Cyclopropanation tandem with Cope

As mentioned, rhodium-catalyzed cyclopropanation reaction of diazoketones is quite useful. As we saw in Section 11.12.C, Davies used a carbene insertion reaction in tandem with a Cope rearrangement to prepare... 

A stereoselective convergent synthesis of hydroazulenes 538 was also based on a tandem intermolecular cyclopropanation-Cope rearrangement sequence with predictable stereocontrol (equation 211)262. 

A method for highly efficient asymmetric cyclopropanation with control of both relative and absolute stereochemistry uses vinyldiazomethanes and inexpensive a-hydroxy esters as chiral auxiliaries263. This method was also applied for stereoselective preparation of dihydroazulenes. A further improvement of this approach involves an enantioselective construction of seven-membered carbocycles (540) by incorporating an initial asymmetric cyclopropanation step into the tandem cyclopropanation-Cope rearrangement process using rhodium(II)-(5 )-N-[p-(tert-butyl)phenylsulfonyl]prolinate [RhjtS — TBSP)4] 539 as a chiral catalyst (equation 212)264. 

The reaction of vinylcarbenoids with allylic C-H bonds leads to a remarkable transformation, a combined C-H insertion/Cope rearrangement, which is reminiscent of the tandem cyclopropanation/Cope rearrangement of vinylcarbenoids. An interesting application of this chemistry is the asymmetric synthesis of the antidepressant (-i-)-ser-traline 191 (Scheme 14.26) [134]. The Rh2(S-DOSP)4-catalyzed reaction of the vinyldia-zoacetate 189 with 1,3-cyclohexadiene generates the 1,4-cyclohexadiene 190 in 99% enantiomeric excess. The further conversion of 190 to (-t)-sertraline 191 is then achieved using conventional synthetic transformations. 

The tandem cyclopropanation/Cope rearrangement sequence between metal-stabilized vinylcarbenoids and dienes is more widely applicable, since this method allows cyclopropanes with a wide range of substitution patterns to be synthesized, and the carbenoids are readily prepared by heating a vinyldiazomethane in the presence of a metal salt829,... 

The tandem cyclopropanation/Cope rearrangement sequence is also applicable to the synthesis of cycloheptatriene derivatives by using dienes with a potential leaving group, e.g., 23f and 23g824. 

Instead of dienes, aromatic substrates can also participate in tandem cyclopropanation/Cope rearrangement sequences893 894. Rhodium(II) trifluoroacetate catalyzed decomposition of 17 affords the unstable bicyclo[3.2.2] compound 149 in 29% yield893. The reactions of anisol and 1-methoxynaphthalene with 17 show that in the case of electron-rich aromatics side reactions (alkylation reactions) can compete with cyclopropanation reactions due to dipolar intermediates and products 150 and 151, respectively, are formed893. 

This method of diastereoselective cyclopropanation can also be used with reasonable success for the enantioselective entry to tropanes by a tandem cyclopropanation Cope rearrangement of the 2-diazobut-3-enoate with the (i )-pan-tolactone auxiliary group in the presence of N-( err-butoxycarbonyl)pyrrole (8.185). The product 8.186 was obtained by Davies and Huby (1992) with 69% ee. It can be transferred in three steps into 8-azabicyclo[3.2.1]octane-2-carboxylates (8.187), which are the parent compounds for the corresponding 3-aryl derivatives. The latter are valuable probes for studying the neurochemistry of cocain abuse (Carroll et al., 1992 Lewin et al., 1992 Abraham et al., 1992). 

To avoid the formation of alkylated products, the reaction was repeated with iV-acylated pyrroles, such that the pyrrole ring would be less electron-rich and less prone to rearomatize. Rhodium(II) acetate catalyzed decomposition of the vinyldiazomethane 4 in the presence of A-carbomethoxy pyrrole results in the formation of the [3+4] annulation product (entry 1, Table 12), and this reaction is applicable to a range of vinylcarbenoid derivatives. The tropanes are formed as the endo isomers, which is the expected stereochemistry for the tandem cyclopropanation/Cope rearrangement sequence. 

Even [3-1-2] cycloadditions occur when cyclopropyl ketones are treated with (1) under photolytic or Lewis acid conditions to produce cyclopentane systems. Cyclopropanations of (1) are well known, in all cases adding to the more electron-rich sUy-loxy alkene. The vinylcyclopropanol silyl ethers can be converted into a number of different products, e.g. cyclopentanones, 2-methylcyclobutanones, vinyl ketones, and -alkoxy ketones (eq 10). One clever use of (1) in synthesis is the tandem [2 + 21-Cope process which converts (34) into (35) (eq 11). ... 

Stephenson and Tucker discovered an approach to fused 3-pyrrolin-2-ones via a tandem Ir-mediated radical cyclization and Cope rearrangement (Scheme 36 20110L5468). Treatment of cyclopropane-substituted propar-gylamide 170 with an iridium reagent and triethylamine led to the formation of fused 3-pyrrohn-2-one 172. The reaction manifold that explains the outcome of the reaction includes a radical cyclization to the spirocyclic intermediate 171, Cope rearrangement and re-aromatization. 

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