Cyclopropane formation transfer

Without question, the most powerful method for cyclopropane formation by methylene transfer is the well-known Simmons-Smith reaction [6]. In 1958, Simmons and Smith reported that the action of a zinc-copper couple on diiodomethane generates a species that can transform a wide variety of alkenes into the corresponding cyclopropanes (Scheme 3.3) [7]. 

In order to rationalize the catalyst-dependent selectivity of cyclopropanation reaction with respect to the alkene, the ability of a transition metal for olefin coordination has been considered to be a key factor (see Sect. 2.2.1 and 2.2.2). It was proposed that palladium and certain copper catalysts promote cyclopropanation through intramolecular carbene transfer from a metal carbene to an alkene molecule coordinated to the same metal atom25,64. The preferential cyclopropanation of terminal olefins and the less hindered double bond in dienes spoke in favor of metal-olefin coordination. Furthermore, stable and metastable metal-carbene-olefin complexes are known, some of which undergo intramolecular cyclopropane formation, e.g. 426 - 427 415). 

Whereas step 1 is stoichiometric, steps 2 and 3 form a catalytic cycle involving the continuous generation of carbenium ions via hydride transfer from a new hydrocarbon molecule (step 3) and isomerization of the corresponding carbenium ion (step 2). This catalytic cycle is controlled by two kinetic and two thermodynamic parameters that can help orient the isomer distribution, depending on the reaction conditions. Step 2 is kinetically controlled by the relative rates of hydrogen shifts, alkyl shifts, and protonated cyclopropane formation, and it is thermodynamically controlled by the relative stabilities of the secondary and tertiary ions. (This area is thoroughly studied see Chapter 3.) Step 3, however, is kinetically controlled by the hydride transfer from excess of the starting hydrocarbon and by the relative thermodynamic stability of the various hydrocarbon isomers. 

The mechanism of the [3 + 2] cycloaddition is summarized in Scheme The first intermediate results from charge transfer interaction between the eli tronically excited aromatic compound at its singlet state S1 with the alkene w] leads to the formation of the exciplexes K. A more stable intermediate is generated by the formation of two C-C bonds, leading to the intermediates These intermediates have still singlet multiplicity and therefore possess zwii ionic mesomeric structures mainly of type M. In most cases and especially intramolecular reactions, chiral induction occurs during the formation of L. final products are then obtained by cyclopropane formation in the last step. 

The formation of norcaradiene derivatives with naphthalene [reaction (22)] lends some support to this scheme. This mechanism resembles a bimolecular two-step process suggested for the reaction of chloromethyl-aluminum compounds with olefins (199-201). On the other hand, a bimolecular one-step methylene transfer mechanism is generally accepted for the formation of cyclopropane derivatives by the reaction of halo-methylzinc compounds with olefins. This difference between the mechanism proposed for the cyclopropane formation from olefin and that for the ring expansion of aromatic compound may be ascribable to the difference in the stability of intermediates the benzenium ion (XXII) may be more stable than an alkylcarbonium ion (369). 

As already mentioned for rhodium carbene complexes, proof of the existence of electrophilic metal carbenoids relies on indirect evidence, and insight into the nature of intermediates is obtained mostly through reactivity-selectivity relationships and/or comparison with stable Fischer-type metal carbene complexes. A particularly puzzling point is the relevance of metallacyclobutanes as intermediates in cyclopropane formation. The subject is still a matter of debate in the literature. Even if some metallacyclobutanes have been shown to yield cyclopropanes by reductive elimination [15], the intermediacy of metallacyclobutanes in carbene transfer reactions is in most cases borne out neither by direct observation nor by clear-cut mechanistic studies and such a reaction pathway is probably not a general one. Formation of a metallacyclobu-tane requires coordination both of the olefin and of the carbene to the metal center. In many cases, all available evidence points to direct reaction of the metal carbenes with alkenes without prior olefin coordination. Further, it has been proposed that, at least in the context of rhodium carbenoid insertions into C-H bonds, partial release of free carbenes from metal carbene complexes occurs [16]. Of course this does not exclude the possibility that metallacyclobutanes play a pivotal role in some catalyst systems, especially in copper-and palladium-catalyzed reactions. 

The reactions of aryl-substituted carbenes are extensively covered in Houben-Weyl Vol. E 19b, pp 824-1021, where procedures for all typical carbene transfer methods are reported. The simple diastereoselectivity is highly dependent on the carbene source and the reaction conditions, as demonstrated by the additions of phenylcarbenoids, generated by different methods, to cyclohexene. The highest endo selectivity is obtained with the diiodo(phenyl)methane/diethylzinc reagent3. Other cyclic or acyclic olefins show a similar moderate to high preference for endo- or cw-cyclopropane formation. 

Our initial explanation of the negative activation energies postulated that the carbene-alkene additions involved the intermediate and reversible formation of loose carbene/alkene change-transfer complexes. The partitioning of these intermediates between cyclopropane formation and reversion to PhCCl and alkene would determine the observed rate constants and their temperature dependence. [95] However, although carbene-arene Jt complexes do appear to modulate the chemistry of some carbenes in solution, carbene-alkene complexes have not been supported by theoretical studies. [96]... 

A review of silver carbenoid reactions including the Wolff rearrangement, carbene-transfer reactions, aziridination, cyclopropanation, formation and reactions of... 

Loss of alkene stereochemistry upon cyclopropane formation occurs during the transfer of ethylidene from [(Cp)(CO)2pe=CHMe to a series of para-substituted styrenes to give cis- and trans-... 

Treatment of the carbene complex [Cr C(OMe)Ph (CO)6] with certain alkenes yields cyclopropanes by transfer of the carbene entity. The reaction of diethyl fumarate with (- )-(/ )-methyIphenylpropylphosphine(phenylmethoxycarbene)tetracarbonyl-chromium produces the optically active cyclopropane (19), the formation of which demonstrates that no free carbene is involved in the mechanism for the reaction. ... 

Intramolecular oxonium ylide formation is assumed to initialize the copper-catalyzed transformation of a, (3-epoxy diazomethyl ketones 341 to olefins 342 in the presence of an alcohol 333 . The reaction may be described as an intramolecular oxygen transfer from the epoxide ring to the carbenoid carbon atom, yielding a p,y-unsaturated a-ketoaldehyde which is then acetalized. A detailed reaction mechanism has been proposed. In some cases, the oxonium-ylide pathway gives rise to additional products when the reaction is catalyzed by copper powder. If, on the other hand, diazoketones of type 341 are heated in the presence of olefins (e.g. styrene, cyclohexene, cyclopen-tene, but not isopropenyl acetate or 2,3-dimethyl-2-butene) and palladium(II) acetate, intermolecular cyclopropanation rather than oxonium ylide derived chemistry takes place 334 ). 

The q1-coordinated carbene complexes 421 (R = Ph)411 and 422412) are rather stable thermally. As metal-free product of thermal decomposition [421 (R = Ph) 110 °C, 422 PPh3, 105 °C], one finds the formal carbene dimer, tetraphenylethylene, in both cases. Carbene transfer from 422 onto 1,1-diphenylethylene does not occur, however. Among all isolated carbene complexes, 422 may be considered the only connecting link between stoichiometric diazoalkane reactions and catalytic decomposition [except for the somewhat different results with rhodium(III) porphyrins, see above] 422 is obtained from diazodiphenylmethane and [Rh(CO)2Cl]2, which is also known to be an efficient catalyst for cyclopropanation and S-ylide formation with diazoesters 66). 

It has been widely accepted that the carbene-transfer reaction using a diazo compound and a transition metal complex proceeds via the corresponding metal carbenoid species. Nishiyama et al. characterized spectroscopically the structure of the carbenoid intermediate that underwent the desired cyclopropanation with high enantio- and diastereoselectivity, derived from (91).254,255 They also isolated a stable dicarbonylcarbene complex and demonstrated by X-ray analysis that the carbene moiety of the complex was almost parallel in the Cl—Ru—Cl plane and perpendicular to the pybox plane (vide infra).255 These results suggest that the rate-determining step of metal-catalyzed cyclopropanation is not carbenoid formation, but the carbene-transfer reaction.254... 

A different result was obtained in the cycloaddition to methylenecyclo-propanes 216-218 tearing alkoxycarbonyl substituents on the cyclopropyl ring. In this instance, 1,2,3-triazoles 220 isomeric with the triazolines 219 were formed in the reaction [57]. The formation of triazoles 220 is rationalised by the intermediate formation of triazolines 219, which are unstable under the reaction conditions and undergo a rearrangement to the aromatic triazoles via a hydrogen transfer that probably occurs with the assistance of the proximal ester carbonyl (Scheme 35). The formation of triazoles 220 also confirms the regio-chemistry of the cycloaddition for the methylene unsubstituted methylene-cyclopropanes, still leaving some doubt for the substituted ones 156 and 157. 

The formation of cyclopropanes from 7C-deficient alkenes via an initial Michael-type reaction followed by nucleophilic ring closure of the intermediate anion (Scheme 6.26, see also Section 7.3), is catalysed by the addition of quaternary ammonium phase-transfer catalysts [46,47] which affect the stereochemistry of the ring closure (see Chapter 12). For example, equal amounts of (4) and (5) (X1, X2 = CN) are produced in the presence of benzyltriethylammonium chloride, whereas compound (4) predominates in the absence of the catalyst. In contrast, a,p-unsatu-rated ketones or esters and a-chloroacetic esters [e.g. 48] produce the cyclopropanes (6) (Scheme 6.27) stereoselectively under phase-transfer catalysed conditions and in the absence of the catalyst. Phenyl vinyl sulphone reacts with a-chloroacetonitriles to give the non-cyclized Michael adducts (80%) to the almost complete exclusion of the cyclopropanes. 

The generation of the dichloromethane under phase-transfer conditions may be facilitated by the addition of a trace of ethanol. Alkoxide anions, generated under the basic conditions, are more readily transferred across the two-phase interface than are hydroxide ions (see Chapter 1). Although this process may result in the increased solvolysis of the chloroform, it also produces a higher concentration of the carbene in the organic phase and thereby increases the rate of formation of the cyclopropane derivatives from reactive alkenes. 

Diols generally react with dichlorocarbene to produce a mixture of alkenes and chlorinated cyclopropanes or chloroalkanes, depending on the reaction conditions whereas, under phase-transfer catalysed conditions, the major products are the alkenes and epoxides produced by ring closure of the initial adduct (Scheme 7.20) [14]. When an excess of chloroform is used, further reaction of the alkenes with dichlorocarbene produces the cycloadducts. In addition to the formation of the alkene and epoxide, 1,2-dihydroxycyclooctane yields cyclooctanone, via a 1,2-hydride shift within the intermediate carbenium ion. 

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