| Since their official discovery in 1905 by Hermann Staudinger, ketenes have played an important role in organic chemistry. Very recently, they have been “rediscovered” as valuable precursors in asymmetric Lewis acid and Lewis base catalysis. Although many protocols have been developed for the preparation of disubstituted ketenes, monosubstituted ketenes are the synthetically more useful class of substrates. Unfortunately, the latter are very reactive and tend to dimerize, therefore often requiring specialized reaction conditions. In many applications they are accessed through in situ dehydrohalogenation from acid halides and must be reacted quickly thereafter. This dissertation describes the use of mostly monosubstituted ketenes and their application in asymmetric catalysis. Through the use of chiral nucleophilic catalysts we have successfully developed the first catalytic, asymmetric β-lactam synthesis as well as the first catalytic, asymmetric a-halogenation protocol.; Following a detailed introduction on the history and preparation of ketenes and their application in organic synthesis, Chapter 2 describes many novel procedures developed in our labs for the in situ generation of mono—as well as disubstituted ketenes. Chapter 3 presents our results ranging from the nucleophilic catalysis of β-lactams, its enantio- and diastereoselective version, to the first catalytic, asymmetric α-chlorination and bromination. Mechanistic and spectroscopic evidence is also presented to support the formation of “zwitterionic enolate” intermediates that ketenes form with suitable Lewis bases. Finally, in Chapter 4 we present the asymmetric synthesis of the first dimeric cyclophane diol structure, which we envision to use as chiral ligand in conjunction with various Lewis acids. |
