Nickel Catalyzed Dicarbofunctionalization of Alkenes with C(sp2) and C(sp3) Coupling Reagents
Restricted (Penn State Only)
- Author:
- Wickham, Laura
- Graduate Program:
- Chemistry (PHD)
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- September 29, 2022
- Committee Members:
- Philip Bevilacqua, Major Field Member
Philip Bevilacqua, Program Head/Chair
Ramesh Giri, Chair & Dissertation Advisor
Elizabeth Elacqua, Major Field Member
Bert Chandler, Outside Unit & Field Member - Keywords:
- organic chemistry
method development
dicarbofunctionalization
organometallic - Abstract:
- Alkene difunctionalization is a powerful method in organic synthesis. Recently, difunctionalization of alkenes with two carbon sources, termed alkene dicarbofunctionalization, has emerged as a formidable reaction with immense promise to synthesize complex molecules expeditiously from simple chemicals. This process is generally achieved with transition metals (TMs) through interception by carbon sources of an alkylmetal [-H-C(sp3)-[M]] species; a key intermediate prone to undergo rapid b-H elimination. Therefore, reports in this area, since Chiusoli and Catellani’s work in the early eighties, have focused on the use of bicyclic and disubstituted terminal alkenes. In these alkenes, -H elimination is avoided by geometric restriction or complete lack of -H’s. We reasoned that [-H-C(sp3)-[M] intermediates could be rendered amenable to interception with the use of 1st row late TMs; and the formation of coordination-assisted transient metallacycles. This led to the successful development of novel dicarbofunctionalization reactions of alkenes. Chapter 1 focuses on three-component alkene dicarbofunctionalization performed in the field, as well as in our own group. It presents the evolution of the field of dicarbofunctionalization starting with early reactions that utilized bicyclic alkenes, conjugated dienes and disubstituted terminal alkenes as substrates. Next, the use of a removable coordinating group to form a transient -H-C(sp3)-metallacycle is presented. Finally, the use of electronically polarized alkenes is addressed. The methods illustrate the expansion of both scope and depth of dicarbofunctionalization reactions. Chapter 2 presents a novel intermolecular Ni-catalyzed regioselective reductive 1,3-dialkenylation reaction that we were able to successfully develop, further building on one product previously observed in low yields (15%). This reductive dicarbofunctionalization reaction uses alkenyl triflates as the electrophile to create two new carbon-carbon bonds in a single step. Based on NMR analysis, a high degree of regioselectivity was achieved as only the 1,3-regioisomer is observed for this dialkenylated product. Additionally, this reaction is able to occur without the necessity for an external auxiliary moiety. Chapter 3 highlights two dicarbofunctionalization reactions that were developed and optimized by Dr. Roshan K. Dhungana. The first reaction discussed, Ni-catalyzed dialkylation, uses benzyl halides and alkylzinc reagents to produce two new alkyl-alkyl bonds. The second reaction is the arylbenzylation of alkenylarenes using benzyl halides and arylzinc reagents. My contribution to this work is the isolation and characterization of 26 compounds via 1H, 13C and 19F NMR, which are displayed accordingly. Additionally, I performed the collection of IR data to further confirm the structures of 91 synthesized products. Chapter 4 presents the experimental procedures used to optimize and develop the aforementioned reactions. This includes the procedures for general reaction screening, procedures for the preparation of organometallic reagents and substrates. Additionally, the characterization data for new compounds are given.