Transition metal-catalyzed tandem carbon-oxygen and carbon-carbon bond forming reactions of alkynes in (1) the addition-cyclization of carboxylic acids with 1,6-diynes and in (2) the total synthesis of frondosin B.

다국어 초록 (Multilingual Abstract)

Tandem C-O and C-C bond forming reactions, where oxygen functionalities can be installed with the requisite carbon-carbon bonds being formed in a single reaction step, can be a powerful synthetic tool for the manipulation of organic structures. One of the most important and well established versions of this type of reaction is the carboalkoxylation of alkenes, where a carbon atom and an oxygen atom are formally added across the unsaturation to give alkyl ethers. Such procedures usually take the form of alkoxycarbonylation reactions, where the carbon atom is derived from a carbonyl group or from carbon monoxide. These reactions have seen wide usage in organic synthesis. The carbooxidation of alkynes is far less studied and has seen little application in synthesis. This dissertation explores two different versions of such processes and their applications in synthesis.
The first example to be introduced is the ruthenium-catalyzed addition of carboxylic acids to 1,6-diynes to give six-membered carbocyclic and heterocyclic ring systems. This reaction displays a novel formal reactivity pathway through transition metal catalysis---the formation of a cyclic diene with incorporation of a carboxylic acid from an acyclic diyne which assembles six-membered ring systems, in a field where five-membered ring formation, via addition-cyclization, is ubiquitous. The scope and utility of the reaction is explored as well as the utility of the reaction products. The mechanistic aspects of the reaction are also explored in detail and several rational mechanistic proposals for this reaction are presented.
The second example to be introduced, will explore the endo-cyclative oxy-carbonylation reaction of ortho-alkynyl phenols in the context of the total synthesis of frondosin B. Although some of the formal reactions have been reported and explored, they have never seen any application in total synthesis. Several novel routes, centering around this general reaction theme, are presented.