee Meeeeeee/Meeeeeeeeeeeeeee eee Meeeeee/Meeeeee Meeeeeeee[‌88‌]

Meeeeeeeeeee Meeeeeeee

(M)-8-Meeee-8-eeeeeeeeeee-8-ee [Meeeeeeee Meeeeee eeee (M)-8-Meeee-8-eeeeeeeeeeeee (‌88‌, M8 = M8 = M; M8 = Me; M8 = MM8)]; Meeeeee Meeeeeeee:[‌88‌]

MMMMMMM: Meeeeeeeeeee ee eeeeeeeee, e eeeee- eee eeee-eeeeeeeee eeeeeeeee, eee ee eee, eeee, eee eeeeeeeeeee eeeee eeeeeeee.

Meeeeeeeeeee (‌88‌, M8 = MM8; M8 = M; 8 eeee) eee MeMM (8.8 ee; 8.88 eeee) eeee eeeee ee e eeeeeee ee (M)-8-[8-(eeeeeeeeeeeeeee)eeeeeeee-8-ee]eeeeeeeeeee (‌88‌; 8.88 eeee, 8 eee%) eee eeeeeeeeeeeeee (‌88‌, M8 = M; M8 = Me; 8 eeee) ee M8M (8 eM). Mee eeeeeeeee eeeeeeee eee eeeeeee eee 88 e ee ee. Me eeeeeeeee eee eeeeeeeeeeeeeeeeeee, e MeMM8 eeeeeeeee eee eeeeeeeee. M eeee ee eee eeeee eeeeeee eeeeeeeeee (M)-8-eeeee-8-eeeeeeeeeeeee (‌88‌, M8 = M8 = M; M8 = Me; M8 = MM8) ee MeMM (88 eM) eee eeeee eeeeeeee ee e eeeeee (−8 °M) eeee ee MeMM8 (88.8 ee, 8.8 eeee) ee MeMM (88 eM). Mee eeeeeee eee eeeeeee ee −8 °M eee 88 eee (MMM, MeMMe/eeeeee 8:8) eee eeeeeeeeee eeeeeeee eeee M8M (88 eM) eee eeeeeeeee eeee MM8Me8 (8 × 88 eM). Mee eeeeeeee eeeeeee eeeeee eeee eeeeee eeee eeeee eee eeeee (MeMM8). Mee eeeeeee eee eeeeeeeeee, eee eee eeeee eeeeeee eee eeeeeeee ee eeeeeeeeeeeeee (MeMMe/eeeeee 8:8) ee eeeeee (M)-8-eeeee-8-eeeeeeeeeee-8-ee; eeeee: 88%.

γ-Meeee Meeeeee ‌88‌ (M8 = MM8; M8 = M); Meeeeee Meeeeeeee:[‌88‌]

Mee eeeee ‌88‌ (8.8 eeee), 8-eeeee-8-eeeeeeeeeeeeeee (‌88‌; 88.8 ee, 8.88 eeee), eee MeMM (88.8 ee, 8.88 eeee) ee M8M (8.8 eM) eeee eeeeeee ee ee eee 8 eee. Meeee 8-eeeeeeeeeeee (‌88‌, M8 = MM8; M8 = MM8Me; 88.8 ee, 8.8 eeee) eee eeeee eee eee eeeeeee eee eeeeeee ee ee eee e eeeeeeeee eeeeeeee eeee eeeeee (eee ‌Meeeee 88‌). Me eeeeeeeee eee eeeeeeeeeeeeeeeee, eeeeeeeeee/eeeeeeeeeeeeeee ee eee eeeeeeeeeeeeee eeeee ee eeeeeeee eeeeeeee ‌88‌ (M8 = MM8; M8 = MM8Me) eee eeeeeeeee. MeMM (8.8 eM), M8M (8.8 eM), eee Me8M (8.8 eM) eeee eeeee ee eee eeeeeee, eee eee eeeeeeeee eeeeeee eee eeeeeee ee 88 °M. Meeee eeeee eeeeeee eee 8 e, eee eeeeeee eee eeeeeeeee eeee MeMMe. Mee eeeeeee eeeee eee eeeee (MeMM8) eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee. Mee eeeee eeeeeee eee eeeeeeee ee eeeeee eeeeeeeeeeeeee (eeeeee eee, eeeeee/MeMMe 8:8) ee eeee eee γ-eeeee eeeeee ‌88‌ (M8 = MM8; M8 = M); eeeee: 88–88%.

Meeeeee (8M,8M)-8-Meeeee-8-eeeeeeeeeeeeeeeeee-8,8-eeeeeeeeeeeee (‌88‌); Meeeeee Meeeeeeee:[‌88‌]

Meeeeeeeeeeeee (8.88 eeee) eee eeeee ee e eeee ee eeeeeeee ‌88‌ (8.88 eeee) ee M8M (8 eM). Mee eeeeeee eee eeeeeee eee 88 eee eee eeee eeeeeee eeeeeeeeeeeee (‌88‌; 8.8 eeee) eee eeeee ee eee eeeeeee eee eeeeeeee eee eeeeeeeee ee ee eee 88 e. M8M (8 eM) eee MM8Me8 (88 eM) eeee eeee eeeee, eee eeeeee eeee eeeeeeeee, eee eee eeeeeee eeeee eee eeeeeeeee eeee MM8Me8 (8 × 88 eM). Mee eeeeeeee eeeeeee eeeeeeeee eeee eeeeeeeee, eeeee (Me8MM8), eee eeeeeeee, eee eee eeeeeee eee eeeeeee eeeee eeeeeee eeeeeeee. Mee eeeee eeeeeee eee eeeeeeee ee eeeee eeeeee eeeeeeeeeeeeee (eeeeeee/MeMMe 8:8) ee eeeeee eeeeeee (8M,8M)-8-eeeeee-8-eeeeeeeeeeeeeeeeee-8,8-eeeeeeeeeeeee (‌88‌); eeeee: 88%.

References