Synthesis, chiroptical properties and absolute configuration of spiro[1,3-benzodioxole-methanocyclooct[b]indole]

Abstract

The synthesis of chiral 1'H-spiro[1,3-benzodioxole-2,12'-[6',10']methanocyclooct[b]indole] 3, a fused polycyclic structure derived from bicyclo[3.3.1]nonane, was accomplished via the Fisher indolization reaction. Enantiomers of this structure were obtained by chiral HPLC enantiomer separation on a swollen microcrystalline triacetylcellulose column. Chiroptical properties of the resolved enantiomers containing indole and 1,2-methylenedioxybenzene chromophores were studied. Application of the sector rule to the 1,2-methylenedioxybenzene chromophore to establish the absolute configuration of this polycyclic structure did not lead to an unequivocal conclusion which is likely to be due to the transannular interaction of the chromophores. The enantiospecific synthesis from enantiomerically enriched (-)-(1R,5S)-bicyclo[3.3.1]nonane-2,9-dione 1 was performed to prove unequivocally the (+)-(6'R,10'S)-configuration of the title structure. This study demonstrates that semiempirical rules should be applied cautiously to the determination of the absolute configuration of molecules containing several chromophores.

Determination of Absolute Configuration Using Concerted ab Initio DFT Calculations of Electronic Circular Dichroism and Optical Rotation: Bicyclo[3.3.1]nonane Diones

“…Optically active 2,9-dione, 3 , has been obtained by using chiral chromatography of racemic 3 9 and via asymmetric cyclization of an enamine of 2-(methoxymethyl)pyrrolidine. , Transparent spectral region specific rotations 9,18 and UV CD 9 have been reported. The AC of 3 was first determined by using the UV CD and the Octant Rule, with the result (1 R ,5 S )-(+)/(1 S ,5 R )-(−) .…”

A study of planar chromophores in dichromophoric molecules by circular dichroism spectroscopy

“…4 The angle between the planes of these chromophores in the minimized structure of 9 was found to be about 808 (Fig. 4 cf.…”

“…Recently it was demonstrated that the application of the sector rule to the 1,2-methylenedioxybenzene chromophore to establish the absolute configuration of the polycyclic compound did not lead to an unequivocal conclusion, which is likely to be due to the interaction of the chromophores. 4 Thus CD spectroscopy is not only a tool for studying the absolute configuration of organic molecules but also is a means to examine interactions between functional groups, i.e. chromophores.…”

Different routes for the construction of biologically active diversely functionalized bicyclo[3.3.1]nonanes: an exploration of new perspectives for anticancer chemotherapeutics

“…afforded the chiral [b] indole 585 in high yields (Scheme 130). 291 A couple of years later, another article from the same team unveiled the synthetic route toward a C 2 -symmetric methylenebridged product 588. This time, hydrazine 586 obtained from 4hydroxy-6-methyl-2(1H)-pyran-2-one 292,293 was treated with diketone 577, and the 2,9-diaza-3,10-dimethyl-1,8-dioxo-2,5,6,7,9,12,13,14octahydro-6,13methanocycloocta[1,2-b:5,6b ′ ] diindole 588 was obtained through the bishydrazone 587 (Scheme 131).…”

“…afforded the chiral 1′H-spiro [1,3-benzodioxole-2,12′-[6′,10′]methanocyclooct [ b ]indole 585 in high yields ( Scheme 130 ). 291 …”