Alkenes umpolung

Thiols catalyse radical-chain addition of primary aliphatic aldehydes (R CH2CH0) to terminal alkenes (H2C=CR R ) to give ketones, R CH2C0CH2CHR R. The thiol acts as an umpolung catalyst to promote the transfer of the aldehydic hydrogen to the carbon-centred radical formed when an acyl radical adds to the alkene. 

In Chapter 30, you came across the idea of umpolung, the inversion of the usual reactivity pattern of a molecule. You may have already noticed that radicals often have an umpolung reactivity pattern. Alkyl halides are electrophiles in polar reactions yet they generate nucleophilic radicals that react with electrophilic alkenes. 

In the present context, the term electron rich alkenes refers primarily to enol ethers, enol sulfides, and A-vinylamides or A-vinylamines. Such alkenes are typically much more readily ionizable than are simple alkenes. The conversion of these substrates to the corresponding (highly electron deficient) cation radicals represents a sharp Umpolung. The Diels-Alder additions of tra j -anethole, phenyl vinyl ether, phenyl vinyl sulfide, 1,3-dioxole, and A-methylindole to 1,3-cyclohexadiene have been reported (Scheme 22) [49, 52]. 

A more general approach to pyrazines is based on an FGA strategy. Removal of the alkene also removes all the problems. Disconnection 186 of hydrazine gives the same simple 1,4-diketone 177 we saw before and the most obvious ways to make that 187 are the d1 + a3 or d2 + a2 strategies, both requiring some umpolung. 

Aside from the standard use of natural synthons and the routes via double umpolung, there is the possibility of enlisting 1,3-dipolar cycloadditions to form 7,5-difunctionalized molecular skeletons. Typical examples include the addition of nitrones, silyl nitronates [94], or nitrile oxides to alkenes. The initial products of the latter cycloaddition are isoxazolines, which may be refunctionalized in various ways (Scheme 2.52). When this generates sensitive functionalities, refunctionalization may be postponed until later in the synthesis sequence [95]. 

In 2009, You et al. [60] reported an interesting NHC-catalyzed umpolung reaction of aldehydes 49 with 3-(l-arylsulfonylalkyl)indoles 50 as electrophiles. The alkene 51, generated in situ, were believed to be the real intermediate (Scheme 7.40). 

The asymmetric a-sulfenylation of ketones is a particularly challenging reaction, as demonstrated by the poor success reported in the stereoselective variants via classical enolate/azaenolate reaction with an electrophilic sulfur reagent [71]. An umpolung approach has been devised by Coltart and co-workers [72] to effect the first asymmetric a-sulfenylation of ketones with arene thiols. Nitroso alkene derivatives, in i/tM-generated under basic conditions from a-chloro oximes, reacted with arene thiols in the presence of cinchona thiourea 27, which promoted the conjugate addition of thiophenol (Scheme 14.25). The chiral nonracemic a-sulfenylated oximes were directly hydrolyzed by IBX to ketones in high yield and good enantioselectivity. 

Highly functionalized alkenes R CH2CH=C(E)CH(Nu)R have been prepared via the PhjP-catalysed /3 -umpolung addition of nucleophiles, such as ROH, RR NH, CH2(CN)2, RCH(CN)C02Et, and PhSH, to activated a-disubstituted allenes R CH=C=C(E)CH2R (E = C02Et, CN), often with high stereoselectivity. ... 

Heteroatom (S, Se, or Si) substituted alkenes figure in many carbonyl syntheses with umpolung. General methods for the construction of such alkenes thus widen the strategies available for syntheses of aldehydes and ketones. 

Turks M, Exner CJ, Hamel C, Vogel P. Umpolung with sulfur dioxide carbon-carbon cross-coupling of electron-rich 1,3-dienes and alkenes application to the enantioselective synthesis of long-chain polyketide fragments. Synthesis 2009 ... 

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