Cyclopentane derivatives stereoselective synthesis

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... 

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"). ... 

P. Chand, P. L. Kotian, A. Dehghani, Y. El-Kattan, T. H. Lin, T. L. Hutchison, Y. S. Babu, S. Bantia, A. J. Elliott, and J. A. Montgomery, Systematic structure-based design and stereoselective synthesis of novel multisubstituted cyclopentane derivatives with potent antiinfluenza activity, J. Med. Chem., 44 (2001) 4379-4392. 

M. R. V. Etheridge, Z. C. Khan, S. Hitchcock, P. B. Pairaudeau, G. Vile, S. Stereoselective synthesis of polyfunctionalised hydroxylated cyclopentanes from dihydroxylated 2-cyclopen-tenone derivatives. Tetrahedron 2001, 57, 6295-6303. 

Homeman, A.M. et al. Stereoselective Radical Induced Cyclisation of Unsaturated Aldonolactones Synthesis of Highly Functionalized, Enantiomerically Pure Cyclopentane Derivatives. 2.1 1995 [124]... 

Nickel-catalyzed carbozincation can also proceed smoothly vith alkynes for the synthesis of substituted alkenes regio- and stereoselectively. The reaction may proceed via an intramolecular version leading to tri- or tetrasubstituted alkenes. Thus, treatment of ry-iodoalkyne with RjZn in the presence of 7.5 mol% Ni(acac)2 in THF and NMP yield the cyclopentane derivative in 62% yield [102,112]. Presumably, a reductive elimination step from the corresponding organonickel intermediate may occur. It is noteworthy that no cydization is observed when internal alkyne is used. 

Cyclopentene-l-carboxaldehydes are obtained from cyclohexene precursors by the sequence cyclohexene - cyclohexane-1,2-diol -> open-chain dialdehyde - cyclopentane aldol. The main advantage of this ring contraction procedure is, that the regio-and stereoselectivity of the Diels-Alder synthesis of cyclohexene derivatives can be transferred to cyclopentane synthesis (G. Stork, 1953 G. BUchi, 1968). 

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]. 

Based on a domino Knoevenagel/cne reaction, Tietze and Steinmetz developed a stereoselective solid-phase synthesis of cyclopentane and cyclohexane derivatives of type 326 and 327 using a Merrifield resin modiiled with a propandiol linker 320 as shown in Scheme 4.6.3. Subsequent reaction with monomethyl malonoyl chloride 321 afforded the polymer-bound malonate 322, which, in a two-component domino reaction was treated with unsaturated aldehydes 323 in the presence of a catalytic amount of piperidinium acetate and zinc chloride. Except for a-substituted aldehydes, the initial Knoevenagel condensation occurred without addition of dehydrating agents and the subsequent intramolecular ene reaction gave cyclopentane and cyclohexane derivatives 325 after cleavage firom the resin either by reduction or transesterification. 

On the other hand, Wang and co-workers [28, 29] made two important contributions to the synthesis of cyclopentene derivatives. Both reactions were initiated with a carbo-conjugated addition of malonates derivatives. The first one was a double Michael addition between enals and 7-malonate-a,(3-imsaturated esters catalyzed by XII rendering the final cyclopentanes with three stereogenic centers in good yields (87-92%) and excellent stereoselectivities (84—99% ee) [28]. As for the second one, Wang and co-workers focus on the synthesis of cyclopentenes. This reaction was based on a Michael-aldol sequence followed by dehydration, between aromatic enals and dimethyl 2-oxoethylmalonate [29]. A set of densely functionahzed chiral cyclopentenes were synthesized in high yields (63-89%) and excellent enantiose-lectivities (91-97% ee) (Scheme 10.13). 

A comprehensive review has appeared this year on the conversion of carbohydrate derivatives to functionalized cyclopentanes and cyclohexanes, and another review has described the synthesis of natural products from carbohydrates using the Perrier rearrangement.2 (+)-Methyldihydroepijasmonate 2 has been prepared from levoglucosenone (Scheme 1). The n-pentyl group was introduced by stereoselective cuprate addition, and the carbocyciic ring was formed via 5-exo-trig alkylation of the enolate derived from 1 (Scheme 1)2... 

Tietze, L.F. and Steinmetz, A., Stereoselective solid phase synthesis of cyclopentane and cyclohexane derivatives by two component domino reactions Generation of combinatorial libraries, Angew. Chem. Int. Ed. Engl, 35 (1996) 651-652. 

The product distribution depends on the nickel-phosphine ratio and the best yield of A (70% cis/trans = 19/1) is obtained when bisdiene is treated in toluene at 60 °C with llmol% Ni(COD)2 and 33mol% PhjP [124]. When a phosphite ligand is used, cyclohexene B or cyclopentane C derivatives are the major products. Functional groups such as esters, ketones, or ethers remain intact under the reaction conditions. The reaction is stereoselective and has been used for the synthesis of polycyclic natural products [125-128]. For example, the key intermediate for the enantioselective synthesis (-H)-asteriscanolide is obtained from a similar synthetic route [128]. The use of this strategy for the construction of a taxan skeleton has been briefly explored [129]. 

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