Novel Sesquiterpene Skeletons by Multiple Wagner–Meerwein Rearrangements of a Longipinane-1,9-diol Derivative

Abstract

The tricyclic sesquiterpene (1R,3R,4S,5S,7S,8S,­9S,10R,11R)-7,8-diangeloyl­oxylongipinan-1,9-diol, or rasteviol (7), underwent multiple Wagner–Meerwein molecular rearrangements and several hydride shifts when treated with Et2O–BF3 to generate the six new compounds (1R,3R,4S,5R,7S,­8S,9S,10R,11S)-7,8-diangeloyloxy-1,9-epoxyjiquilpane (8), (1R,3R,4S,5R,7R,­8S,9S,11S)-8-angeloyloxy-1,7-epoxyzamor-10­(14)-ene (11), (2S,3R,4R,5R,6R,­7R,8S,9S,10S)-7,8-diangeloyloxy-6,9-epoxyjanitziane (14), (4R,5R,7S,8S,9S,­10S,11S)-7,8-diangeloyloxy-9-hydroxyjiquilp-3­(15)-ene (16), (2S,3S,5R,7S,­8R,10S,11R)-7,8-diangeloyloxyiratzian-9-one (18), and (2S,3S,5R,10S,11R)-8-angeloyloxyiratzi-7-en-9-one (22), of which 8, 11, 14, and 18 possess new hydrocarbon skeletons. Their structures were determined by 1D and 2D NMR in combination with single-crystal X-ray diffraction analyses of derivatives 10, 15, 20, and 21, which allowed confirmation of their absolute configurations by means of the Flack and Hooft parameters. In addition, some reaction mechanism information was gained from deuterium labeling experiments.

Novel Sesquiterpenoid Skeletons by Wagner–Meerwein Rearrangements of Longipinane-9,13-diol-1-one Derivatives

“…The reaction mechanisms for the rearrangement of 2 into 10 and 11 (Schemes and ) are proposed in accordance with the extensive reports for terpenoid transformations, ,,− supporting the existence of 1,2-hydride shifts and retro-aldol cleavages. − For the formation of 10 (Scheme ), Lewis acid coordination at the C-9 angeloyloxy group of 2 induces migration of the antiperiplanar C-4–C-10 bond to form the C-4–C-9 bond. The carbocation at C-10, shown in A + , then undergoes a C-1–C-11 bond migration to form the C-1–C-10 bond, providing the C-11 cation B + , which is prone to form a tetrahydrofuran ring by attack of the C-13 hydroxy group.…”

“…The transformation of tertiary carbocation A + into the less stable secondary carbocation B + during the rearrangement of 2 into 10 (Scheme ) and that of F + into G + and H + during the rearrangement of 2 into 11 (Scheme ) may be understood considering that, in each case, there is a rapid equilibrium whose next step is the driving force toward more stable species. These transformations may also be rationalized in terms of nonclassical carbocations as recently considered for related molecular rearrangements …”

“…It is known that the degree of functionalization and stereochemistry of the functional groups present in the longipinane skeleton are decisive in directing the rearrangements toward the six- or the seven-membered ring. This allows rearrangements in highly functionalized longipinanes to generate various novel skeletons and provide valuable information about their chemical behavior, which is very useful for the design of new synthetic strategies. − …”

Deuterium effects on the vibrational circular dichroism spectra of flavanone

“…The presence of deuterium in an organic molecule has allowed us to make very detailed reaction mechanism studies because chemical means allow the incorporation of the heavier isotope of hydrogen at regiospecific molecular locations 2 . The isotope incorporation can be monitored by hydrogen nuclear magnetic resonance ( 1 H‐NMR) measurements where specific deuterium labeling even allows detailed studies of complex molecular rearrangements 3 …”

“…2 The isotope incorporation can be monitored by hydrogen nuclear magnetic resonance ( 1 H-NMR) measurements where specific deuterium labeling even allows detailed studies of complex molecular rearrangements. 3 NMR spectra are routinely determined in deuterated solvents, a usage that has been extended to vibrational circular dichroism (VCD) studies because the difference in IR absorptions of the C-H vibration of CHCl 3 , as compared to the C-D vibration of CDCl 3 , extends the spectroscopic absorption window from around 1250 to 950 cm −1 , an expansion that can further go down to 850 cm −1 if solubility allows to measure spectra in CCl 4 .…”