Cyclopropane derivatives ring-opening

The tail-to-tad coupling of two geranylgeranyl diphosphate units proceeds via a cyclopropane intermediate. Cleavage of the diphosphate from the primary cyclopropane derivative, ring-opening of the resulting cyclopropyhnethyl carbo-... 

With a,P unsaturated ketones the expected cyclopropanes could not be isolated, but acrylonitrile derivatives can also be used as acceptor olefins 40). They provide cyanocyclopropanes in good yield (entries 6, 7), which might be interesting precursors for other cyclopropanes or ring opened compounds because of the synthetic versatility of the nitrile group. 

Cyclopropanations by azo-extrusion of dihydro-pyrazoles may be accompanied by rearrangement of substituents. For instance, Hamaguchi and Nagai (1989) showed that, in 4-(arylseleno)- and 4-(arylthio)-4,5-dihydro-pyrazoles, these heteroaryl groups migrate into the 5-position with formation of cyclopropanes or ring opening to ethene derivatives. 

We envisioned that an alkynyl substituent on a cyclopropane could be complexed as a cobalt hexacarbonyl derivative [8], which would enable activation of the cyclopropane toward ring opening in order to undergo subsequent cycloadditions. This is explained by the ring-opening of a cobalt complexed cyclopropanediester I under the influence of a Lewis acid to form the Nicholas carbocation 2 as illustrated in Scheme 10.3. 

While generation of a Mn(V)oxo salen intermediate 8 as the active chiral oxidant is widely accepted, how the subsequent C-C bond forming events occur is the subject of some debate. The observation of frans-epoxide products from cw-olefins, as well as the observation that conjugated olefins work best support a stepwise intermediate in which a conjugated radical or cation intermediate is generated. The radical intermediate 9 is most favored based on better Hammett correlations obtained with o vs. o . " In addition, it was recently demonstrated that ring opening of vinyl cyclopropane substrates produced products that can only be derived from radical intermediates and not cationic intermediates. ... 

Radicals are known to open cyclopropane derivatives, although high dilution techniques are often required. The three-membered ring is opened as the new ring... 

Similar ring-opening reaction leading to a 4 1 mixture of 355 and 356 occurs when cyclopropane derivative 354 is treated at room temperature with PTAD. The products formed are not stable and only the products of their hydrolysis, 357 and 358, respectively, are obtained (Scheme 53) <1996JCM82>. 

Copper-catalyzed cyclopropanation of benzene and its derivatives by a diazoacetic ester yields a norcaradiene 230 which undergoes spontaneous ring opening to cyclo-heptariene 231. At the temperatures needed for successful cyclopropanation, sigma-tropic H-shifts leading to conjugated isomers of cycloheptatriene carboxylates cannot be avoided. The situation is complicated by the formation of regioisomers upon cyclopropanation of substituted benzenes, and separation of the cycloheptatriene isomers may became tedious if not impossible. 

Furans and some of its derivatives have been cyclopropanated with the ketocarbenoids derived from ethyl diazoacetate and copper catalysts. The 2-oxabicyclo[3.1.0]hex-3-enes thus formed are easily ring-opened to 1,4-diacylbutadienes thermally, thermo-catalytically or by proton catalysis 14,136). The method has been put to good use by Rh2(OAc)4-catalyzed cyclopropanation of furan with diazoketones 275 to bicyclic products 276. Even at room temperature, they undergo electrocyclic ring-opening and cis, trans-dienes 277a are obtained with fair selectivity 257,258). These compounds served as starting materials in the total syntheses 257 259) of some HETE s (mono-... 

The two articles in this current volume describe recent developments with small ring compounds which have not teen compiled in such a context before. T. Hirao discusses selective transformations initiated by transition derivatives in the construction of functionally substituted five-, six- and seven-membered rings as well as open-chair compounds. Cycloadditions onto methylene- and alkylidene-cyclopropane derivatives, described by A. Goti, F. M. Cordero and A. Brandi, not only yield products with spirocyclopropane moieties which can be desirable as such or as potential mimics of gem-dimethyl groupings, but also intermediates which can undergo further transformations with ring-opening of the cyclopropane units. 

The formation of the [5-lactam derivative 597 remains an isolated case. For example, several alkenylidenecyclopropanes react with CSI and toluene-sulfonylisocyanate, but [2 + 2] adducts are formed only by attack on the double bond not linked to the cyclopropane ring when this bond is attacked only products derived from cyclopropane ring opening are formed [158]. 

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). 

More recent reports from Cordova [155] and Wang [156] have described the cyclopropanation of a, P-unsaturated aldehydes 99 with diethyl bromomalonates 100 and 2-bromo ethyl acetoacetate catalysed by a series of diaryIprolinol derivatives. Both describe 30 as being the most efficient catalyst in many cases and optimal reaction conditions are similar. Some representative examples of this cyclopropanation are shown in Scheme 40. The transformation results in the formation of two new C-C bonds, a new quaternary carbon centre and a densely functionalised product ripe for further synthetic manipulation. Triethylamine or 2,6-lutidine are required as a stoichiometric additive in order to remove the HBr produced during the reaction sequence. The use of sodium acetate (4.0 equivalents) as an additive led to subsequent stereoselective ring opening of the cyclopropane to give a,P-unsaturated aldehydes 101. It can be envisioned that these highly functionalised materials may prove useful substrates in a variety of imin-ium ion or metal catalysed transformations. 

The Tafel rearrangement only occurs in acid medium. Simultaneous reduction of both carbonyl groups leads to interaction and formation of a cyclopropane. Acid catalysed cyclopropane ring opening follows to yield an a-diketone 28 which undergoes the electrochemical Clemmensen reduction step to the hydrocarbon. Side products include the two monoketones derived by partial deoxygenation of the a-diketone and the secondary alcohols from reduction of these raonoketones. Separate experiments show that the a-diketone 28 can be reduced to the hydrocarbon. 

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