Chiral cyclopentanones

Recently, an enantioselective total synthesis of ( )-18,19-dihydroantirhine has been reported by Kametani s group (140). They started from the chiral cyclopentanone derivative 211, obtained from the previously prepared (/ )-1,2-isopropylideneglyceraldehyde (141). Utilizing a number of reaction steps, 211 was transformed to 215 with the desired stereochemistry at the future C-15 and... 

The hydrodimerization of cinnamate esters formed with a chiral alcohol leads to asymmetric induction at the carbon-carbon bond formation step. The ester with bomeol gives a chiral cyclopentanone with greater than 95% enantiomeric excess [55]. A second approach towards achieving a chiral carbon-carbon bond formation has been to use the asymmetric oxazolidones 15 as substrates. These are reduced at... 

Scheme 18 shows interesting kinetic discrimination in the reduction of a chiral cyclopentanone 10b). Although (S)-BINAL-H is almost inert to the PGE derivative, reduction with the enantiomeric R reagent... 

Intramolecular hydroacylation, on the other hand, is an attractive catalytic process because it produces cyclic ketones. Furthermore, with appropriate chiral phosphine ligands, this reaction could convert prochiral 4-pentenals into chiral cyclopentanones (Scheme 5) [14]. 

Chiral cyclopentanones. The rcgiosclectivc cyclization of a diazo-(i-keto esters to cyclopentanones (11, 4.59) is also cnantiosclcctivc with substrates derived from chiral alcohols. Preliminary studies show that steric factors affect the diastereoselectivity the highest diastereoselectivity is obtained with esters of the alcohol 1. which is available from camphor, and in which both the bornane and the naphthalene rings can exert steric effects on the diastereoselectivity. 

The unusual pentacyclic system of (+)-pentacycloanammoxic acid (1) was created in 21 steps with an overall yield of 2%. The stereochemistry of the target was established relatively late in this convergent synthesis by a novel diastereoselective de Mayo reaction using the chiral cyclopentanone 7. Determination of the absolute configuration of (+)-l was accomplished in the course of the total synthesis by X-ray diffraction of the a,P-unsaturated ketone 25. Although many photochemical transformations occur in this total synthesis, the authors are in doubt about the involvement of photochemical processes in the biosynthesis of 1, as the natural environment of C. B. anammoxidans is dark and anaerobic. 

Miscellaneous Azides. Ethyl (A-methanesulfonyl)azidoformimidate [N3C (0Et)=NS02Me] has been used to aminate chiral cyclopentanone enamines but the yields are low and the reaction could not be extended to the corresponding cyclohexanone enamines.303 Trimethylsilyl azide (TMSN3) transfers the TMS rather than the azide group to a lactam enolate.339... 

Chiral cyclopentanones and y-butyrolactones are obtained by asymmetric hydrogenation of the corresponding alkylidene derivatives, catalyzed by binap-Ru complexes in 94-98% e.e. . Olefin geometry does not affect stereochemistry and enantioselectivity. 

A synthesis of (+)-estradiol from an alkyl 1,3-dihydrobenzo[c]thiophene-2,2-dioxide involving o-quinodimethane formation by thermal extrusion of SO2 and subsequent cycloaddition has been achieved in an overall yield of 50% (ref. 143). Thus a chiral cyclopentanone component (ref. 144) was used to alkylate the appropriate benzothiophene dioxide and the required tetracyclic stucture obtained directly with avoidance of the customary hydrogenation. It was found desirable at the alkylation stage to enhance deprotonation at Cl by having a cyano group in the benzenoid ring. The ( anotetracycle (R CN) was reacted... 

Circular dichroism measurements on R-(+)-2-methyl-l-tetralone have shown that it adopts a sofa conformation with a pseudo-equatorial methyl group. From a detailed study ° of the c.d. of chiral cyclopentanones and related compounds the 71 M band data suggest that C,—H bonds make dominant contributions in the octant-dissignate anti-octant sense. The magnitude of a —H contribution is... 

Incorporation of the new catalysis concept and N-heterocyclic carbene catalysis into multicatalytic systems emerged as a new direction to build up a complex scaffold such as those often found in natural products. Liu et al. developed an enantioselective Diels-Alder reaction via trienamine catalysis of indole-2,3-quinodimethane and activated alkenes. More recently, they combined this Diels-Alder process with N-heterocyclic carbene catalysis for the rapid generation of chiral cyclopentanone-fused tetrahydrocarbazoles with diverse substitution [30]. Mechanistically, with the... 

Yamamoto et al. have reported the synthesis of optically active 8-lactones by Baeyer-Villiger oxidation of chiral cyclopentanones [77] (Scheme 34). Asymmetric hydrogenation of enones 175 and 176 in the presence of 0.01 equivalent of Ru2Cl4[(5)-p-Tolyl-Binap]2NEt3 catalyst afforded chiral ketones 177 and 178 in good yield and with excellent enantioselectivity. These chiral ketones were found to show a fundamentally jasmine-like floral odor. Chiral ketones 177 and 178 were then transformed to 8-lactones 179 and 180 by Baeyer-Villiger oxidation with... 

A conceptually surprising and new route to prostaglandins was found and evaluated by C.R. Johnson in 1988. It involves the simple idea to add alkenylcopper reagents stereo-selectively to a protected chiral 4,5-dihydroxy-2-cyclopenten-l-one and to complete the synthesis of the trisubstituted cyclopentanone by stereoselective allylation of the resulting enolate. 

Asymmetric dimerization with cyclopentanone-2-carboxylate using BPPM as a chiral ligand gave the telomer in 41% eefSS]. 

Bis(4-hydroxyphenyl) sulphoxides butadienyl - see Butadienyl sulphoxides carbamoyl - see Carbamoyl sulphoxides chiral - see Chiral sulphoxides complexes of 567-573 conformational analysis of 84-89 cyclic - see Cyclic sulphoxides cyclopentanone - see Cyclopentanone sulphoxides... 

Nair and co-workers have demonstrated NHC-catalysed formation of spirocyclic diketones 173 from a,P-unsaturated aldehydes 174 and snbstitnted dibenzylidine-cyclopentanones 175. Where chalcones and dibenzylidene cyclohexanones give only cyclopentene products (as a result of P-lactone formation then decarboxylation), cyclopentanones 175 give only the spirocychc diketone prodncts 173 [73]. Of particular note is the formation of an all-carbon quaternary centre and the excellent level of diastereoselectivity observed in the reaction. An asymmetric variant of this reaction has been demonstrated by Bode using chiral imidazolium salt 176, obtaining the desymmetrised product with good diastereo- and enantioselectivity, though in modest yield (Scheme 12.38) [74],... 

The design of simulated moving bed chromatography and its application to the separation of cycloheptanone and cyclopentanone as test substances to validate the system for subsequent chiral chromatography has been described.27 Briefly, eight silica-packed columns were hooked up in series to form a cyclic flow path. On the first pair, preliminary separation of the components was performed, with the less-retained raffinate being directed to waste. Following the second pair of columns, eluent was added. After the... 

The sequence of chiral 1,4-reduction of a fi-substituted cyclopentenone followed by electrophilic trapping of the intermediate enolate provides an efficient route to chiral 2,3-disubstituted cyclopentanones that generates two chiral centers in the process (Eq. 352)459... 

Early work on the asymmetric Darzens reaction involved the condensation of aromatic aldehydes with phenacyl halides in the presence of a catalytic amount of bovine serum albumin. The reaction gave the corresponding epoxyketone with up to 62% ee.67 Ohkata et al.68 reported the asymmetric Darzens reaction of symmetric and dissymmetric ketones with (-)-8-phenylmenthyl a-chloroacetate as examples of a reagent-controlled asymmetric reaction (Scheme 8-29). When this (-)-8-phenyl menthol derivative was employed as a chiral auxiliary, Darzens reactions of acetone, pentan-3-one, cyclopentanone, cyclohexanone, or benzophenone with 86 in the presence of t-BuOK provided dia-stereomers of (2J ,3J )-glycidic ester 87 with diastereoselectivity ranging from 77% to 96%. 

After completing the enantioselective total synthesis of (+)-18,19-dihydro-antirhine [(+)-14](i40), Kametani et al. reported (394) the synthesis of (—)-antirhine [(-)-ll] by using (3S)-[3-hydroxy-( )-prop-l-enyl]cyclopentanone as a chiral synthon. 

Catalysed enantioselective aldol additions of latent enolate equivalents have been reviewed and electronic effects of the aldehyde component on such reactions of trichlorosilylenolates of cyclopentanone and cycloheptanone, catalysed by chiral phos-phoramides, have been interpreted in terms of initial aldehyde coordination to the trichlorosilyl enolate and aldolization via a six-membered boat-like transition state. 

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