Synthesis and Absolute Configuration of Enantiomerically Pure D₃‐Trishomocubanes(Pentacyclo [6.3.0.0^2,6.0^3,10.0^5,9] undecane) and Trishomocubanones

Abstract

Complete separation of the enantiomers ( 2 a ) and ( 3 a ) was achieved by liquid chromatography of their diastereomeric esters (2c) and ( 3 c ) with (-)-camphanic acidr4] [silica gel columns, petroleum ether/ethyl acetate (92 : 8), separation factor: 1.11. Pure (2c) can also be obtained in 30% yield by By Giinter Helinchen and Gerhard Staiged"] Rigid chiral hydrocarbons and ketones are of special interest as test cases for chiroptic theories. Outstanding representatives are the enantiomeric trishomocubanes (Zf) and ( 3 f ) , in that they are apparently the smallest stable organic molecules of the point symmetry group Dj[l1.While racemic trishomocubane is very readily accessible via rearrangement of the alcohols ( 1 a ) and (1 b ) to the stereoisomeric 4,7-diiodotrishomocubanes with hydriodic acid and their subsequent reduction with zinc, only relatively tedious methods exist for the synthesis of derivatives appearing suitable for separation of the enantion~ers[21. We have how found that 4-hydroxy-7-iodotrishomocubanes are formed in good yields as intermediates in the first mentioned reaction and that these can be easily resolved into their enantiomers. The structures and properties of the new compounds are summarized in Table 1l3]. ( a ) : X = Y = OH, Z = H ( b ) : X = Z = O H , Y = H (c): X, Y = 0, Z = H P [**I This work was supported by the Deutsche Forschungsgemeinschaft.

Synthesis and chemistry of homocubanes, bishomocubanes, and trishomocubanes

“…'~~ Shortly after rac-8 had been synthesized, three research groups independently developed methods for preparing each of the enantiomers of 8 in optically pure form. The absolute configuration of each enantiomer determined.143-146 Helmchen and Staiger143 separated the mixture of diastereoisomeric esters that resulted from the reaction of rac-endo-4-hydroxy-exo-7-iodopentacyclo[6.3.0.02~6.03J0.05~9]undecane (182) with (-)-camphanic acid.Once an individual diastereoisomer, 184, had been obtained in optically pure form, it was converted into enantiomerically pure (3-8 by using the reaction sequence shown in Scheme 64 143. Nakazaki and co-worker~'~~ utilized Smith and Barborak's procedure141 to generate rac-cis-pentacyclo-[6.3.0.02~6.03J0.05~g]undecane-4,7-diol (186).…”

Systematic Enumeration and Symmetries of Cubane Derivatives

“…The syntheses of 104 / ( 102 / ) have been reported by Underwood125 and by Kent et al120 The absolute configuration of (−)‐ D 3 ‐trishomocubane 104 ( 102 ) has been determined by Helmchen and Staiger,121 while the absolute configuration of (+)‐ D 3 ‐trishomocubane ( ) has been determined by Nakazaki et al122…”

“…Although cubane itself1 and its derivatives such as basketane118,119 and D 3 ‐trishomocubane120–122 have attracted the interest of synthetic organic chemists,123,124 the theoretical foundations are restricted to qualitative phases without mathematical formulations. The edge strategy applied to a cubane skeleton aims at providing more quantitative perspectives.…”

Cage-Shaped Molecules Derived by Applying the Edge Strategy to a Cubane Skeleton

“…[18] and by Kent et al [10]. The absolute configuration of (−)D 3 -trishomocubane 17 has been determined by Helmchen and Staiger [11], while the absolute configuration of (+)D 3 -trishomocubane 17 has been determine d by Nakazaki et al [12].…”

“…The present article is devoted to the application of the edge strategy to a cubane skeleton of o h -symmetry, because cubane itself [7] and its derivatives such as basketane [8,9] and D 3 -trishomocubane [10][11][12] have attracted the interest of synthetic organic chemists, as summarized in a review [13]. Although systematic discussions based on D 3 -twisted bicyclo[2.2.2]octane molecular framework as a common structural unit have appeared [14], the edge strategy applied to a cubane skeleton aims at providing more quantitative perspectives.…”