| Cycloaddition reactions represent powerful procedures for the production of complex products. The main benefit of utilizing cycloadditions to produce complex products is that they allow for the formation of multiple bonds and multiple stereogenic centers in a single synthetic operation.; Cycloaddition methods for seven-membered ring synthesis have been few in number and limited in scope, even though targets containing a seven-membered ring are numerous and are frequently medicinally significant. In the absence of general methods for the synthesis of seven-membered ring systems, the Wender group devised the first rhodium-catalyzed intermolecular [5+2] cycloaddition of an unactivated alkyne-vinylcyclopropane.; Reported herein are the first examples of rhodium(I)-catalyzed intramolecular [5+2] cycloadditions of alkenes and allenes with unactivated vinylcyclopropanes. Alkyl substitution at various positions of the allene, alkene or the vinyl portion of the substrates was typically well accepted. Reaction of alkene-vinylcyclopropanes led exclusively to the formation of cis-fused 5,7-bicyclic systems. In contrast, various allene-vinylcyclopropanes reacted to form mixtures of cis- and trans-fused diastereomeric cycloadducts. Extending this project beyond methodology, the total synthesis of (+)-dictamnol, a trinor-guaine sesquiterpene isolated from the roots of Dictamnus dascarpus TURCZ, was achieved via a [5+2] cycloaddition of an allene-vinylcyclopropane substrate.; The first analysis of the effects of cyclopropane substitution on the stereoselectivity, regioselectivity, and efficiency of the [5+2] cycloaddition is reported. For 1,2-disubstituted systems, while two regioisomers are possible only one isomer is observed and is derived from cleavage the less substituted bond. Additionally, for these substrate the 1,2-disubstituted systems, stereochemistry is transferred during the cycloaddition, translating into a 1,4-stereorelationship in the product.; Described herein is an efficient preparative scale synthesis of 1-(2-methoxyethoxy)-1-vinylcyclopropane and the investigation of the utility of this reagent as a new five-carbon component in metal-catalyzed [5+2] cycloadditions. A new cycloaddition procedure is also described that proceeds up to 12-fold faster and with 10-fold less catalyst than previously described, providing cycloheptenones in minutes with isolated yields of 75–97%.; Overall, the [5+2] cycloaddition serves as an efficient process for the formation of mono-and bicyclic seven-membered ring containing systems. This research has addressed issues of practicality, efficiency and generality for the rhodium-catalyzed [5+2] cycloaddition. |
