Science of Synthesis

Ramón, D. J.; Yus, M., Science of Synthesis: Stereoselective Synthesis, (2011) 2, 371.

Various chiral carbonyl compounds have been used in the Darzens reaction to obtain the corresponding chiral epoxides ‌38‌. The reaction can produce four different isomers: two cis-epoxides and two trans-epoxides, with the trans-epoxides being the only ones displayed in ‌Table 19‌. Initial studies were carried out using haloacetate derivatives (R1 = alkoxy in ‌37‌), where it was found that the trans/cis isomer ratio was greatly affected by the nature of the halogen atom, with chloride giving practically the same amount of all possible isomers but bromine yielding mainly the cis-epoxide.[‌155‌] The nature of the ester moiety has little impact on the diastereoselectivity found for either trans- or cis-isomers, being never higher than 60% (entries 1–4). The use of a two-step sequence to afford the corresponding epoxides does not produce any significant improvement (entry 5).[‌156‌] The Darzens reaction with a ketone derivative, however, gives better results (entry 6).[‌157‌] Although the reaction with aromatic aldehydes gives, in all tested cases, essentially only one of the four possible diastereomers with excellent results, the reaction with aliphatic starting materials is more disappointing. The final product (trans,Si)-‌38‌ can be easily transformed into the corresponding α,β-epoxy acid derivatives by treatment with ammonium cerium(IV) nitrate. Density functional theory calculations show that the process proceeds via the two expected steps: an aldol-type reaction and epoxide formation, with the hydroxy group of the starting ketone playing a fundamental role in the stereoselectivity.[‌158‌] The above-mentioned menthyl[‌159‌] and 8-phenylmenthyl esters[‌160‌] have also been used in the Darzens reaction with various ketones, but with modest results.

‌Meeee 88‌ Meeeeee Meeeeeee Meeee Meeeeee Meeeeeeee[‌888‌–‌888‌]

Meeee	M8	M8	M	Meeeeeeeee	Meeee (eeeee/eee)	Meeee (%) ee (eeeee,Me)-‌88‌	Meeee (%) ee (eeeee,Me)-‌88‌	Mee
8		Me	Me	e-MeMM (888 eee%), Me8M, −88 ee 8 °M, 88 e	8.88:8	88	88	[‌888‌]
8		Me	Me	e-MeMM (888 eee%), Me8M, −88 ee 8 °M, 88 e	8.88:8	8	8	[‌888‌]
8		Me	Me	e-MeMM (888 eee%), Me8M, −88 ee 8 °M, 88 e	8.8:8	88e	88e	[‌888‌]
8		Me	Me	e-MeMM (888 eee%), Me8M, −88 ee 8 °M, 88 e	8.88:8	8e	8e	[‌888‌]
8		eMe	Me	8. MeMe8 (888 eee%), eMe8MMe (888 eee%), −88 °M, 8 e 8. M8MM8, MeMM, 88 °M	8:8	8	88	[‌888‌]
8		Me	Me	MMM (888 eee%), Me8M, −88 °M, 8 e	88:8	<8	88	[‌888‌]

e Meeeeeeeeeeee eee eeeeeeeeee.

Me eeeeeeeeeee eeeeeeee eeee ee eeeeeeeeee-eeeeeee eeeeeeeee eeeeeeeee ee e eeeeee eeeeeeeeeee.[‌888‌] Mee eeeeeeee eeee eeeeeeeee ee −88 °M eeeee eeeeeeeee eeeeeeeee ee eeee eeeee eee eeeeeeeeeeeee α,β-eeeee eeeee eeeeeeeeeee eeee eeeeeeeee eeeeeeee eeeeee (88–88%) eee eeeeeeeeeeee eeeeeeee ee ee 88%.

Meeeeeeeeeee Meeeeeeee

{(8M,8M,8M)-8-Meeeeee-8,8,8-eeeeeeeeeeeeeeee[8.8.8]eeeeee-8-ee}[(8M,8M)-8-eeeeeeeeeeee-8-ee]eeeeeeeee {(eeeee,Me)-‌88‌, M8 = 8-Meeeeee-8,8,8-eeeeeeeeeeeeeeee[8.8.8]eeeeee-8-ee; M8 = Me}; Meeeeee Meeeeeeee:[‌888‌]

M eeeeeee ee eMe8MM (8.88 eM, 8.8 eeee) eee eeeee MeMe (8.88 e, 8 eeee) ee eee MMM (88 eM) eee eeeeee ee −88 °M eeeee e M8 eeeeeeeeee eee e 8.8 M eeee ee MeMe ee eeeeee (8.88 eM, 8.8 eeee) eee eeeee eeeeeeee. Meeee eeeeeeee eee 88 eee ee eee eeee eeeeeeeeeee, e eeee ee 8-eeeee-8-{(8M,8M,8M)-8-eeeeeee-8,8,8-eeeeeeeeeeeeeeee[8.8.8]eeeeee-8-ee}eeeeeeee (8.888 e, 8 eeee) ee eeeee MMM (8 eM) eee eeeee eeeeeeee. Mee eeeeeeeee eeeeeee eee eeeeeee eee 8 e eee eeee e eeeeeeeee (−88 °M) eeee ee eeeeeeeeeeee (8.88 eM, 8.8 eeee) ee MMM (88 eM) eee eeeee eeeeeeee. Mee eeeeeeeee eeeeeee eee eeeeeee eee e eeeeeee 8.8 e. Mee eeeeeee eee eeee eeeeeeee ee eeeeeeee eeeeeeee ee eee. ee MeMMM8 (8 eM). Meee eeeeeee eee eeeeeee ee eeee ee 88 °M, eee eeeeee eeee eeeeeeeee, eee eee eeeeeee eeeee eee eeeeeeeee eeee MM8Me8 (8 × 88 eM). Mee eeeeeeee eeeeeee eeeeee eeee eeeee (MeMM8) eee eee eeeeeeee eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee. Mee eeeee eeeeeee eee eeeeeeee ee eeeeee eeeeeeeeeeeeee (eeeeee eee, eeeeee/MeMMe/Me8M 888:8:8.8); eeeee: 8.888 e (88%); ee 888–888 °M.

References