Cyclopropyl derivatives ring opening

Much of the initial work on the solvolyses of non-ring-fused cyclopropyl derivatives was carried out to determine the effects of the nature and stereochemistry of substituents on their rates of reaction and direction of cyclopropyl-allyl ring-opening. The reviews by DePuy , Schollkopf, Wendisch and especially by Aksenov, and coworkers summarize this early work which agreed with the theoretical predictions of Woodward and Hoffmann . Examples of some of the kinetic results are shown in Scheme 1 ... 

Deuteration by cyclopropyl ring opening Ijas been used also for the stmcture elucidation of a photolysis product (241) of cholesta-3,5-diene. This bicyclobutyl derivative is very reactive and readily hydrolyzed by aqueous dioxane. When the ring opening is carried out in the presence of deuterium oxide, a deuterium is incorporated in the 4y -position of the resulting 6jS-hydroxy-3a,5a-cyclocholestane (242). ... 

Reaction of the cyclopropyl-substituted pivalate (25) with dimethyl benzylidenema-lonate in the presence of a palladium catalyst gave a mixture of alkylidenecyclo-propane (26) and vinylcyclopropane (27). The ratio of these two adducts is found to be quite sensitive to the choice of ligand and solvent. While triisopropyl phosphite favors the formation of the methylenecyclopropane (26), this selectivity is completely reversed with the use of the bidentate phosphite ligand dptp (12). Interestingly there was no evidence for any products that would have derived from the ring opening of the cyclopropyl-TMM intermediate (Scheme 2.8) [18]. 

Ring opening due to intramolecular hydrogen abstraction has been demonstrated for cyclopropyl ketone derivatives 1035 ... 

The discovery of carbene and carbenoid additions to olefins was the major breakthrough that initiated the tapping of this structural resource for synthetic purposes. Even so, designed applications of cyclopropane chemistry in total syntheses remain limited. Most revolve around electrophilic type reactions such as acid induced ring opening or solvolysis of cyclopropyl carbinyl alcohol derivatives. One notable application apart from these electrophilic reactions is the excellent synthesis of allenes from dibromocyclopropanes 2). 

The cuprate derived from the cis isomer of this reagent undergoes conjugate addition with cyclohexenone with unusually high diastereoselectivity (5 1, Eq. 23)24). In this case, electrophilically initiated ring opening with mercuric acetate chemo-selectively attacks the sterically least hindered cyclopropyl bond to give a branched product 7. Reductive work-up produces 8 in which the stereochemistry of the... 

Other factors which affect the case of electrocyclic ring opening include the nature of substituents which can stabilize or destabilize the development of possible charge and the release of strain in small cyclic systems. Thus different stereochemistries have been observed in the ring opening of cyclopropyl derivatives. All cis derivatives generate an all-cis allyl cation but the anti derivatives will form the all trans cation. 

Sulfuryl chloride isocyanate with 1 gave the expected )5-lactam 177 only as a minor product, the principal product being the y-lactam derivative 178. It is reasonable to assume that the 1,4-zwitterionic intermediate 176 is responsible for the formation of 177 and 178 (Scheme 39) [104,130]. Sulfonation of 1 with SO3 also proceeds with ring opening of one of the cyclopropyl groups to give quantitatively the spirocyclopropane-y-sultone 179 (Scheme 39) [76,132]. 

Miiller has used cyclopropyl clock experiments to test for the possible intermediacy of radical species prior to C-N bond formation (Scheme 17.7). The diphenylcyclopro-pane derivative 3, which fragments at a rate of 2x10 ° s , affords nosylated amine 4 no product from ring opening is observed. Such a result mitigates the viability of a productive stepwise oxidation process, though it is important to note that sulfonamide 4 is formed in only 5% yield. 

Perhydrofuro[2,3- ]pyrans can be synthesized via a ring-opening reaction of sugar derivatives containing a 1,2-cyclopropyl group <20070L1331>. 

Solvolysis of cyclopropyl derivatives leads directly to the allyl cation the ring opening is disrotatory as predicted. The most direct demonstration is the transformation of the 2,3-dimethyl-1-chlorocyclopropanes at — 100°C in strong acid... 

The unusual structure of cycloclavine as the first known pentacyclic clavine alkaloid was derived from physical data (mass spectrum M+ 238 NMR signals of the cyclopropyl methylene group = 0.46 and 1.60) and some chemical transformations (hydrogenation, reductive ring opening, and quaternization). The remaining details of its constitution were finally determined by an X-ray analysis of the metho-bromide. Thus it was shown that the chirality of 11 is 5B, 8R, 10R. 

It is known that ketones, which are capable of aldol condensation, react with trichlorogermane in a particular way. First, an aldol condensation occurs and then trichlorogermane adds to the C=C double bond of the product of condensation74. However, in the case of methyl cyclopropyl ketone, the condensation does not occur and a single isomer derived from the ring opening reaction is formed with 65% yield (equation 28)75. 

The only products of solvolysis of the tosylate 60 from the 1 -ethynylcyclopropanol 9, with R = CH3 was the allyl derivatives 61 (R = CH3) from the ring opening of the cyclopropane ring, while unrearranged cyclopropanols (or derivatives) 62 were obtained in high yields when R = cyclopropyl or aryl, Eq. (18)13>. 

Similarly, carbinols 237 are converted to dienes 238 having two benzenethio substituents (Scheme 11)101). Here again starting materials are dichloro-cyclopropyl ketones 235 (cf. Scheme 5), which can be transformed to the desired dithioacetals 236 by treatment with sodium benzene thiolate. Cyclopropanes 236 are ring opened to P,y-unsaturated ketones 240, y-oxothioesters 241, or for R1 = H expanded to furan derivative 239102 t03>. 

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