Cycloaddition five-membered rings formation

Cyclopropenes and mcthylcnccyclopropanes serve as multifunctional reagents in transition metal catalyzed reactions22. Methylenecyclopropanes, via C-C bond cleavage, are also used as trimethylenemethane precursors in transition metal catalyzed [3 + 2] cycloadditions for selective five-membered-ring formation. Low-valent nickel and palladium complexes are used as catalysts. This method has been extensively reviewed 22 and stereoselective applications are fully described in Section D.1.6.1.2.3. 

The evidence obtained clearly indicates that the above photorearrangements proceed by a mechanism involving a nitrile ylide intermediate since cycloadducts could be isolated when the irradiations were carried out in the presence of trapping agents. Intramolecular cycloaddition of the nitrile ylide followed by a 1,3-sigmatropic hydrogen shift of the initially formed five-membered ring readily accounts for the formation of the final product. 

In the same way as arylcarbene complexes, alkenylcarbene complexes typically react with alkynes to provide [3C+2S+1C0] Dotz cycloadducts (see Chap. ccChromium-Templated Benzannulation Reactions , p. 123 in this book). However, some isolated examples involving the formation of five-membered rings through [3C+2S] cycloaddition processes have been reported [71]. In this context, de Meijere et al. found that /J-donor-substituted alkenylcarbene complexes react with alkynes to give cyclopentene derivatives [71a]. This topic is also discussed in detail in Chap.ccThe Multifaceted Chemistry of Variously Substituted a,/J-Unsaturated Fischer Metalcarbenes , p. 21 of this book. 

Dipolar [3 + 2] cycloadditions are one of the most important reactions for the formation of five-membered rings [68]. The 1,3-dipolar cycloaddition reaction is frequently utihzed to obtain highly substituted pyrroHdines starting from imines and alkenes. Imines 98, obtained from a-amino esters and nitroalkenes 99, are mixed together in an open vessel microwave reactor to undergo 1,3-dipolar cycloaddition to produce highly substituted nitroprolines esters 101 (Scheme 35) [69]. Imines derived from a-aminoesters are thermally isomerized by microwave irradiation to azomethine yhdes 100,... 

Formation of trans isomers in overwhelming predominance in the ISOC reaction leading to five-membered rings (Entries a-d) has been ascribed to the orientation in which H% H , and R are on the exo face of TS 182b (this avoids a possible strain between R and NO or between H and [48b] that is presumably present in TS 182 a). Since elimination of silanol involving H in no way interferes with the orientation of H and R, a trans relationship between H and is abundantly clear. This fully accords with the widely accepted view that approach of the dipole and dipolarophile takes place in two parallel planes [49] and that the endo TS is preferred in the absence of obvious steric effects [50]. Formation of approximately 5% cis isomer when the dipolarophile terminus is disubstituted is accountable in terms of the cycloaddition taking place via TS 182a. 

The formation of a diverse array of five-membered ring heterocycles via the cycloaddition of isocyanides with furan- or pyrrole-based enones was reported. The reaction mechanism is discussed and an example is shown below <06OL3975>. 

In synthetic efforts toward the DNA reactive alkaloid naphthyridinomycin (164), Gamer and Ho (41) reported a series of studies into the constmction of the diazobicyclo[3.2.1]octane section. Constmction of the five-membered ring, by the photolytic conversion of an aziridine to an azomethine ylide and subsequent alkene 1,3-dipolar cycloaddition, was deemed the best synthetic tactic. Initial studies with menthol- and isonorborneol- tethered chiral dipolarophiles gave no facial selectivity in the adducts formed (42). However, utilizing Oppolzer s sultam as the chiral controlling unit led to a dramatic improvement. Treatment of ylide precursor 165 with the chiral dipolarophile 166 under photochemical conditions led to formation of the desired cycloadducts (Scheme 3.47). The reaction proceeded with an exo/endo ratio of only 2.4 1 however, the facial selectivity was good at >25 1 in favor of the desired re products. The products derived from si attack of the ylide... 

The strong preference for cyclization in the indicated manner in both sensitized reactions lends support to the view that cycloaddition reactions of triplets involve two steps with the intermediate formation of biradicals. It has recently been shown290 that cyclization of free radicals forms five-membered rings in preference to six-membered rings. 

Further cycloaddition reactions of silylenes generated by the photolysis of cyclotrisilanes have been published since Weidenbruch and coworkers summarized these reactions in an excellent review. Different siliranes were prepared by [2+1]-cycloaddition of di-t-butylsilylene to various alkenes and dienes (Scheme 6)46. Quite interesting results are obtained from the photolysis of hexa-i-butylcyclotrisilane in the presence of unsaturated five-membered ring compounds47 (Scheme 7). With cyclopentadiene and furane, [4 + 2]-cycloaddition of the photolytically generated disilene occurs only as a side reaction. Furthermore, [2 + 1]-cycloaddition of the intermediately formed silylene is highly favored and siliranes are primarily obtained. A totally different course is observed for the reaction in the presence of thiophene. The disilene abstracts the sulfur atom with the formation of the 1,2-disilathiirane as the major product with an extremely short Si—Si distance of 230.49 pm. 

The first structurally confirmed [2 + 4] adduct of a disilene and a 1,3-diene was compound 89, obtained from cyclopentadiene and 4174. The formation of the tricyclic compound 95 from furan and the cyclotrisilane 40 is probably initiated by a [2 + 4] cycloaddition of 41 to the five-membered ring to afford 94, which then undergoes a [2 + 1] addition at the newly formed double bond with the silylene 42 formed concomitantly in the photolysis of 40 (equation 16)74. 

The reaction of 9 with nitrobenzene is probably initiated by a [2 + 3] cycloaddition to give the adduct 113, which can be identified at low temperature by NMR spectroscopy. On increasing the temperature, the Si—Si bond is cleaved to afford the rearranged five-membered ring product 114 (equation 24).116 The similarity to the formation of the ring system 100 is noteworthy. 

Eq. 52 and 53 demonstrate remarkable characteristics of this [3 + 2]-cycloaddition starting with a pure diastereomer 130, two stereoisomeric cyclopentanes 131 are obtained. This stereorandom outcome is most simply rationalized assuming a stepwise mechanism with a 1,5-zwitterion as an intermediate in the cycloaddition. The vinylcyclopropane 132 only gives five-membered ring products 133 and no cyclo-heptene derivative, which would result from a conceivable [5 + 2]-cycloaddition. Less activated olefins or cyclopropanes do not undergo a similar [3 + 2]-cycloaddition. Due to the specific substitution pattern, the cyclopentane formation from these siloxycyclopropanes is of no preparative value. 

The reaction of 2-diazopropane with geometrical isomers of different types of sulfines yields A3-l,3,4-thiadiazoline 1-oxides as the single product by a concerted regiospecific cycloaddition process. Introduction of bulky substituents in either of the reactants will sterically hinder the cyclization to a five-membered ring, and give rise to non-stereospecific formation of episulfoxides (Scheme 26) (73TL3589). 

In the area of [3 + 2]-cycloadditions (1,3-dipolar cycloadditions), chiral silver catalysts have been utilized extensively for the enantioselective formation of five-membered rings from prochiral substrates. For example, Zhang and co-workers360 have reported the highly enantioselective Ag(i)-catalyzed [3 + 2]-cycloaddition of azomethine ylides to electron-deficient alkenes. Thus, reaction of ct-imino esters 442 with dimethyl maleate in the presence of catalytic amounts of silver(i) acetate and the chiral bisferrocenyl amide phosphine 443 provided the chiral pyrrolidines 444 with high stereoselectivities and chemical yields (Scheme 131). Only the endo-products were isolated in all cases. 

The presence of five-membered rings such as cyclopentanes, cyclopentenes, and dihydrofurans in a wide range of target molecules has led to a variety of methods for their preparation. One of the most successful of these is the use of trimethylenemethane [3 + 2] cycloaddition, catalysed by pal-ladium(O) complexes. The trimethylenemethane unit in these reactions is derived from 2-[ (trimethylsilyl)methyl]-2-propen- 1-yl acetate which is at the same time an allyl silane and an allylic acetate. This makes it a weak nucleophile and an electrophile in the presence of palladium(0). Formation of the palladium 7t-allyl complex is followed by removal of the trimethylsilyl group by nucleophilic attack of the resulting acetate ion, thus producing a zwitterionic palladium complex that can undergo cycloaddition reactions. 

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