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Unveiling Incipient Reactivity via Tandem Hydrosilylation Reaction Cascades and the Progress Toward the Total Synthesis of (–)-Cylindrocyclophane A


Casselman, Tyler Daniel (2023) Unveiling Incipient Reactivity via Tandem Hydrosilylation Reaction Cascades and the Progress Toward the Total Synthesis of (–)-Cylindrocyclophane A. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/92b3-2d90.


The two pillars of synthetic organic chemistry, reaction methodology development and total synthesis of complex natural products, has remained the focus of chemical research for synthetic chemists since their fundamental inception. In particular, harnessing the reactivity of unstable, but useful, chemical intermediates through telescoping reaction conditions is emerging as an attractive approach to rapidly access complex molecular architecture from readily available building blocks. Herein is described two unique reaction methodologies relying on tandem hydrosilylation reaction cascades to synthesis saturated N-heterocyclic products in a stereoselective manner. We have developed a diastereoselective Mannich reaction combining α-substituted-γ-lactam pronucleophiles with N-silyl imine electrophiles generated in situ via catalytic hydrosilylation of aryl nitriles. Additionally, we have developed a tandem hydrosilylation, enantioselective allylic alkylation reaction of substituted pyridines to yield chiral tetrahydropyridine products. This serves as the first example of using hydrosilylation of pyridines to generate enamine nucleophiles that can undergo an asymmetric allylic alkylation reaction. The final portion of this thesis describes the progress toward a total synthesis of (–)-cylindrocyclophane using C–H functionalization logic. We were able to access the necessary [7.7]-paracyclophane core in 8 steps from a feedstock aryl diazoacetate compound and n-hexene. Through functional group manipulations, we were able to advance this paracyclophane core to an intermediate possessing the exact stereocenters and carbon framework in (–)-cylindrocyclophane A. We are currently modeling the necessary deoxygenation needed to advance this intermediate and complete the total synthesis.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Asymmetric Catalysis, Total Synthesis, Hydrosilylation, Mannich Reaction, Allylic Alkylation, Dearomatization, C–H Functionalization
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Stoltz, Brian M.
Thesis Committee:
  • Reisman, Sarah E. (chair)
  • Agapie, Theodor
  • Fu, Gregory C.
  • Stoltz, Brian M.
Defense Date:10 May 2023
Non-Caltech Author Email:tdc2122 (AT)
Record Number:CaltechTHESIS:06022023-191413115
Persistent URL:
Related URLs:
URLURL TypeDescription adapted for Ch. 2
Casselman, Tyler Daniel0000-0002-1691-3969
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:16059
Deposited By: Tyler Casselman
Deposited On:02 Jun 2023 23:41
Last Modified:08 Nov 2023 00:39

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