Vinylcarbene cycloadditions

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). 

Based on his previous work on the catalytic double addition of diazo compounds to alkynes173 using Cp RuCl(COD),174 Dixneuf has developed an efficient one-step synthesis of alkenyl bicyclo[3.1.0]-hexane derivatives of type 163 from enyne precursors 162 (Scheme 43). The catalytic cycle starts with the formation of an Ru=CHR species. It then adds to an alkyne to form ruthenacyclobutene 166, which evolves into vinylcarbene 167. [2 + 2]-Cycloaddition of 167 gives ruthenacyclobutane 168. The novelty in this transformation is the subsequent reductive elimination to give 170 without leading to the formation of diene 169. This can be attributed to the steric hindrance of the CsMes-Ru group. 

The chemical behavior of heteroatom-substituted vinylcarbene complexes is similar to that of a,(3-unsaturated carbonyl compounds (Figure 2.17) [206]. It is possible to perform Michael additions [217,230], 1,4-addition of cuprates [151], additions of nucleophilic radicals [231], 1,3-dipolar cycloadditions [232,233], inter-[234-241] or intramolecular [220,242] Diels-Alder reactions, as well as Simmons-Smith- [243], sulfur ylide- [244] or diazomethane-mediated [151] cyclopropanati-ons of the vinylcarbene C-C double bond. The treatment of arylcarbene complexes with organolithium reagents ean lead via conjugate addition to substituted 1,4-cyclohexadien-6-ylidene complexes [245]. 

The reaction of enynes with Fischer-type carbene complexes can also lead to the formation of cyclobutanones (Figure 2.23) [315]. The mechanism for this reaction is likely to be rearrangement of the intermediate, non-heteroatom-substituted vinylcarbene complex to a vinylketene, which undergoes intramolecular [2 -i- 2] cycloaddition to form the observed cyclobutanones. 

Experimental Procedure 2.2.8. [4 + 3] Cycloaddition of a Chromium Vinylcarbene Complex to a 1-Azadiene rranj-i-(2-Furyl)-2-inethoxy-5-methyl-4,5-dihydro-3H-azepine [390]... 

As mentioned in Sections 3.1.6 and 4.1.3, cyclopropenes can also be suitable starting materials for the generation of carbene complexes. Cyclopropenone di-methylacetal [678] and 3-alkyl- or 3-aryl-disubstituted cyclopropenes [679] have been shown to react, upon catalysis by Ni(COD)2, with acceptor-substituted olefins to yield the products of formal, non-concerted vinylcarbene [2-1-1] cycloaddition (Table 3.6). It has been proposed that nucleophilic nickel carbene complexes are formed as intermediates. Similarly, bicyclo[1.1.0]butane also reacts with Ni(COD)2 to yield a nucleophilic homoallylcarbene nickel complex [680]. This intermediate is capable of cyclopropanating electron-poor alkenes (Table 3.6). 

Alternatively, [2 -1- 2] cycloaddition of carbene complexes to alkynes, followed by [2 -I- 2] cycloreversion can also lead to the formation of vinylcarbene complexes (Sections 3.2.5.6 and 2.2.4). 

Formal 1,3-Dipolar Cycloadditions of Acyl- and Vinylcarbene Complexes... 

In particular the synthetic approach to dihydrofurans (first equation in Figure 4.23) represents a useful alternative to other syntheses of these valuable intermediates, and has been used for the preparation of substituted pyrroles [1417], aflatoxin derivatives [1418], and other natural products [1419]. The reaction of vinylcarbene complexes with dienes can lead to the formation of cycloheptadienes by a formal [3 + 4] cycloaddition [1367] (Entries 9-12, Table 4.25). High asymmetric induction (up to 98% ee [1420]) can be attained using enantiomerically pure rhodium(II) carboxylates as catalysts. This observation suggests the reaction to proceed via divinylcyclopropanes, which undergo (concerted) Cope rearrangement to yield cycloheptadienes. 

Table 4.25. Formal 1,3-dipolar cycloaddition of acyl- and vinylcarbene complexes to alkenes, alkynes, and dienes.

The cycloaddition of the carbene 5 to 6 occurs stereospecifically, i.e. with retention of the alkene configuration, and diastereoselectively, i.e. the more bulky trichloroethenyl group ends up predominantly trans to the most bulky substi-tuent(s) on the original alkene 6 [7-10,13]. The high efficiency with which this vinylcarbene can be intercepted intermolecularly to give vinylcyclopropanes is most surprising [14]. 

Cyclobutanones3 The reaction of pentacarbonyl(methoxymethylmethylene)-chromium (1) with the enyne 2 in acetonitrile results in two isomeric bicyclohep-tanones [(E)-3 and (Z)-3] as the major products. These probably arise by initial reaction with the triple bond to give a vinylcarbene complex (a), which undergoes insertion of CO to give a vinylketene complex (b). An intramolecular [2 + 2] cycloaddition results in the cyclobutanones (3). 

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. 

No [4+2] cycloaddition of the vinylcarbene complex 249 with the optically active diene 248 takes place. Instead, the cyclopropane 250 is obtained, and the Cope... 

At first, cycloaddition of alkyne to the carbene complex 259 gives the chromacyclobutene 260, which is cleaved to form the vinylcarbene complex 261. It is claimed that vinylcarbenes 255 and 261 are formed directly without forming chromacyclobutenes 254 and 260 (M = Cr) [83]. The 67r-electrocyclization of 261... 

On standing for 18 h at 20 °C in the absence of an alkene, cyclopropene (151, R = Et) rearranges to the vinylsulphine (154), which can be trapped by cycloaddition to diazopropane photolysis of (150, R = 4—MeC6H4) in a similar way leads to a high yield of (155), and an intermediate vinylcarbene (153, R = 4—MeC6H4) may be trapped by ethyl vinyl ether. In each case the intermediate vinyl carbene apparently... 

Recently, cyclopropane derivatives were produced by a ruthenium-catalyzed cyclopropanation of alkenes using propargylic carboxylates as precursors of vinylcarbenoids [51] (Eq. 38). The key intermediate of this reaction is a vinylcarbene complex generated by nucleophilic attack of the carboxylate to an internal carbon of alkyne activated by the ruthenium complex. Then, a [2+1] cycloaddition between alkenes and carbenoid species affords vinylcyclo-propanes. 

Treatment of the vinylcarbene chromium complex 97 with /-BuC=P affords the dihydrophosphetylketene complex 98 (Scheme 26). This transformation is believed to proceed via r -phosphaalkyne carbene-, phosphaalkenylcar-bene-, and phosphaalkenylketene complexes as intermediates. An intramolecular [2+2] cycloaddition completes the reaction sequence.53 Different carbene/carbon monoxide/phosphaalkyne cycloaddition products (e.g., 1,3-oxaphospholes, phosphaphenanthrenes) are obtained depending on substitution at the carbene ligand (vide infra). 

Cyclopropenones show considerable biological activity, " and have recently been employed as a key structural unit for a novel inhibitor of a cysteine protease. The utility of cyclopropenone acetals has recently been recognized for vinylcarbene formation, " asymmetric synthesis, and other processes. Cycloaddition reactions of cyclopropenone acetals and congeners have also proven to be useful for chiral functionalization of buckminsterfiillerenes. 

The reaction proceeds through a vinylketene (54) formed via a vinylcarbene (53) the product of ring-opening of the cyclopropene ring. Then, the ketene undergoes intramolecular cycloaddition in benzene or is trapped by methanol (equation 35) °. 

The formation of (39) was further confirmed by its cycloadditions with furan and pyrrole to give the corresponding Diels-Alder adducts. When heated, (39) suffers valence isomerization, yielding the cyclopropenyl ketone (41), presumably via the vinylcarbene (40) (Scheme 4). 

The first possiblity involves a stereoselective 1,2-addition to a cyclopropene double bond. The second consists of an in-situ generation of vinylcarbenes followed by a [2+ l]-cycloaddition reaction. 

In the meantime thermal65 and metal catalyzed66,67> rearrangements of cyclopropenes have been detected as convenient methods for the preparation of vinylcyclo-propanes via formal [2+ l]-cycloadditions of vinylcarbenes to alkenes (Eq. 9) (for an alternative entrance starting from allylidene dichloride or 1,3-dichloropropene, see Ref. 68)). 

Mechanistically, on the basis of the above reactions, it can be assumed that either nickelacy-clobutenes or the tautomeric nickel vinylcarbenes 26 are reactive intermediates of these [2-1-1] cycloadditions. Insertion of an electron-poor alkene into a nickel-carbon bond of 26 would result in the formation of 27, that can produce the substituted ethenylcyclopropanes via a reductive elimination step. 

However, yields in the intermolecular cycloaddition reactions of vinylcarbene complexes, formed by intramolecular insertion of an alkynyl tethered metal carbene complex, are higher when molybdenum rather than chromium or tungsten carbene complexes are employed. Mild thermolysis (THF, 65 °C, 1 h) in the presence of ten equivalents of an electronically undemanding alkene directly leads to the 2-alkyl-2-(2-methoxycyclopentenyl)cyclopropanes 31. ... 

Fischer-type chromium carbene complexes with 1-ethoxycyclopropylalkynyl substituents at the carbene carbon, e.g. 25, on reaction with dimethylamine and subsequent conversion of the resulting vinylcarbene with alkynes surprisingly did not give phenol derivatives, as would be expected from the known Dotz reaction, but gave cyclopenta[ )]pyrans, e.g. 26. The reaction is interpreted as a double alkyne-insertion/CO-insertion sequence with formation of a trienylketene intermediate, which undergoes intramolecular hetero-Diels-Alder cycloaddition and dimethylamine elimination. ... 

In a related reaction two molecules of cyclopropene 2 were converted into a cyclohexadiene 5 in a reaction which has been explained in terms of ring opening of one molecule of 2 to a vinylcarbene 3 which undergoes a 1,4-hydrogen shift to produce a diene 4 this then undergoes cycloaddition to the second molecule of 2 and the product undergoes cyclopropyl to allyl rearrangement. ... 

The corresponding trichloride 1 (X = Cl) underwent normal addition to give 3. The formation of 2 can be explained in terms of ring opening to a vinylcarbene and a formal 3-center plus 3-center cycloaddition of this to the nitrile oxide.The fact that 1 (X = Cl) undergoes a normal cycloaddition may reflect the fact that it ring opens to a carbene at a rather lower rate than 1 (X = H), allowing cycloaddition to the cyclopropene to compete. 

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