New methodology for the synthesis of tetrasubstituted alkenes

• Applicant: Dr. Hui Xie, Ph.D.
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 555471609

The efficient regio-, and stereoselective synthesis of tetrasubstituted alkenes presents a particular challenge in organic synthesis. The congested nature of the double bond can make it difficult for reagents to approach, and the eclipsing interactions in the products destabilize both the products and the transition states leading to them. This eclipsing destabilization can be severe enough to force geometric distortions of the sp2 centers. These issues are compounded by the modern expectation of forming single isomers on diverse scaffold. The significance of tetrasubstituted olefins is reflected in their presence in natural products, drug molecules and material chemistry, and chemical biology. Methods for alkene synthesis have been actively pursued for more than a century, which include carbometallation/electrophilic trapping of internal alkynes and transition-metal catalyzed crossing-coupling of multi-substituted alkenyl (pseudo) halides. However, the former method requires the use of electronically/sterically biased internal alkynes or directing groups to achieve high regioselectivity, while the latter creates a new problem of preparing the multi-substituted alkenyl (pseudo)halides selectively. Thus, new strategies to construct tetrasubstituted alkenes that involve combining simple starting materials would be highly attractive and would complement current olefination methodologies. Our project aims to address the challenges in the synthesis of tetrasubstituted alkenes by using C(sp)-B ‘-ate’ complexes derived from 9-BBN. Following addition of an electrophile, 1,2-migration of the substituent on boron to the adjacent alkynyl carbon will furnish a tetrasubstituted alkene bearing a borane with control of double bond geometry. Subsequent oxidation will furnish a more stable and isolable borinic ester which can be engaged in a large variety of further transformations. Following exploration of the scope of electrophiles and substituents that can be employed, we will explore the potential of the borinic esters for further stereoselective transformations including the selective creation of vicinal quaternary centres. The success of this project will lead to improved understanding of the chemistry of C(sp)-boron and borinic esters, and provide transformative approaches for the stereoselective synthesis of tetrasubstituted alkenes from simple feedstocks.

• DFG Programme: WBP Fellowship
• International Connection: United Kingdom
• Host: Professor Varinder Kumar Aggarwal, Ph.D.