3.3- Disubstituted cyclopropenes

Cycloalkene Derivatives Cyclopropenes readily interact with nitrile oxides. Reactions of a broad series of 3,3-disubstituted cyclopropenes with 4-substituted benzonitrile, methoxycarbonyl- and cyanoformonitrile oxides (229) as well as with di(isopropoxy)phosphorylformonitrile oxide (230) give 2-oxa-3-azabicyclo[3.1.0]hexene derivatives 62. Stereoselectivity of the cycloaddition is governed by both steric and polar factors. In particular, steric factors are supposed to prevail for 3-methyl-3-phenylcyclopropene affording 62 [R1 =... 

Addition of distannane to alkenes has been achieved only with strained cyclopropenes (Equation (60)).158 3,3-Disubstituted cyclopropenes undergo highly face-selective distannation in the presence of the palladium-isocyanide complex to afford m-adducts. 

Reactions with cyclopropene.11 Lithium organocuprates react with the cyclo-propenone ketal 1 (12, 152-154) to form a copper species (a) that behaves as an enolate of a cyclopropanone. Thus it reacts with alkyl halides to form cis-2,3-disubstituted derivatives of 1. 

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). 

Whereas the repeated lithiation-trimethylsilylation sequence of trimethyl-silylbicyclopropylidene 43 a yielded predominantly the cyclopropene derivative 51 [54], bicyclopropylidenecarboxylates 42-Me, 42-fBu after repeated deprotonation and carboxylation retain the bicyclopropylidene moiety and give 2,2-disubstituted products 52-R only (Scheme 9) [55]. So far, alkylbicyclopropyl-idenes 43 e, f, g have not been induced to undergo deprotonation and a second substitution [56a]. The urethane 53 with a nitrogen directly attached to the skeleton, more easily than any other bicyclopropylidene derivative, rearranges to... 

As for additions of allylic Grignard reagents, the relative reactivity order of the olefins appears to be 1-alkenes < styrene < 1,3-butadiene < ethylene and a,oi-or a,/3-disubstituted alkenes do not react94. However, strained alkenes such as cyclopropenes constitute an exception. Indeed, dicrotylzinc smoothly reacted with 3,3-dimethylcyclopropene and afforded the dicyclopropylzinc reagent 130 resulting from a syn addition process (equation 62)93. 

Unfortunately, additions to mono- or disubstituted alkenes other than the strained cyclopropenes cannot be so easily achieved due to their considerably lower reactivity. 

The intermediacy of >/2-cyclopropene complexes of nickel has been proposed in catalyzed 2+1 reactions of free cyclopropene with electron-poor olefins, to give vinylcyclo-propanes. For example, the reaction of fumarate esters with 3,3-disubstituted cyclopropenes in the presence of Ni(COD)2 catalyst gave vinyl-substituted trans-2,3-cyclopropane dicarboxylate esters (equation 235)72 302. However, when maleic esters were used instead, a mixture of both cis and trans vinylcyclopropane diesters is obtained. 

Functionalized cyclopropenes are viable synthetic intermediates whose applications [99.100] extend to a wide variety of carbocyclic and heterocyclic systems. However, advances in the synthesis of cyclopropenes, particularly through Rh(II) carboxylate—catalyzed decomposition of diazo esters in the presence of alkynes [100-102], has made available an array of stable 3-cyclopropenecarboxylate esters. Previously, copper catalysts provided low to moderate yields of cyclopropenes in reactions of diazo esters with disubstituted acetylenes [103], but the higher temperatures required for these carbenoid reactions often led to thermal or catalytic ring opening and products derived from vinylcarbene intermediates (104-107). 

In a similar manner, 3,3-disubstituted l,2-bis(trimethylsilyl)cyclopropenes rearrange to l,l-bis(trimethylsilyl)allenes, most likely by 1,2-silyl shift of primarily formed (1-silylvinyl)silylcarbenes. According to ab initio calculations, this reaction pathway is energetically more favorable than those including a 2,2-disilylcyclopropylidene or a 2,3-disilylpropylidene90b. 

The mechanism of the cycloaddition of singlet dibromocarbene to formaldehyde was studied using DFT at the B3LYP/6-31G level of theory 47 The energy barrier is estimated as 13.7 kJ mol-1. Reaction paths for the addition of dichlorocarbene to 1,2-disubstituted cyclopropenes were studied using the same level of theory as above.48 The addition gives 1,3-dienes or bicyclobutanes and was predicted to be concerted following an asymmetric approach. 

Dirhodium(II) tetrakis(carboxamides), constructed with chiral 2-pyrroli-done-5-carboxylate esters so that the two nitrogen donor atoms on each rhodium are in a cis arrangement, represent a new class of chiral catalysts with broad applicability to enantioselective metal carbene transformations. Enantiomeric excesses greater than 90% have been achieved in intramolecular cyclopropanation reactions of allyl diazoacetates. In intermolecular cyclopropanation reactions with monosubsti-tuted olefins, the cis-disubstituted cyclopropane is formed with a higher enantiomeric excess than the trans isomer, and for cyclopropenation of 1-alkynes extraordinary selectivity has been achieved. Carbon-hydro-gen insertion reactions of diazoacetate esters that result in substituted y-butyrolactones occur in high yield and with enantiomeric excess as high as 90% with the use of these catalysts. Their design affords stabilization of the intermediate metal carbene and orientation of the carbene substituents for selectivity enhancement. 

The ring opening of cyclopropenes may also be induced by metal salts or complxes. 3,3-Dimethylcyclopropene is converted to adducts (192) by treatment with Ni(COD)2 in the presence of electron poor alkenes with diethylmaleate the reaction proceeds with predominant retention of stereochemistry4,135. Other 3,3-disubstituted compounds are converted to adducts in good yield by reaction with (EtO)3P CuCl in the presence of alkenes at —40 to 20 °C. In the absence of a trap, a triene (193) is isolated103 ... 

Ring opening of 1,3- and 1,2-disubstituted cyclopropenes has also been examined. The ester (194) rearranges on heating to 98 °C in the presence of copper to give furan (195) the less substituted cyclopropene single bond appears to be cleaved to produce a carbene-metal derivative, which cyclises to the ester group 136). A similar photochemical transformation of a cyclopropene-3-ester to a fiiran has already been described 115). 

Lithium aluminium hydride reduction of 1,2-disubstituted cyclopropene-3-carboxy-lates occurs initially at the ester group, but with additional reagent good yields of cis-1,2-disubstituted-rranj-3-methanols are obtained 176). The reduction of the double bond is regioselective, leading to the more stable carbanion, and the attack of the hydride ion exclusively cis to the 3-substituent may be explained in terms of initial formation of an alkoxyaluminium complex followed by intramolecular hydride transfer 176). In the case of cyclopropene-1-carboxylates, direct reduction to the saturated alcohol occurs thus (253) is converted to the rranj-alcohol177) ... 

The dehydrohalogenation of a monobromo- or monochlorocyclopropane provides one of the simplest routes to a range of cyclopropeneslb. For 3,3-disubstituted cyclopropanes carrying alkyl or aryl groups, the reaction is normally achieved using potassium /-butox-ide or potassium hydroxide in DMSO and in some cases the cyclopropene distils directly from the reaction mixture (Table 1). 

It is noticeable that all the above examples do not have alkyl substituents at C-l or C-2, and that they are generally 3,3-disubstituted. The reason for this is often that the product cyclopropenes in other cases either react further, e.g. by migration of the double bond induced by base9, or, in the case of 1-halo-l-alkylcyclopropanes, eliminate directly to produce the less strained methylenecyclopropane22 ... 

Without question, the most important developments in this field over the past 10 years have been in the area of enantioselective hydroborations. New chiral catalyst systems are typically tested in hydroborations of vinyl arenes, as reactions using HBcat and a cationic rhodium catalyst are well known to give selective formation of the unusual branched isomer. In related studies, enantiopure 2,2-disubstituted cyclopropyl boronates were easily prepared via the catalytic asymmetric hydroboration of 3,3-disubstituted cyclopropenes using a number of chiral neutral rhodium complexes (equation 13). Directing groups, such as esters and alkoxymethyl substituents, were necessary for achieving... 

Disubstituted cyelopropenes. The McMurry coupling reaction is convenient for preparation of 3,3-disubstituted cyclopropenes of type 3 and 4, even, though these products are considerably strained (equation I). 

A little-used route to stereoselectively labeled cyclopropanes is nucleophilic addition to the corresponding cyclopropene. Access to both labeled and unlabeled cyclopropenes from the corresponding 1-alkynes allows preparation of both diastereomers of the labeled product. This route is one of the few that would allow easy preparation of a 1,1-disubstituted-cyclopropane-2-d. Cyclopropanation of the corresponding alkene would in principle achieve the same goal but preparation of such alkenes with a label in a defined stereochemical position is not easy. An example of the approach is shown in Figure 10. ... 

Ionic additions which transform cyclopropenes into cyclopropanes are well known. The electrophilic addition of sulphenyl halides proceeds by a two-step mechanism to give trans-disubstituted products but with little regioselectivity. Cyclic sulphonium ion intermediates are probably involved as illustrated for 1-methylcyclopropene. Electrophilic... 

Cyclopropenyl cations can be reacted with Grignard reagents or Uthium alkyls to yield cyclopropenes (equation 19). The disubstituted cyclopropenyl salts... 

In most cases, cyclopropene and its derivatives are easily prepared l5>. Especially the 3,3-disubstituted cyclopropenes can be obtained on a multigram scale in a two-step process 24-26) with overall yields as high as 80% (Eq. 1)... 

Disubstituted cyclopropenes do not react in the above sence. 1,2-dimethyl-cyclopropene polymerizes at 0 °C in the presence of [(T)3-C3H5)PdCl]2 30). 1,2-Diphenylcyclopropene cyclodimerizes nearly quantitatively in the presence of Pd(dba)2 or Pd(r)5-C5H5)(r 3-C3H5) to yield 1,2,4,5-tetraphenyl-cyclohexa-1,4-diene 72) (see p. 96). 

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