Intermediate cyclopropanes

The Simmons-Smith cyclopropanation method has also found application for the a-methylation of ketones via an intermediate cyclopropane. The starting ketone—e.g. cyclohexanone 9—is first converted into an enol ether 10. Cyclopropanation of 10 leads to an alkoxynorcarane 11, which on regioselective hydrolytic cleavage of the three-membered ring leads to the semiketal 12 as intermediate, and finally yields the a-methylated ketone 13 ... 

The work of Sharp and his many co-workers at Edinburgh cannot be underestimated. In a more recent communication they have extended the scope of his cyclisation of diene-conjugated nitrile ylides to triene homologues <96CC2739>. Thus cyclisation of the triene 21 afforded the cyclopropa[c]isoquinoline 22, which on heating gave a mixture of 23 and 24. The isomeric triene 25 also gave 24 as the sole product (Scheme 4). In this instance the intermediate cyclopropane could not be isolated. 

DIS(B)(42)1892]. Thermal decomposition in 2,3-dimethyl-2-butene gave a mixture of 144 and 145 [81DIS(B)(42)1892] (Scheme 39). Compound 145 might arise from attack of the carbene 139 (R = Ph) on the double bond of the 2,3-dimethyl-2-butene to give an intermediate cyclopropane... 

The power of chiral C2-symmetric bis(oxazolines) in cyclopropanation reactions has also been exhibited in total synthesis. One example is Corey and co-workers synthesis of sirenin 63 using bis(oxazoline) ligand 8 (Fig. 9.19). They showed that the intramolecular cyclopropanation of diazo derivative 61 proceeded in 77% yield and with 90% ee. Shibasaki and co-workers constructed prostratin 67 through the intermediate cyclopropane 66, also shown in Figure 9.19. Using bis(oxazoline) ligand 64 and copper(I) triflate-derived catalyst, compound 66 was prepared in 70% yield and 92% ee from diazo derivative 65. ... 

Cyclopropanation of the enol ether 159 and normal ring cleavage introduces a second methoxycarbonylmethyl group, but deprotonation of the intermediate cyclopropane 160 now occurs at the more acidic side chain CH2 and not at the cyclopropane core. Therefore a ring opening followed by elimination yields the electrondeficient diene 161 (Eq. 70) 61). 

The ability of a methanesulphonate substituent to function as a leaving group (compare equation 124, Section VI.E.2) in an intermediate cyclopropane permits transformation of a bicyclo[4.4,0]decene derivative into a compound with a hexahydroazulene skeleton having potential for sesquiterpene synthesis(equation 76). 

The reaction of brominated alkylidenemalononitriles (298) with sodium methoxide in methanol leads to A -pyrrolines (309) in a Thorpe-type reaction involving an addition of the anion 296 to the cyano function in the intermediate cyclopropane 299 (equation 95) . The acetals (308) can be isolated if the malononitriles are treated with pyridine-methanol. 

However, it is not clear if these products are derived from an 8 2 reaction or from a rearrangement of intermediate cyclopropanes . 

A particular rearrangement of an intermediate cyclopropane derivative 720 occurs when the methoxycycloheptatriene derivative 719 is transformed into a spiro compound (721) on treatment with dilute sulphuric acid (equation 252f. It should be pointed out that the... 

Other reversible ET-catalyzed stereoisomerizations of cyclopropanes have been observed with cjs-l-methyl-2-phenyl-, r-1-phenyl-l-methyl-c-2-methyl- and optically active l-methyl-2,2-diphenylcyclopropane (190, 191 and ( + )-(/ )-49, respectively) . Experimental evidence for the existence of intermediate cyclopropane radical anions like CIS- or trans-llH" (Scheme 18) has not been found in the course of these investigations. 

Both isomers of the intermediate cyclopropane were converted into product 16, the two undergoing a rapid equilibration. 

The product of thermal isomerization of this cyclopropane, dimethyl (l-naphthyl)malonate, was also formed (5-10%), together withtetramethyl2,3-benzo-ant -tricyclo[5.1.0.0 ]oct-2-ene-5,5,8,8-tetracarb-oxylate (5-15%) and dimethyl 377-benzocycloheptatriene-3,3-dicarboxylate (5-10%) which is likely to arise from an intermediate cyclopropane arising from carbene addition to the 2,3-bond of naphthalene. 

In case of the formation of 1, an intermediate cyclopropane was detected by NMR spectroscopy. 

The mechanism of this rearrangement has yet to be proved, though a free radical process with an intermediate cyclopropane-containing radical would fit the available data [36]. The conversion of the phenyllactoyl moiety of littorine into the tropoyl moiety of hyoscyamine or scopolamine involves a mutase reaction [37]. 

The anion radicals of the SET sensitizers, N-methylphthalimide, chloranil (CA), naphthoquinone, 2,3-dichloronaphthoqui-none, - and 9, lO-dicyanoanthracene (DCA) undergo similar nucleophilic additions to intermediate cyclopropane cation radicals in sensitized photoreactions of arylcyclopropanes. For instance, the CA-sensitized photoreaction of 9 in the presence of methanol gives the CA/methanol adduct 12. - Presumably, nucleophilic substitution of 9 by methanol initially takes place to form 11, to which CAH adds to form 12. The steady-state photolysis of a solution of 9, DCA, and Cu(BF4)2 in acetonitrile containing methanol or t-butanol gives 13 and 14, respectively. Similar photoreaction of 9 in acetonitrile containing methanol and t-butanol gives 15 and 16. Apparently, Cu oxidizes not only DCA but also radical 11. Under these sensitized conditions, the rate constants for the nucleophilic substitution,... 

Addition of carbenes to aromatic systems leads to ring-expanded products. Methylene itself, formed by photolysis of diazomethane, adds to benzene to form cycloheptatriene in 32% yield a small amount of toluene is also formed by an insertion reaction. The cycloheptatriene is formed by a Cope rearrangement of the intermediate cyclopropane (a norcaradiene). More satisfactory is the reaction of benzene with diazomethane in the presence of copper salts, such as copper(I) chloride, which gives cycloheptatriene in 85% yield (4.87). The reaction is general for aromatic systems, substituted benzenes giving mixtures of the corresponding substituted cycloheptatrienes. 

The biosynthesis of indolizomycin 297 has not been studied, but its structural similarity to cyclizidine 296 makes it probable that it has a similar biosynthesis. However, the branched four-carbon unit of 297 which replaces the cyclopropyl group of 296 cannot be directly produced by a polyketide route. By analogy with the biosynthesis of cyclizidine, it is conceivable that these four carbons are derived from two acetate units by a rearrangement involving an intermediate cyclopropane ring [295]. 

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