Conjugate enolates cyclopropanes

This reaction is extended to the intramolecular ring closure of the intermediate radical 224 with olefinic or trimethylsilylacetylenic side chains [121]. Cu(BF4)2 is also effective as an oxidant (Scheme 89) [122]. Conjugate addition of Grignard reagents to 2-eyclopenten-l-one followed by cyclopropanation of the resulting silyl enol ethers gives the substituted cyclopropyl silyl ethers, which are oxidized to 4-substituted-2-cyclohexen-l-ones according to the above-mentioned method [123]. (Scheme 88 and 89)... 

Few examples exist for the conjugate addition of ester enolates to a,(3-unsaturated esters typically the incipient enolate undergoes decomposition and secondary reactions. The first examples, described by Schlessinger,144 are the addition of /-butyl lithioacetate and /-butyl a-lithio-a-(methylthio)propionate to butenolide (176 Scheme 69). Similarly, Normant reported that cyclopropanes are obtained from a-ha-loesters (177) and ethyl acrylate or acrylonitrile.145... 

In the first attempts to use a chiral a-sulfinyi ester enolate as donor in Michael additions to a -un-saturated esters, only low selectivities were observed.185 186 Better results are obtained when the a-lithio sulfoxide (174), a chiral acyl anion equivalent, is employed. Conjugate addition of (174) to cyclopent-enone derivatives occurs with reasonably high degrees of asymmetric induction, as exemplified by the preparation of the 11-deoxy prostanoid (175 Scheme 63).187 188 Chiral oxosulfonium ylides and chiral li-thiosulfoximines can be used for the preparation of optically active cyclopropane derivatives (up to 49% ee) from a, -unsaturated carbonyl compounds.189... 

The synthetic implications of this discovery were slow to be exploited. Base-initiated dimerizations of 2-cycloalkenones, known to give crystalline solids,3233 remained puzzling for some time before conjugate additions were suggested to account for some of the possible products 34 indeed, the product of base-catalyzed dimerization of 4,4-dimethyl-2-cyclopentenone, which proceeds via a double Michael addition sequence, was not identified until 1969 (Scheme 2).35 An unanticipated cyclopropanation reaction of acrylaldehyde36 37 using ethyl bromomalonate and proceeding by means of a similar Michael addi-tion-Sw enolate alkylation represents an early synthetic use of tandem vicinal difunctionalization. 

The reductive opening of a cyclopropane ring of a conjugated cyclopropyl ketone with lithium in liquid ammonia can be viewed as an overall two electrons reduction which yields the equivalent of a carbanion and an enolate ion (cf. 237). Successive protonations of 237 then gives the reduced ketone. 

So the cyclopropane 36 isomerises at high temperature, no doubt via the [1,3] shift to 37, formation of the extended enol 38 and movement of the alkene into conjugation follows. The product 39 was used in a synthesis of the natural product zizaene.10... 

Once again, the zinc enolates generated in the conjugate addition can be trapped with various electrophiles besides protons. For example, reaction of the enolate 270 obtained by treating cyclohex-2-enone with dimethylzinc in the presence of Cu(OTf)2 and phosphoramidite 269 with trimethylsilyl triflate and diiodomethane provided the cyclopropanation product 271 with good diastereoselectivity and high enantiomeric excess and chemical yield... 

CO)2Fe (THF) BFT A transition state model for the syn stereoselective cyclo-propanations of alkenes with diazoacetic ester by Rh-porphyrin catalysts has been proposed. Alkenes , conjugated dienes and enol ethers are stereoselectively cyclopropanated with Rh(II) -stabilized 1- (alkoxycarbonyl)vinyl carbenoids derived from the diazo precursors and Rh2(OAc)4 (equation 95). The Cu(acac)2-catalyzed reactions of Me3SiCH2COCHN2 with alkenes provide the expected adducts in good yields ". ... 

Cyclopropyl ketones (29) behave as weakly conjugated compounds, with significant orbital overlap between one ty-bond (or sometimes two) of the cyclopropane ring and the jr-orbital of the carbonyl group (p. 242). The three-membered ring is reduced by lithium in liquid ammonia, with rupture of whichever cr-bond most effectively overlaps the carbonyl tt-orbital [280]. The reduction probably involves transfer of an electron to the jS -carbon atom of this cr-bond, so that conjugative overlap can be maintained during a smooth transition to the species (30) which is both a carbanion and a resonance-stabilised enolate radical. A second electron trans-... 

A novel concept for performing one-pot cyclopropanations of a, 9-unsaturated carbonyl compounds, consists of conjugate addition of an appropriate phenylthio-stabilized organolithium compound followed by treatment of the resulting enolate anion with copper(I) trifluoro-methanesulfonate. The cyclopropanes generated by this procedure can be simply substituted, for example, by silyl- and sulfur-bearing groups, or they can be vinylcyclopropanes (Table 13). 

So lithium enolates react with the halide 73 by conjugate substitution. The lithium enolate of the enantiomerically pure heterocycle 74 prepared from natural alanine gives one diastereoisomer of E-75 in reasonable yield. After further manipulation the heterocycle was hydrolysed to give cyclopropanes that are glutamate antagonists.12... 

Diacylcyclopropanes. The tin reagent promotes Michael reactions. Contrary to common tin enolates, which are not Michael donors, those derived from a-chloro-ketones react well, and cyclization following the conjugate addition results in cyclopropanes. 

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