Hydrindanones synthesis

A similar intramolecular Diels-Alder strategy was employed in an efficient synthesis to an appropriately functionalized hydrindanone nucleus (212). After functionalization, Diels-Alder cyclization, and appropriate functional group manipulation, this hydrindanone was converted into ( )-cortisone. The overall process afforded ( )-cortisone in a total of 18 chemical steps in approximately 3% yield. 

Scheme 10.4 Fallis s synthesis of hydrindanone in the approach to retigeranic acid...

Scheme 10.6 Trauner s synthesis of hydrindanone intermediates for sesterterpenes...

Scheme 10.7 Trauner s synthesis of ent-hydrindanone as intermediate for ent-retigeranic acid...

It was envisioned that hydrindanone 83 and cyclopentene 85 could be used as intermediates in the synthesis of e f-retigeranic acid A (1) and e f-retigeranic acid B (2), respectively. To prepare the building block 90, cyclopentene 85 was reduced with diimide (93 %) in order to prevent isomerization and subsequently deprotected with PPTS to yield hydrindanone 90 (quant.), which could provide access to <77/-retigeranic acid B (2) (Scheme 10.7). Hydrindanone 83 was reduced via an enol triflate and then subjected to Pd-catalyzed reduction to provide cyclopentene 91 (87 % from 83). Upon hydrogenation of 91 with Pd/C and cleavage of the acetal with iodine, protected hydrindanone 92 (95 % from 91) was obtained. The deprotection of 92 provided ent-60, whose enantiomer was used in previous syntheses of retigeranic acid A (1) by Corey [14] and Hudlicky [46, 47]. 

The cycloaddition-isomerization strategy has also been applied to the synthesis of hydrindanone. Thus, by using a modified Kanematsu s procedure, the keto aldehyde 40, a hydrindanone of the steroid C-D ring type, can be synthesized from a substituted furan via a cycloaddition-isomerization procedure and is followed by subsequent transformations . 

An approach to the synthesis of angularly substituted polycyclics through the Diels-Alder cycloaddition of dihydrothiophenes has been devised (69JA7780). The easily prepared 2,5-dihydro-4-methoxycarbonyl-2-thiopheneacetic acid methyl ester (316) was heated at 180 °C with excess butadiene to yield (317). Desulfurization and double bond reduction of the cycloadduct with W-5 Raney nickel gave (318) which was characterized by conversion to the corresponding diacid and comparison with an authentic sample. Dieckmann cyclization of (318) is known to lead to the 5-methyl-1-hydrindanone (319 Scheme 68). The use of other dienes in the [4 + 2] cycloaddition process will, of course, produce more highly functionalized hydrindanones. 

The first synthesis of racemic coriamyrtin (9) was presented by Inubushi et al. 128, 129, 205, 206). To achieve this aim, the authors developed a new protocol for the preparation of highly substituted cis-hydrindanones. 

A powerful catalyst for [2+2]cycloaddition is created from the bicyclic oxazaborolidine 135 and AlBr3. A hydrindanone frequently used in total synthesis of natural products is readily available from one such adduct in chiral form. ... 

Norbornenone is a frequently used starting material for the synthesis of highly functionalized ra-hydrindanones, as the geminal methoxy substituents also direct the nucleophilic attack to the endo position, e.g., in 6, 8, and jo1060,1061. 

Monosubstituted norbornenones may also be used as precursors for stereoselective rearrangements provided that the 7-substituent has a syn orientation to the carbonyl group. For example, dimethyl acetal 40 is used in the total synthesis of the iridoid monoterpene ( + )-dimethyl secologanoside 0-methyl ether (43)1068 as well as the synthesis of the civ-fused hydrindanone 471069. 

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