Cyclopentane derivs 5-membered

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... 

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). 

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... 

Versatile [3 + 2]-cycloaddition pathways to five-membered carbocycles involve the trimethylenemethane (= 2-methylene-propanediyl) synthon (B.M. Trost, 1986). PaIladium(0)-induced 1,3-elimination at suitable reagents generates a reactive n - -methylene-1,3-propa-nediyl complex which reacts highly diastereoselectively with electron-deficient olefins. The resulting methylenecyclopentanes are easily modified, e.g., by ozonolysis, hydroboration etc., and thus a large variety of interesting cyclopentane derivatives is accessible. 

What about the comparison of isomeric 1-ethylcycloalkenes and ethylidenecycloalkanes, generically 21a and 21b respectively This is perhaps a fairer competition because both olefins are internal, i.e. neither has a =CH2 group, and so it is expected that the enthalpies of formation will be closer. For the isomeric cyclopentane derivatives, the idene isomer is more stable by but 1.6 1.3 kJmol-1. For the isomeric olefins with a 6-membered ring, the difference is 1.9 1.3 kJmol-1. 

Dipolar cycloadditions, closely related to the Diels-Alder reaction,1,2 result in the synthesis of a five-membered adduct including cyclopentane derivatives.417"426... 

A number of researchers have reported and demonstrated that maintaining the appropriate position of the substituents on a cyclic scaffold to interact with the established conserved amino acid residues involved in substrate binding can lead to development of new classes of influenza virus sialidase inhibitors [117]. Two drugs based on five-membered ring scaffolds have been developed as potent sialidase inhibitors. Cyclopentane derivative 24 (BCX-1812, peramivir) [117, 118] and pyrrolidine derivative 25 (ABT-675) [119] show nanomolar levels of inhibition of both influenza A and B viral sialidases (Fig. 17.13). 

An interesting carbocyclization process was observed when alkenyl stannanes were treated with electrophilic selenenylating reagents containing a non-nucleo-philic counterion. Thus, Nicolaou showed that compound 213 reacted with AT-PSP 11 to form the intermediate 214 which then afforded the cyclopropane derivative 215 (Scheme 32) [109]. Further examples were reported by Herndon [110]. As indicated in Scheme 32, in the presence of tin tetrachloride, the stannane 216 was converted into the cyclopentane derivative 217. This cyclization reaction proved to be quite general with respect to a variety of substitution patterns but it appears to be restricted to the formation of three- and five-membered ring. 

A number of natural sesquiterpenes like hirsutene 90 or corioline 91 have as their common structural unit a system of linearly fused five-membered rings (Scheme 3.21). The standard pathway of the retrosynthetic analysis of this system involves the search for strategic bonds in one of the rings. A, B, or C, disconnection of which would lead to the simplification of the target molecule and eventually to simple cyclopentane derivatives as available starting materials. As a result, diverse synthetic plans were devised and successfully employed in numerous synthetic studies in this field(see also the set of syntheses described in Section 2.23.2). 

It is noteworthy that the ring closures of 1,2-disubstituted cyclohexane, cycloheptane and cyclooctane derivatives revealed no appreciable differences in the reactivities of the cis and trans isomers in the formation of six-membered 1,3-heterocycles [117]. In contrast, striking differences were observed in the cyclizations of the cis and trans cyclopentane derivatives. For instance, the above cyclizations to pyrimidinones, starting from the trans counterparts, were unsuccessful. The attempted ring closure from 104 did not result in the cyclized products, but gave hydrolysed derivatives 105 and 106 [111]. 

Cyclopentane Derivatives - The isoxazolidinocarbocyclic derivative 72 was produced (together with a six-membered compound (89)-see Section 2.2) from cyclization of the nitrone 73, itself generated in situ from the iV-benzylhydroxyl-amine derivative of 3-C-allyl-l,2-0-isopropylidene-a-D-riZw>-pentodialdofuranose. The formation of the cyclopentane adduct predominated in non polar and polar aprotic solvents while the cyclohexane adduct predominated in polar protic solvents. ... 

The carbocyclic analogue of the trehalase inhibitor, trehazolin, has been prepared and reported to have potency indistinguishable from the natural product." The synthesis of other antibiotic-related cyclopentane derivatives such as analogues of mannostatin A, allosamidin (and allosamizolin) and a 4-membered carbocyclic thiazole analogue of oxetanocin, are covered in Chapter 19. 

The scope of catalytic ring-opening [3+2] cycloadditions was expanded to include simple cyclopropyl ketones, which combine with vinyl ketones to provide substituted cyclopentane derivatives (Scheme 3-32). Cyclopropyl imines were also found to be effective cycloaddition substrates under similar conditions, as illustrated in the sample procedure below. " Oxidative additions of nickel(O) to cyclopropyl ketones were found to produce six-membered metallacyclic nickel (9-enolates, which were competent species in the [3+2] cycloaddition process. " ... 

In most of the prior syntheses, optically active starting materials were used to synthesize isocarbacyclin (4) and different analogs. Many of these synthetic routes involve either annulation of a five-membered ring onto an optically active cyclopentane derivative (8-11 Fig. 4) that is commercially available or using a starting material that already has a bicyclo[3.3.0]octane skeleton (12 and 13 Fig. 4). An issue that Umited these approaches is how to selectively introduce the endocyclic double bond. 

Fused Five-membered Rings.—An attractive general method for the elaboration of fused five-membered rings, as well as monocyclic cyclopentane derivatives, involves a [3 + 2]cycloaddition of readily available silylallenes to enones (Scheme 5). Yields are usually high, and the method can also be used to prepare spirocyclic systems e.g. (79) - (80). 

A catalytic asymmetric cycloaddition reaction between norbomadiene and methylenecyclopropane can also be achieved in the presence of a [Ni(cod)2]-(—)-benzylmethylphenylphosphine catalyst to give the cycloadduct (72) in an optically active form. This reaction may proceed via a metallocyclopentane intermediate. The reactions of methylenecyclopropane with [Ni(cod)2l-phosphine systems do not appear to involve cleavage of the three-membered ring. However, the bis(acrylonitrile)nickel-catalysed cycloaddition reaction of methylenecyclopropane with methyl acrylate, which yields 3-methoxy-carbonylmethylenecyclopentane (73), does involve C—C bond cleavage. Reaction with the deuterium-substituted compound CHD=CDC02Me gives the cyclopentane derivative (74). An intermediate of the type (75) may be involved in this reaction. 

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