Cyclopropyl carbene intermediates

Reactions of cyclopentyne with alkenes gives [2+2] cycloadduct with complete retention of stereochemistry (Scheme 24) [120], Laird and Gilbert observed the expected [2+2] cycloadduct along with the polycyclic adduct in the reaction of norbomyne with 2,3-dihydropyran (Scheme 24) [121], and located a cyclopropyl-carbene intermediate [122],... 

If an addition alkene is present, then the cyclopropyl carbene intermediate may be intercepted to effect cyclopropanation of the second alkene. Cyclopropanation can become the dominant pathway, as in the platinum-catalysed reaction of enyne 6.266 (Scheme 6.108). ° Whether this occurs, however, once... 

Gold-catalysed ene-yne cyclization has been employed in two closely related and simultaneous syntheses of englerin A 6.278, a sesquiterpene that has shown anti-tumour activity (Scheme 6.111). Both syntheses relied upon the intramolecular nucleophilic trapping of the cyclopropyl carbene intermediate 6.280 by a ketone nucleophile, followed by counterattack of the anionic t -vinyl gold species onto the oxonium ion 6.281 formed in this way, to form the skeleton of the molecule, but differed in their approach to the other functionality. 

Regioselective ring expansion of alkynyl cyclopropanes to cyclobutenes has been reported via a copper-catalysed cycloaddition of an alkyne with an arylsulfonyl azide and a silver-catalysed carbene formation followed by ring expansion of a cyclopropyl carbene intermediate (Scheme 75)7° ... 

This formal [2h-2h-2] alkyne/alkene/carbonyl cycloaddition proceeds through the opening of the cyclopropyl carbene intermediate 1-4 by the carbonyl group to form oxonium cation 1-5, which undergoes nucleophilic attack by the vinylgold intermediates in a Prins-type cyclization to give tetrahydropyranyl cation 1-6. 

The cycloisomerization invokes the initial formation of a cyclopropyl carbene intermediate 101 followed by its intramolecular attack from the proximal carbonyl group to provide intermediate 102. Further cyclization furnishes the core structure of englerins in a highly stereoselective fashion. 

Alkoxycarbene complexes with unsaturation in the alkyl side chain rather than the alkoxy chain underwent similar intramolecular photoreactions (Eqs. 10 and 11) [60]. Cyclopropyl carbene complexes underwent a facile vinyl-cyclopropane rearrangement, presumably from the metal-bound ketene intermediate (Eqs. 12 and 13) [61]. A cycloheptatriene carbene complex underwent a related [6+2] cycloaddition (Eq. 14) [62]. 

Photoelimination of nitrogen from diazirines, for example, proceeds via carbene intermediates. 3-tert-Butyldiazirine (395) is converted into the cyclopropane 396 and the alkene 397 with the formation of the carbene insertion product being favored from the singlet state.328 3-Cyclopropyl-3-chlorodiazirine (398) has similarly been converted to the carbene 399 which undergoes both rearrangement to l-chlorocyclobutene(400)329 and addition... 

Under suitable conditions, carbon atoms react with olefines to form allenes 46 presumably via intermediate cyclopropyl carbenes viz. 

The assembly of highly functionalized cydohexene derivatives was achieved by Lee and Shin using a highly stereoselective tandem reaction. In this process, the nucleophilic partidpation of the O-Boc group appeared to intercept a carbocationic (or cyclopropyl carbene) gold intermediate [163]. 

The more bulky 1-ethoxycyclopropyl group also induced a complete Z-diastereoselec-tivity to the Michael reaction of the ethynyl carbene complex with dimethylamine (equation 179)246. This is due to the sterically favored arm-position acquired by the bulky group in the intermediate. Unlike the parent cyclopropyl carbene complex, which gave only... 

Nakajima has shown that a-cyclopropyl acyl silane (23) results from reaction of 1-trimethylsilyl cyclopropyl lithium with dichloromethyl methyl ether at low temperature in THF solution, in a reaction said to involve a carbene intermediate and a 1,2-silicon shift (Scheme 56)147. 

Because of these and other useful molecules containing three-membered rings, methods to make them are important as well as interesting. Most chemical syntheses of compounds containing cyclopropyl groups make use of the addition of a carbene, or carbene equivalent, to an aikene. What do we mean by carbene equivalent Usually, this is a molecule that has the potential to form a carbene, though it may not actually react via a carbene intermediate. One such example is a zinc carbenoid formed when diiodomethane is reacted with zinc metal it reacts with alkenes just as a carbene would—it undergoes addition to the 7t bond and produces a cyclopropane. 

It is important to note in an overview of this chemistry that the formation of most of the products can be mechanistically explained as proceeding via cyclopropyl gold carbene intermediates. The involvement of these species has been previously proposed in enyne cyclizations with other metals and their structures have been later determined by calculations. ... 

Electron-rich aromatic and heteroaromatic compounds add to 1,6-enynes in the presence of Au(I) catalysts (equations 62 and 63). This reaction leads stereospecifically to adducts related to the products in the aUcoxycychzation by nucleophihc addition on cyclopropyl gold carbene intermediates. Interestingly, in a few cases, addition of the nucleophile takes place at the carbene carbon to give adducts of the type in equation (63). ... 

Interaction of a strong base with nitrosoureas 601 led to the formation of di-azocyclopropanes 603, which proved to be less stable and to decompose via a carbene intermediate (622) (for trapping of 603, see Refs 43,101,174, 606), rearranging to allenes (624)39 3-85,88.141,174,606.607 (Scheme 16). Allene rearrangement was also reported for a cyclopropyl-l,2-bisnitrosourea 5. By the sequence 623 -4 624 allenes could be synthesized in good yields. It was shown that optical activity was transferred from the nitrosourea precursor 601 (central chirality) to the allene product 624 (axial chirality) 5o. 6s. ss... 

A review has discussed the photochemical cyclization of a variety of aryl- and heteroaryl-prop-2-enoic acids. Irradiation (A,>340nm) of the cyclohexenone (119) in argon purged benzene solution affords the cyclized derivatives (120) as a 3 1 mixture of diastereoisomers. The formation of the cyclopropyl group arises via the carbene (121) and insertion into a C-H bond of a neighbouring methyl group. This carbene is formed, presumably, from the biradical (122) which arises by addition of the alkene to the excited state of the enone. Further evidence for the carbene intermediate comes from a reaction in methanol when the diastereo-isomeric mixture of the ethers (123) and (124) is obtained." ... 

Hydrazones of a number of alkyl cyclopropyl ketones have been converted to the corresponding vinylcyclopropanes, generally by treatment with a base and conceivably via carbene intermediates. In most cases the reactions were carried out using tosylhydrazones, ° -... 

Stoichiometric use of transition-metal-carbene complexes in organic synthesis has been thoroughly reviewed.Various examples using carbene complexes containing cyclopropane subunits have been reported.Here, the cyclopropyl moiety is either attached directly to the carbene carbon or is placed in a more remote position. This section only discusses isolated carbene complexes. Related transition-metal-catalyzed conversions of diazo compounds containing cyclopropane subunits, which are interpreted to proceed via carbene intermediates (e.g. ref 130), are not discussed here. 

In a study of reductive McMurry-type coupling of carbonyl compounds with (OR)3WsW(OR)3 (R = 2,2-dimethylpropyl), a dinuclear cyclopropylmethylidene complex 14 was isolated and structurally characterized by X-ray.The cyclopropyl group remained intact (also in subsequent coupling reactions with other carbonyl compounds) thus, no long-lived carbene intermediate (or cation or anion) is involved and the tungsten carbon bond must have considerable covalent [Pg.1893]

Electrophilic Au(I) complexes or their halide AuX analogoues typically cyclize enynes (I, Scheme 58) (475) by a 5-exo-dig pathway to give a variety of cycloisomerization and addition derivatives. The mechanism is proposed to involve formation of a cyclopropyl gold-carbene intermediate... 

Cyclopentenones have been also obtained from alkoxy(cyclopropyl)carbene complexes and alkynes via a cyclopentadienone intermediate. [85] The intramolecular version of this type of reaction has been studied intensively. 

There has also been a renewal of interest in reactions catalyzed by ru-thenium(II) porphyrin complexes, simultaneously with the development of new chiral ruthenium porphyrins [175-178]. Although these reactions focus mainly on asymmetric epoxidation of olefins [179,180], in some cases asymmetric cyclopropanations were very successful As a recent example, the intermolecular cyclopropanation of styrene and its derivatives with ethyl diazoacetate afforded the corresponding cyclopropyl esters in up to 98% ee with high trans/cis ratios of up to 36 and extremely high catalyst turnovers of up to 1.1 X 10 [140]. The structure of the metalloporphyrin is given in Fig. 2. Asymmetric intramolecular cyclopropanations were also reported with the same catalyst [140]. hi this case, the decomposition of a series of aUyhc diazoacetates afforded the cyclopropyl lactones in up to 85% ee. Both the inter-and intramolecular cyclopropanation were proposed to proceed via a reactive chiral ruthenium carbene intermediate. The enantioselectivities in these processes were rationahzed on the basis of the X-ray crystal structures of closely related stable chiral carbene complexes obtained from the reaction of the chiral complex with N2CPh2 and N2C(Ph)C02CH2CH = CH2. 

The intermolecular reaction of gold carbene intermediates with alkenes can lead to two different products, depending on the starting material. 1,6-Enynes with a substituent at C-1 afforded cyclopropyl-substituted bicyclo[3.1.0]hexanes via the gold carbene formed by 5-exo-dig attack at the activated triple bond (Scheme 4-28). If no substituent is present at C-1 of the enyne, then the gold carbene undergoes a rapid... 

In the presence of a nucleophile, the bicyclic gold carbene intermediates can be trapped to afford monocyclic products with opening of the cyclopropyl ring (Scheme 4-37). " Depending on the bond cleaved, functionalized cyclopentenes... 

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