Cyclopropenes diazo compounds

Cyclopropene diazo compound 327 treated with PTAD provides Dewar benzene analogue 330 in good yield (Scheme 56). Formation of this product is rationalized by way of intermediate dipolar urazole 328, which then undergoes a 1,2 shift to dipolar species 329, which collapses into the final product 330 (82CB3796). 

The majority of preparative methods which have been used for obtaining cyclopropane derivatives involve carbene addition to an olefmic bond, if acetylenes are used in the reaction, cyclopropenes are obtained. Heteroatom-substituted or vinyl cydopropanes come from alkenyl bromides or enol acetates (A. de Meijere, 1979 E. J. Corey, 1975 B E. Wenkert, 1970 A). The carbenes needed for cyclopropane syntheses can be obtained in situ by a-elimination of hydrogen halides with strong bases (R. Kdstcr, 1971 E.J. Corey, 1975 B), by copper catalyzed decomposition of diazo compounds (E. Wenkert, 1970 A S.D. Burke, 1979 N.J. Turro, 1966), or by reductive elimination of iodine from gem-diiodides (J. Nishimura, 1969 D. Wen-disch, 1971 J.M. Denis, 1972 H.E. Simmons, 1973 C. Girard, 1974),... 

This synthetic appproach has been used in a few cases for the preparation of pyridazines from diazo compounds and cyclopropenes. In general, cycloadducts (176) are formed first and these rearrange in the presence of acid or alkali to pyridazines (Scheme 98) (69TL2659, 76H(5)40l). Tetrachlorocyclopropene reacts similarly and it was found that the stability of the bicyclic intermediates is mainly dependent on substitution (78JCR(S)40, 78JCR(M)0582>. 

Alkinyloxy)diazoacetic esters 11 give rise to product mixtures that could be separated only partially. The isolated products result from a tandem intramolecular cyclopropenation/cyclopropene —> vinylcarbene isomerization (12, 14) and from a twofold intermolecular (3+2)-cycloaddition of the intact diazo compound (13). 

H-Pyr azoles readily undergo photochemically induced elimination of nitrogen to yield the corresponding cyclopropenes, often by way of detectable vinyl diazo intermediates. l-Aryl-3-methyl-2-phenyl-l-diazobut-2-enes have, in fact, been prepared in this way from the appropriate pyrazoles.345 The vinyl diazo compounds 416, obtained by irradiation of the 3//-pyrazoles 417, were further converted to cyclopropenes 418 via vinylmethylene intermediates 419 by irradiation at 10°C.346 1-Acylcyclopropenes have been... 

Scheme 7) and the reaction was monitored by IR spectroscopy, no significant amount of 33 could be detected [106], Instead, at the initial stage of the irradiation, an intermediate diazo compound was observed, which was assigned the structure 33-D. Further irradiation gave rise to a compound, which was identified with the help of calculations as substituted cyclopropene Z-36 (Scheme 7). Although it is possible that 36 is formed directly from 33-D, it is more likely that 33 is an intermediate of the reaction, as the ESR data imply. ESR spectroscopy is generally more sensitive than IR, and the failure of the latter to detect 33 is likely due to its inherently weak-intensity vibrational absorptions (as indicated by calculations) and/or its high photoreactivity.

A carbene has been generated at position 3 of the bislactim ether derived from cyclo(L-Val-Gly) via the lithio derivative and the diazo compound. The carbene has been trapped by an acetylene to provide a cyclopropene [88AG(E)433]. Hydrolysis with 0.1 N HC1 leads to the cyclopropene aminoacid esters (Scheme 70). 

Cyclopropanation reactions are one set in an array of C-C bond-forming transformations attributable to metal carbenes (Scheme 5.1) and are often mistakenly referred to by the nonspecific term carbenoid. Both cyclopropanation and cyclopropenation reactions, as well as the related aromatic cycloaddition process, occur by addition. Ylide formation is an association transformation, and insertion requires no further definition. All of these reactions occur with diazo compounds, preferably those with at least one attached carbonyl group. Several general reviews of diazo compounds and their reactions have been published recently and serve as valuable references to this rapidly expanding field [7-10]. The book by Doyle, McKervey, and Ye [7] provides an intensive and thorough overview of the field through 19% and part of 1997. 

The Cu(I)-catalyzed decomposition of (alkynyloxysilyl)diazoacetates 119 furnishes the silaheterocycles 120 and/or 121 (equation 30) in modest yield63. In these cases, the photochemical extrusion of nitrogen from 119 does not lead to defined products and the thermal reaction is dominated by the 1,3-dipolar cycloaddition ability of these diazo compounds. In mechanistic terms, carbene 122 or more likely a derived copper carbene complex, is transformed into cyclopropene 123 by an intramolecular [1 + 2] cycloaddition to the triple bond. The strained cyclopropene rearranges to a vinylcarbene either with an exo-cyclic (124) or an endocyclic (125) carbene center, and typical carbene reactions then lead to the observed products. Analogous carbene-to-carbene rearrangements are involved in carbenoid transformations of other alkynylcarbenes64. 

Cycloaddition of the carbene derived from 205 to bis(trimethylsilyl)acetylene yields the expected cyclopropene in low yield both photochemically (20%) and under catalysis by copper triflate at 80 °C (10-13%)119. The latter version of the reaction is accompanied by [3 + 2] cycloaddition of the diazo compound to the alkyne, and the photochemical route yields a by-product which obviously comes from carbenic C,H insertion at a SiMe3 group of the alkyne. 

R = R1 = Ph) in very high yield by photolysis, the pyrazole is formed in only 3 % yield from diphenylethyne.50) The formation of cyclopropenes from pyrazoles apparently occurs via the corresponding diazo-compound. Thus photolysis of (53, R = R1 = Ph) at between 330 and 410 nm has been shown to lead to the diazo-compound (56) which on further photolysis or pyrolysis is converted to (54)50). Indeed, photolysis of vinyldiazoalkanes provides a good route to cyclopropenes thus photolysis of E- (57) leads to 3-alkoxycarbonyl-3-cyanocyclopropene51), while (58) leads either to the corresponding cyclopropene or to reversal to the pyrazole5Z). 

In other cases cyclopropenes have been obtained by direct reaction of an alkyne with a diazo-compound in. the presence of a suitable catalyst. Typical of these is the reaction of ethyl diazoacetate with alkynes in the presence of copper, which is reported to lead to about 40-50 % conversion to cyclopropene per equivalent of diazo-compound. This has been applied to the synthesis of the important naturally occurring cyclopropene, sterculic acid, (66) 56) ... 

Although some carbenes are reported not to add to cyclopropenes207, there are several examples of inter- and intra-molecular addition leading initially to the formation of bicyclobutanes. l,2-Diphenylcyclopropene-3-carboxylates are converted to a mixture of three stereoisomeric bicyclo[1.1.0]butanes by reaction with ethoxy-carbonylcarbene generated from the thermolysis of ethyl diazoacetate an additional product is the diene (278) which is apparently formed by rearrangement of an intermediate zwitter ion208). It should be noted, however, that cyclopropenes readily undergo addition to diazo-compounds, and that subsequent transformations may then lead to bicyclobutanes (see Section 8), and that a free carbene may therefore not be involved in the above process. 

The ruthenium-catalyzed addition of diazo compounds to alkynes has led to the selective synthesis of functional 1,3-dienes by the combination of two molecules of diazoalkane and one of alkyne [106] (Eqs. 82,83). The stereoselective formation of these conjugated dienes results from the selective creation of two C=C double bonds rather than leading to the cyclopropene derivative. This is expected to be due to the possibility for the C5Me5RuCl moiety to accomodate two cis carbene ligands. 

The most common source of a,j5-unsaturated carbenes for cyclopropene synthesis is from the decomposition of 3H-pyrazoles which are, in turn, available from the addition of a diazo compound to an alkyne. On photolysis these compounds suffer ring cleavage to an a>diazoalkene prior to nitrogen loss and carbene formation. In this way cyclopropene 27 is available from either 25 or 26 by way of common diazo and carbene intermediates. ... 

Cyclopropenes readily undergo cycloaddition to diazoalkanes (often at below 20 °C) to form 2,3-diazabicyclo[3.1.0]hex-2-enes (see also Section 4.2.1.1.2.), although in a number of cases these react further by opening of the three-membered ring to give either diazo compounds or 1,4-dihydropyridazines. 

The reactions of diazo compounds with cyclopropenes bearing various types of functionality are summarized in Table 17. 

Using this route, a variety of tricyclo[2.1.0.0 ]pentanes are available from cyclopropenes, with the latter being most easily prepared from the metal-catalyzed reaction of a diazo compound and an alkyne (see Section 1.2.1.2.1. for related reactions). Alkyl- and aryl-substituted cyclopropenes 1 react with copper catalysts, such as copper powder, to yield the tricyclic products 2 in low to moderate yield. ... 

Other applications of diazo compounds in this manner are shown for the formation of cyclopropenes 2, while reactions in which pyrazoles are converted into cyclopropenes without the isolation of a diazo compound are given in Section 3.2.1.1. 

The cycloaddition of a diazo compound to an alkyne followed by extrusion of nitrogen under various conditions from an isolated pyrazole represents one of the standard routes to cyclopropenes (Section 3.2.1.1.). In certain cases the reaction is carried out under conditions which might involve direct addition of a carbene derived from the diazo species, e.g. formation of 7, 8, and9. For8(R = cyclopropyl), the product rearranged under the reaction conditions to 1-cyclopropyl-1-trimethylsilylallene. ... 

Although the addition of diazo compounds to cyclopropenes generally leads to diazabicyclo-[3.1.0]hexanes, in some cases these cannot be isolated and lead directly to diazoalkenes. A dihydropyridazine is also formed in some cases these are discussed later (Section 3.3.2.2.). Diazo compounds which are isolated directly from the addition to a cyclopropene are summarized opposite. 

The addition of diazo compounds to cyclopropenes often gives diazabicyclo[3.1. OJhexenes which rearrange under more vigorous conditions to pyridazines or dihydropyridazines these reactions are discussed elsewhere (see Sections 1.A.1.1.6.1.5.3.1. and 1.A.4.2.1.1.2.). In some cases, however, the bicyclic systems cannot be isolated and a pyridazine is produced directly from a cyclopropene examples of such reactions are the formation of 1/33.134 2135-138 3 io4... 

This type of intramolecular addition reaction had previously been observed in low yield on photolysis by Biichi and White.4 A mixture of the two isomeric diazo compounds (6) was photolyzed the hydrocarbon fraction contained ( )-thujop-sene (7) in low yield the main component was the cyclopropene (8). 

A diazo transfer reaction takes place, however, between diazoalkanes and derivatives of cyclopropene. Thus, in the reaction of dimethyl 3,3-dimethyl-cyclo-propene-l,2-dicarboxylate (2.200) with diazomethane, the primary product 2.201, a diaza bicyclo[3.1.0]hexene, isomerizes on irradiation to the diazo compound 2.202 (2-79). Acid catalysis, however, leads to the isomerization of 2.201 to the 1,4-dihydro-pyridazine 2.203 (Franck-Neumann and Buchecker, 1969). An analogous reaction of... 

Cycloaddition of 1,3-dipolarophiles to alkynes for the synthesis of diazo compounds can also be applied to reaction of diazoalkanes with alkynes (2-91). 2-Diazopropane and 1,2-diarylethynes readily form 3//-pyrazoles (2.229). These pyrazoles isomerize photochemically to the 4-diazo-2-methyl-3,4-diarylbutenes (2.230), i.e., to a vinyldiazo compound (Pincock et al., 1973 Arnold et al., 1976 Leigh and Arnold, 1979). Some cyclopropene (2.231) is formed in a consecutive dediazoniation, i. e., by cyclization of the carbene formed. The method is not useful for unsymmetrically substituted alkynes because these cycloadditions are not regiospecific. It is, however, applicable to the synthesis of diazoalkenes with alicyclic... 

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