Substituted cyclopentene product

The change from substituted cyclohexene to substituted cyclopentene products can readily be accounted for in terms of the comparative stabilities of the rearranged radicals. For instance, with the 6,6-dimethyl-2-methylenebicyclo[3.1. Ojhexane derivatives, )S-scission of the outer cyclopropane bond, giving the five-membered ring, was favored because this afforded the thermodynamically more stable tertiary radical. 

The predominance of steric over electronic factors has been also used to explain the product distribution obtained by addition of I2 in pyridine which takes place exclusively at the least substituted cyclopentene double bond of 79. Under similar conditions the reaction of the unsubstituted diene 78 occurs by direct addition at the cyclohexene double bond98. 

Cyclopentene annelation. The known rearrangement of vinyl cyclopropanes to cyclopentenes (cf. 7, 190 9, 83, 265) can be used to obtain silyl-substituted cyclopentenes. The precursors, (l-trimethylsilylcyclopropyl)ethylenes (2), are usually prepared by addition of 1 to an aldehyde or a ketone followed by cyclopropanation (C2HjZnI, CH2I2) of the adduct. The products are then dehydrated by TsOH to 2 (equation I).1... 

In 1995, Mioskowski and co-workers reported a new carbenoid 1,2-alkyl rearrangement of a-hydroxy-substituted cyclopentene and cyclohexene oxides treatment of such systems with 3 equiv of an organolithium resulted in the formation of two products, as exemplified by the synthesis of dihydrojasmone and its regioisomer 99 (Scheme 44) <1995JA12700>. 

Treatment of the semicarbazone (55) under Wolff-Kishner conditions (KOH, NaOMe, KOBu, no solvent) has been utilized to synthesize the substituted cyclopentenes cis- and trans-(,S6 equation 17). In DE<3 at 225 C, the normal Wolff-Kishner product was obtained. ... 

Z, )-4-Phenyl-l-bromobuta-l,3-diene [(Z, )-15], if converted with norbomene (9) in the presence of a hydride source, gives cyclopentene 17 and cyclopropane 18 if catalyzed with pallad-ium(O) complexes. In the absence of a hydride source a substituted nortricyclene product 16 is formed. ... 

Substituted cyclopentenes were also the main products obtained from the addition of benzenethiol and tetrahalomethanes to some substituted 2-methylenebicyclo[3.1.0]hexanes (Table 5). 

Furthermore, 1-substituted cyclohexenes 105 were also determined to be suitable substrates, providing the C-H/Cope products 166 in 31-68% yield, >98% de and 95-99% ee (Scheme 40) [114], A major competing side reaction seen with this system, however, was the direct C-H insertion to provide 167. When the transformation was extended to 1-substituted cyclopentenes, the yields dropped off even further due to undesired competing reactions, including both the direct C-H insertion as well as cyclopropanation of the olefin. The product ratios seem to be sensitive to sterics and electronics of both the olefin and the reacting C-H bonds, and further optimization studies will be needed. 

The reaction is carried out in benzene at 60 °C over a period of 14 hours, using the various components in a mole ratio of dibromo ketone, olefin/ Fe2(CO)9 1 4 1.2. The simple diastereose-lectivity of the cycloaddition has been found to be rather moderate, with mixtures of cis- and Oau.T-products observed. An extension of this procedure involves addition to the C—C double bond of enamines5. Following elimination of the appropriate amine, the procedure provides an efficient route to substituted cyclopentenes, in some cases with very high tram selectivity. 

In contrast, the reaction of a range of P-dicarbonyl nucleophiles with a variety of alkynyliodonium salts substituted with an alkyl group possessing a y-CH bond results in the cyclopentene products derived by carbene insertion [51] as illustrated in Scheme 3-5. In fact, as shown in Eq. (22), the alkyl chain need not be restricted to the alkynyliodonium salt but may instead be part of the enolate nucleophile [51]. 

Concern for the stereochemistry of the 1,3-shift portion of the reaction, i.e. the pathway for formation of cyclopentene, was addressed by examination of numerous substituted materials, but ultimate resolution of the problem was provided by pyrolysis of 5 y/2- -2,3,2 -trideuteriovinylcyclopropane at 300°C to roughly only 1 % conversion, which resulted in a 16 60 24 ratio of Z,Z-, E,Z, and -3,4,5-trideuteriocyclopentene, respectively. Pyrolysis of 5 y/2-Z-2,3,2 -trideuteriovinyl-cyclopropane to obtain roughly 1% of cyclopentene product resulted in a 23 41 36 ratio of Z,Z-, E,Z-, and , -3,4,5-trideuteriocyclopentene, respectively (Scheme 6.15). The Z,Z- and E,E- products from syn-E are formed by the ar and ai pathways, respectively, and these same products from syn-Z are formed by the sr and si pathways, respectively, thus providing data on the relative utilization of the four pathways. 

This domino ROM/enyne CM/RCM process has been exploited for a regio-and chemoselective ring expansion of substituted cyclopentenes to provide 1,3-cycloheptadienes (Scheme 2.30) [17d]. Thus, reaction of the cyclopentenes 75, 77, and 79 with different alkynes and Gmbbs catalyst 2 readily afforded the depicted products 76, 78, and 80, respectively. 

Davies s group also extended this methodology toward the asymmetric syntheses of substituted cyclopentenes. Although chiral monocyclic VCPs isomerized to racemic cyclopentenes under the reaction conditions, the use of fused chiral VCPs led to the products in high yields with excellent enantioselectivity f Scheme 11.14T ... 

Despite these data, the high level of stereoselectivity usually observed in the rearrangement of enantiopure VCPs suggests that the concerted, symmetry-controlled pathway might be operational as well. For exanple, Baldwin s group reported that the rearrangement of trans-methyl-substituted VCP led to four different stereoisomeric cyclopentene products. The... 

Since this report in 1976, numerous studies of stereoselective ring opening reactions of variously substituted and enantioenriched VCPs have been reported. The formation of different stereoisomeric cyclopentene products suggests that die mechanism of the rearrangement might involve both the concerted and diradical pathways to different extents, depending upon the nature of substituents and their precise orientation on the corresponding... 

Armesto et al. studied the photochemical rearrangement of l-substituted-3-(2,2-diphenylvinyl)-2,2-dimethylcyclopropanes under both triplet-sensitized irradiation as well as direct irradiation conditions. Unfortunately, the majority of the VCP starting materials were recovered as mixtures of cis-trans stereoisomers, and only low yields of cyclopentene products were obtained tScheme 11.39. Eq. 

For the distal position of the allene, C-3 with respect to the silyl group, both hydrogen and alkyl substitution is tolerated. Only at the extreme limit of steric congestion of both the allene and the enone are low yields observed. For example, reaction of yS-dimethyl a,y -unsaturated ketone 46 with 3,3-dimethylallene 47 under standard conditions provides only 7% yield of the cyclopentene product 48. ... 

The Danheiser annulation has also been reported to be useful for the preparation of substituted azulene products." For example, treatment of silylallene 58 with tropylium cation 59 at 23 °C produces intermediate cyclopentene dihydroazulene 60, which is not isolated but rather undergoes in situ dehydrogenation with a second equivalent of tropylium cation 59 to provide azulene 61. The use of the tert-butyldimethylsilyl group as opposed to the trimethylsilyl group is necessary since the trimethylsilyl group tends to undergo premature desilylation rather than cyclization to the azulene. Substitution at the 3-position of the allene was also found to significantly... 

In marked contrast to the behaviour of the carbonyl adducts of 1-lithiocyclo-propane (147 Y = O, S, or Se), the corresponding silicon-substituted compounds do not undergo acid-catalysed ring expansion to cyclobutane derivatives, but rather are smoothly dehydrated in good yield to the cyclopropylallylsilanes [148 R R = —(CH2)4—These latter products, however, can be thermally rearranged to silyl-substituted cyclopentenes (149) which have been further... 

The first synthesis of an enantiopure N-protected bicycloproline rehes on the Rh-catalyzed intramolecular C(sp )—H amination of carbamate 35. This reaction is the key step to install the quaternary aminated center of the substituted cyclopentene ring. After a large screening of reaction parameters, the desired as-oxazohdinone 36 was obtained in 35% yield, along with the secondary C—H insertion product 37, and small amounts oftheaziridine38 (Scheme 39). It should be noticed that the Ag(I)-catalyzed... 

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. 

Nair and coworkers showed in 2006 that Michael acceptors (112) can also act as electrophiles for achiral imidazolium-derived homoenolates, although the expected cyclopentanone products were not obtained [96]. Instead, dx-substituted cyclopentenes 114 resulting from a proton transfer, aldol, P-lactone formation, and decarboxylation sequence were isolated (Scheme 18.20). 

Oxirane on thermolysis or photolysis suffers C—O homolysis to give a plethora of products (Scheme 2). Substituted oxiranes behave similarly on thermolysis although some C—C cleavage is observed (Scheme 3). Cyclopentene and cyclohexene oxides undergo only C—O cleavage (Scheme 4). 

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