Alkoxy accelerated beta-fragmentations of alcohols and lactols with lead tetraacetate and copper(II)acetate: Study of the regioselectivity of chromium-mediated [6+4] cycloadditions using thiepin-1,1-dioxide and application to the synthesis of calamenene

New conditions to perform alkoxy accelerated β-fragmentation of lactols, which produced an alkene and a carbonyl moiety in a single step, were discovered. The scope and limitation of this methodology toward the fragmentation of alcohols and lactols were studied. It was found that although these conditions gave excellent results in certain cases, it was not a universal methodology and in other cases many side reactions occurred. Nevertheless, this methodology was found to be a useful alternative to existing conditions.;The knowledge and understanding of the regioselectivity of a reaction is a key factor in the design of a total synthesis. Thermal concerted reactions such as the Diels-Alder are known to be controlled by electronics. Unfortunately, an earlier study in our laboratory showed that electronics did not play a major role in the control of the regioselectivity of chromium(0)-mediated cycloadditions. Warshakoon discovered that sterics might play an important role in this matter and therefore a systematic study on the effect of sterics on the regiocontrol of these reactions was undertaken using monosubstituted thiepin-1,1-dioxides as trienes. New methodologies for the preparation of thiepin dioxides were explored and synthesis of various monosubstituted thiepin dioxides were achieved. Chromium(0)-mediated cycloadditions involving 4-substituted thiepin dioxides gave excellent regioselectivity, whereas reactions involving 3-methylthiepin dioxides gave poor selectivity. A possible mechanistic explanation for this regioselectivity trend is outlined. Postcycloaddition manipulations were performed and produced ten-membered ring systems containing cis-conjugated trienes as well as bicyclic systems containing an aromatic ring.