Vinylcyclopropanes allenes

Unlike reactions with alkenes and alkynes, relatively few examples of intramolecular transition metal-cataly2ed reactions of allenes have been reported so far. Continuing our endeavor to extend the synthetic reach of transition-metal-catalyzed reactions, we have directed our attention at the use of an allene as the n-system. As with the alkene systems, two stereochemical outcomes are possible for the intramolecular [5+2] cycloaddition of allene-vinylcyclopropanes. The use of an allene moiety also presents an interesting opportunity to incorporate chirality into the substrate. Additionally, because ene-vinylcy-clopropane substrates substituted at the alkene terminus are not amenable to [5+2] cycloaddition, the use of an allene allows access to the same framework that would be obtained by cycloaddition of terminally substituted alkene substrates, thereby circumventing one of the few limitations encountered with ene-vinylcyclopropane cycloadditions. 

The effect of even greater substitution of the allene terminus was explored next. Allene-vinylcyclopropane 58, which bears r-butyl substitution, was chosen for this study. In the presence of 1 mol% tris(triphenylphosphine)rhodium(I) chloride in toluene at 100 C for 5 h, 58 undergoes efficient cycloaddition to provide a 96% yield of 59 as a single diastereomer with a cis ring fusion (Eq. 65). Thus,... 

The effect of substitution at the internal carbon of the allene was examined next, driven in part by the potential use of this process in the synthesis of targets bearing an angular substituent. In the presence of a catalyst system derived from 5 mol% RhCKPPhjlj and 5 mol% AgOTf in toluene at 110 °C, allene-vinylcyclopropane provides 61 in 44% yield (Eq. 66). In contrast to the cycloaddition of 54, cycloaddition of 60 produces 61 as a single diastereomer. 

To determine whether increased substitution of the allene terminus would have a similar beneficial effect on the yield as seen with the cycloaddition of 58, allene-vinylcyclopropane 62 was selected for study. The yield of cycloaddition improved to 70% by including f-butyl substitution of the allene terminus (Eq. 67). 

A point of further significance is whether the chirality of a non-racemic substrate would be transferred to the cycloadduct. Based on the high diasteieoselectivity and unparalleled efficiency of the cy-cloaddition of allene-vinylcyclopropane 58, this substrate was selected to study chirality transfer. This substrate is prepared from ethylene glycol in 10 steps. In the presence of 1 mol% RhCl(PPh3)j... 

Gold(I)-catalysed allene-vinylcyclopropane cycloisomerization has been reported to give the tricyclic framework of the protoilludanes in a single step involving cyclopropane ring expansion and a Prins cyclization (Scheme 122). ... 

Generally, cycloproylallenes are prepared by the same methods as employed for the synthesis of other allenic hydrocarbons. Thus, cyclopropylallene (17) itself has been obtained from vinylcyclopropane (139) via its dibromocarbene adduct 140 using the DMS method (Scheme 5.19) [54],... 

In 1998, Saigo et al. [150] discovered the Rh(I)-catalyzed allenic version of the vinylcyclopropane rearrangement. With a subsituent on the cyclopropane ring two different isomers can be formed depending on which of the different allylic C-C bonds in the three-membered ring is broken. Depending on R2, different regioselec-tivites were obtained with 250. Alkyl-substituted substrates lead to 251 and aryl-substituted substrates to 252 (Scheme 15.79) [150]. 

Rhodium-catalyzed [5 + 2]-cycloaddition of an allene and a vinylcyclopropane proceeds with complete chemo-, endo/exo- and diastereoselectivity, representing an effective general route to bicyclo[5.3.0]decane derivatives (Scheme 16.75) [81]. This cydoaddition protocol has been applied successfully to asymmetric total syntheses of natural products [82, 83]. 

Scheme 16.75 Rh-catalyzed intramolecular [5 + 2]-cycloadditions of allenes and vinylcyclopropanes.

Rhodium catalysis has played a critical role in the development of this type of reaction. The rhodium-mediated [4 + 2] carbocyclization between dienes and unactivated olefins or alkynes is a notable early example of this concept [2]. Further investigations demonstrated the extension of this methodology to the reaction between a diene and an allene [3]. Expansion of the scope of this strategy, to both the intra- and intermolecular [5-1-2] homologs of the Diels-Alder reaction, was accomplished with a vinylcyclopropane and either an alkyne or an olefin to afford the carbocyclization adducts (Scheme 11.1) [4, 5]. 

If the double bond is connected directly to the three-membered ring, i.e. if the substrate is a dihalo-vinylcyclopropane derivative, a vinylcyclopropylidene to cyclopentadiene isomerization, the so-called Skattebol rearrangement, takes place upon treatment with alkyllithium. Again, this ring-forming step competes with a ring-destruction process leading to allenic hydrocarbons (vinylallenes,... 

The rhodium-cataiyzed intramoiecuiar [5+2] cycioaddition of an allene and vinylcyclopropane was the key step in the asymmetric total synthesis of the trinorguaiane sesquiterpene (+)-dictamnol by P.A. Wender and co-workers.The cyclization precursor allene-cyclopropane was assembled starting from commercially available cyclopropane-carbaldehyde. Using the HWE oiefination, the Weinreb s amide moiety was installed and subsequently reacted with a primary alkyllithium that was generated via lithium-halogen exchange. 

The cyclodecatetraene (94), incorporating an allene unit, undergoes transannulation accompanied by rearrangement in the presence of HgS04, producing a mixture of the bicyclo[4.4.0]decenol (95) and the vinylcyclopropane (96 Scheme 11). ... 

The Rh-catalyzed [5 + 2] cycloaddition combines a vinylcyclopropane and an alkyne (or an alkene or allene) to give a cycloheptadiene. 

Allenes 23 can also serve as precursors for allyl complexes which undergo intramolecular allylic alkylation to give vinylcyclopropanes 25. This conversion, however, competes with cyclopentene formation. Several other examples of this type have been reported. ... 

The diazotization route is frequently accompanied by products derived from solvolysis of the initially formed cyclopropylidene or the rearranged cyclopentenylidene (Skattebol rearrangement) in the case of vinylcyclopropylidene with alcohol solvent, although allenes still account for the major products in the case of vrc-disubstituted cyclopropylidenes. It is noteworthy that the stereochemistry of the ring substituents (Table 2, entries 2 and 3) is an important factor in affecting yields of allenes. gcw-Disubstitution of vinylcyclopropanes diminishes formation of allenes in favor of products from the Skattebol rearrangement (entry 6). 

Simultaneous introduchon of both sulfur and selenium functions into carbon-carbon unsaturated compounds via a radical mechanism is also demonstrated by selenosulfonahori [149] and selenothiocarboxylatiorl [150] (Scheme 15.70). In these addihon reactions, attack of sulfur-centered radicals at the terminal position of alkenes and the subsequent Sh2 reaction on the selenium lead to the formahon of anti-Markovnikov adducts regioselechvely. The selenosulfonahon can be apphed to a variety of unsaturated compounds, for example alkynes, allenes, and vinylcyclopropanes, and combination with the selenoxide syn-elimination procedure... 

The reaction was also tested with a substrate containing a four-atom tether (Eq. 68). Consistent with our earlier observations, the yield of the cycloaddition improves with increasing substitution of the allene (Eq. 69). Interestingly, the reaction times for substrates with both three- and four-atom tethers are comparable, in contrast to our earlier findings with ene-vinylcyclopropane cycloadditions in which a one-atom increase in tether length profoundly increases the reaction time. 

The earlier proposal that vinylcyclopropane (365) was implicated in the solvolysis of (366) and (367) has now been substantiated, with all three compounds reacting from the common intermediate (368). A similar, though more complex, situation holds for the allenes (369)—(372). ... 

Wender s group has also developed rhodium-catalyzed intermolecular [5-1-2] cycloadditions. At first, they found the catalysis system of Rh(PPh3)3Cl for the intramolecular reactions was not effective at all for the intermolecular reactions. To effect the intermolecular [5-1-2] cycloadditions, [Rh(CO)2Cl]2 must be used and oxygen substitution of the cyclopropane was necessary (see (17)) [37-39]. Then they successfully expanded the substrate to unactivated vinylcyclopropanes by adjusting the substituents. For monosubstituted alkynes, the substitution on the olefin terminus directs the formation of single isomer that minimized steric hindrance (see (18)) [40]. The [5-1-2] cycloadditions can also be applied to VCPs with allenes (see (19)) [41]. It should be noted that the alkyne substituent did not interfere with the reaction, indicating that allenes as reaction partners were superior to alkyne in the [5-1-2] cycloadditions. Curiously, the authors didn t report the corresponding intermolecular [5-1-2] cycloadditions of VCPs with alkenes. 

Asymmetric cyclopropanation with allenes was smdied by Gregg et al. Aryldiazoacetate 165 underwent asymmetric cyclopropanation with monosubstimted allenes in the presence of Rh2(5-DOSP)4 160 and vinylcyclopropanes 166 were obtained in 80-90% ee (Scheme 1.77) [122]. The Hammett plots of the reaction revealed that the reaction rate depended on allene substituents, and the p value was estimated to be -0.25 [123]. 

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