Acid-Catalyzed Decomposition of O-Silylated α-Diazo-β-hydroxy Esters: Access to Mixed Monosilyl Acetals

Abstract

Acid-catalyzed decomposition of diazocarbonyl compounds triggers a wide range of transformations leading to synthetically useful building blocks with high diversity. In this field, the chemistry of α-diazo-βhydroxyester substrates is largely dominated by migration processes. We describe herein a new approach to original mixed monosilyl acetals from O-protected α-diazo-β-hydroxy-β-aryl esters and alcohols, catalyzed by TMSOTf. The ratio between these original mixed acetals, the symmetric acetals and the migration products fluctuates, depending on the catalyst, the nature of the alcohols and the substituent on the aromatic ring. Fiftysix examples are reported herein with yields up to 71% and diastereoselectivity up to 6:1. Such mixed monosilyl acetals constitute a synthetic equivalent of α-substituted β-oxoesters with high potential for further transformations.

Rhodium(I)-Catalyzed O–H Insertions on O-Protected α-Diazo-β-Hydroxyesters

“…The initial study was performed on O - tert -butyldimethysilyl α-diazo-β-hydroxy-β-( p -nitro)-phenyl ester 1a . This diazo substrate was easily prepared by the nucleophilic addition of ethyl lithiodiazoacetate on p -nitrobenzaldehyde, , followed by the protection of the resulting alcohol as a TBS silyl ether, well suited for the prospect of natural product synthesis.…”

“…Gratifyingly, in the presence of [Rh­(COD)­Cl] 2 (1 mol%), at room temperature, 1a reacted readily with propan-1-ol, used as the solvent, to yield the O–H insertion product 9aa in 61% isolated yield along with the 1,2-H migration product (11% isolated yield) (Table , entry 1). It is important to note that an experiment conducted in the presence of Rh 2 (OAc) 4 instead of [Rh­(COD)­Cl] 2 led exclusively to the formation of the migration products, in accordance with our previous results . Building on this encouraging result, the amount of propan-1-ol was decreased to five equivalents, and the reaction was conducted in various solvents (Table ), in order to extend the methodology to a wide range of alcohols.…”

“…While the use of Rh 2 (OAc) 4 , copper­(I) salts, and silver­(I) salts led to the formation of the 1,2-H and 1,2-Ar migration products (Scheme a), the use of Lewis acids such as TMSOTf provided original mixed monosilyl acetals 2 in moderate to good yields (Scheme b). The ratio between these original acetals and the migration products fluctuates, depending on the catalyst used, the nature of the alcohol, and the substituents on the aromatic ring …”