Thesis advisor: Amir H. Hoveyda / Chapter 1. Efficient Z-Selective Synthesis of Allylic- and Alkenyl Boronates by Catalytic Cross-Metathesis Efficient Z-selective cross-metathesis reactions to furnish Z-(pinacolato)-allylboron and Z-(pinacolato)alkenylboron compounds through catalytic cross-metathesis are disclosed. Z-allylic boron compounds are generated by the use of catalytic amounts of a W-based monoaryloxide monopyrrolide (MAP) complex in up to 91% yield and 96:4 dr after allylation to benzaldehyde. Alkenylboron compounds are prepared in high yields and high Z selectivity in up to 93% yield and 97:3 Z:E. Cross-metathesis reactions with 1,3-dienes and aryl olefins are efficient and highly Z-selective. Combination of cross-metathesis and cross-coupling to synthesize anticancer agent combretastatin A-4 highlights the utility of this approach. Chapter 2. Synthesis of Macrocyclic and Acyclic Z-Enoates and (E,Z) or (Z,E) Dienoates by Catalytic Cross-Metathesis The first examples of kinetically controlled catalytic olefin metathesis reactions to generate Z-α,β-unsaturated macrocyclic and acyclic esters are disclosed. The synthesis of (E,Z) or (Z,E)-dienoates are also presented. Reactions promoted by 3.0–10 mol % of Mo-based monoaryloxide monopyrrolide complex proceed to completion to the desired macrocycles within 2–6 h at room temperature. Macrocycles of diverse ring sizes are formed in 79:21 to >98:2 Z:E selectivity. Pure Z isomers can be obtained after purification in up to 75% yield. Acyclic Z-α,β-unsaturated esters are prepared in the presence of acetonitrile to avoid using excess amounts of the more valuable cross-partner substrate. Spectroscopic investigations and X-ray analysis rationalize the positive effect of acetonitrile in the reaction system. Linear (Z)-enoates are generated in up to 71% yield and up to >98:2 Z:E. (E,Z)-Dienoates are generated with high Z selectivity as well. The utility of the ring-closing metathesis and cross-metathesis is highlighted by the synthesis of an (+)-aspicilin precursor and the C1–C12 fragment of biologically active natural product (–)-laulimalide. Chapter 3. Application of E-Selective Catalytic Ring-Closing Metathesis in the Total Synthesis of Dolabelides A, B, C and D Efforts towards the enantioselective synthesis of the dolabelide family of anti-cancer macrolides is presented. Development of a total synthesis incorporating a late-stage kinetically E-selective RCM is illustrated. Previous attempts to synthesize the macrolide by ring-closing metathesis (RCM) have demonstrated poor efficiency and low selectivity for the E isomer. Methodology developed in our group with acyclic trisubstituted cross-metathesis demonstrates that high selectivity can be achieved with stereodefined 1,2-disubstituted and trisubstituted olefins by the use of the proper catalyst and reaction design. Modern catalytic and stereoselective approaches towards the two main fragments of dolabelide are presented. More efficient and concise routes will be pursued to highlight the utility of the proposed disconnections and practicality of the total synthesis / 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_107714 |
| Date | January 2018 |
| Creators | Yu, Elsie |
| 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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