Cyclopentane synthesis reactions

Taylor and Wei have also developed a versatile method for the synthesis of cyclopentanes employing readily available organolithium compounds as difunctional, conjunctive reagents. This strategy represents an anionic [3 + 2] approach to substituted cyclopentanes. The reactions of lithiated alkenes 149 with activated alkenes 150 afford cyclopentane derivatives 151 in reasonable yield and, in some cases, with excehent stereocontrol. The alkenes 150 must be added over extended times to minimize polymerization processes. The... 

The copper(I) catalysed photo-cycloaddition reactions of the dienes (160) have been studied. This process provides an efficient route to the (2+2) cycloadducts (160a) in the ratios and yields shown under the appropriate structures. These adducts are key components in an approach to the synthesis of A -capnellene. Copper triflate controlled photocycloadditions have also been used as a key step in the synthesis of some cyclopentanes. The reaction involves the cyclization of the dienes (161) under the copper(I) controlled conditions into the adducts (162) and this is followed by thermal reactions that bring about rearrangement and ring opening. 

In the first of these sequences, often called the Torgov-Smith synthesis, the initial step consists in condensation of a 2-alkyl-cyclopentane-l,3-dione with the allyl alcohol obtained from 6-methoxy-l-tetralone and vinylmagnesium chloride. Although this reaction at first sight resembles a classic SN displacement, the reaction is actually carried out with only a trace of base. 

A direct application of the ring-opening reaction of an epoxide by a metal enolate amide for the synthesis of a complex molecule can be found in the synthesis of the trisubstituted cyclopentane core of brefeldin A (Scheme 8.35) [68a]. For this purpose, treatment of epoxy amide 137 with excess KH in THF gave a smooth cyclization to amide 138, which was subsequently converted into the natural product. No base/solvent combination that would effect cyclization of the corresponding aldehyde or ester could be found. 

Ring contractions, such as the Tavorskii reaction on (38), or the cyclopentane aldehyde synthesis on p 374... 

RhH(PPh3)4 (1 mol%) exhibited higher catalytic activity and promoted a complete reversal in stereoselectivity to provide the trans isomer of 24 and 25 as the major reaction product. The czs-cyclopentane 29, derived from optically active 28, was converted to the differentially protected cyclopentane triol 29, which, in turn, converted to the differentially protected tetrad 30, a key intermediate in the synthesis of enantiopure bioactive carbo-cyclic nucleosides [19]. 

Tam and coworkers [311] developed a method for the synthesis of 1,3-disubsti-tuted cyclopentanes 6/4-124 and cyclopentenes. Thus, reaction of the condensed isoxazolines 6/4-123, easily obtainable by a 1,3-dipolar cycloaddition, gave 6/4-124 in good yields using Mo(CO)6 (Scheme 6/4.30). 

The synthesis of new 11-deoxyprostaglandin analogs with a cyclopentane fragment in the oo-chain, prostanoid 418, has been accomplished by a reaction sequence involving nitrile oxide generation from the nitromethyl derivative of 2-(oo-carbomethoxyhexyl)-2-cyclopenten-l-one, its 1,3-cycloaddition to cyclopenten-l-one and reductive transformations of these cycloadducts (459). Diastereoisomers of a new prostanoid precursor 419 with a 4,5,6,6a-tetrahydro-3aH-cyclopent[d isoxazole fragment in the oo-chain have been synthesized. Reduction of 419 gives novel 11-deoxyprostanoids with modified a- and oo-chains (460). 

The first catalytic 1,4-addition of diethylzinc to 2-cyclopentenone with over 90% ee was described by Pfaltz and Escher, who used phosphite 54 with biaryl groups at the 3,3 -positions of the BINOL backbone.46 Chan and co-workers achieved high enantioselectivity in the same reaction (up to 94% ee) by using chiral copper diphosphite catalyst (R,R,R)-41 48,48a 48d Hoveyda and co-workers used ligand 46 to realize excellent enantiocontrol (97% ee) in the 1,4-additions of 2-cyclopentenones,52 which may be used in the practical asymmetric synthesis of some substituted cyclopentanes (including prostaglandins). 

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... 

Cycloisomerization represents another approach for the construction of cyclic compounds from acyclic substrates, with iridium complexes functioning as efficient catalysts. The reaction of enynes has been widely studied for example, Chatani et al. reported the transformation of 1,6-enynes into 1-vinylcyclopentenes using [lrCl(CO)3]n (Scheme 11.26) [39]. In contrast, when 1,6-enynes were submitted in the presence of [lrCl(cod)]2 and AcOH, cyclopentanes with two exo-olefin moieties were obtained (Scheme 11.27) [39]. Interestingly, however, when the Ir-DPPF complex was used, the geometry of olefinic moiety in the product was opposite (Scheme 11.28) [17]. The Ir-catalyzed cycloisomerization was efficiently utilized in a tandem reaction along with a Cu(l)-catalyzed three-component coupling, Diels-Alder reaction, and dehydrogenation for the synthesis of polycyclic pyrroles [40]. 

Simultaneously to the synthetic studies described above, our model studies had progressed. Although the synthetic challenge in this part of the project was marginal the structure elucidation of the final products was complicated [41]. Starting material for the syntheses was 1-acetyl-1-cyclopentene (58) which was converted into the frans-cyclopentane rac-59 by a Sakurai reaction and a carbonyl olefination (Scheme 16). The synthesis of czs-cyclo-... 

Similar to Rueping s procedure, Hua and coworkers developed a BiCl3-catalyzed synthesis of 1,1-diarylalkanes also starting from electron-rich arenes and styrenes [68]. They found that styrenes 37 could be transformed to the substituted cyclopentanes 39 if catalytic amounts BiCl3 were applied (Scheme 30). This reaction is believed to proceed via an intermolecular ene-reaction between styrene and the carbocationic intermediate I, followed by an intramolecular Friedel-Crafts alkylation of the resulting intermediate II. 

The procedure described here serves to illustrate a general [3+2] annulation method for the synthesis of cyclopentane derivatives. A unique feature of this one-step annulation is its capacity to generate regio-specifically five-raembered rings substituted at each position, functionally equipped for further synthetic elaboration. As formulated in the following equation, the reaction proceeds with remarkably high stereoselectivity via the effective suprafacial addition of the three-carbon allene component to an electron-deficient olefin ("allenophile"). ... 

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