Cyclopentene, 4-hydroxy-4- synthesis

As discussed in Section 12.2.2, homoenolates can be accessed from a-hydroxy-enones, and an asymmetric synthesis of cyclopentenes has been achieved using this strategy with enones (Scheme 12.42) [15]. 

The first phase of our efforts was the unambiguous synthesis of each model substrate. PN and PX were already well characterized materials (1) While direct synthesis of the phenyl and carbomethoxy compounds from PN and/or PX was attempted, this approach was unsuccessful due to the sluggish reactivity of the norbornenyl double bonds in these molecules (2). A successful approach to CBN and (fiBN based on N-phenyl maleimide (NPMI) trapping of the respective thermodynamically favored 1-substituted cyclopentadienes is shown in Equation 1. Similarly, kinetic trapping of 2-phenyl cyclopentadiene, from the in situ dehydration of 3-hydroxy, 3-phenyl cyclopentene, gives a clean yield of (f)VN (Equation 2). The remaining phenyl isomer (VX) and the three other carbomethoxy isomers (CBX, CVN, CVX) were all obtained by the thermal isomerization chemistry described in the next section of this paper. They were each isolated in pure form by liquid chromatography We were unable to obtain any (f)BX or any of the 7-substituted isomers by any means. 

Park, K.H. et al. Enantioselective Synthesis of (IR,4S)-I-Amino-4-(hydroxy-methyl)-2-cyclopentene, a Precursor for Carbocyclic Nucleoside Synthesis. 2.4 1994 [165]... 

Although (1 R,4S)-(+)- and (lS,4R)-(-)-4-hydroxy-2-cyclopentenyl acetate are both available by enzyme-promoted enantioselective hydrolysis,8 9 different enzymes are, of course, required to achieve this stereochemical divergence. Economy would be realized if one of these enantiomeric products could serve as the starting point for the preparation of both antipodal forms of structurally more advanced intermediates. The importance of (4R)-(+)-10>11 and (4S)-(-)-tert-butyldimethylsiloxy-2-cyclopenten-1-one12 to prostaglandin synthesis is well established. The latent potential of these highly functionalized building blocks for the enantiospecific synthesis of other natural... 

This collection begins with a series of three procedures illustrating important new methods for preparation of enantiomerically pure substances via asymmetric catalysis. The preparation of 3-[(1S)-1,2-DIHYDROXYETHYL]-1,5-DIHYDRO-3H-2.4-BENZODIOXEPINE describes, in detail, the use of dihydroquinidine 9-0-(9 -phenanthryl) ether as a chiral ligand in the asymmetric dihydroxylation reaction which is broadly applicable for the preparation of chiral dlols from monosubstituted olefins. The product, an acetal of (S)-glyceralcfehyde, is itself a potentially valuable synthetic intermediate. The assembly of a chiral rhodium catalyst from methyl 2-pyrrolidone 5(R)-carboxylate and its use in the intramolecular asymmetric cyclopropanation of an allyl diazoacetate is illustrated in the preparation of (1R.5S)-()-6,6-DIMETHYL-3-OXABICYCLO[3.1. OJHEXAN-2-ONE. Another important general method for asymmetric synthesis involves the desymmetrization of bifunctional meso compounds as is described for the enantioselective enzymatic hydrolysis of cis-3,5-diacetoxycyclopentene to (1R,4S)-(+)-4-HYDROXY-2-CYCLOPENTENYL ACETATE. This intermediate is especially valuable as a precursor of both antipodes (4R) (+)- and (4S)-(-)-tert-BUTYLDIMETHYLSILOXY-2-CYCLOPENTEN-1-ONE, important intermediates in the synthesis of enantiomerically pure prostanoid derivatives and other classes of natural substances, whose preparation is detailed in accompanying procedures. 

In 1995, Mioskowski and co-workers reported a new carbenoid 1,2-alkyl rearrangement of a-hydroxy-substituted cyclopentene and cyclohexene oxides treatment of such systems with 3 equiv of an organolithium resulted in the formation of two products, as exemplified by the synthesis of dihydrojasmone and its regioisomer 99 (Scheme 44) <1995JA12700>. 

Some studies directed at the synthesis of the b + c + d rings of gibberellic acid, and in particular the fragment (134), have been reported.The Diels-Alder addition of butadiene to the cyclopentenone (135) afforded (136), which was converted via its iodo-lactone (137) into the tricyclic compound (138). However, the synthesis broke down at the removal of the ring D substituents. l-Hydroxy-7-methylenebicyclo[3,2,l]octane (139) provides a model for the gibbane-steviol c/d ring system. A synthetic route involves the photoaddition of allene to 1-cyclopentene-l-aldehyde to give l-formyl-7-methylenebicyclo-... 

Corey and coworkers , in a synthesis of prostaglandins, prepared diene 34 by alkylation of the lithiodithiane 32 with 2-bromomethyl-l,3-butadiene (equation 41). A synthesis of jasmone (35), in an overall yield of 50%, has been reported by Ellison and Woessner in which the bisdithianylethane 33 was sequentially alkylated, followed by hydrolysis and cyclization (equation 42). A similar route for preparation of 4-hydroxy-2-cyclopenten-l-ones has been reported . This method appears to provide a general route to 1,4-diketones via 1,3-dithianes. 

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