Cyclopentene formation annulations

Nair and co-workers have extended the use of enals for homoenolate generation to allow ring annulation with enones [13], Cyclopentene formation is achieved via... 

The cyclopentene annulations can also occur in the reactions of alkynyliodo-nium salts with nitrogen- and sulfur nucleophiles (Scheme 61). Specifically, azi-docyclopentene 155 is formed upon treatment of octynyliodonium tosylate 154 with sodium azide in dichloromethane [123]. The reaction of alkynyliodonium salt 156 with sodium toluenesulfinate results in the formation of substituted indene 157 via alkylidene carbene aromatic C-H bond insertion [124]. 

Scheme 18). The formation can be explained by the initial conjugate umpolung of the aldehyde and subsequent 1,4-addition to the unsaturated ketone. After proton transfer, an intramolecular aldol-type addition results in the formation of the aforementioned zwitterions. Nucleophilic displacement of the imidazolium moiety by the alkoxide provides the p-laclonc, which exhibits increased strain, since it is annulated to a cyclopentane ring. Consequently, the P-lactone breaks apart and liberates CO2 and the observed cyclopentene products (Scheme 19). 

Danheiser cyclopentene annulation Formation of cyclopentenes from enones and allenes. 124... 

An alternate approach to the iridoid core, again developed by Biichi, utilized the [2+2] cycloaddition of cyclopentene 28 and tricarbonyl 29 (Scheme 6). Following photochemical annulation, the resulting cyclobutane 30 underwent a retro-aldol reaction and hemiacetal formation to provide racemic cyclopenta[c]pyran 31. Elaboration of 31 to loganin (16) required 10 additional steps. ... 

The use of both LIU and HIU has been shown to increase the efficiency of the P-K reaction, which involves the formation of cyclopentenone from the annulation of a cobalt alkynyl carbonyl complex and an alkene. The use of low-power ultrasound, as for example, from a cleaning bath, although capable of producing intramolecular P-K reactions, generated relatively low cyclization yields. The motivation for the use of high intensity came from its ability, as previously described, to effectively decarbonylate metal carbonyl and substituted metal carbonyl complexes. Indeed, HIU produced by a classic horn-type sonicator has been shown to be capable of facile annulation of norbornene and norbornadiene in under 10 min in the presence of a trimethylamine or trimethylamine N-oxidc dihydrate (TMANO) promoter, with the latter promoter producing cleaner product mixtures. This methodology also proved effective in the enhancement of the P-K reaction with less strained alkenes such as 2,5-dihydrofuran and cyclopentene, as well as the less reactive alkenes -fluorostyrene and cycloheptene. The mechanism has been postulated to involve decarbo-nylation of the cobalt carbonyl alkyne, followed by coordination by the amine to the vacant coordination sites on the cobalt. 

The use of other electrophiles in the Danheiser annulation for the formation of cyclopentenes is relatively unexplored. Ynones have been reported to imdergo cycloaddition, although examples are limited. Thus treatment of butynone 64 with silyl allene 47 under the usual conditions delivered cyclopentadiene 65 in 53% yield. Danheiser has reported that nitroalkenes do not provide annulation products furnishing instead acyclic alkynes. For example, treatment of nitroalkene 66 with silylallene 34 under standard conditions gives alkyne 67 rather than the cyclopentene 68. afi-Unsaturated aldehydes have been reported to be problematic, failing to provide isolable cyclopentene products. Treatment of methacrolein (69) with silylallene 34 under the standard conditions produced only a complex mixture of unidentified products. 

Two methods for accomplishing a formal [3 + 3] cycloadditions using the Danheiser annulation have been reported. Angle et al. reported that formation of dihydronaphthalene 99 was formed in 77% yield from the reaction of benzyl alcohol 97 with silylallene 98 in the presence of SnCU. Alternatively, the use of hydroxysubstituted benzyl alcohols provides the spirofused cyclopentene products. Treatment of hydroxybenzyl alcohol 100 with silylallene 98 in the presence of SnCU produces spirocyclopentene 101 in 76% yield. Depending on the nature of the substituents on the aryl ring, mixtures of dihydronaphthalenes and spirocyclopentenes may be obtained. 

A phosphane-catalyzed [4 - -1] annulation between nitroalkenes and Morita-Baylis-Hillman carbonates was performed by He and co-workers. " The authors claimed the in situ formation of an allylic phosphorus ylide as an active intermediate. Allenoates and enones were able to form cyclopentenes via two cycloaddition reactions they underwent a [3 -F 2] or a [2 -F 4] process in the presence of catalytic phosphines or amines, respectively (Scheme 15). To explain such a different reactivity, Huang, Lankau and Yu, carried out M06-2X/6-31- -G calculations to study the role of ylide intermediates. ... 

Treatment of phenol with 1,2-diols and excess of cyclopentene (Sequiv.) in the presence of a well-defined cationic ruthenium hydride complex [(C6H6)(PCy3)(CO)RuH]+BF4- (1 mol%) in toluene at 100 C for 8-12h led to the formation of benzofuran derivatives (Eq. (7.18)) [24]. The catalytic C-H couphng method exhibited a broad substrate scope, tolerated carbonyl and amine functional groups, obviated the use of any expensive and often toxic metal oxidants, and liberated water as the only by-product. Furthermore, excellent regioselective addition of the linear 1,2-diols were observed, which yielded the -substituted benzofuran products exclusively. Such dehydrative C—H alkenylation and annulation reactions could be applied for a number of functionalized phenol and alcohol substrates of biological importance. 

The authors gave the following rationalization to explain the ylide annulation (Scheme 20.25). Triphenylphosphine reacts with bromide 26 to form a phospho-nium salt, which is deprotonated by K2CO3 to generate the corresponding phos-phonium ylide in situ. A Michael addition of the ylide to the electron-deficient olefins, followed by another intramolecular Michael addition of the zwitterionic intermediates, and then P-eHmination of triphenylphosphine completes the catalytic cycle. The formation of the two isomers can be explained by a- or y-attack of yHde to dually activated olefins 28. Of course, the possibility of migration of the double bond in cyclopentene products 30 under the reaction conditions cannot be excluded. 

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