1,3-Aza-Brook Rearrangement of Aniline Derivatives: In Situ Generation of 3‑Aminoaryne via 1,3-C-(sp²)‑to‑N Silyl Migration

The design, synthesis, and validation of 3-aminobenzyne precursors induced by C-(sp2)-to-N 1,3-aza-Brook rearrangement have been achieved, allowing access to diverse aniline derivatives. Through crossover experiments, we demonstrated the intramolecular mechanism of 1,3-C-to-N silyl transfer. To gain insight into the regioselectivity observed in the reactions, we performed density functional theory calculations. Finally, the method was applied to the synthesis of xylanigripones A in five linear steps in an overall yield of 30%

Diversity-Oriented Synthesis of 2,4,6-Trisubstituted Piperidines via Type II Anion Relay Chemistry

An effective, general protocol for the Diversity-Oriented Synthesis (DOS) of 2,4,6-trisubstituted piperidine congeners has been designed and validated. The successful strategy entails a modular approach to all possible stereoisomers of the selected piperidine scaffold, exploiting Type II Anion Relay Chemistry (ARC), followed in turn by intramolecular SN2 cyclization, chemoselective removal of the dithiane moieties and carbonyl reductions

Regioselectivity in the Stille Coupling Reactions of 3,5-Dibromo-2-pyrone

The Stille couplings of 3,5-dibromo-2-pyrone normally take place regioselectively at C3, lower in electron density than C5, thus oxidative addition proceeds faster . When the reactions are carried out with Cu(I) in DMF or other polar aprotic solvent, however, the couplings occur predominantly at C5. The observed regiochemical reversal is attributed to the preferred formation of 5-pallado-2-pyrone intermediate which, in addition, turned out to be more reactive than 3-pallado-2-pyrone intermediate

Uniting Anion Relay Chemistry with Pd-Mediated Cross Coupling: Design, Synthesis and Evaluation of Bifunctional Aryl and Vinyl Silane Linchpins

Union of type II Anion Relay Chemistry (ARC) with Pd-induced Cross Coupling Reactions (CCR) has been achieved, in conjunction with the design, synthesis, and evaluation of a new class of bifunctional linchpins, comprising a series of vinyl silanes bearing β- or γ-electrophilic sites. The synthetic tactic permits both alkylation and Pd-mediated CCR of the anions derived via 1,4-silyl C(sp2)→O Brook Rearrangements

A Scalable Route to Trisubstituted (<i>E</i>)-Vinyl Bromides

An effective, readily scalable two-step synthesis of trisubstituted (E)-vinyl bromides involving bromination of α,β-unsaturated lactones followed by hydrolytic fragmentation has been developed. Several trisubstituted (E)-vinyl bromides, including multigram quantities of (+)-(E)-4-bromo-2-methyl-3-pentenol, a synthetic intermediate required for the C(8)−C(11) moieties of (+)-tedanolide (1) and (+)-13-deoxytedanolide (2), illustrate the utility of this protocol

Continuous Flow Synthesis of <i>N</i>‑Sulfonyl-1,2,3-triazoles for Tandem Relay Cu/Rh Dual Catalysis

The continuous flow synthesis of N-sulfonyl-1,2,3-triazoles, which are convenient reactive azavinyl carbene precursors, for tandem relay Cu/Rh dual catalysis has been developed. Most reactions readily proceeded at 75 °C in a short residence time of 13.09 min in the presence of 2.5 mol % of CuTC. The scope of the reactions was explored by synthesizing diversely functionalized N-sulfonyl and sulfamoyl triazoles in yields ranging from 92 to 98%. To demonstrate the scalability of the process, the reaction was conducted on a 5.4 mmol scale with residence and collection times of 13.09 and 60 min, respectively. Furthermore, a series of controlled experiments were performed to investigate the compatibility of Cu and Rh in a batch or a continuous flow system. Finally, the first integrated flow system using the azavinyl carbene intermediate under the tandem relay Cu/Rh dual catalysis was developed for the synthesis of various cis-diamino enones from alkynes and sulfonyl azides

The [1,5]-Brook Rearrangement: An Initial Application in Anion Relay Chemistry

The [1,5]-Brook rearrangement proceeds efficiently in a series of hydroxyl dithiane substrates with sodium and potassium bases; less effective are lithium bases. That the mode of silyl migration is intramolecular was demonstrated by a crossover experiment. Finally, the tricomponent anion relay chemistry (ARC) coupling tactic was demonstrated employing the [1,5]-Brook rearrangement

Copper-Catalyzed Chan–Lam Coupling between Sulfonyl Azides and Boronic Acids at Room Temperature

A mild and efficient method for the synthesis of <i>N</i>-arylsulfonamides in the presence of 10 mol % of CuCl is demonstrated. The reaction proceeds readily at room temperature in an open flask using a variety of sulfonyl azides and boronic acids without any base, ligand, or additive

A Synthetic Approach to <i>N</i>‑Aryl Carbamates via Copper-Catalyzed Chan–Lam Coupling at Room Temperature

A mild and efficient synthesis of <i>N</i>-arylcarbamates was achieved by reacting azidoformates with boronic acids in the presence of 10 mol % of copper chloride catalyst. The reaction proceeds readily in an open flask at room temperature without additional base, ligand, or additive. Rapid access to urea analogues via a two-step one-pot procedure is enabled by reacting <i>N</i>-arylcarbamates with aluminum–amine complexes. In addition, among several boronic acid derivatives prepared, dimethyl­phenyl boronate was found to react rapidly in its reaction with benzyl azido­formate, invoking <i>in situ</i> generation of this species in the catalytic cycle

Multicomponent Type II Anion Relay Chemistry (ARC): One-Pot Syntheses of 2,3-Disubstituted Furans and Thiophenes

Effective, one-pot syntheses of 2,3-disubstituted furans and thiophenes, exploiting 2-tert-butyldimethylsilyl-3-formylfuran and -thiophene as the respective bifunctional linchpins, have been developed. The synthetic protocol involves multicomponent type II Anion Relay Chemistry (ARC) mediated by a solvent-controlled C(sp2)→O 1,4-Brook rearrangement. Simple organolithiums and α-disubstituted ester enolates prove effective as the initiating nucleophiles