Cyclopropane derivatives transfer reactions

Epoxidation of aldehydes and ketones is the most profound utility of the Corey-Chaykovsky reaction. As noted in section 1.1.1, for an a,P-unsaturated carbonyl compound, 1 adds preferentially to the olefin to provide the cyclopropane derivative. On the other hand, the more reactive 2 generally undergoes the methylene transfer to the carbonyl, giving rise to the corresponding epoxide. For instance, treatment of P-ionone (26) with 2, derived from trimethylsulfonium chloride and NaOH in the presence of a phase-transfer catalyst Et4BnNCl, gave rise to vinyl epoxide 27 exclusively. ... 

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... 

In a rather remarkable reaction, methylene groups activated by two electron-withdrawing substituents react with non-activated alkenes under soliddiquid phase-transfer conditions in the presence of a molar equivalent of iodine to yield cyclopropane derivatives (Scheme 6.29) [62, 63], The reaction fails, when the catalyst is omitted or if iodine is replaced by bromine or chlorine. The intermediate iodomethylene systems are unstable in the absence of the reactive alkene and dimerize to produce, for example, ethane-1,1,2,2-tetracarboxylie esters and ethene-1,1,2,2-tetracarboxy lie esters. 

In qualitative terms, the rearrangement reaction is considerably more efficient for the oxime acetate 107b than for the oxime ether 107a. As a result, the photochemical reactivity of the oxime acetates 109 and 110 was probed. Irradiation of 109 for 3 hr, under the same conditions used for 107, affords the cyclopropane 111 (25%) as a 1 2 mixture of Z.E isomers. Likewise, DCA-sensitized irradiation of 110 for 1 hr yields the cyclopropane derivative 112 (16%) and the dihydroisoxazole 113 (18%). It is unclear at this point how 113 arises in the SET-sensitized reaction of 110. However, this cyclization process is similar to that observed in our studies of the DCA-sensitized reaction of the 7,8-unsaturated oximes 114, which affords the 5,6-dihydro-4//-l,2-oxazines 115 [68]. A possible mechanism to justify the formation of 113 could involve intramolecular electrophilic addition to the alkene unit in 116 of the oxygen from the oxime localized radical-cation, followed by transfer of an acyl cation to any of the radical-anions present in the reaction medium. 

Table 1. Electron Transfer Induced Reactions of Cyclopropane Derivatives... 

Carbenes and substituted carbenes add to double bonds to give cyclopropane derivatives (1 + 2 cycloaddition).1008 Many derivatives of carbene, e.g., PhCH, ROCH,1009 Me2C=C, C(CN)2, have been added to double bonds, but the reaction is most often performed with CH2 itself, with halo and dihalocarbenes,1010 and with carbalkoxycarbenes1011 (generated from diazoacetic esters). Alkylcarbenes HCR have been added to olefins,1012 but more often these rearrange to give olefins (p. 201). The carbene can be generated in any of the ways normally used (p. 198). However, most reactions in which a cyclopropane is formed by treatment of an olefin with a carbene precursor do not actually involve free carbene intermediates. In some cases it is certain that free carbenes are not involved, and in other cases there is doubt. Because of this, the term carbene transfer is often used to cover all reactions in which a double bond is converted to a cyclopropane, whether a carbene or a carbenoid (p. 199) is actually involved. 

Double-bond compounds that undergo the Michael reaction (5-17) can be converted to cyclopropane derivatives with sulfur ylides.1068 Among the most common of these is di-methyloxosulfonium methylide (108),l,l6, which is widely used to transfer CH2 to activated... 

In a long-term research project, Hossain and coworkers investigated the usefulness of the CpFe(CO)2+ fragment [35-38] in the cydopropanation reaction of alkenes by a carbene transfer utilizing diazo esters as the carbene source (Scheme 9.17). The cydopropanation products of styrene derivatives could be obtained in good yields of up to 80% and excellent cis selectivity by using an excess of the alkene, whereas the cydopropanation of aliphatic alkenes was less effective, yielding the desired cyclopropane derivative in up to 51% yield. 

The separated diastereoisomers 4a and 4b, and also the optically active derivatives 5, with Br instead of Cl, have been used as methylene-transfer reagents for the preparation of cyclopropanes in the reaction with trans-j8-methylstyrene (30, 31). The optical yields obtained (9-38%) are much... 

Some substituted cyclopropanes have been shown to undergo nucleophilic addition of suitable solvents (CH3OH) [231]. For example, the electron transfer reaction of phenylcyclopropane (47, R = H) with p-dicyanobenzene resulted in a ring-opened ether (48), formed by anfi-Markovnikov addition. More recently, the reaction of a 2,3-dimethyl derivative (47, R = CH3) was shown to occur with essentially complete inversion of configuration at carbon, suggesting a nucleophilic cleavage of the one-electron bond [233]. This result is significant, since it requires an intermediate with the unperturbed stereochemistry of the parent molecule. 

Several iodonium ylides, thermally or photochemically, transferred their carbene moiety to alkenes which were converted into cyclopropane derivatives. The thermal decomposition of ylides was usually catalysed by copper or rhodium salts and was most efficient in intramolecular cyclopropanation. Reactions of PhI=C(C02Me)2 with styrenes, allylbenzene and phenylacetylene have established the intermediacy of carbenes in the presence of a chiral catalyst, intramolecular cyclopropanation resulted in the preparation of a product in 67% enantiomeric excess [12]. 

Treatment of diethyl malonate and related compounds with 1,2-dihaloethane in the presence of base constitutes a classical method of cyclopropane synthesis. The reaction can be conveniently carried out under PTC conditions. An improved method utilizing solid-liquid phase transfer catalysis has been reported The reaction of dimethyl or diethyl malonate with 1,2-dibromoalkanes except for 1,2-dibromethane tends to give only low yields of 2-alkylcyclopropane-l, 1-dicarboxylic esters. By the use of di-/ r/-butyl malonate, their preparations in satisfactory yields are realized (equation 134). The 2-alkylcyclopropane derivatives are also obtained from the reaction of dimethyl malonate and cyclic sulfates derived from alkane-1,2-diols (equation 135) Asynunetric synthesis... 

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). 

Among the simple cycloalkanes, we first discuss electron transfer from the three-to eight-membered cycloalkane prototypes to electron holes generated by radiolysis in different matrices, giving rise to the simple cycloalkane radical cations. Because of the significant interest they have attracted, the electron-transfer reactions of cyclopropane and, to a lesser extent, cyclobutane derivatives will be treated separately. Finally, electron transfer from some bicyclic hydrocarbons and the resulting radical cations will be discussed in a separate section (Section 2.4). 

Having discussed the electron-transfer reactions of cyclopropane derivatives in some detail, we only touch briefly on the related reactions of the larger ring systems. Cyclobutane, cyclohexane, and cyclooctane have degenerate HOMOs (Section 2.3.1) thus, their radical cations are Jahn-Teller active. It is reasonable to expect that suitable substitution will lift the degeneracy and favor one radical cation structure over the other. Qualitative predictions of the preferred structure are readily derived. 

Hi. MIRC reactions mth ylides. Numerous cyclopropane derivatives have been synthesized via methylene transfer generated from sulphur ylides, such as dimethylsulpho-xonium methylide, to electron-deficient alkenes. This is shown in the examples in... 

The third returns the reader to chemi-ionization of cyclopropane derivatives with excited state electron acceptors. In the particular, it has been observed that oxidation of l,6-dimethylbicyclo[4.1.0]hept-3-ene (46) and [4.4.l]propella-2,6-diene (47) result in 2,6-dimethylcycloheptatriene (48) and l,6-methano[10]annulene (49) (equations 28 and 29 respectively). The former compound is conceptually the deprotonation product of the dication wherein the C-C bond between the bridgehead carbons has been totally depleted of electrons. In this case, however, the dication is not expected to be as stable as in the above pyramidal or cyclobutadiene cases and indeed, the product is seemingly not formed via the dication route. The methanoannulene likewise does not arise from the tetracation of its precursor. Rather, proton and electron transfer reactions involving merely radical cations proceed to remove hydrogens sequentially. 

In contrast to the wealth of chemistry reported for catalyzed reactions of diazocarbonyl compounds, there are fewer applications of diazomethane as a carbenoid precursor. Catalytic decomposition of diazomethane, CH2N2, has been reported as a general method for the methylenation of chemical compounds [12]. The efficacy of rhodium catalysts for mediating carbene transfer from diazoalkanes is poor. The preparative use of diazomethane in the synthesis of cyclopropane derivatives from olefins is mostly associated with the employment of palladium cat-... 

SET Induced Reactions - Further studies on ring opening reactions of 1,2-diarylcyclopropanes have focused on compounds (83) bearing an acetyl functional group.All of the cyclopropane derivatives studied show efficient cis.trans isomerism with reasonable quantum efficiency. The isomerism reaction involves an acetophenone-like triplet state with lifetimes shorter than 1 ns. The formation of ring opened products also takes place but inefficiently to give a mixture of the two alkenes (84) and (85). A study of the electron-transfer-induced photochemical reactivity of the cyclopropane (86) has been reported in the co-sensitisation system (biphenyl/phenanthrene/DCA). ... 

SET induced cyclisations have been carried out on a series of non-conjugated dienes one component of which is a silyl ether. Irradiation in acetonitrile of dienes such as (330, R = H) using DCA as the electron accepting sensitiser results in the formation of the radical-cation of the diene which on cyclisation affords the cyclic ketone (331) in 25% yield. The reaction is solvent sensitive and in a mixture of acetonitrile/propan-2-ol yields three products which are identified as (331, 30%) and two minor products (332, 11%) and (333, 9%). The reaction is suggested to have some considerable synthetic potential and the effect of chain length and substituents on the reaction has been evaluated. Thus (334) is converted into (335, 11%) while (330, R = Me) affords an isomeric mixture of products (336). Other studies with silyl ether derivatives have examined the electron transfer-induced ring opening processes encountered with the cyclopropane derivatives (337). ... 

The reaction of allyl alcohol with dichlorocarbene, generated from bromodichloro-methyl(phenyl)mercury/heat or chloroform/base/phase-transfer catalyst, does not afford the corresponding cyclopropane derivative. In the first case, allyl chloride, allyl formate and chloroform were formed and in the second case, tris(allyloxy)ethane (20%), l,l-dichloro-2-... 

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