Cyclopentane derivs

Some straightforward, efficient cyclopentanellation procedures were developed recently. Addition of a malonic ester anion to a cyclopropane-1,1-dicarboxylic ester followed by a Dieckmann condensation (S. Danishefsky, 1974) or addition of iJ-ketoester anions to a (l-phenylthiocyclopropyl)phosphonium cation followed by intramolecular Wittig reaction (J.P, Marino. 1975) produced cyclopentanones. Another procedure starts with a (2 + 21-cycloaddition of dichloroketene to alkenes followed by regioselective ring expansion with diazomethane. The resulting 2,2-dichlorocyclopentanones can be converted to a large variety of cyclopentane derivatives (A.E. Greene. 1979 J.-P. Deprds, 1980). 

Hydrosilylation of I-vinyl-1-cyclohexene (77) proceeds stereoselectively to give the (Z)-l-ethylidene-2-silylcyclohexane 78, which is converted into (Z)-2-ethylidenecyclohe.xanol (79)[74]. Hydrosilylation of cyclopentadiene affords the 3-silylated 1-cyclopentene 80. which is an allylic silane and used for further transformations[75.75a]. Cyclization of the 1,3,8, lO-undecatetraene system in the di(2.4-pentadienyl)malonate 69 via hydrosilylation gives the cyclopentane derivative 81. which corresponds to 2.6-octadienylsilanc[l8,76]. 

Furthermore, intramolecular cyclization of acyclic chiral imines, in which the imine and the enone groups are separated by alkyl chains, yield optically active cyclohexane and cyclopentane derivatives. /ra .v-l,2-Disubstitutcd carbocyclic compounds are exclusively or predominantly formed with diastereomeric ratios in the range 80 20 100 0, strongly dependent on the conditions used to induce cyclization, i.e. heat, pressure or Lewis acid (MgBr2) catalysis227. 

Aliphatic nitriles (m/z 41 and 54 also may be present), C4H(,N C5H8 (cyclopentane derivatives), — CH2CH2CH2CN, NCCH2C(0)... 

Chan T-H, Xin Y-C, von Itzstein M (1997) Synthesis of phosphonic add analogs of siaUc acids (Neu5Ac and KDN) as potential sialidase inhibitors. J Org Chem 62 3500-3504 Chand P, Kotian PL, Dehghani A, El-Kattan Y, Lin T-H, Hutchison TL, Babu YS, Bantia S, Elliott AJ, Montgomery JA (2001) Systematic structure-based design and stereoselective synthesis of novel multisubstituted cyclopentane derivatives with potent antiinfluenza activity. J Med Chem 44 4379 392... 

Chand P, Babu YS, Bantia S, Rowland S, Dehghani A, Kotian PL, Hutchison TL, Ali S, BrouUlette W, El-Kattan Y, Lin T-H (2004) Syntheses and neuraminidase inhibitory activity of multisubstituted cyclopentane amide derivatives. J Med Chem 47 1919-1929 Chand P, Bantia S, Kotian PL, El-Kattan Y, Lin T-H, Babu YS (2005a) Comparison of the antiinfluenza virus activity of cyclopentane derivatives with oseltamivir and zanamivir in vivo. Bioorg Med Chem 13 4071 077... 

Scheldt and co-workers have also accessed enolate equivalents from enals to furnish cyclopentanes 236 asymmetrically. Formation of the enolate equivalent from enals 235 with the NHC, followed by an intramolecular Michael reaction and 0-acylation, gives the lactone products 236, which are readily opened by either alcohols or amines to generate functionalised cyclopentane derivatives 237 in excellent ee. 

One experimental test for the involvement of radical intermediates is to study 5-hexenyl systems and look for the characteristic cyclization to cyclopentane derivatives (see Part A, Section 11.2.3). When 5-hexenyl bromide or iodide reacts with LiAlH4, no cyclization products are observed. However, the more hindered 2,2-dimethyl-5-hexenyl iodide gives mainly cyclic product.164... 

An enantioselective variant of the diene cydization reaction has been developed by application of chiral zirconocene derivatives, such as Brintzinger s catalyst (12) [10]. Mori and co-workers demonstrated that substituted dial-lylbenzylamine 25 could be cyclized to pyrrolidines 26 and 27 in a 2 1 ratio using chiral complex 12 in up to 79% yield with up to 95% ee (Eq. 4) [ 17,18]. This reaction was similarly applied to 2-substituted 1,6-dienes, which provided the analogous cyclopentane derivatives in up to 99% ee with similar diastereoselectivities [19]. When cyclic, internal olefins were used, spirocyclic compounds were isolated. The enantioselection in these reactions is thought to derive from either the ate or the transmetallation step. The stereoselectivity of this reaction has been extended to the selective reaction of enantiotopic olefin compounds to form bicyclic products such as 28, in 24% yield and 59% ee after deprotection (Eq. 5) [20]. 

The domino reaction is initiated by the chemoselective attack of the carbanion 2-458 on the terminal ring carbon atom of epoxyhomoallyl tosylate 2-459 to give the alkoxides 2-460 after a 1,4-carbon-oxygen shift of the silyl group. The final step to give the cyclopentane derivates 2-461 is a nucleophilic substitution. In some cases, using the TBS group and primary tosylates, oxetanes are formed as byproducts. 

In a similar way as described for the hydroformylation, the rhodium-catalyzed silaformylation can also be used in a domino process. The elementary step is the formation of an alkenyl-rhodium species by insertion of an alkyne into a Rh-Si bond (silylrhodation), which provides the trigger for a carbocyclization, followed by an insertion of CO. Thus, when Matsuda and coworkers [216] treated a solution of the 1,6-enyne 6/2-87 in benzene with the dimethylphenylsilane under CO pressure (36 kg cm"2) in the presence of catalytic amounts of Rh4(CO)12, the cyclopentane derivative 6/2-88 was obtained in 85 % yield. The procedure is not restricted to the formation of carbocycles rather, heterocycles can also be synthesized using 1,6-enynes as 6/2-89 and 6/2-90 with a heteroatom in the tether (Scheme 6/2.19). Interestingly, 6/2-91 did not lead to the domino product neither could 1,7-enynes be used as substrates, while the Thorpe-Ingold effect (geminal substitution) seems important in achieving good yields. 

Malacria and coworkers [274] used an intermolecular trimerization of alkynes to gain efficient access to the skeleton of the phyllocladane family. Thus, the Co-cata-lyzed reaction of the polyunsaturated precursor 6/4-4 gave 6/4-5 in 42% yield. Here, six new carbon-carbon bonds and four stereogenic centers are formed. The first step is formation of the cyclopentane derivative 6/4-6 by a Co-catalyzed Conia-ene-type reaction [275] which, on addition o f his( Iri me ill y I si ly 1) e thy ne (btmse), led to the benzocyclobutenes 6/4-7 (Scheme 6/4.2). The reaction is terminated by the addition of dppe and heating to reflux in decane to give the desired products 6/4-5 by an electrocyclic ring opening, followed by [4+2] cycloaddition. 

Another example of the formation of an octalin is the conversion of the cyclohexenone 127 into the enol acetate 128 by the action of acetic anhydride and perchloric acid in the presence of acetic acid (equation 65)75. The acid-induced ring-closure of the cyclopentane derivative 129 gives a 85% yield of a mixture of the octahydroazulenes 130 and 131... 

Treatment of the diester 211 (E = CC Et) with lithium IV-benzyltrimethylsilylamide, followed by aqueous acid, yields the cyclopentane derivative 212, the product of an intramolecular Michael addition (equation 104)110. 1-Methylindane is produced in moderate yield by the electrochemical reduction of o-bromo-(3-butenyl)benzene (equation 105)111. 

Diastereoselective intramolecular cyclization of bis(diene)s in the presence of a palladium catalyst has been reported, providing cyclopentane derivative stereoselectively (Equation (62)).125... 

Dipolar addition is closely related to the Diels-Alder reaction, but allows the formation of five-membered adducts, including cyclopentane derivatives. Like Diels-Alder reactions, 1,3-dipolar cycloaddition involves [4+2] concerted reaction of a 1,3-dipolar species (the An component and a dipolar In component). Very often, condensation of chiral acrylates with nitrile oxides or nitrones gives only modest diastereoselectivity.82 1,3-Dipolar cycloaddition between nitrones and alkenes is most useful and convenient for the preparation of iso-xazolidine derivatives, which can then be readily converted to 1,3-amino alcohol equivalents under mild conditions.83 The low selectivity of the 1,3-dipolar reaction can be overcome to some extent by introducing a chiral auxiliary to the substrate. As shown in Scheme 5-51, the reaction of 169 with acryloyl chloride connects the chiral sultam to the acrylic acid substrate, and subsequent cycloaddition yields product 170 with a diastereoselectivity of 90 10.84... 

The intramolecular cyclization of l,2-dien-7-ynes and l,2-dien-6-ynes regiospecifically affords the corresponding titanacycles, which react with protons, carbon monoxide, aldehydes, or imines to give single products, as shown in Eqs. 9.56 and 9.57 [102], As the formation of titanacycles and their subsequent reaction with externally added reagents such as carbon monoxide (Eq. 9.56) or an aldehyde (or imine) (Eq. 9.57) proceeds with excellent chirality transfer, this represents a new method for synthesizing optically active cyclopentane derivatives from optically active allenes [102]. 

An interesting application of a 1,2-disubstituted cyclopropanol in a seven-membered ring-annelation methodology has been developed by Cha et al. [82], The cyclopropanol 124, obtained from methyl 1-cyclopentenecarboxylate (123) and 4-(triisopropylsilyloxy)-butylmagnesium chloride, was converted to a 1,2-dialkenylcyclopropanol bis-silyl ether, which, by a subsequent facile Cope rearrangement, afforded the cycloheptadiene-anne-lated cyclopentane derivative 125 in 32% overall yield (Scheme 11.32). 

Scheme 11.32. Transformation of methyl 1-cyclopentenecarboxylate (123) to cycloheptadienyl-annelated cyclopentane derivative 125 via cyclopropanol 124 [82].

The methoxycylobutene (473) also underwent ozonolysis in the presence of MeOH and yielded (474) after reductive work-up with S02 163). The cyclopentane derivative (474) was finally converted to ll-deoxy-PGEx 163). 

This procedure uses readily available starting materials and in one operational step generally gives higher yields of cyclopentanecarboxaldehyde than other preparations described in the literature. Because mercuric sulfate is an expensive reactant, a method of regenerating the mercury products is given. Cyclopentanecarboxaldehyde is a useful intermediate for many cyclopentane derivatives. 

Gasoline varies widely in composition, and even those with the same octane number may be quite different. The variation in aromatics content as well as the variation in the content of normal paraffins, branched paraffins, cyclopentane derivatives, and cyclohexane derivatives all involve characteristics of any one individual crude oil and influence the octane number of a gasoline. 

On the other hand, Beckwith rules [22] are useful guidelines for predicting the stereoselectivity in the cyclisation of substituted hexenyl radicals i) 1- or 3-substituted radicals give preferentially cij-disubstituted cyclopentane derivatives and ii) 2- or 4-substituted radicals give mainly rrans-disubstituted derivatives. These rules can be explained in terms of 1,3-diaxial interactions present in a chair-like transition state. Some examples which demonstrate such an effect are [19b] ... 

Intramolecular carbene C-H insertion frequently leads to the formation of five-membered rings [967,990,1021,1113-1128], In particular l-diazo-2-alkanones tend to yield cyclopentanones exclusively when treated with rhodium(ll) carboxylates. The use of enantiomerically pure catalysts for diazodecomposition enables the preparation of non-racemic cyclopentane derivatives [1005,1052,1074,1092,1129]. Intramolecular 1,5-C-H insertion can efficiently compete with 1,2-C-H insertion... 

The inversion process accompanying Sn2 reactions may have particular significance in cyclic compounds. Thus, if we consider the disubstituted cyclopentane derivative shown undergoing an Sn2... 

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