Eric Welin | California Institute of Technology (original) (raw)

Publications by Eric Welin

Concise total syntheses of (–)-jorunnamycin A and (–)-jorumycin enabled by asymmetric catalysis, 2018

The bis-tetrahydroisoquinoline (bis-THIQ) natural products have been studied intensively over th... more The bis-tetrahydroisoquinoline (bis-THIQ) natural products have been studied intensively over the past four decades for their exceptionally potent anticancer activity, in addition to strong gram-positive and -negative antibiotic character. Synthetic strategies toward these complex polycyclic compounds have relied heavily on electrophilic aromatic chemistry, such as the Pictet-Spengler reaction, that mimics their biosynthetic pathways. Herein we report an approach to two bis-THIQ natural products, jorunnamycin A and jorumycin, that instead harnesses the power of modern transition-metal catalysis for the three major bond-forming events and proceeds with high efficiency (15 and 16 steps, respectively). By breaking from biomimicry, this strategy allows for the preparation of a more diverse set of non-natural analogs.

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Science, 2017

Transition metal catalysis has traditionally relied on organometallic complexes that can cycle th... more Transition metal catalysis has traditionally relied on organometallic complexes that can cycle through a series of ground-state oxidation levels to achieve a series of discrete
yet fundamental fragment-coupling steps. The viability of excited-state organometallic catalysis via direct photoexcitation has been demonstrated. Although the utility of triplet sensitization by energy transfer has long been known as a powerful activation mode in organic photochemistry, it is surprising to recognize that photosensitization mechanisms to access excited-state organometallic catalysts have lagged far behind. Here, we demonstrate excited-state organometallic catalysis via such an activation pathway: Energy transfer from an iridium sensitizer produces an excited-state nickel complex that couples aryl halides with carboxylic acids. Detailed mechanistic studies confirm the role of photosensitization via energy transfer.

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Angewandte Chemie, International Edition, 2015

The combination of photoredox catalysis and enamine catalysis has enabled the development of an e... more The combination of photoredox catalysis and enamine catalysis has enabled the development of an enantioselective α-cyanoalkylation of aldehydes. This synergistic catalysis protocol allows for the coupling of two highly versatile yet orthogonal functionalities, allowing rapid diversification of the oxonitrile products to a wide array of medicinally relevant derivatives and heterocycles. This methodology has also been applied to the total synthesis of the lignan natural product (–)-bursehernin.

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Chemical Reviews, 2017

Stereoconvergent catalysis is an important subset of asymmetric synthesis that encompasses stereo... more Stereoconvergent catalysis is an important subset of asymmetric synthesis that encompasses stereoablative transformations, dynamic kinetic resolutions, and dynamic kinetic asymmetric transformations. Initially, only enzymes were known to catalyze dynamic kinetic processes, but recently various synthetic catalysts have been developed. This Review summarizes major advances in nonenzymatic, transition-metal-promoted dynamic asymmetric transformations reported between 2005 and 2015.

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Organic Syntheses, 2011

A method for the preparation of indazoles is described. Oximes derived from 2-aminoacetophenone ... more A method for the preparation of indazoles is described. Oximes derived from 2-aminoacetophenone derivatives are mesylated, resulting in the direct formation of indazoles in a simple and high-yielding process.

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Concise total syntheses of (–)-jorunnamycin A and (–)-jorumycin enabled by asymmetric catalysis, 2018

The bis-tetrahydroisoquinoline (bis-THIQ) natural products have been studied intensively over th... more The bis-tetrahydroisoquinoline (bis-THIQ) natural products have been studied intensively over the past four decades for their exceptionally potent anticancer activity, in addition to strong gram-positive and -negative antibiotic character. Synthetic strategies toward these complex polycyclic compounds have relied heavily on electrophilic aromatic chemistry, such as the Pictet-Spengler reaction, that mimics their biosynthetic pathways. Herein we report an approach to two bis-THIQ natural products, jorunnamycin A and jorumycin, that instead harnesses the power of modern transition-metal catalysis for the three major bond-forming events and proceeds with high efficiency (15 and 16 steps, respectively). By breaking from biomimicry, this strategy allows for the preparation of a more diverse set of non-natural analogs.

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Science, 2017

Transition metal catalysis has traditionally relied on organometallic complexes that can cycle th... more Transition metal catalysis has traditionally relied on organometallic complexes that can cycle through a series of ground-state oxidation levels to achieve a series of discrete
yet fundamental fragment-coupling steps. The viability of excited-state organometallic catalysis via direct photoexcitation has been demonstrated. Although the utility of triplet sensitization by energy transfer has long been known as a powerful activation mode in organic photochemistry, it is surprising to recognize that photosensitization mechanisms to access excited-state organometallic catalysts have lagged far behind. Here, we demonstrate excited-state organometallic catalysis via such an activation pathway: Energy transfer from an iridium sensitizer produces an excited-state nickel complex that couples aryl halides with carboxylic acids. Detailed mechanistic studies confirm the role of photosensitization via energy transfer.

Bookmarks Related papers MentionsView impact

Angewandte Chemie, International Edition, 2015

The combination of photoredox catalysis and enamine catalysis has enabled the development of an e... more The combination of photoredox catalysis and enamine catalysis has enabled the development of an enantioselective α-cyanoalkylation of aldehydes. This synergistic catalysis protocol allows for the coupling of two highly versatile yet orthogonal functionalities, allowing rapid diversification of the oxonitrile products to a wide array of medicinally relevant derivatives and heterocycles. This methodology has also been applied to the total synthesis of the lignan natural product (–)-bursehernin.

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Chemical Reviews, 2017

Stereoconvergent catalysis is an important subset of asymmetric synthesis that encompasses stereo... more Stereoconvergent catalysis is an important subset of asymmetric synthesis that encompasses stereoablative transformations, dynamic kinetic resolutions, and dynamic kinetic asymmetric transformations. Initially, only enzymes were known to catalyze dynamic kinetic processes, but recently various synthetic catalysts have been developed. This Review summarizes major advances in nonenzymatic, transition-metal-promoted dynamic asymmetric transformations reported between 2005 and 2015.

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Organic Syntheses, 2011

A method for the preparation of indazoles is described. Oximes derived from 2-aminoacetophenone ... more A method for the preparation of indazoles is described. Oximes derived from 2-aminoacetophenone derivatives are mesylated, resulting in the direct formation of indazoles in a simple and high-yielding process.

Bookmarks Related papers MentionsView impact