Thesis advisor: Amir H. Hoveyda / A previously developed catalytic system which can catalyze a variety of efficient and enantioselective allyl additions has been expanded to include regio-, diastereo-, Z-, and enantioselective crotyl addition reactions. As discussed in Chapter 1, we were able to carry out efficient crotyl additions to N-phosphinoyl imines by discovering a sufficiently Lewis acidic co-catalyst, zinc(II) methoxide. This finding enabled us to vastly improve reaction efficiency, in addition to enabling a 1,3-borotropic shift during the course of the reaction, turning a previously α selective transformation into a γ-selective one. These findings allowed us to develop a catalytic, enantioselective crotyl addition to N-phosphinoyl imines utilizing the commercially available Z-crotyl–B(pin). When the reaction conditions elucidated for crotyl additions to imines were utilized on a more electrophilic substrate, such as trifluoromethyl ketones, an entirely different finding was observed (Chapter 2). We found that if direct addition is more facile than 1,3-borotropic shift the transformation will again be α-selective, furnishing a linear product, rather than the typically observed, branched crotyl addition product. This finding allowed us to establish the first broadly applicable, efficient, regio-, Z-, and enantioselective crotyl addition to trifluoromethyl ketones. We then highlighted the utility of these products by using this method in tandem with Z-selective olefin metathesis, affording complex, enantioenriched, trifluoromethyl-containing homoallylic alcohols. During the course of these studies, and through density functional theory computations, we learned that Z- and E-crotyl–B(pin) react through distinct transition states to form the same Z-olefin-containing product with varying levels of enantioselectivity. These findings led us to the results reported in Chapter 3, the first examples of enantioselective aminophenol-promoted allyl additions to aldehydes. We were able to utilize Z-CF3-allyl–B(pin) and Z-Cl-allyl–B(pin) (both accessed through catalytic olefin metathesis) in Z- and enantioselective additions to aldehydes, affording products which cannot be accessed readily through previously reported methods. We quickly realized the potential of Z-chloro-substituted homoallylic alcohols for the synthesis of Z-homoallylic alcohols, to demonstrate this potential, we carried out the total synthesis of mycothiazole, which we accomplished in seven steps from commercially available materials and 17% overall yield, a marked improvement over the previous synthetic strategy. / Thesis (PhD) — Boston College, 2018. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.
| Identifer | oai:union.ndltd.org:BOSTON/oai:dlib.bc.edu:bc-ir_108140 |
| Date | January 2018 |
| Creators | van der Mei, Farid Willem |
| Publisher | Boston College |
| Source Sets | Boston College |
| Language | English |
| Detected Language | English |
| Type | Text, thesis |
| Format | electronic, application/pdf |
| Rights | Copyright is held by the author, with all rights reserved, unless otherwise noted. |
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