Alkenes carbene generation

Reactions involving free carbenes are very exothermic since two new theoretical treatment of the addition of singlet methylene to ethylene suggests that there is no activation barrier.168 The addition of carbenes to alkenes is an important method for synthesis of many types of cyclopropanes and several of the methods for carbene generation listed in Scheme 10.8 have been adapted for use in synthesis. Scheme 10.9, at the end of this section, gives a number of specific examples. 

The addition of dichlorocarbene, generated from chloroform, to alkenes gives dichlorocyclopropanes. The procedures based on lithiated halogen compounds have been less generally used in synthesis. Section D of Scheme 10.9 gives a few examples of addition reactions of carbenes generated by a-elimination. 

The most common rearrangement reaction of alkyl carbenes is the shift of hydrogen, generating an alkene. This mode of stabilization predominates to the exclusion of most intermolecular reactions of aliphatic carbenes and often competes with intramolecular insertion reactions. For example, the carbene generated by decomposition of the tosylhydrazone of 2-methylcyclohexanone gives mainly 1- and 3-methylcyclohexene rather than the intramolecular insertion product. 

Miscellaneous. An interesting synthesis of 1,1-difluoro-l-alkenes from ylides and chlorodifluoromethane has been described.47 The ylide acts both as a carbene generator and trapping agent (Scheme 11). 

The reactivity of heterocyclic systems with carbenes, generated under phase-transfer catalytic conditions, has been reviewed for the period up to 1983 [1]. Most unsaturated non-heteroaromatic systems react with carbenes in the manner expected of alkenes, amines, amides, ketones, etc. (see Sections 7.3,7.5 and 7.6). 

The non-nitrogenous carbene precursor (102) was used for the photochemical generation of the carbene (103) without complications due to reactions of diazirine or diazo species. In the presence of alkenes, carbene (103) gave rise to cyclopropanes and in the absence of alkenes was proposed to undergo [1,2]-C shift to form (104), which suffered retro-Diels-Alder reaction to give a triene. 

Cycloalkyl(silyl)carbenes with an a-C—H bond have not yet been investigated systematically. When cyclohexyl(trimethylsilyl)carbene was generated by thermal a-elimination from cyclohexyl-bis(trimethylsilyl)methanol at 500 °C, only the (1,2) hydride shift took place, whereas cyclopentyl(trimethylsilyl)carbene, generated analogously, gave both the endocyclic alkene and the 1,3-C,H insertion product85,86 (equation 47). 

Metathesis of alkene 6 to give the new alkenes 11 and 15 is explanined by the following mechanism. The first step is [2+2] cycloaddition between metal carbene 5 and alkene 6 to generate the metallacyclobutane 7 as an intermediate. The real catalyst 8 is generated by retrocycloaddition of the metallacyclobutane 7. Reaction of 8 with alkene 6 generates the metallacyclobutanes 9 and 10 as intermediates. The intermediate 10 is a nonproductive intermediate, which reproduces 6 and 8, while 9 is a productive intermediate and yields the new alkene 11 and the real catalyst 12. Cycloaddition of 12 to alkene 6 produces the productive intermediate 14, from which the new alkene 15 and the active catalytic species 8 are formed. The intermediate 13 is a nonproductive one. 

Despite the expected enhanced reactivity of trifluoromethyl-substituted carbenes as electrophilic species, yields in their [2+ l]-cycloaddition reactions with alkenes are highly dependent on the nature of the second substituent of the carbene. Furthermore, the method of carbene generation has a large influence on carbene reactivity. 

Currently accepted mechanism of the Wittig reaction of aldehydes with non-stabilized ylides involves the formation of oxaphosphetanes through a [2-I-2]-cycloaddition-like reaction . The oxaphosphetanes are thermally unstable and collapse to alkene and phosphine oxide below room temperature. Under salt-free conditions there is no formation of betaine intermediates. The salt-free ylides can be prepared by the reaction of phosphines with carbenes generated in situ. Vedejs etal proposed a puckered 4-centre cyclic transition state I for sy -oxaphosphetane and planar structure J for anff-oxaphosphetane. In general, the flnfi-oxaphosphetane J is more stable than the syn-oxaphosphetane I, and under equilibrium conditions (when stabilized ylides are used) the E-alkene product is favoured (Scheme 4.24). However, kinetic control conditions, which appear to dominate when non-stabilized ylides are used, would lead to Z-alkene. 

A number of different bases, usually KOH or NaOH [45] with a phase-transfer catalyst [46] or crown ether [47], have been used for generating carbenes which can be trapped by nucleophilic species such as alkoxides, thiolates and, more usually, alkenes. This approach to carbene generation is still popular due to the low cost and the ease of handling the reagents used some examples are given in Figure 6.34 [45, 46, 48]. 

The second cyclopropanation occurs at the only remaining alkene with a carbene generated a diazoester. The stereoselectivity comes from attack on the opposite side of the ring to the r membered ring already present. 

A chromium carbene generated in situ firom C1CI2 and a dihaloalkyl daivative, has been utilized to form a variety of ( )-disubstituted alkene compounds (480). The general reaction is summarized in equation (110). Alkenyl halides, sulfides and silanes, as well as dialkyl-substituted alkenes, have been synthesized by this method. 

Coupling of a Fischer carbene complex with an alkene can generate a vinylcarbene intermediate 12 via an insertion-rearrangement reaction, which can then further react with a double bond. For intramolecular reactions of tethered enynes 10, the products formed are bicyclic cyclopropanes 14 intermolecular reactions lead to cycloalkenylcyclopropanes. 

Table 1. Arylcyclopropanes from Alkenes and Carbenes, Generated from Arylhalomethane or Aryldihalomethane with Organolithium Compounds... 

Whether a cyclopropanation reaction is stereospecific or not, is often tested with (Z)- and ( )-but-2-ene, but of course, this problem also holds for other diastereomeric alkenes. The following carbenes, generated by direct irradiation of the corresponding a-diazocarbonyl compound, undergo stereospecific or highly stereoselective cycloaddition to (Z)- and ( )-but-2-ene methoxycarbonylcarbene, chloro-, bromo- and iodo(ethoxycarbonyl)carbene, ° eth-oxycarbonyl(trimethylsilyl)carbene, ethoxycarbonyl(trimethylgermyl)carbene, ethoxy-... 

Cyclopropanedicarbonitriles were formed in moderate to good yields by the reaction of dicyanocarbene with different alkenes (Table 2). The carbene, generated by either thermolysis or photolysis of diazomalononitrile (see Houben-Weyl, Vol. E19b, p 1203), reacts with essentially any of the usual solvents. Therefore, the respective alkene was used as the solvent. In the case of gaseous substrates, the reaction was carried out in a steel cylinder under high pressure. Insertion of the carbene into available allylic C-H bonds of the substrate occurs as a minor side reaction. 

Addition of chloro(phenyl)carbene, generated from diazirine, to alkenes is stereospecific, yet diethyl (Z)-but-2-enedioate isomerized partially to give a mixture of stereoisomeric cyclopropanes(for a more detailed discussion see Houben-Weyl, Vol. E19b, p995). 

Historically, potassium /er/-butoxide was the first base used for the preparation of 1,1-dibromo-cyclopropanes from bromoform and an alkene. Since generation and cycloaddition of dibromo-carbene to alkenes proceeds rapidly, this method is still in laboratory practice. 

Table 37. l-Alkoxy(or -Aryloxy)-l-halocyclopropanes from Carbenes, Generated from Diazirines, and Alkenes... 

Methoxy-2,2,3,3-tetramethyl-l-phenylcyclopropane [the addition product of methoxy-(phenyl)carbene, generated thermally or photolytically from 3-methoxy-3-phenyl-3//-diazirine, to 2,3-dimethylbut-2-ene] can be prepared in a low yield (in addition to a significant amount of azine) provided that the freshly purified alkene is used. The use of the commercial alkene leads exclusively to the formation of peroxyacetal, the product of the carbene reaction with 3-hydroperoxy-2,3-dimethylbut-l-ene which in turn results from oxidation of 2,3-dimethylbut-... 

The reaction of alkenes with bis(phenylsulfonyl)carbene generated from the iodonium ylide photolytically (400-W low-pressure mercury lamp), or thermally [in the presence of bis(acetylacetonato)copper(ll), in chloroform or benzene], apart from the expected cyclopropanes 4, always affords bis(phenylsulfonyl)methane and phenyl benzenethiosulfonate. °... 

Addition versus rearrangement of chloro(methyl)-, chloro(ethyl)-, benzyl(chloro)-, chlo-ro(methoxymethyl)- and chloro(isopropyl)carbene generated by photolytic or thermal decomposition of 3-alkyl-3-chloro-3//-diazirines has also been investigated.81 However, it is known that chloro(isopropyl)- or ie/7-butylchlorocarbene does not undergo addition to 2,3-dimethyl-but-2-ene, which is used as a carbene trap. Photolysis or thermolysis of 3-arylmethyl-3-chloro-3//-diazirines in the presence of an alkene has also been studied extensively.84 Addition of the ambiphilic benzylchlorocarbene82 to an alkene to give 1-benzyl-1-chlorocyclopropanes is usually accompanied by its rearrangement to co-chlorostyrene (1,2-hydride shift, for details see ref 83). This isomerization was seriously impeded when the decomposition of 3-benzyl-3-chloro-3//-diazirines was performed in the presence of an alkene,85 with 2,3-dimethylbut-2-ene only traces of co-chlorostyrene were observed.81,86 The results of reactions of benzylchlorocar-benes with some alkenes are collected in Table 6.85... 

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