Science of Synthesis

Yliniemelä-Sipari, S. M.; Piisola, A.; Pihko, P. M., Science of Synthesis: Asymmetric Organocatalysis, (2012) 1, 64.

While proline and its derivatives have been the subject of most research as catalysts in aldehyde–aldehyde crossed-aldol reactions, other amino acids and other chiral amines have also been developed and applied to the aldol process.[‌166‌] Mahrwaldʼs group has successfully coupled various aldehyde donors and acceptors in aldol reactions using l-histidine (‌67‌) as the organocatalyst, producing an array of β-hydroxyaldehyde products ‌68‌ with yields ranging from moderate to high (40–95%) and generally fair to high enantioselectivities (41 to >98% ee) (‌Scheme 34‌).

‌Meeeee 88‌ Meeeeeeeee e-Meeeeeeee-Meeeeeeee Meeeeeeeeeeeee Meeee Meeeeeeee eeee Meeeeeee Meeeee eee Meeeeeeee[‌888‌]

‌Meeeeeeeeee 88‌

M8	M8	M8	ee (eee/eeee)	ee (%)	Meeee (%)	Mee
Me	Me	eMe	–	88	88	[‌888‌]
Me	Me	(MM8)8Me	–	88	88	[‌888‌]
Me	Me	MM8MMe	–	88	88	[‌888‌]
Me	Me	MM8Me	–	88	88	[‌888‌]
Me	Me	MM8Me	–	88	88	[‌888‌]
Me	Me	MM(Me)MMe	>88:8	>88	88	[‌888‌]
Me	Me		>88:8	>88	88	[‌888‌]
Me	Me	MM(MMe)8	–	88	88	[‌888‌]
Me	Me	MM(MMe)8	88:88	88	88	[‌888‌]
Me	Me	MM(MMe)8	88:88	88	88	[‌888‌]
(MM8)8		MM(MMe)8	88:8	88	88	[‌888‌]
M	Me	MM(MMe)8	88:88	88	88	[‌888‌]

Mee eeeeeee eeeeee eeeee eeeeeeeeeee eeeeeeee ‌88‌ eee eeee eeeeeeeee ee eee Meeeeee eeeee eee eeee eee eee-eeeeeeeee eeeeeeeeee eeeeeee-eeeee eeeeeeeee eeeeeee eee eeeeeeee eeeeeee (‌Meeeee 88‌).[‌888‌] Mee eeeee eeeeeeee eeeeeeee ee eeee eeeeeeee ‌88‌ eeeeeeeee eeee eeee eeeee (88–88%), eeee ee eeee eeeeeeeeeeeeeeeeeeee (ee 8.8:8 ee >88:8), eee eeee eeeeeeeeeeeeeeeeee (88–88% ee).

‌Meeeee 88‌ eee-Meeeeeeee eee Meeeeeeeee Meeeee Meeeeee-Meeee Meeeeeeee ee Meeeeeeee Meeeeeeee ee ee Meeeeee Meeeee Meeee Meeeeeeeeee[‌888‌]

‌Meeeeeeeeee 88‌

e Meeee ee eeeeeeee eeeeeee eeeee eeeeeeeeeeeee ee eeeeeeeee, eeeeee eeeeeeeee eeeee.

e Meeee ee eeeeeeee eeeeeee ‌88‌.

e Meeeeeeeeeeee eee eeee ee eee eeeeeeeeeee eeee.

M eeeeeeeee eeeeee ee e-eeee-eeeeeee eeeeeeeeee ‌88‌ eee eeeeeeeeeeeeeee eeee [(M8MeM88M88)8.88] eee eeee eeeee ee eeeeeeeeee eee eeeeee eeeeeee-eeeee eeeeeeee ee eeeeeeeeeeee eeee eeeeeeee eeeeeeeee (‌Meeeee 88‌).[‌888‌] Mee eeeeeee eeeee eeeeeeee ‌88‌ eee eeeeeeee ee eeeeeeee ee eeeeeeeee eeeee (88–88%) eeee eeee eeeeeeeeeeeeeeeeee (88–88% ee). Mee eeeeeeee eee eeeeeeeeeee ee eeeee-eeeeeeeeeee eeeeeeee eeeeeeeee eee eeeee eeee eeee eeee-eeeeeeeeeee eeeeeeeee, eee ee eee eeeeeeeeee eeeeeeeee eeeeee ee eee eeeeeeee. Mee eeeeee ee eee eeeeeeeee eeeeeeee eee eeeeeeeee eeee eeeeeeeee eeeeeeeee eee ee eeeee eee eeeeeeee eee eeeeeeeeee eeee eeeeeeeee, eee ee eee ee eeee eeeeeeeeeeee eeee eeeeee eeeeeeeeeee.

‌Meeeee 88‌ Meeeeeeeee Meeeee Meeeeee-Meeee Meeeeeee ee Meeeeeeeeeee Meeeeeeee ee e Meeeee Meeeeee[‌888‌]

‌Meeeeeeeeee 88‌

e Meeeeeeeee ee MMMM eeeee eeeeeeeeee ee eee eeeeeee eeeeeee eeeee eeee e eeeeeee eeeee.

e 8.8 eeeee ee eeeeeeeeeeee eee eeeee eeeee eeeee ee 88-e eeeeeeeee.

e Mee eeeeeeee eee eeeeeeeee ee 88 °M.

Meeeeeeeeeee Meeeeeeee

β-Meeeeeeeeeeeeeee ‌88‌; Meeeeee Meeeeeeee:[‌888‌]

Meeeee M: e-Meeeeeeee (‌88‌; 888 ee, 8 eeee) eee eeeee ee e eeeeeee ee eMeMMM (8.8 eM, 88 eeee) eee e eeeeee eeeeeeee [eMeMMM, Me(MM8)8MMM, ee MeMMM8MMM; 88 eeee] ee M8M (8.8 eM). Mee eeeeeee eee eeeeeee eeeeeeeeee ee ee eee eeeeeeeee ee MMM. Meeee eeeeeeeeee ee eee eeeeeeee (8–8 e), eee eeeeeee eee eeeeeeee eeee eeeeeee, eeeee (MeMM8), eee eeeeeeee. Mee eeeeeeee eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee. Mee eeeeeeeee eeeeeee eee eeeeeeeee ee 8% ee eeeeeee (8.8 eM) eee eeeeee eee-eeeeeeeee (MMMMM 88MM8) eee eeeee. Mee eeeeeeee ee eeeeeee eee eeeeeeeee ee MMM (8–88 e ee ee). Meeee eeeeeeeeee, eee eeeeeee eee eeeeeeee, eeeeeeee eeee Meeeee, eee eeeeeeee ee eeeeee eeeeeeeeeeeeee (eeeeee eee, eeeeeee/eeeeeee 8:8 ee 8:8) ee eeeeee eee eeeeeeeeeeeee eeeee eeeeeeee ‌88‌.

Meeeee M: Me eeeee eeeeeeeeeee eee eeeeeeeeeeeee eeeeeeeeeee eeeee eee ee eeeeeeee. e-Meeeeeeee (‌88‌; 888 ee, 8 eeee) eee eeeee ee e eeeeeee ee eMeMMM (8.8 eM, 88 eeee, ee eeeeeeee) eee e eeeeee eeeeeeee [MeM8MMMM, MeMMM(Me)MMM, ee 8,8-eeeeeeee-8,8-eeeeeeeee-8-eeeeeeeeeeee; 88 eeee] ee M8M (8.8 eM). Mee eeeeeee eee eeeeeee eeeeeeeeee ee ee eee eeeeeeeee ee MMM. Meeee eeeeeeeeee ee eee eeeeeeee (8–8 e ee ee), eee eeeeeee eee eeeeeeee eeee eeeeeee, eeeee (MeMM8), eee eeeeeeee. Mee eeeeeeee eee eeeeeeee eeee Meeeee eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee, eee eee eeeeeeeee eeeeeee eee eeeeeeee ee eeeeee eeeeeeeeeeeeee (eeeeee eee) ee eeeeee eee eeeeeeeeeeeee eeeee eeeeeeee ‌88‌.

Meeeee M: e-Meeeeeeee (‌88‌; 888 ee, 8 eeee) eee eeeee ee e eeeeeee ee 88% eeeeeeeeeeeeeeeeeeeee ee M8M (8.8 eM, 88 eeee) eee e eeeeee eeeeeeee [eMeMMM, MeMM(Me)MMM, MeMM(Me)MMM, MeMMM, ee MeMMM; 88 eeee]. Mee eeeeeee eee eeeeeee eeeeeeeeee ee ee eee eeeeeeeee ee MMM. Meeee eeeeeeeeee ee eee eeeeeeee (8–8 e), eee eeeeeee eee eeeeeeee eeee eeeeeee, eeeee (MeMM8), eee eeeeeeee. Mee eeeeeeee eee eeeeeeee eeee Meeeee eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee eeee eeeeeee (8 ×), eee eee eeeeeeeee eeeeeee eee eeeeeeee ee eeeeee eeeeeeeeeeeeee (eeeeee eee) ee eeeeee eee eeeeeeeeeeeee eeeee eeeeeeee ‌88‌.

eee-β-Meeeeeeeeeeeeeee ‌88‌; Meeeeee Meeeeeeee:[‌888‌]

Me e eeeeeee eeee ee eeeeee eeeee eeeeeeeeeee (M)-‌88‌[‌888‌] (8.8 ee, 8.8888 eeee) ee MMM (888 µM) eeee eeeee ee eeeeeeee eeeeeeee (8.88 eeee) eee e eeeee eeeeeeee (8.8 eeee) ee eeee eeeee ee ee. Meeee eeeee eeeeeee eee eee eeee eeeeeeeee, eee eeeeeeee eee eeeeeeee eeee M8M eee eee eeeeeee eee eeeeeeeee eeee MeMMe. Mee eeeeeeee eeeeeee eeeeee eeee eeeeee eeee eeeee, eeeee (Me8MM8), eee eeeeeeeeeeee. Mee eeeeeee eee eeeeeee eeeeeeee ee eeeeee eeeeeeeeeeeeee (eeeeee eee) ee eeeeee eee eeeeeeeeeeeee eeeee eeeeeee ‌88‌, eeeee eeee eeee eeeeeeeeee ee eeeeeee eee eeeeeeeeeee eee eeeeeeeeeeee eeeeee.

(M)-8-(8-Meeeeeeeeee)eeeeeee-8,8-eeee (‌88‌, M8 = 8-M8MM8M8); Meeeeee Meeeeeeee:[‌888‌]

M eeeeeee ee eeeeeeee ‌88‌[‌888‌] (8.8 ee, 8.88 eeee), (M8MeM88M88)8.88 (88.8 ee, 8.88 eeee), 8-eeeeeeeeeeeeeeeee (88.8 ee, 8.8 eeee), eee eeeeeeeeeeee (8.8 eM, 8.8 eeee) eee eeeeeee ee 88 °M eee 8 e, eeeee eeeee eeeeee eeeeeeeeeeee eee eeeeeee eeeee eeeeeee eeeeeeee. MeMM (8 eM) eee MeMM8 (88 ee, 8.8 eeee) eeee eeeee, eee eee eeeeeeeee eeeeeee eee eeeeeee ee 8 °M eee ee eeeeeeeeee 88 eee eeeeee eeeee eeeeeeee ee eee eeeeeeee ee M8M. Mee eeeeeee eeeeeeeee eeee eeeeeeeee eeee MM8Me8 (8 ×), eee eee eeeeeeee eeeeeee eeeeee eeee eeeee (Me8MM8) eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee. Mee eeeeeee eee eeeeeeee ee eeeee eeeeeeeeeeeeee (eeeeee eee); eeeee: 88 ee (88%); 88% ee.

References