The directed remote metallation-carbamoyl migration reaction. Total syntheses of the defucogilvocarcins and arnottin I and synthesis of heteroarylfused benzopyranones

Total synthesis of the naturally occurring 6H-naptho[1,2- b]benzo[d]pyran-6-one defucogilvocarcin V 149d has been accomplished in 9 steps and 14% overall yield. A high yielding Suzuki coupling reaction allows the preparation of the key biaryl carbamate for the DreM - carbamoyl migration process. Investigation of several protecting groups (TBS, i-Pr and MOM) allowed a determination of the stability of these groups to the DreM conditions. Preparation of the required AB ring coupling partner was carried out in two ways; a detailed investigation of benzyne chemistry provided one route to the desired O-naphthylcarbamate. A more efficient route based on the selective carbamoylation of juglone derivatives was adopted. From a common triflate, introduction of substituents required for the preparation of defucogilvocarcins M and E was accomplished, using Pd(0) catalyzed cross coupling chemistry.; Total synthesis of the naturally occurring arnottin I 158 was accomplished using DreM - carbamoyl migration methodology combined with DoM and cross coupling. The methylenedioxy group was found to be unstable to the DreM conditions and several alternative groups for protection of catechols were investigated (i-Pr, MOM). Efficient synthesis of the AB coupling partner 306 was accomplished via an aryne based route. The total synthesis was accomplished in 11 steps and 1.8% overall yield.; The synthesis of four thieno[3,2-c]benzo[e]pyran-4-ones 499a-d was accomplished using the DreM - carbamoyl migration strategy combined with DoM and cross coupling. The 2-heteroarylcarbamates were prepared by either the Negishi or Suzuki reaction. In general, the Suzuki coupling proved more efficacious; however, the coupling reactions invariably were more efficient when the heteroaryl coupling partner contained the metal species. In a similar manner, several other classes of heteroarylbenzopyranones were prepared including 6H-thianaphtheno[2,3-c]benzo[ e]pyran-6-one, a previously unknown ring system.