Regiodivergent Ligand‐Controlled Rhodium‐Catalyzed [(2+2)+2] Carbocyclization Reactions with Alkyl Substituted Methyl Propiolates

Abstract

The importance of transition metal-catalyzed reactions may be attributed, at least in part, to the manner in which they can control the formation of a specific product using ancillary ligands on the metal center. In this context, metal-catalyzed [2+2+2] carbocyclization reactions present a formidable challenge with respect to controlling chemo-, regio-, and various aspects of stereoselectivity. A fundamental objective in this area is the ability to predict and control the outcome of a specific transformation without recourse to extensive experimentation. In a program directed towards the development and understanding of this type of transformation, we described the first regioand enantioselective rhodium-catalyzed [(2+2)+2] carbocyclization of 1,6-enynes 1 with aryl substituted methyl propiolates 2 for the construction of bicyclohexa-1,3-dienes 3 (Scheme 1). As a consequence of this study, we were intrigued by the factors that control regioselectivity and whether the ancillary ligands could be modified to switch the regioselective outcome to provide selective access to both regioisomers. Herein, we now describe the regiodivergent rhodiumcatalyzed [(2+2)+2] carbocyclization of 1,6-enynes 1 with alkyl substituted methyl propiolates 2 for the construction of the bicyclohexa-1,3-dienes 3 and 4 (Scheme 1). Furthermore, these studies provide another example of the detrimental role that silver salts have on selectivity in a metalcatalyzed reaction, which has important implications for development and rationalization of related higher-order carbocyclization reactions. Table 1 outlines the preliminary studies to probe the feasibility of the regiodivergent carbocyclization reaction. Treatment of the 1,6-enyne 1a (X=NTs) and methyl 2-