New directions in pincer chemistry: 1) formation of iridium(III) allene complexes via isomerization of internal alkynes, 2) expanded substrate scope, and progress towards catalytic and enantioselective methodologies
The C-H bond is pervasive in organic molecules, and activation of this bond using transition metals has been intensely studied. Interest in developing Ir(III) complexes for C–H bond functionalization has been growing rapidly. Despite the significance of allenes in organic synthesis, very few metal mediated syntheses of allenes are reported, specifically, via C-H activation mechanisms. This thesis describes our efforts aimed at developing a new synthetic method capable of the synthesis of allenes via activation of C-H bonds by using Ir-pincer complexes. We believe such technology would expedite the synthesis of high value target molecules by eliminating the pre-functionalization steps that are commonly employed in modern synthetic chemistry, a practice that is inherently inefficient and results in the production of large amounts of chemical waste. While many highly efficient processes have been developed, one drawback is often the generation of undesired waste products. Recently there has been increasing emphasis on the development of processes built around oxidative addition reactions of C-H bonds. Such transformations offer potential advantages including (a) elimination of by-products (“atom economy”), (b) readily available substrates, (c) potential shortening of synthetic sequences, and (d) unique reactivity patterns.
The first section of this dissertation focuses on the development of a novel methodology for the isomerization of internal alkynes to the corresponding Ir-allene complexes which we propose to occur via a mechanism which incorporates C-H bond activation using the tBu4(POCOP)IrH2 pincer complex. This discovery encouraged us to more broadly examine the use of such complexes in the preparation of allenes. We also propose a C-H activation mechanism for the isomerization and internal alkynes involving the 14e- phosphinito Ir(I) complex [tBu4(POCOP)Ir], and further discussed the deuterium labelling experiments that support our mechanistic cycle. The results suggest the presence of a propargylic H in the substrate alkyne is of critically important for isomerization to occur. With this result in hand this thesis also involves the application of our isomerization protocol towards variety of non-symmetrical alkynes for synthesis of allenes. Further, in this chapter we have reported the kinetic studies of rate of isomerization of different substrates, along with the calculations of thermodynamic parameters. Lastly, the thesis consists of the extended application of our novel isomerization methodology in the synthesis of 9,10Δ-Tricosadiene (allene) naturally occurring in Australian beetles.
Second part of this dissertation involves our preliminary results involved in the development of catalytic protocol of our isomerization methodology for synthesis of allenes. In this chapter, we discuss three different approaches to render the isomerization occur catalytically by; (1) liberation of free allene under CO atmosphere, (2) tandem Diels-Alder reaction of Ir-bound allene, (3) building one armed-bidentate, sterically favored pincer ligand systems. We have reported our initial experiments involving tBu4(POCOP)IrH2 in presence of CO, successfully resulted to give a catalytic turnover (TON 20). Preliminary experiments related to tandem Diels Alder reaction of allenes with a dienophile has demonstrated the feasibility of our tandem reactions approach. We have also discussed the synthesis of bidentate pincer ligand systems and suggested future experiments. And finally, we have discussed out interest to develop an enantioselective isomerization protocol for the synthesis of chiral allenes using the BINAP type chiral Ir pincer complexes.