Enantioselective Vicinal Bis-Acylation of Olefins

Abstract

A two‐step sequence for the asymmetric vicinal acylation of olefins by a [2+2+1] strategy is reported. The key reaction is a [2+2] cycloaddition of an olefin to a chiral keteniminium salt derived from N‐tosylsarcosinamide. This is followed by a regioselective Baeyer–Villiger oxidation of the resulting cyclobutanone to yield a lactol derivative that is equivalent to the product of addition of a carboxyl and a carbonyl group to the olefin. N‐Tosylsarcosinamides derived from prolinol methyl ether and 2,5‐dimethylpyrrolidine gave the best yields and diastereoselectivities. Five‐ and six‐membered cycloolefins only gave cis products as expected. With seven‐ and eight‐membered rings and cis 1,2‐disubstituted acyclic olefins, partial or complete epimerisation of the cis to the trans adducts was observed. Facial selectivities were generally good except for terminal olefins. The oxidation step proceeded in high yields to give crystalline compounds which could usually be obtained in enantiopure form by simple recrystallisation.

Keteniminium Salts: Reactivity and Propensity toward Electrocyclization Reactions

“…Keteniminium salts (KI) are versatile and reactive intermediates in organic chemistry. , Historically, the pioneers of the use and synthesis of KI are Viehe and Ghosez. , These salts are an improved alternative to their ketene analogues, due to their higher reactivity and high electrophilicity. Furthermore, KI do not undergo undesired side reactions, such as dimerization or polymerization, as readily as ketenes. − …”

Four-Membered Ring-Containing Spirocycles: Synthetic Strategies and Opportunities

“…The analogous reactions displayed in Scheme have been previously described. The example illustrated in eq b relies on the generation of a reactive ketiminium intermediate that is formed by treatment of dimethylacetamide with triflic anhydride and collidine, following a procedure originally described by Ghosez . Adducts, such as 786 , from this cycloaddition are produced directly, and unlike those generated from the cycloaddition reaction of dichloroketenes do not require dechlorination of the cycloadduct in a following step.…”

Stereocontrolled Synthesis and Functionalization of Cyclobutanes and Cyclobutanones

“…In 2002 Ghosez and co-workers developed an excellent two-step sequence for the asymmetric vicinal acylation of olefins by a [2+2+1] strategy [53]. The key reaction of this methodology is a [2+2] cycloaddition of an olefin 19 to a chiral keteniminium salt 18 derived from N-tosylsarcosinamide 17 yielding stereoselectivelly only cis -α-aminocyclobutanones 20 with good enantioselectivity (68%–98% ee ) through the intermediate 18 .…”