Hydrindane system

Only the heteroannular diene 523 is formed by treatment of both a- and, 3-allylic carbonates 522 and 524 in a hydrindan. system with a Pd catalyst. No homoannular diene is formed. 

The thallium trinitrate-mediated ring contraction of frani-decal-2-ones has opened up a new route to the hydrindane system, and fluorinative ring contraction of cyclic alkenes to afford difluorocycloalkanes has been induced by iodotoluene difluoride and EtsN-HF. A possible mechanism is shown in Scheme 78. The double bond of the cyclohexene ring is attacked by iodotoluene difluoride activated by HF from the axial direction, followed by the addition of a fluoride ion from the trans direction. Reductive elimination of iodotoluene from the resulting adduct, ring contraction and the addition of the fluoride ion to the carbocation stabilized by fluorine then take place to give the ring-contracted difluorinated product. 

In an aldol condensation an enolate adds to a carbonyl group. Among the various methods which have been developed to achieve regioselectivity those involving polarity alternation accentuation are a time-honored technique. For example, the closure of a more strained diquinane nucleus rather than a hydrindane system is possible by installing a phosphoryl group in the a-position of the appropriate ketone [148]. 

Cycloaddition of 4-phenyl-3//-l,2,4-triazole-3,5(4//)-dione to provitamin D3 affords exclusively the product formed by addition to the least hindered a-face of the more reactive diene, the structure was determined by X-ray8. The diastereoselectivity appears to be determined by the steric effect of the rran.v-hydrindane system, although the mechanism has not been elucidated. The cycloaddition of 4-phenyl-3//-l,2,4-triazole-3,5(4//)-dione was exploited to temporarily protect the diene group in the syntheses of la-hydroxy vitamin D3 7 a(X = H)8,9 and la,25-dihydroxy vitamin D3 7b (X = OH, starting from 25-hydroxy provitamin D3)10. Complete stereocontrol was observed in the cycloreversion step. For related cycloadditions to vitamin D3 see Section 7.2,10.3.4. 

Enantioselective bicvclization can be initiated by the Lewis acid catalyzed ring opening of a chiral acetal40. The C-O bond next to the axial methyl group breaks and the olefin attacks from the opposite face. A chairlikc transition state leads to the optically active /ranx-hydrindane system. Formation of the anti-trans-bicycle 3 is favored over reaction to the syn-/w/tx-produc13. 

Replacing the C-11 methyl group by a chiral a-hydroxyl substituent results in reduced yields and stereoselection presumably due to the negative inductive effect of the hydroxyl unit on the nucleophilicity of the double bond. Nevertheless, complete stereoselection is observed with the C-11 efs-hydrindane system which is isolated in 10% yield. Enantiomerically pure 11-hydroxy-norandrostene can be obtained from a chiral carbinol83. 

Moreover, tran.f-hydrindane systems can be obtained via sequential Claisen rearrangements and cyclization starting, e.g., with 3,4-dihydroxycyclohexenes 29242 398 or diol 30428. 

Formation of a tra 5-fused 5,6-ring junction can sometimes also be achieved selectively. In an early example from Stork, radical cyclization of silyl ether 126 proceeded in 36% yield but with complete stereoselectivity affording the frans-fused hydrindane system [51a]. In this case, the methyl and O Bu groups presumably reinforce the directing effect of the convex, newly formed silatricycle and H-abstraction is forced to occur from the sterically less hindered face (Scheme 10-43). 

A trans hydrindane system was also accessible by trapping the radical intermediate resulting from the first cyclization with an allyl group with net trans addition across the double bond establishing the desired trans ring junction (Scheme 10-57). 

Consistent with the observations detailed above, annelation of the vinyl bromide 49 under identical conditions (1.1 equiv of KH, 5 mol % Pd(dppe), THF, 55 °C) also proceeded with diastereoselectivity. Bicycle 50 was obtained as a single isomer with a trans-hydrindane system in 70% yield (Scheme 22). ° ... 

Stork published a series of seminal papers that evolved this concept to the alcohol-directed hydroxymethylation and methylation of decaUn and hydrindane systems. ... 

The important trans-fused, angularly methylated hydrindane system has been synthesized by means of an internal Michael reaction. Thus, treatment of the enone (85) with zirconium isopropoxide gave, after dehydration and hydrogenation of the ketol (86), a 40 1 mixture of trans- to cw-hydrindanes (87). ... 

D. Since any reaction in which the 0 4 atom takes place in a configuration-ally unstable form (free radical, carbanion, carbonium ion) leads to the stable cis-hydrindan system of rings C and D, the only possibility for obtaining the natural trans-C/D linkage is the use of catalytic hydrogenation. 

Ferraz HMC, Silva LF Jr. Thallium trinitrate mediated ring contraction of trawj-2-decalones an alternative entry to the hydrindane system, y. Org. Chem. 1998 63 1716-1718. 

The application of nonenzymic biogenetic-like olefinic cyclizations for the stereospecific construction of polycyclic systems, developed by W. S. Johnson and his school, represents an exciting new approach to steroid total synthesis. The synthesis of progesterone, outlined below, is based on the finding that an appositely placed acetylenic bond participates in polyolefinic cyclizations directly to produce the C/D trans-fused hydrindane system... 

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