Palladium-Catalyzed Synthesis and Racemization of Conjugated Allenynes

Abstract

Allenes are structurally unique compounds that can possess axial chirality. The most common strategy for allene synthesis is transition metal-catalyzed cross coupling with propargyl electrophiles. While these are powerful methods, they produce stoichiometric amounts of potentially toxic waste. Further, stereospecific variants of these reactions often suffer from substantial racemization of the enantioenriched allenyl products. Presented herein is the development of an atom economical and environmentally benign approach to synthesize both racemic and enantioenriched allenes, as well as the evaluation of the stereochemical effect palladium catalysts have on the generated enantioenriched allenes. Chapter 1 is an overview of the strategies most commonly employed for allene synthesis. The majority of the methods presented are transition-metal addition of preformed organometallic reagents which require harsh conditions and produce stoichiometric amounts of waste. As an alternative, the development of the palladium-catalyzed, decarboxylative coupling of propargyl propiolates is presented in Chapter 2. The developed coupling of propargylic esters selectively forms di- and trisubstituted allenynes in good yields. Further, the developed reaction requires no additional organometallic reagents or base, producing CO2 as the sole byproduct. As palladium-catalyzed couplings with propargylic electrophiles had been demonstrated to be stereospecific in the literature, Chapter 3 describes our attempt to develop the stereospecific variant of the palladium-catalyzed decarboxylative coupling of propargyl propiolates. It was demonstrated that the decarboxylative coupling can occur stereospecifically. However, like many other palladium-catalyzed syntheses of allenes, the coupling suffered from racemization of the enantioenriched product. Thus the remainder of Chapter 3 presents the kinetic studies employed to gain a greater understanding of the mechanism for palladium-catalyzed racemization of allenes, as only a small handful of reports in literature have lightly touched on the subject. Both palladium(0) and palladium(II) catalysts are explored as both species are present within the proposed catalytic cycle for the palladium-catalyzed decarboxylative coupling.