Chiral bicyclic ketones

The use of chiral auxiliary groups on the amide function permits the synthesis of chiral bicyclic ketones, e.g. 15, with enantioselectivity maximized with two chiral groups on the amide function.15... 

The racemic axially chiral bicyclic ketone 4 reported by Schuster and Suarez underwent partial photoresolution with /-CPL irradiation and a PSS was achieved in 6.7 h with 0.4% ee (Fig. 5.8), which is in a good agreement with the calculated ee value from the anisotropy factor (g = 0.0105 at 305 nm) [38]. However, when this compound was employed as a dopant, the enantiomeric enrichment was not sufficient to induce the phase transition from nematic to cholesteric state probably due to the low HTP. The Schuster s group further designed and synthesized a series of these... 

FIGURE 5.8 CPL-induced deracemization of axially chiral bicyclic ketone 4 and 5. 

The carbocyclic nucleosides 172 (X = Cl, Br, N3) of 5-fluorouracil have been made as racemates, the group X being introduced by displacement of a 3 - up mesylate,203 and the 6 -fluorospecies 173 (B = T, Ad) have been prepared by modification of earlier work in which a chiral bicyclic ketone was manipulated via strained tricyclic intermediates (see Vol. 23, p. 222 and Vol. 25, p. 262).204 The fluoroalkenes 174 (both isomers) have been made as potential inhibitors of adenosylhomocysteine hydrolase, by the same method as was reported last year in the ribonucleoside case (see Vol. 25, p. 250-251). ... 

Bonne, J. R., Reduction of Cyclic and Bicyclic Ketones by Complex Metal Hydrides, 11, 53. Bonner, W. A., Origins of Chiral Homogeneity in Nature, 18, 1. 

A final example, from the work of Trost (49), represents the only case in which an intramolecular Michael reaction has been catalyzed by a chiral amine. When the achiral cyclohexanone is treated with (- )-quinine and heated in toluene solution, the bicyclic ketone is formed in 83% chemical and 30% enantiomeric yield (eq. [8]). 

Extension of this elimination to the similar -hydroxy sulfoximines 5 having a chiral bicyclic ring system which can be obtained in a similar way from the corresponding chiral ketone and (R) or (.S )-.S -lithiomethyl-/V-methyl-5 -phenylsulfoxime, leads to the formation of the diastereomeric alkenylsulfoximines 6 in the same diastereomeric ratio of S 98 2. The steric course of the elimination of these /i-hydroxy sulfoximines is determined by the configuration of the sulfoximine group. 

Deprotonation of carbonyl compounds by chiral amide bases followed by trapping with silylating agents or aldehydes has become a common method for de-symmetrizing prochiral and conformationally locked 4-substituted cyclohexanones and bicyclic ketones. The literature through 1997 has been reviewed [45]. 

This finding has been exploited using other ketones and chiral bases. Thus deprotonation of the bicyclic ketone 30 by chiral base 3 in THF yielded the silylenol ether 31 in 84% ee under external quench conditions with added LiCl (Scheme 22)49. In absence of LiCl the ee was lowered to 33%. Internal quench conditions gave an ee of 82%. 

Photo induced interconversion of the configuration at an asymmetric C atom, has not been reported. For tyrosine it has been excluded even under high-intensity laser irradiation [66]. This chiral unit seems to be very stable. A bicyclic ketone system with (formal) double epimerization is described by Zandomeneghi et al. [67] (Eq. 33). This reaction proceeds, however, by a complex rearrangement mechanism and will be discussed in Sec. II.B. 

An example of the utilization of a bridged bicyclic ketone for preparation of an acyclic moiety is the stereoselective synthesis of the C-21 to C-27 segment of rifamycin-S, a member of the ansamycin family of antibiotics (Scheme 18). Rao et alP used ketone (61), derived from furan, to prepare lactone (62). Exhaustive reduction of (62) provided the segment (63), which contains five chiral centers of lifamycin-S. 

Another example of a highly regio- and enantiospccific microbial Baeyer-Villiger reaction is the transformation of racemic bicyclic ketone 17 by Acinetobacter TD 63433. This leads to chiral lactones 18 and 19 which are of particular interest as synthons for prostaglandin synthesis. Interestingly, each enantiomer of the racemic substrate reacts with a different regioselectivity for the oxygen atom insertion, and the enantioselectivity of the reaction is excellent. 

The adduct (157) derived in>m (5)-(141) and an a,p-unsaturated ketone (156) undergoes Simmons-Smith cyclopropanation which is directed by the coexisting p-hydroxysulfoximine chiral center. As outlined in Scheme 36, this is a new methodology for optical activation of cyclopropyl ketones (159). Indeed, optically active tricyclic ketones (-)-(161) and (-f)-(161) were synthesiz firm a bicyclic ketone (160) in optical purities of 96% and 94%, respectively (equation 36). 

A novel class of chiral indenes (verbindenes) was prepared from enantiopure verbenone by K.C. Rupert and coworkers who utilized the Shapiro reaction and the Nazarov cyciization as the key transformations. The bicyclic ketone substrate was treated with triisopropylbenzenesulfonyl hydrazide to prepare the trisyl hydrazone that was then exposed to n-BuLi. The resulting vinyllithium intermediate was reacted with various aromatic aldehydes to afford the corresponding allylic alcohols. 

For the enantioselective reduction of cyclic meso-imides and 1 -siloxy-2-alkanones, 1,2-reduction of other enones,the prototypal chiral bicyclic oxazaborolidine is adequate, although 81 has been used to reduce a-phenylthio-p-phenyl ketones to obtain precursors of a-hydroxy thioesters. The enantiomer of 81 mediates reduction of enediones to the corresponding chiral diols. ... 

Chemists have investigated asymmetric P-K reactions, using chiral diphosphine and diphosphite ligands to induce enantioselectivity. When (,S )-BINAP was added to a catalytic amount of Co4(CO)12, (S)-bicyclic ketone 106 formed in 55% yield with an ee of 88% (equation 12.99). Experimental evidence suggested that the active catalyst was dicobalt complex 107, in which BINAP binds in bidentate... 

The asymmetric cyclopropanation of functionalized double bonds bearing chiral auxiliaries has been successfully exploited in several recently reported syntheses, especially in the field of natural products. The Simmons-Smith reagent produced from diethylzinc/diiodomethane was used in the asymmetric functionalization of conformationally distinctive symmetric cis [n.3.1]bicyclic ketones. The methylene insertion on the chiral functionalized enol ethers 96 obtained from these ketones occurred with high 7t-facial selectivity, with only one exception (formation of 98 and 99), affording diastereomerically pure products 97. ... 

An appreciation of the ability of 48 to attain appreciable levels of double diastereoselection when reacted with chiral (racemic) vinyl organocerium reagents had earlier been gained in this laboratory [32]. Consequently, it occasioned no surprise to observe that 49 [33] adds to this bicyclic ketone with customary endo stereoselectivity to deliver 50 and 51 in a relative ratio of 92 8. The major product, easily purified by chromatographic means, was smoothly isomerized to 52 under anionic conditions at room temperature. For structural reasons, this sigmatropic change is required to proceed via a boat-like transition state. The all-... 

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