Alkyl oxalates are new bench-stable alcohol-activating groups for radical generation under visible light photoredox conditions. Using these precursors, the first net redox-neutral coupling of ...tertiary and secondary alcohols with electron-deficient alkenes is achieved.
Organic chemists are now able to synthesize small quantities of almost any known natural product, given sufficient time, resources and effort. However, translation of the academic successes in total ...synthesis to the large-scale construction of complex natural products and the development of large collections of biologically relevant molecules present significant challenges to synthetic chemists. Here we show that the application of two nature-inspired techniques, namely organocascade catalysis and collective natural product synthesis, can facilitate the preparation of useful quantities of a range of structurally diverse natural products from a common molecular scaffold. The power of this concept has been demonstrated through the expedient, asymmetric total syntheses of six well-known alkaloid natural products: strychnine, aspidospermidine, vincadifformine, akuammicine, kopsanone and kopsinine.
The use of sp³ C–H bonds—which are ubiquitous in organic molecules—as latent nucleophile equivalents for transition metal–catalyzed cross-coupling reactions has the potential to substantially ...streamline synthetic efforts in organic chemistry while bypassing substrate activation steps. Through the combination of photoredox-mediated hydrogen atom transfer (HAT) and nickel catalysis, we have developed a highly selective and general C–H arylation protocol that activates a wide array of C–H bonds as native functional handles for cross-coupling. This mild approach takes advantage of a tunable HAT catalyst that exhibits predictable reactivity patterns based on enthalpic and bond polarity considerations to selectively functionalize α-amino and αoxy sp³ C–H bonds in both cyclic and acyclic systems.
Direct C-H functionalization and arylation of benzyl ethers has been accomplished via photoredox organocatalysis. The productive merger of a thiol catalyst and a commercially available iridium ...photoredox catalyst in the presence of household light directly affords benzylic arylation products in good to excellent yield. The utility of this methodology is further demonstrated in direct arylation of 2,5-dihydrofuran to form a single regioisomer.
In this study we demonstrate that molecular fragments, which can be readily coupled via a simple, in situ RO-C═OR bond-forming reaction, can subsequently undergo metal ...insertion-decarboxylation-recombination to generate Csp(2)-Csp(3) bonds when subjected to metallaphotoredox catalysis. In this embodiment the conversion of a wide variety of mixed anhydrides (formed in situ from carboxylic acids and acyl chlorides) to fragment-coupled ketones is accomplished in good to high yield. A three-step synthesis of the medicinal agent edivoxetine is also described using this new decarboxylation-recombination protocol.
An asymmetric decarboxylative Csp(3)-Csp(2) cross-coupling has been achieved via the synergistic merger of photoredox and nickel catalysis. This mild, operationally simple protocol transforms a wide ...variety of naturally abundant α-amino acids and readily available aryl halides into valuable chiral benzylic amines in high enantiomeric excess, thereby producing motifs found in pharmacologically active agents.
A concise and highly enantioselective total synthesis of the akuammiline alkaloid (-)-vincorine has been accomplished. A key element of the synthesis is a stereoselective organocatalytic Diels-Alder, ...iminium cyclization cascade sequence, which serves to construct the tetracyclic alkaloid core architecture in one step from simple achiral precursors. The challenging seven-membered azepanyl ring system is installed by way of a single electron-mediated cyclization event initiated from an acyl telluride precursor. The total synthesis of (-)-vincorine is achieved in nine steps and 9% overall yield from commercially available starting materials.
The direct decarboxylative arylation of α‐oxo acids has been achieved by synergistic visible‐light‐mediated photoredox and nickel catalysis. This method offers rapid entry to aryl and alkyl ketone ...architectures from simple α‐oxo acid precursors via an acyl radical intermediate. Significant substrate scope is observed with respect to both the oxo acid and arene coupling partners. This mild decarboxylative arylation can also be utilized to efficiently access medicinal agents, as demonstrated by the rapid synthesis of fenofibrate.
The direct decarboxylative arylation of α‐oxo acids has been achieved by synergistic visible‐light‐mediated photoredox and nickel catalysis. This method offers rapid entry to aryl and alkyl ketone architectures from simple α‐oxo acid precursors via an acyl radical intermediate. Significant substrate scope is observed with respect to both the oxo acid and arene coupling partners.
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