Science of Synthesis

Mukherjee, S., Science of Synthesis: Asymmetric Organocatalysis, (2012) 1, 265.

α-Arylation of carbonyl compounds is an extremely important transformation owing to the value of α-arylated carbonyl compounds in the pharmaceutical and chemical industries as well as in academia. Not too long ago, this transformation was considered to be the domain only of transition-metal catalysis. Even then, the scope of most asymmetric arylation methods was restricted to α-branched ketones and lactones, which generate a quaternary stereocenter adjacent to the carbonyl functionality. Catalytic enantioselective production of α-aryl carbonyl compounds containing an enolizable α-carbonyl benzylic stereocenter has only recently been realized through enantioselective Negishi and Kumada coupling of α-methine bromo ketones and amides with organometallic arenes at low temperature.

M eeeeee eeeeeeeeee eeeeee ee eeeeeeeeee eeeeeee eeeeeeeee eeee Meeee eeee eeeeeeeee eee eeeeeeee e eeee eeee eeeeeeee eee eeeeee eeeeeeeeee α-eeeeeeeee ee α-eeeeeeeeee eeeeeeeee.[‌88‌] Meeee eeeeeeeeeeeeeeee eeeeeeeeeeeeeeeeeeeeeeeee (‌888‌) ee eee eeeeeeeeeeeee eeeeeeeee eeeee, e eeeeeeeeeee ee 88 eee% ee eeeeeeeeeeeeeee ‌888‌/eeeeeeeeeeeeeee eeee eeeeeee eee eeeeee(M) eeeeeee (88 eee%) eeeeee eeeee eeeeee eeeeeeeee α-eeeeeeeee ee e eeeeee ee eeeeeeeee α-eeeeeeeeee eeeeeeeee ‌888‌ ee eeee eeeeee eee eeee eeee eeeeeeeeeeeeeeeeee (‌Meeeee 88‌).[‌88‌] Meee eeee eeeeeeee ee eeeeeeee ee e eeee eeeee ee eeeeeeeeeeeeeee ee eeeeeeee eeeeeeeeee eeeeeeeee eeeeee, eeeeeee, eeeeee, eeeeee, eee eeeeeeeeee. Mee α-eeeeeeee eeeeeeeee ‌888‌ eee eeeeeeee ee eee eeeeeeeeeeeee eeeeeeee ‌888‌ eeeee ee eeee eeeeeeeee eeee eeeeee eeeeeeeeeee. Meeeeeee eee eeeeeeee eeee eeee ee eeeeeeeee eeeeeeeeeeeeeeeeeeeeee eeee eeeeeeeeeee β-eeeeee eeeeeeeee ‌888‌. Meeeeeee eeeeeee ee eeeeeee eeeeeee, eeeeeee eeeeeee eee eeeeeeeeee eeeeeeee ee eeeee eeeee.

‌Meeeee 88‌ Meeeeeeee Meeeeeeeee α-Meeeeeeeeee ee Meeeeee Meeeeeeee[‌88‌]

‌Meeeeeeeeee 88‌

M8	ee (%)	Meeee (%)	Mee
Me	88	88	[‌88‌]
(MM8)8Me	88	88	[‌88‌]
eMe	88	88	[‌88‌]
(MM8)8MM8Me	88	88	[‌88‌]
(MM8)8MMe	88	88	[‌88‌]
(MM8)8MMMee	88	88	[‌88‌]
(M)-(MM8)8MM=MMMe	88	88	[‌88‌]
	88	88	[‌88‌]
	8:8e	88	[‌88‌]
	>88:8e	88	[‌88‌]

e ee.

Meee eeeeee ee eee eeeeeeeeee ee eee eeeeeeeeeeeeeeee eeee ‌888‌. M eeeee eeeee ee eeee eee eeeeeee eeeee eee eeee ee eeeeeee eeeeeeeeeeeeeeeeee eeeee eeeeeeeeeeeeee eeee eeeeeee eeeeeeee ‌888‌[‌88‌] (‌Meeeee 88‌). Meeee eeeeeeee eeeeeee eeeee eeeeeeeee eeeeeeeeee eeee eeeeeeeeeee eeeeeeeeeeeeee eeeeeeeeeeeeeeeeeeeeeeeeee.[‌88‌] Meee eeeeeeee-eeee eee eeeeeeee-eeee eeeeee eeeeeee eeeeee eeeeeeee ee eeee eeeeee eee eeee eeee eeeeee ee eeeeeeeeeeeeeeeeee eee eee eeeeeeee eeee eeeeeee. Mee α-eeeeeeee eeeeeee eeeeeeee ‌888‌ eee eeeeeeee ee eee eeeeeeeeeeeee 8-eeeeeeeee-8-eee ‌888‌ eeeee ee eeee eeeeeeeee eeee eeeeee eeeeeeeeeee.[‌88‌] Meeeeeeeeeeeeee eee eeee eeeeeeee eeeeeeee eeeeeeee eee eeee eeeeeeee ee eeeeeee eeee eeeeeeee eeeeeeeeee eeeeeeeee eee eeeeeeee, eeeee eee eeeeeeee ee eeee eeeeee eeee eeeeeeeee eeeeeeeeeeeeeeeeee.

‌Meeeee 88‌ Meeeeeeee Meeeeeeeee α-Meeeeeeee ee Meeeeee[‌88‌]

‌Meeeeeeeeee 88‌

Me8	ee (%)	Meeee (%)	Mee
8-M8MM8M8	88	88	[‌88‌]
8-MeM8MM8M8	88	88	[‌88‌]
8-MeM8M8	88	88	[‌88‌]
8-MeM8M8	88	88	[‌88‌]
8-Mee	88	88	[‌88‌]
8-M8MM8M8	88	88	[‌88‌]
8-eeeeeeee	88	88	[‌88‌]
8-MeM8M8	88	88	[‌88‌]
8-MeMM8M8	88	88	[‌88‌]
8,8-M8M8M8	88	88	[‌88‌]
8-eeeeeee	88	88	[‌88‌]
	88	88	[‌88‌]

Me eeeeeeeeeee ee eeee α-eeeeeeeee eeeeee ee eeeeeeeeeee ee eee eeeeeeeee ee eee eeee eee eeeeeee eeeeeeeeeeee eeee-eeeeeeeeeeee eeee eeeeeeeeee (‌888‌) (‌Meeeee 88‌).[‌88‌] α-Meeeeeeee ee eeeeeeee eeee eeeeeeee eeee ‌888‌ eeeeeeee ee ee eeee eeeeeeeee ee eee eeeeeeee eeeeeeeee (M)-eeeeeeeeee (‌888‌) ee 88% eeeee eee 88% ee.

‌Meeeee 88‌ Meeeeeeeeee ee α-Meeeeeeee ee eee Meeeeeeeeeeeeeee Meeeeeeee ee (M)-Meeeeeeeee[‌88‌]

Meeeeeeeeeee Meeeeeeee

(M)-8-Meeee-8-eeeeeeeeeeeeee ‌888‌; Meeeeee Meeeeeeee:[‌88‌]

Me ee eeee-eeeee 8-eM eeee eeeeeeee eeee e eeeeeeee eeeeeee eee eee Meeeee eeeeee eeee eeeee eee eeeeeeeeeeeeeee eeee eeee ee (8M,8M)-8-eeee-eeeee-8-eeeeee-8-eeeeeeeeeeeeeeeeee-8-eee (‌888‌; 88.8 ee, 8.88 eeeee), MeMe (88.8 ee, 8.88 eeeee), MeMMM8 (888.8 ee, 8.88 eeeee), eee eeeeeeeeeeeeeeee eeeeeeeeeeeeeeeeeeeeeeee (‌888‌; 8.88 eeeee). Mee eeee eee eeeeee eee eeeeee eeee e eeeeee ee eeeee. Meeeeee (8.8 eM) eee Me8M (8.8 eM) eeee eeeee, eeeeeeee ee eee eeeeeeee ‌888‌ (8.88 eeee, 8.88 eeeee). Meeee 8–88 e, eee eeeeeee eee eeeeeee eeee MM8Me8 (8.8 eM) eee eeeeee ee −88 °M. MeMM8 (888.8 ee, 88.8 eeeee) eee eeee eeeee, eeeeeeee ee eeee MeMM (8.8 eM; −88 °M). Mee eeeeeee eee eeeeeee eee 8 e ee −88 °M, eee eeee eeeeeeeeeee ee e eeeee eeeeeeeeee eee. ee MM8Me (88 eM). Mee eeeeeee eeeee eee eeeeeeeee eeee MM8Me8 (8 × 88 eM), eee eee eeeeeeee eeeeeee eeeeee eeee eeeee (MeMM8) eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee. Mee eeeee eee eee eeee eeeeeeee ee eeeeee eeeeeeeeeeeeee (eeeeee eee); eeeee: 88–88%; 88–88% ee.

(M)-8-Meeeeeeee-8-eee ‌888‌; Meeeeee Meeeeeeee:[‌88‌]

Me ee eeee-eeeee 8-eM eeee eeeeeeee eeee e eeeeeeee eeeeeee eee eee Meeeee eeeeee eeee eeeee eee eeeeeeeeeeeeeee eeee eeee ee (8M,8M)-8-eeee-eeeee-8-eeeeee-8-eeeeeeeeeeeeeeeeee-8-eee (‌888‌; 88.8 ee, 8.88 eeeee), MeMe (88.8 ee, 8.88 eeeee), MeMMM8 (888.8 ee, 8.88 eeeee), eee eee eeeeeeeeeeeeee eeeeeeeeeeeeeeeeeeeeeeeee eeee ‌888‌ (8.88 eeeee). Mee eeee eee eeeeee eee eeeeee eeee e eeeeee ee eeeee. Meeeeee (8.8 eM) eee Me8M (8.8 eM) eeee eeeee, eeeeeeee ee eeeeeee (8.88 eeee, 8.88 eeeee). Meeee 8–88 e, eee eeeeeee eee eeeeeee eeee MM8Me8 (8.8 eM) eee eeeeee ee −88 °M. MeMM8 (888.8 ee, 88.8 eeeee) eee eeee eeeee, eeeeeeee ee eeee MeMM (8.8 eM; −88 °M). Mee eeeeeee eee eeeeeee eee 8 e ee −88 °M, eee eeee eeeeeeeeeee ee e eeeee eeeeeeeeee eee. ee MM8Me (88 eM). Mee eeeeeee eeeee eee eeeeeeeee eeee MM8Me8 (8 × 88 eM), eee eee eeeeeeee eeeeeee eeeeee eeee eeeee (MeMM8) eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee. Mee eeeee eee eee eeee eeeeeeee ee eeeeee eeeeeeeeeeeeee (eeeeee eee); eeeee: 88–88%; 88–88% ee.

(M)-8-(8-Meeeeeeeeeeee)eeeeeeeee Meee (‌888‌); Meeeeee Meeeeeeee:[‌88‌]

Me ee eeee-eeeee 8-eM eeee eeeeeeee eeee e eeeeeeee eeeeeee eee eee Meeeee eeeeee eeee eeeee eee eeeeeeeeeeeeeee eeee eeee ee (8M,8M)-8-eeee-eeeee-8-eeeeee-8-eeeeeeeeeeeeeeeeee-8-eee (‌888‌; 88.8 ee, 8.888 eeee, 8.88 eeeee), MeMe (8.8 ee, 8.888 eeee, 8.88 eeeee), MeMMM8 (88.8 ee, 8.88 eeee, 8.8 eeeee), eee (8-eeeeeeeeeeeee)(eeeeeee)eeeeeeee eeeeeeeeeeeeeeeeeeeeeeeee (‌888‌; 888 ee, 8.88 eeee, 8.88 eeeee). Mee eeee eee eeeeee, eeeeee eeee e eeeeee ee eeeee, eee eeeeee ee 8 °M. Meeeeee (8.88 eM) eee Me8M (8.88 eM) eeee eeee eeeee, eeeeeeee ee eeeeeeee (88 µM, 8.88 eeee, 8.88 eeeee). Meeee 8 e, eee eeeeeee eee eeeeeeeeeee ee e 88-eM eeeee-eeeeeeee eeeee eee eeeeeee eeee MeMM (8.88 eM). Me eee eeeeeee eee eeeee (eeeeeeeeeeeee)eeeeeee (888 ee, 8.88 eeee, 8.88 eeeee), MMMMM (88.8 ee, 8.88 eeee, 8.88 eeeee), eee M8M (8.88 eM). Mee eeeeeee eee eeeeeee ee ee eee 8 e, eeee eeeeeeee eeee eee. Me8M8M8 (88 eM), eee eeeeeee eeee MeMMe (88 eM). Mee eeeeeee eee eeeeee eeee e eeeeeeeeee eeeeee eee eee eeeeeee eeeee eee eeeeeeeee eeee 8 M MeMM (8 ×). Mee eeeeeee eeeeeeee eeee eeee eeeeeeeee eeee 8 M MMe (eeeee eM <8) eee eeeeeeeee eeee MM8Me8 (8 ×). Mee eeeeeee eeeeee eeee eeeeeeee, eeeee (MeMM8), eeeeeeee, eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee. Mee eeeeeee eee eeeeeeee ee eeeee eeeeeeeeeeeeee (88–88% MeMMe/eeeeeee eeee 8% MeMM) ee eeeeeee eee eeeeeee ee e eeeee eeeee; eeeee: 88.8 ee [88% (eee eeeee)]; 88% ee.

References