Towards the catalytic formation of α,β-vinylesters and alkoxy substituted γ-lactones (original) (raw)
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Chemistry, an Asian journal, 2012
The acid-catalyzed Friedel-Crafts reaction of alcohols and electron-rich aromatic compounds is a highly atom-efficient method for the preparation of aromatic compounds with diverse applications, and only water is generated as the byproduct. During the past decade, significant progress has been made in the development of a catalytic version of this transformation, including the construction of hindered allcarbon quaternary centers. Generally, carbenium ions are invoked as intermediates in this SN 1 -type reaction, and substituents that can stabilize the intermediates could facilitate this reaction ( ). Accordingly, most of the known catalytic protocols are based on alcohols with electron-donating groups that could stabilize the intermediate carbocations. The limited catalytic arylation reactions of alcohols with an a-electron-withdrawing substituent have been restricted to alcohols that could form reactive oxonium [3e] or vinylogous iminium [3f-k] intermediates. If the catalytic Friedel-Crafts arylation reaction could be extended to alcohols with an a-electron-withdrawing group such as a-hydroxyesters or a-hydroxyketones, it would provide a facile method for the a-arylation of esters and ketones. However, to the best of our knowledge, the catalytic version of this reaction has not been reported. The a-quaternary carbonyl compounds, especially a-diaryl or a-triaryl-substituted carbonyl compounds, have wide applications in organic synthesis, medicinal research, and catalyst design. However, synthetic methods to afford these building blocks are very limited, and they often involve multistep synthesis. For example, triarylacetic acid derivatives were often prepared by the reaction of CO 2 and organolithium compounds derived from triarylmethyl chlorides, which were obtained from the corresponding a-triaryl-substituted tertiary alcohols. [6b] Therefore, the development of efficient methods for the diverse synthesis of these compounds is highly desirable.
This is the eleventh theoretical assay in the series: “The Organic Chemistry Notebook Series, a Didactical Approach”. The aim of this series of studies is to help students to have a graphical view of organic synthesis reactions of diverse nature. We have taken a series of reactions compiled by W. Carruthers in ‘Some modern methods of organic synthesis’, and we have proposed didactical and mechanistic views for them. This theme is included in the chapter “Formation of carbon-carbon double bonds” in the mentioned text. In chapter 11, we expose a complementing of Claisen rearrangements of ally-vinyl ethers started two papers ago. Now it’s turn for the use of a variation of the Claisen rearrangement: the ester-enolate variation (also known as the ketene acetal variation). In this sense, the synthesis of the natural product: methyl santolinate is briefly exposed in a mechanistic manner. Also, the mechanism of the synthesis of -unsaturated amino acid derivative and ulterior lactone hydrochloride from the Z-crotyl glicine ester is proposed on the basis of theoretical approaches. The condensation between allylic alcohols and cyclic orthoesters to produce (via Claisen rearrangement) lactones with the inverted allyl group as a substituent is mechanistically exposed. Vinyl lactones can be converted into cycloalkenes (via Claisen rearrangement of cyclic enol ethers); we’ve analyzed the mechanism.
A direct synthesis of α-(hydroxymethyl) and α-alkyl-vinyl alkyl ketones
Tetrahedron Letters, 2006
Reaction of 2,4-diketoesters 3a-c with aqueous formaldehyde using potassium carbonate solution as base affords the corresponding a-methylene-b-hydroxyalkanones 4a-c which provide a route to a,b-unsaturated alkyl ketones 6a-e via coupling of a-acetoxymethyl alkyl vinyl ketone 5a with Grignard reagents in the presence of a catalytic amount of LiCuBr 2 at low temperature.