1 -Hydrindanone

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. 

The conversion of tricyclo-[4,4,0,0]-decan-4-one (237) into the moiiodeutera-ted hydrindanone (238) serves as a good illustration of this labeling proce-... 

A similar dissection of the excited states responsible for reaction by quenching has been carried out on cis- and /ra 5-8-methyl-1 -hydrindanone and cis- and frans-9-methyl-l-decalone with the purpose of determining the... 

Table 4.4. Cleavage and Isomerization of 8-Methyl-l-hydrindanones and 9-Methyl-l-decalonesaS),a...

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 . 

Scheme 9. Enantioselective domino reaction for the formation of hydrindanones with heterobimetallic catalysts...

Only Cram (36) has published a rationale for the very high (99%) enantiomeric excess achieved in the reaction of methyl vinyl ketone and the hydrindanone in the presence of the chiral crown ether. This mechanism envisions a bimolecular complex comprising the potassium cation and chiral host as one entity and the enolate anion of the hydrindanone as the counterion. Methyl vinyl ketone lies outside this complex. The quinine-catalyzed reaction appears to have a termo-lecular character, since the hydroxyl of the alkaloid probably hydrogen bonds with the methyl vinyl ketone—enhancing its acceptor properties—while the quin-uclidine nitrogen functions as the base forming the hydrindanone—alkaloid ion pair. 

Modifications in the benzyl portion of the molecule are significant. The nitro group in the benzyl portion of the molecule apparently increases the local polarity of the transition state. The influence on the chemical and enantiomeric yield of variations in the benzyl portion of the quininium salt was dramatically confirmed recently by the work of Dolling and coworkers on the phase-transfer alkylation of a hydrindanone (83). 

Useful bicyclic ring systems are obtained by (TMS)3Si radical-mediated fragmentation of strained ketoalkene precursors. For example, the ketoalkene 64 reacted with 1.5equiv of silane to give 95% of hydrindanone 65 (Reaction 7.67) [78]. (TMS)3Si radical adds first to the terminal alkene and the carbon-centred radical can relieve the strain by cleaving the adjacent C—C bond. 

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. 

Several groups have prepared cyclopentane systems by intramolecular Michael addition.72 Reaction of the triester (292 Scheme 37) with phenyl vinyl ketone (293) and base produces the cyclopentane (295) in good yield via an intermolecular (giving 294) and subsequent intramolecular Michael addition.72 When the Michael acceptor is a cyclohexenone (Scheme 38), the c/s-fused hydrindanone is produced (298 or 297).72b 72f Spiro systems can also be formed by these reactions (300a,b equation 66) in which the Michael addition gives a spiro ring fusion. 

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