Bicyclic 3-diketone reduction

By complexation of the rac-bicyclic diketone (rac-133) with 10a, R)- -)-l33 was included enantioselectively to give a 1 1 complex of 10a and enantiomerically pure R)-(-)-133. Treatment of the complex with NaBH4 in the solid state gave R,R)- -)-l34 of 100% ee in 54% yield [28]. Not only enantioselective but also regioselective reduction of the cyclopentanone moiety of 133 occurred. X-ray... 

Bicyclic diketone monoethylene ketal (162) prepared following the procedure of Kitahara et al. [53] was converted into octalin ketal (163) in one pot sequence which involves (a) reduction with liq. NH3, (b)... 

Reductions of symmetrical bicyclic diketones may also be effected selectively, as illustrated in Scheme 12. The stereospecificities of the HLADH-catalyzed transformations of the unsaturated decalin-diones (25) and (27) to the corresponding hydroxy ketones (26) and (28), and in fact all specificity aspects of this enzyme, are fully predictable using a simple to use, cubic-space model of the enzyme s... 

A novel approach to prostanoic acid was reported from Ayerst Laboratories. Irradiation of unsaturated keto ester 59a and I-chloro-3-oxooct-l-ene 40 led to the formation of bicyclic diketone 4. Treatment of the photoadduct with zinc and acetic acid led to the formation of methyl 9,15-dioxoprostanoate 42. This was transformed under varying reductive conditions to compounds 43 - all of which showed prostag I and in-1 ike activities in different pharmacological tests. 

The plan was to assemble the first carbocyclic ring of 3 by intramolecular aldol condensation of the keto aldehyde 15. The enantiomericaUy-pure secondary methyl substituent of 15 derived from the commercial monoester 10. Activation as the acid fluoride followed by selective reduction led to the volatile lactone 11. Opening of the lactone with HjCONHCHj HCl gave, after protection, the Weinreb amide 12. Alkylation of the derived hydrazone 13, selectively on the methyl group, led, after deprotection, to 15. The intramolecular aldol condensation of 15 did dehver the imstable cyclohexenone 1. Under the acidic conditions of the aldol condensation, the enol derived from the piperidone added in a Michael sense, from the axial direction on the newly-formed ring, to give the frans-fused bicyclic diketone 2. 

To add rings B and A to the diketone (100), Stork [13] first used the comparatively readily accessible [1053] 4-chloromethyl-3-methylisoxazoles as alkylating agents. The alkylation of the sodium enolate of the bicyclic diketones (100) with 3,5-dimethyl-4-chloromethylisoxazole led to compound (376) in good yield. The reduction of the A -bond in it did not affect the isoxazole ring, forming the trans-decalone (377). The transformation of the isoxazolylmethyl residue into the desired tricyclic system (383) was readily effected by the action of boron trifluoride etherate with subsequent treatment with bases in this case an intermediate was the diketone (380). 

Kat, M, Sarvary I, Frejd T, Hahn-Hagerdal B, Gorwa-Grauslund MF. An improved stereoselective reduction of a bicyclic diketone by Saccharomyces cerevisiae combining process optimization and strain engineering. Appl. Microbiol. Biotechnol. 2002 59 641-648. 

An interesting bridged-sulfur compound, which is a natural constituent of Iranian oil, has been synthesized 478) by the reaction of a bicyclic bis-enamine with sulfur dichloride and subsequent Wolff-Kishner reduction of an initial sulfur-bridged diketone. Sulfur dichloride has also been added to a number of vinylogous amides 479). 

Other systems, involving j5-diketones were also investigated and their reduction led to bicyclic products. For example, a 1,2-cyclopropanediol derivative (12) was isolated as its diacetate from the electrolysis of (11). 

The bicyclic ketone 324, initialily used to prepare lineatin (296) (below), has also been converted to the precursor 325 of grandisol (295). Ozonolysis of 324 yielded a diketone, 326, the structure of which was confirmed by X-ray crystallography. Selective reduction of the cyclobutane carbonyl group was effected by borohydride reduction of the specifically formed... 

Later, p-acetoxy-substituted cyclic enones 87 with various ring sizes were also examined for intramolecular Stetter cyclization. Under the optimized Stetter conditions (1.0 equiv. of thiazolium salt 88 and 1.2 equiv. of EtsN in EtOH under reflux), bicyclic enedione 89 could be synthesized effectively (Scheme 4.27), but the yields mainly depended on the size of the ring in the substrate 87." Increasing the substrate ring size led to improved yields of 89. Cycloheptenone and cyclooctenone derivatives 87c,d afforded the desired enediones 89c,d in 80% yields. To reduce the conjugated C-C double bond, McMurry s procedure" using TiCls as a reductant was employed to give diketones 90 in excellent yields. 

Total syntheses of steroids by the allgrlation of cyclic 1,3-diketones with bicyclic bromides are illustrated in Scheme 34. The product of the Birch reduction of resorcinol dimethyl ether (350), which is in the dienol ether of the diketone (338) gives, on alkylation with the bromide (3) and hydrolysis, the tricyclic ABD diketone (351), the cyclization of which with polyphosphoric acid leads to the 18-nor-D-homo derivative (352) [447]. 

Figure 28 Reduction of bridged bicyclic P-diketones with baker s yeast.

Asymmetrical reduction of some bridged bicyclic p-diketones 58, 60, 62, and 64 yielded ketols 59 [26], 61 [74], 63 [74], and 65 [74], respectively, as shown in Fig. 28. The hydroxy ketones 5 and 59 were the building blocks for the synthesis of glycinoeclepin A (Fig. 29), a degraded triterpenoid with remarkable hatch-stimulating activity against the... 

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