Carbon-Carbon Bond-Forming Ligand Coupling through Sulfuranes in Organic Synthesis
Final Report Abstract
Sulfur ligand coupling allows intramolecular covalent bond construction between two organic fragments of hypervalent sulfur intermediates, sulfuranes. This intriguing phenomenon, although known for more than 50 years, has been largely overlooked in the field of synthetic organic chemistry. To illustrate the synthetic utility of sulfur ligand coupling, I aimed to identify a sulfoxide reagent that produces nucleophilic sulfur species, sulfenate anion (RSO–), upon reaction with a Grignard reagent (RMgX), where sulfur ligand coupling is a key step. In this pursuit, I discovered that an easily prepared, bench-stable sulfoxide reagent, benzyl 2-pyridyl sulfoxide, fulfills this role, uniquely enabling a one-pot, three-component assembly of sulfoxides and sulfinamides by trapping the sulfenate anions with appropriate carbon or nitrogen electrophiles. Additionally, by leveraging the ambident nature of the sulfenate anion, I achieved the one-pot, three-component synthesis of unsymmetrical sulfides. Furthermore, I developed a three-component, enantioselective synthesis of sulfinamides using an enantiopure oxaziridine as an effective asymmetric nitrogen transfer agent. My research has culminated in the publication of four original research articles and represents a significant step toward my overarching goal: to provide synthetic and medicinal chemists with first-choice reactions for preparing sulfur functionalities in a catalytic, enantioselective, and three-component manner.
Publications
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A Sulfoxide Reagent for One‐Pot, Three‐Component Syntheses of Sulfoxides and Sulfinamides**. Angewandte Chemie International Edition, 61(52).
Saito, Fumito
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A Sulfoxide Reagent for Sulfinylative Cross-Coupling. Synlett, 34(17), 1939-1942.
Saito, Fumito
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A Sulfur Monoxide Surrogate Designed for the Synthesis of Sulfoxides and Sulfinamides**. Angewandte Chemie International Edition, 62(51).
Austrup, David & Saito, Fumito
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One-Pot, Three-Component Assembly of Sulfides Using a Sulfoxide Reagent as a Sulfur Dication Equivalent. Organic Letters, 25(32), 6057-6061.
Saito, Fumito & Euteneuer, Simon
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Recent Developments on the Synthesis of Sulfoxides via Sulfenate Anions. Synthesis, 56(02), 220-228.
Saito, Fumito
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Enantioselective Synthesis of Sulfinamidines via Asymmetric Nitrogen Transfer from N−H Oxaziridines to Sulfenamides. Angewandte Chemie International Edition, 63(35).
Fimm, Marc & Saito, Fumito
