Alkenes, reaction with carbenoids

The reactive intermediates under some conditions may be the carbenoid a-haloalkyllithium compounds or carbene-lithium halide complexes.158 In the case of the trichloromethyllithium to dichlorocarbene conversion, the equilibrium lies heavily to the side of trichloromethyllithium at — 100°C.159 The addition reaction with alkenes seems to involve dichlorocarbene, however, since the pattern of reactivity toward different alkenes is identical to that observed for the free carbene in the gas phase.160... 

In addition to insertion into p-C—H bonds, cyclopropylidenes can undergo other reactions such as alkylation (c/. Section 4.7.3.2), dimerization, insertion into C—H bonds of the ether solvent (equation 60)183 or reaction with alkenes to afford spirocyclopropanes (equation 61).184 Addition of stoichiometric amounts of Bu OK has been shown to promote the reactions of lithium carbenoids, even at -83 C, with THF to give the insertion product (equation 62).185 Addition to alkenes is also promoted under these conditions. Intramolecular addition of the carbenoid to double bonds has been exploited in the synthesis of spirotricyclic compounds (equation 63).186... 

The mechanism for the formation of this carbenoid and for its reaction with alkenes need not concern us here. Just remember that it reacts as though it is methylene. The Simmons-Smith reaction is an excellent way to prepare cyclopropane derivatives from alkenes, as shown in the following examples. Note the stereochemistry in the second equation. 

The reaction between CHCI3 and HO- is often carried out under phase transfer conditions. " It has been shown that the reaction between PhCHCl2 and t-BuOK produces a carbenoid, but when the reaction is run in the presence of a crown ether, the free Ph(Cl)C is formed instead. The reaction of iodoform and CrCl2 leads to iodocyclopropanes upon reaction with alkenes. Dihalocyclopropanes are very useful compounds that can be reduced to cyclopropanes, treated with magnesium or sodium to give allenes (18-3), or converted to a number of other products. 

The introduction of umpoled synthons 177 into aldehydes or prochiral ketones leads to the formation of a new stereogenic center. In contrast to the pendant of a-bromo-a-lithio alkenes, an efficient chiral a-lithiated vinyl ether has not been developed so far. Nevertheless, substantial diastereoselectivity is observed in the addition of lithiated vinyl ethers to several chiral carbonyl compounds, in particular cyclic ketones. In these cases, stereocontrol is exhibited by the chirality of the aldehyde or ketone in the sense of substrate-induced stereoselectivity. This is illustrated by the reaction of 1-methoxy-l-lithio ethene 56 with estrone methyl ether, which is attacked by the nucleophilic carbenoid exclusively from the a-face —the typical stereochemical outcome of the nucleophilic addition to H-ketosteroids . Representative examples of various acyclic and cyclic a-lithiated vinyl ethers, generated by deprotonation, and their reactions with electrophiles are given in Table 6. 

The cyclopropanation utilizing donor/acceptor rhodium carbenoids can be extended to a range of monosubstituted alkenes, occurring with very high asymmetric induction (Tab. 14.4) [40]. Reactions with electron-rich alkenes, where low enantioselectivity was observed at room temperature, could be drastically improved using the more hydrocarbon-soluble Rh2(S-DOSP)4 catalyst at -78°C. The highest enantioselectivity is obtained when a small ester group such as a methyl ester is used [40], a trend which is the opposite to that seen with the unsubstituted diazoacetate system [16]. 

In contrast to the intermolecular cyclopropanation, the dirhodium tetraprolinates give modest enantioselectivities for the corresponding intramolecular reactions with the do-nor/acceptor carbenoids [68]. For example, the Rh2(S-DOSP)4-catalyzed reaction with al-lyl vinyldiazoacetate 32 gives the fused cyclopropane 33 in 72% yield with 72% enantiomeric excess (Eq. 4) [68]. The level of asymmetric induction is dependent upon the substitution pattern of the alkene cis-alkenes and internally substituted alkenes afford the highest asymmetric induction. Other rhodium and copper catalysts have been evaluated for reactions with vinyldiazoacetates, but very few have found broad utility [42]. 

Functionalized zinc carbenoids have been prepared from carbonyl compounds by an indirect strategy. The deoxygenation of a carbonyl compound to an organozinc carbenoid can be induced by a reaction with zinc and TMSCl. Therefore, the aldehyde or ketone, when treated with TMSCl or l,2-bis(chlorodimethylsilyl)ethane in the presence of an alkene, generates the cyclopropanation product. This method is quite effective for the production of alkoxy-substituted cyclopropane derivatives. A 55% yield of the... 

The most common method to prepare cyclopropenyl derivatives is the reaction between an electrophilic carbenoid and an alkene. On the other hand, sp3-geminated organodimetal compounds possess two nucleophilic sites on the same carbon, so should lead to nucleophilic [2+ 1] reaction with 1,2-diketones. Indeed, the reaction of bis(iodozincio)methane (3) with 1,2-diketones shows a novel [2+1] reaction to form c -cyclopropanediol diastereoselectively as shown in Scheme 3467. 

The double bonds in 2,3-dihydro-l,4-dioxin, 2,3-dihydro-l,4-oxathiin and 2,3-dihydro-1,4-dithiin undergo standard electrophilic addition reactions. Under acid catalysis, methanol adds to 2,3-dihydro-l,4-oxathiin to give 2-methoxy-1,4-oxathiane (66HC(21-2)842). Various examples are available of reactions of the double bonds with carbenoids to give bicyclo[4.1.0]diheteroheptanes (77LA910,78ZC15), and with alkenes in [2 + 2] cycloadditions (78CB3624). 

In order to outline the scope of this chemistry, Sections 4.8.2 and 4.8.3 will discuss the catalysts and carbenoid precursors used. This will be followed by reactions of caibenoids with ir-systems, organized according to the ir-system involved, alkenes (Section 4.8.4), alkynes (Section 4.8.5), benzenes and electron-rich heterocycles (Section 4.8.6). Particular emphasis will be placed on the stereochemical outcome of these reactions with reference to applications in organic synthesis. 

One of the main side reactions that can occur in cyclopropanation reactions is a competitive capture of the carbenoid with unreacted diazo compound rather than with the alkene, which results in the formation of dimeric products such as (18) and (19) (equation 9).146 This reaction is usually avoided by using a five- to ten-fold excess of alkene and ensuring that a low concentration of the diazo compound is maintained. Indeed, Doyle has shown that by very slow addition of the diazo compound it is possible to obtain reasonable yields of cyclopropane even when stoichiometric quantities of the carbenoid precursor and alkene were used.47... 

For alkyl(silyl)carbenes where the alkyl contains an a-C—H bond, 1,2(C C) hydride shift leading to a vinylsilane is the common reaction pathway. Vinylsilane formation has been observed for free (photochemically or thermally generated) carbenes (equations 4384, 4448.49.50 and 45 85,86) but also in carbenoid reactions. In the latter case, the configuration of the alkene could be controlled to a large extent by the choice of the catalyst The -alkene was formed nearly exclusively with copper(I) chloride as catalyst87, whereas rhodium(II) pivalate88 gave mainly the Z-alkene (equation 46). 

Finally, the simplest cycloaddition (1 +j) involves a one-center p orbital, e.g. X = CH2, NH, 0, S, etc. Singlet state O, S, and CH2 might react with alkenes and the syn process would be expected. This stereochemistry has been found with the additions of CH2 and S, although the latter appears to be par of a multistep process (Gunning and Strausz, 1966). Unlike the reactions in which two polyenes react, as in (36), there is no a priori steric problem in making syn or anti bonds, since X is monatomic. The orbital pictures of Fig. 20b,c were drawn for another purpose, but illustrate this point as well. We shall return to 1 +j additions, when carbenoid reactions are discussed. 

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 ". ... 

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