Synthesis of Tertiary α-Hydroxy Acids by Silylene Transfer to α-Keto Esters

Abstract

Alpha-keto esters can be converted into alpha-hydroxy acids in a single flask involving metal-catalyzed silylene transfer, 6pi-electrocyclization, Ireland-Claisen rearrangement, and hydrolysis. This reaction sequence is stereoselective and tolerates alkyl- and aryl-substituted alpha-keto ester substrates as well as an alpha-imino ester.

Silver‐Catalyzed Silylene Transfer

“…119 In every case, the a-hydroxy acid was formed with excellent diastereoselectivity (dr !98 : 2). Their method was tolerant of a range of substitution patterns, although diminished yields were obtained as the size of the R 1 substituent increased (compare 154a and 154c).…”

“…119 Excellent diastereoselectivity was obtained with 152g, containing an allylic methyl group; and even 152h, which contained a benzyl ether substituent that would lie outside the chairlike transition state (TS-156), controlled the facial selectivity of the [3,3]-sigmatropic rearrangement.…”

“…119 Exposure of 157 to gemdimethylsilacyclopropane 89 and substoichiometric amounts of silver tosylate produced azasilalactone 158. In contrast to the above-mentioned synthesis of 154, hydrolysis of 158 was not observed on aqueous extraction.…”

Intramolecular Imino Diels−Alder Reaction: Progress toward the Synthesis of Uncialamycin

“…First attempted intramolecular cycloaddition reaction. The imines 13 and 14 were prepared as previously reported from tartaric acid 13,18 and subjected to the same reaction conditions as above. The imine 13 led to the quinoline 15 and the amine 16 in a 15/16 = 0.33:0.66 ratio while 14 gave 15 and 17 in a 15/17 = 0.5:0.5 ratio and the tetrahydroquinoline 18 and the dihydroquinoline 19 were not detected in the crude reaction mixture (Scheme 4).…”

Silylene transfer to α-keto esters and application to the synthesis of γ-lactones

“…3-6 Given the prevalence of α-hydroxy acids in small molecules, new synthetic methods for their synthesis are desirable 7-13. We recently reported the development of a method to obtain α-hydroxy acids from simple α-keto esters utilizing metal-catalyzed silylene transfer 14. In this paper we report the expanded scope and utility of this methodology.…”