Cyclopentanes racemization

A hydrosilylation/cyclization process forming a vinylsilane product need not begin with a diyne, and other unsaturation has been examined in a similar reaction. Alkynyl olefins and dienes have been employed,97 and since unlike diynes, enyne substrates generally produce a chiral center, these substrates have recently proved amenable to asymmetric synthesis (Scheme 27). The BINAP-based catalyst employed in the diyne work did not function in enyne systems, but the close relative 6,6 -dimethylbiphenyl-2,2 -diyl-bis(diphenylphosphine) (BIPHEMP) afforded modest yields of enantio-enriched methylene cyclopentane products.104 Other reported catalysts for silylative cyclization include cationic palladium complexes.105 10511 A report has also appeared employing cobalt-rhodium nanoparticles for a similar reaction to produce racemic product.46... 

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... 

Microbial reduction of prochiral cyclopentane- and cyclohexane-1,3-diones was extensively studied during the 1960 s in connection with steroid total synthesis. Kieslich, Djerassi, and their coworkers reported the reduction of 2,2-dimethylcyclohexane-l,3-dione with Kloeokera magna ATCC 20109, and obtained (S)-3-hydroxy-2,2-dimethylcyclohexanone. We found that the reduction of the 1,3-diketone can also be effected with conventional baker s yeast, and secured the hydroxy ketone of 98-99% ee as determined by an HPLC analysis of the corresponding (S)-a-methoxy-a-trifluoromethylphenylacetate (MTPA ester).(S)-3-Hydroxy-2,2-dimethy1cyc1ohexanone has been proved to be a versatile chiral non-racemic building block in terpene synthesis as shown in Figure 1. 

Since the isolation of the chitinase inhibitor allosamidin from Streptomyces [90], the aminohydroxy-substituted cyclopentanes have been recognized as powerful and specific inhibitors of glycosidases [91]. The synthesis of (+) [92], as well as of racemic [93] mannostatin, which is a strong mannosidase inhibitor, should be mentioned here (Fig. 1). 

Widenhoefer and co-workers have developed an effective Pd-catalyzed protocol for the asymmetric cyclization/ hydrosilylation of functionalized 1,6-dienes that employed chiral, non-racemic pyridine-oxazoline ligands." " " Optimization studies probed the effect of both the G(4) substituent of the pyridine-oxazoline ligand (Table 7, entries 1-6) and the nature of the silane (Table 7, entries 6-15) on the yield and enantioselectivity of the cyclization/ hydrosilylation of dimethyl diallylmalonate. These studies revealed that employment of isopropyl-substituted catalyst (N-N)Pd(Me)Gl [N-N = (i )-( )-4-isopropyl-2-(2-pyridinyl)-2-oxazoline] [(i )-43f and a stoichiometric amount of benzhydryldimethylsilane provided the best combination of asymmetric induction and chemical yield, giving the corresponding silylated cyclopentane in 98% yield as a single diastereomer with 93% ee (Table 7, entry 15). 

Both fragranol and grandisol skeletons were obtained by treatment of racemic butyl 6,7-epoxygeranyl sulfide with butyllithium in 7V,7V,Ar, 7V -tetramethylethylenediamine (TMEDA). In addition to the trans-product trans-16 (fragranol skeleton) and the ra-product m-16 (grandisol skeleton), a cyclopentane derivative was also isolated.16... 

As an example (Scheme 12), exposure of racemic 72 to sodium methoxide resulted in a smooth fragmentation of the norbomyl backbone to achieve olefinic methyl ester 73, whose elaboration then afforded densely functionalized cyclopentane framework 74. Sodium acetate-mediated displacement of the iodo functionality within 74, followed by elimination of the mesylate group and base-promoted deacetylation finally provided the unsaturated carbasugar 75, which nicely served as a building block for the preparation of a set of neplanocin analogues. 

Oxo-trans-l,2-cyclopentane dimethylcarboxylate is the starting material for two total syntheses of racemic Brefeldine A 236>>.238> (gq 121). 

There are also a few reactions showing more or less preference for an anti SN2 reaction, including a cyclopentane-forming reaction with an enolate nucleophile,589 and a sulfur nucleophile.590 In addition, the reactions of alkyl cuprates with allylic acetates are always stereospecifically anti 5.176 > 5.177, although the formation of racemic product shows that regiocontrol has been lost. 

That the adsorption of the cyclopentane ring seems to proceed mainly flatly in deuterium exchange on films has been stated above (see Section I,D). Of considerable interest are the investigations on asymmetric catalysis initiated by Schwab et al. (273). In their work, one of the optical isomers reacted a little faster than the other in a racemic mixture. Terent yev and Klabunovskii (274, 273) carried out the catalytic asymmetric synthesis from optically inactive substances. The reactions were accomplished on metals deposited on dextro- and levorotatory quartz. Organic optically active carriers and admixtures give a still greater effect. On this problem see Klabunovskii (276). At the present time still more active catalysts for the reaction of asymmetric hydrogenation and polymerization have been revealed (277-279). 

A surprisingly different approach was followed for obtaining both enantiomers of l,2-bis(di-phenylphosphino)cyclopentane 26. a ligand used in catalytic hydrogenations (Section D.2.5.1.2.1.1.) and hydrosilylation (Section D.9.). The racemic product was prepared by the reaction of cyclopentene with white phosphorus and phosphorus trichloride at elevated temperatures, followed by treatment with phenylmagnesium bromide. The racemate formed a complex with nickel(II) bromide which undergoes a Pasteur-type spontaneous resolution on crystallization from dichloromethane. The crystals were separated by hand27. 

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