Periodic Reporting for period 2 - ReverseAndCat (Reversible Creation of Non-Inherent Reactivity Patterns in Catalytic Organic Synthesis)
Reporting period: 2020-05-01 to 2021-10-31
Projects finished in this period:
1. Multicatalytic Approach to One-Pot Stereoselective Synthesis of Secondary Benzylic Alcohols”:
Multicatalytic one-pot procedures bear the potential to rapidly build up molecular complexity without isolation and purification of consecutive intermediates. In this project, emerging from the previous work (https://doi.org/10.1038/s41929-018-0207-1) we established multicatalytic protocols that convert alkenes, unsaturated aliphatic alcohols, and aryl boronic acids into secondary benzylic alcohols with high stereoselectivities (typically >95:5 er) under sequential catalysis that integrates alkene cross-metathesis, isomerization, and nucleophilic addition. Prochiral allylic alcohols can be converted to any stereoisomer of the product with high stereoselectivity (>98:2 er, >20:1 dr).
2. “Enantioselective α-Arylation of Primary Alcohols under Sequential One-Pot Catalysis.”
Intrigued by the potency of our methods for synthesis of secondary benzylic alcohols from unsaturated alcohols under sequential catalysis (https://pubs.acs.org/doi/10.1021/acs.orglett.1c00939) we set off to develop also the enantioselective α-arylation of primary aliphatic under sequential catalysis. the protocol integrates a Ru-catalyzed hydrogen transfer oxidation and a Ru-catalyzed nucleophilic addition. The established method proved to be applicable to various alcohols and aryl nucleophiles tolerating a range of functional groups, including secondary alcohols, ketones, alkenes, esters, NH amides, tertiary amines, aryl halides, and heterocycles.
3. “Transfer CH Borylation of Alkenes under Rh(I)-Catalysis: Insight into the Mechanism, Control of Selectivity & Synthetic Capacity” - The project is going to be reported shortly.
Transfer CH borylation of alkenes – another example of a reversible catalytic reaction - bears the potential to unlock a range of attractive transformations for modular synthesis and late-stage derivatization of complex molecules. However, a limited mechanistic understanding of the reaction with its scarce precedence hinders the development of practical synthetic protocols. In this project, we first established the feasibility and conducted a thorough mechanistic study of the Rh(I)-catalyzed transfer reaction. A series of catalytic and stoichiometric experiments and complementary computational studies elucidated the full catalytic cycle providing insight into the features controlling the reactivity and the selectivity. The mechanism involves an unprecedented yet crucial -boryl elimination step that turned out to be notably easy, in contrast to the well-established alkene insertion into a Rh-B bond. Driven by the mechanistic insight, we devised a protocol that confirmed that the strategy is applicable to electronically and sterically varied terminal and internal alkenes and compatible with a plethora of functional groups, including often problematic motifs (e.g. aldehyde, alkyne, heterocycles). In a broader context, this mechanistic study sets the stage for the development of other plausible transfer CH functionalization reactions undergoing a similar reaction pathway.
4. Binuclear Pd(I)−Pd(I) Catalysis Assisted by Iodide Ligands for Selective Hydroformylation of Alkenes and Alkynes
Reversible reactions involving a catalyst, e.g. reversible activation of a small portion of a catalyst may also prohibit its irreversible deactivation. Intrigued by this concept, we set to address the limitations of hydroformylation, that is, a thoroughly investigated and broadly applied reaction in the industry (>10^7 metric tons yearly). Here, we established a highly selective and exceptionally active catalyst system that is driven by such a novel reversible activation strategy and features a unique Pd(I)−Pd(I) mechanism, involving an iodide-assisted binuclear step to release the product. This method enables β-selective hydroformylation of a large range of alkenes and alkynes, including sensitive starting materials. In a broader context, the new mechanistic understanding enables the development of other carbonylation reactions of high importance to the chemical industry.