Carbenes and Carbenoids to Olefins

Cycloaddition of Carbenes and Carbenoids to Olefins.—The cycloaddition of carbenes or carbenoids, however prepared, to olefins is still the major method of generating a cyclopropane derivative, and theoretical investigations of the process have been published.  

A brief review has also appeared in which various carbene preparative methods are considered. A frequent competing reaction is carbene insertion into an allylic or other C—bond. After generation of cyclopentylcarbene (39X however, it is the intramolecular C—H insertion which generates the cyclopropane ring this has been investigated in detail.  

Base and Substituted Halogenomethane Method. As well as a correction to the literature of last year concerning cycloaddition of 1,2,2-trimethylpropylidene-carbene, there have been reports of routine dihalogenocarbene additions to 1,1-dicyclopropylethylene, cyclo-octa-l,3-diene, bullvalene, vinyl ethers, 1-ethoxybuta-1,3-dienes, and tricyclo[4,4,l,0 ]undeca-3,8-di- 

The mechanism of the addition of dichlorocarbene, generated from sodium methoxide and ethyl trichloroacetate, to the olefins (42) has been investigated.  

Bertrand and C Santelli-Rouvier, Bull Soa chim France, 1972, 2775. 

Cycloadditions of Carbenes and Carbenoids to Olefins.—Base and Substituted Halo-genomethane. Dichlorocarbene adds to 1-aryl-1,3-dienes predominantly at the 3,4-double bond, the relative rate constants correlating with the constants of sub- 

The phase-transfer-catalysed (PTC) or Makosza method grows increasingly popular for the generation of carbenes, and a timely review of its applications to preparative organic chenaistry has appeared. Further details have been published for the PTC addition of dichlorocarbene to cyclo-octatetraene and azepines. Makosza 

In the past, a -unsaturated carbonyl compounds have proved unreactive to many cyclopropanation techniques however, it has now been shown that the Makosza procedure gives good results. Only syn-bishomo-p-quinones have previously been obtained by carbenoid addition to duroquinone, but PTC addition of dichloro-and dibromo-carbenes affords the anti-adducts (63 X = Q or Br) in good yields (95 and 57 %, respectively). 

Greater success compared with the sodium trichloroacetate technique has also been noted in dichlorocarbene addition to several steroidal olefins. 

A modification of the PTC procedure employs dichloromethane as solvent and halogenodi-iodomethanes as a source of di-iodo- or chloroiodo-carbene. This allows the preparation of a number of di-iodocyclopropanes, which were long considered too unstable to be isolable.  

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Synjanti Product Ratios in Cyclopropanes Obtained by the Addition of Carbenes and Carbenoids to Olefins... 

Addition of Carbenes and Carbenoids to Olefins.— The addition of carbenes and carbenoids to olefins provides a standard method for the synthesis of cyclopropanes and much of the current work is concerned with the provision of new carbene sources and the improvement of procedures. 

Addition of Carbene and Carbenoids to Olefins.—The addition of carbenes and carbenoids to olefins continues to be one of the most popular routes used for cyclopropane synthesis. A review of carbenes (and nitrenes) based on the 1973 literature has appeared during the year, and methoxycarbonyl carbene has been the subject of a theoretical study. ... 

Reactions of carbenes and carbenoids with olefins may give unstable cyclopropanes which undergo rearrangement reactions. Use has been made of the facile ringopening of 2-aminocyclopropyl esters in a new, general route to y-keto-esters (Scheme 60). 

The discovery of carbene and carbenoid additions to olefins was the major breakthrough that initiated the tapping of this structural resource for synthetic purposes. Even so, designed applications of cyclopropane chemistry in total syntheses remain limited. Most revolve around electrophilic type reactions such as acid induced ring opening or solvolysis of cyclopropyl carbinyl alcohol derivatives. One notable application apart from these electrophilic reactions is the excellent synthesis of allenes from dibromocyclopropanes 2). 

The Simmons-Smith-type cyclopropanation of olefins is one of the most well-known reactions of carbenes and carbenoids. However, cyclopropanation of simple olefins with magnesium carbenoids is usually very difficult and only cyclopropanation of allylic alcohols was reported. Thus, treatment of allylic alcohols (23) in CH2CI2 at —70°C with i -PrMgCl and diiodomethane for 48 to 60 h afforded cyclopropanes in up to 82% yield as a mixture of syn- and and-isomers. In this reaction, 5yn-isomers were mainly or exclusively obtained (synianti = 5 1-400 1) (equation 10). 

The introduction of carbenes and carbenoids into synthetic organic chemistry revolutionized the synthesis of cyclopropane derivatives21. In particular, cyclopropanation of methylenecycloalkanes became a very useful method for the preparation of SPC. Moreover, since cycloaddition of carbenes to olefins involves a very fast concerted process (i.e. it eliminates any intermediates during the formation of the three-membered ring)21, the method is equally efficient for the preparation of both unstrained and highly strained compounds. 

In a large number of carbene and carbenoid addition reactions to alkenes the thermodynamically less favored syn-isomers are formed 63). The finding that in the above cyclopropanation reaction the anti-isomer is the only product strongly indicates that the intermediates are organonickel species rather than carbenes or carbenoids. Introduction of alkyl groups in the 3-position of the electron-deficient alkene hampers the codimerization and favors isomerization and/or cyclodimerization of the cyclopropenes. Thus, with methyl crotylate and 3,3-diphenylcyclopropene only 16% of the corresponding vinylcyclopropane derivative has been obtained. 2,2-Dimethyl acrylate does not react at all with 3,3-dimethylcyclopropene to afford frons-chrysanthemic add methyl ester. This is in accordance with chemical expectations 69) since in most cases the tendency of alkenes to coordinate to Ni(0) decreases in the order un-, mono-< di- < tri- < tetrasubstituted olefines. 

Volume 9 deals with the majority of addition and elimination reactions involving aliphatic compounds. Chapter 1 covers electrophilic addition processes, mainly of water, acids and halogens to olefins and acetylenes, and Chapter 2 the addition of unsaturated compounds to each other (the Diels-Alder reaction and other cycloadditions). This is followed by a full discussion of a-, y- and S-eliminations (mainly olefin and alkyne forming) and fragmentation reactions. In Chapter 4 carbene and carbenoid reactions, and in Chapter 5 alkene isomerisation (including prototropic and anionotropic, and Cope and Claisen rearrangements), are discussed. 

The most important synthetic use of carbene intermediates is in the synthesis of cyclopropanes. Most of the general methods of carbene generation introduced in Scheme 8.1 lead to cyclopropane formation if the carbene is generated in the presence of an olefin. A number of examples of the use of carbenes and carbenoid reagents in cyclopropane synthesis are given in Scheme 8.2. 

This extremely air-sensitive compound, which is valence isoelectronic to an olefin, has been structurally characterized by X-ray diffraction. It has a short carbon-phosphorus double bond (1.62 A) the phosphorus and carbon atoms adopt a trigonal planar geometry with a dihedral angle of 60° (Fig. 3). This value is significantly larger than that reported for the most crowded olefin.61 Formally, this compound can be viewed as the product of a car-bene-carbenoid coupling between bis(trimethylsilyl)carbene and bis(diiso-propylamino)phosphenium triflate. Note that another route to methylene-phosphonium salt has been reported by Griitzmacher et al.62... 

Carbenes and substituted carbenes add to double bonds to give cyclopropane derivatives (1 + 2 cycloaddition).1008 Many derivatives of carbene, e.g., PhCH, ROCH,1009 Me2C=C, C(CN)2, have been added to double bonds, but the reaction is most often performed with CH2 itself, with halo and dihalocarbenes,1010 and with carbalkoxycarbenes1011 (generated from diazoacetic esters). Alkylcarbenes HCR have been added to olefins,1012 but more often these rearrange to give olefins (p. 201). The carbene can be generated in any of the ways normally used (p. 198). However, most reactions in which a cyclopropane is formed by treatment of an olefin with a carbene precursor do not actually involve free carbene intermediates. In some cases it is certain that free carbenes are not involved, and in other cases there is doubt. Because of this, the term carbene transfer is often used to cover all reactions in which a double bond is converted to a cyclopropane, whether a carbene or a carbenoid (p. 199) is actually involved. 

The reaction also takes place with other bases (e.g., LiH,213 Na in ethylene glycol, NaH, NaNH2) or with smaller amounts of RLi, but in these cases side reactions are common and the orientation of the double bond is in the other direction (to give the more highly substituted olefin). The reaction with Na in ethylene glycol is called the Bamford-Stevens reaction,214 For these reactions two mechanisms are possible—a carbenoid and a carbocation mechanism.215 The side reactions found are those expected of carbenes and carbocations. In general, the carbocation mechanism is chiefly found in protic solvents and the carbenoid mechanism in aprotic solvents. Both routes involve formation of a diazo compound (34) which in some cases can be isolated. 

Oxa-l -silabicyclo[ . 1,0 alkanes (n = 3 111 n = 4 113) were the only products isolated from the photochemical, thermal or transition-metal catalyzed decomposition of (alkenyloxysilyl)diazoacetates 110 and 112, respectively (equation 28)62. The results indicate that intramolecular cyclopropanation is possible via both a carbene and a carbenoid pathway. The efficiency of this transformation depends on the particular system and on the mode of decomposition, but the copper triflate catalyzed reaction is always more efficient than the photochemical route. For the thermally induced cyclopropanation 112 —> 113, a two-step noncarbene pathway at the high reaction temperature appears as an alternative, namely intramolecular cycloaddition of the diazo dipole to the olefinic bond followed by extrusion of N2 from the pyrazoline intermediate. A direct hint to this reaction mode is the formation of 3-methoxycarbonyl-4-methyl-l-oxa-2-sila-3-cyclopentenes instead of cyclopropanes 111 in the thermolysis of 110. 

A further stereochemical complication arises in those cases where a carbene having two different groups attached to the divalent carbon atom (e.g. PhCH ) adds in a stereospecifically cis-manner to olefins, such as cis-2-butene, to give two epimeric (syn- and anti-) products (cf. equation 1). Ratios of yields of syn- and tmtfi-products formed in a variety of carbenoid reactions are listed in Table 8. In general, the ratios... 

Bis(phenylsulfanyl)](trimethylsilyl)methyllithium and trimethylsilyloxirane do not afford a homo-Peterson reaction product, but a cyclopropane 4 a with a shifted phenylsulfanyl group. [Bis(phenylsulfanyl)](trimethylsilyl)methyllithium may be looked on as a carbenoid species which is in equilibrium with carbene and phenylsulfonate. This equilibrium may lie towards the carbanion. On addition of trimethylsilyloxirane, phenylsulfonate is trapped with formation of an alkoxide, which corresponds to the intermediate of a Peterson olefination of formaldehyde, and leads to phenyl vinyl sulfide. This provides a reaction partner for the liberated carbene giving cw-l,2-bis(phenylsulfanyl)-l-trimethylsilylcyclopropane (4a) in a stereospecific [2-1-1]... 

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