Abstract
The addition of a family of β-diketones to β-nitrostyrene was explored using a library of cinchona organocatalysts. A thiourea organocatalyst, under improved reaction conditions, is shown to be much more efficient at catalyzing this reaction than previously reported giving excellent yields and enantioselectivites (up to 95% yield and 97% ee). The same thiourea organocatalyst was employed in the first successful Michael addition of the sterically challenging dipivaloylmethane to β-nitrostyrene (99% ee).
Highlights
The synthesis of enantiopure molecules in a simple and environmentally friendly manner is a major challenge for synthetic chemistry and the chemical industry
Our study indicates that (a) under improved reaction conditions the cinchona thiourea catalyst 2 is much more effective (95% yield after only 1 hour) at catalyzing this reaction than previously reported (47% yield after 48 hours),8(b) the first Michael addition of the sterically challenging dipivaloylmethane to an activated olefin, β-nitrostyrene (99% ee), was achieved using catalyst 2 and (c) both a H-bonding motif and steric bulk is required at C9 to generate a high yielding and enantioselective reaction
We anticipated that solvent choice would have a large effect on the catalytic activity of a bifunctional catalyst4a and began our study by performing a solvent screen for the organocatalyzed Michael addition of 2,4-pentanedione to β-nitrostyrene
Summary
The synthesis of enantiopure molecules in a simple and environmentally friendly manner is a major challenge for synthetic chemistry and the chemical industry. Organocatalysis has emerged as an exciting method of choice for the generation of such efficient asymmetric reactions In this field, the asymmetric Michael addition of carbon-centred nucleophiles to electron deficient nitroolefins is an important and powerful tool.[1,2] The resulting optically active nitroalkanes are versatile synthetic building blocks by virtue of the reactive nitro functional group, which can be transformed into a variety of groups.[1,2] In recent times impressive progress has been made using metal free organocatalysts in the asymmetric addition of aldehydes, ketones, ketoesters and malonate esters to nitroolefins.[1,2,3,4,5] There have been fewer reports of successful additions of diketones to nitroolefins. Takemoto’s catalyst represented a logical extension of earlier work on thiourea H-bonding catalysts by Curran, Jacobsen and Schreiner.[13] Since significant advances have been made in catalyst design with Chen, Soós, Connon and Dixon independently reporting the design and application of new cinchona urea/thiourea catalysts in 2005.5,11,14 In this present study we have screened nine cinchona catalysts in the addition of β-diketones to β-nitrostyrene. Our study indicates that (a) under improved reaction conditions the cinchona thiourea catalyst 2 is much more effective (95% yield after only 1 hour) at catalyzing this reaction than previously reported (47% yield after 48 hours),8(b) the first Michael addition of the sterically challenging dipivaloylmethane to an activated olefin, β-nitrostyrene (99% ee), was achieved using catalyst 2 and (c) both a H-bonding motif and steric bulk is required at C9 to generate a high yielding and enantioselective reaction
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