Hydrindanes synthesis

As the following reaction schemes indicate, the stereoselectivity of the reported hydrindane synthesis can be controlled by the choice of the starting materials. 

In the cis-hydrindane synthesis it is the hydrogen radical that approaches from the convex side of the bicychc silylether intermediate 454 (see 454 ), thus generating the cis-ring juncture of457. 

A third variation of this strategy has been appHed to an enantioselective total synthesis of cortisone. From an appropriately functionalized, scalemic hydrindan that possessed an 11-oxo-group and a masked corticoid side-chain, (+)-cortisol was produced in an 11-step total synthesis (213). 

Winterfeldt E. Enantiomerically Pure Cyclopentadienes Chem. Rev. 199393 827 843 Keywords synthesis of steroid cyclopentadienes, hydrindan dienes and their kinetic resolution... 

Mehta, G. Reddy, D.S. (2000) A Formal Synthesis of Reserpine Hydrindane Approach to the Woodward s Ring-E Precursor. Journal of the Chemical Society Perkin Transactions J, 1399-1404. 

Xb was utilized in the elaboration of the hydrindan XIII and subsequently compound XIV. We expected that Xa could be converted to XIII in the same manner as was in the Sih synthesis. This was confirmed in practice (Scheme II). Oxidation of 569 mg (2.68 mmol) of Xa with pyridinium chlorochromate in methylene chloride furnished 532 mg (94%) of enone Ila (7,21). Treatment of 130 mg of Xa witlj a slight excess of Jones reagent (3,22) afforded 126 mg (98%) of Ila. Allylic brominatlon of Ila with a 20% excess of N-bromosuccinimide (NBS) in refluxing carbon tetrachloride provided Xlla in 98% yield. 

Synthesis of a m-decalin system by the asymmetric cyclization[38] has been carried out with high enantioselectivity[142,143,147,148], Using BINAP as a chiral ligand, 91% ee was achieved in the asymmetric cyclization of 177 to give 178. In order to achieve an efficient asymmetric cyclization, selection of the reaction conditions is crucial, and sometimes added Ag salts play an important role[148], A catalytic asymmetric cyclization of 179 to prepare the key intermediate enone 180 for vernolepin synthesis has been carried out[149]. Highly efficient asymmetric cyclization of 181 to give the tetralin system 182 has been applied to the synthesis of (-)-eptazocine (183)[150], Hydrindans are synthesized in 86% ee[151]. 

Procter employed a highly diastereoselective Sml2-mediated intramolecular 1,4-addition during studies on the synthesis of faurinone treatment of iodide 77 with Sml2 in THF-HMPA gave cis-hydrindane 78 in good yield (Scheme 5.51).84... 

Przezdziecka, A., Stepanenko, W., Wicha, J. Catalytic enantioselective annulation using phenylsulfanylmethyl vinyl ketone. An approach to trans-hydrindane building blocks for ent-vitamin D3 synthesis. Tetrahedron Asymmetry 999, 10,1589-1598. 

Transannular cyclization of the (Z,Z)-isomer (51) of cyclonona-1,5-diene in the presence of a variety of electrophilic reagents provides a useful synthesis of a range of substituted ci.r-hydrindane derivatives (53 Table 4). In each of these cases the 1,5-diene unit in (51) is reacting in the T-conformation shown in (52). 

Table 4 Synthesis of ds-Hydrindane Derivatives (53) from 1,5-Diene (51)...

Scheme IX. Dolby s partial strigol synthesis. Preparation of the hydrindan 15.

A multi-step asymmetric synthesis of a hydrindane framework was achieved in water via asymmetric allylic alkylation, propargylation and aquacatalytic cycloisomerization of a 1,6-enyne, where all three steps were performed in water with the recyclable polymeric catalysts. The racemic cyclohexenyl ester 27 reacted with diethyl malonate under the conditions mentioned in Table 6.1 to give 90-92% ee of 34b. The polymeric chiral palladium complex 23-Pd was reused four times... 

Scheme 6,5 Asymmetric multistep synthesis of a hydrindane framework in water.

The general method described in Sect. 4.1.1 for decalin synthesis has also been applied to the synthesis of 6,5-ring systems through the formation of hydrindans (Scheme 6) [32]. 

Synthesis of frans-hydrindanes via bicyclization is effectively induced by a tetramethylallyl cation. The central double bond undergoes anti attack by the initial cation and the terminating nucleophile implying that E double bonds generate trans ring junctions and (Z)-olefins lead to the corresponding cis systems (Stork-Eschenmoser postulate)9. 

The same annulation method has been used in a stereocontrolled synthesis of picrotoxinin (3), a natural product with the hydrindane skeleton33,48. 

Chiloschyphone (1) is a sesquiterpene ketone isolated from Chiloscyphus polyanthos and its absolute configuration has not been determined (3). The structure of this compound was first reported in 1972 (4), but later a total synthesis of this compound revealed that this original structure was wrong (5). Quite recently the correct structure was proposed by Connolly and his co-workers to be that depicted as in 1 (3). The synthesis of this correct structure has not been achieved yet. We plan to introduce cw-dimethyl groups by 1,4-addition, followed by an intramolecular aldol cyclization to yield a hydrindane skeleton (Scheme 1). The optical resolution must be possible at the stage of compound 4. 

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