Publications by authors named "Alistair D Richardson"

6 Publications

  • Page 1 of 1

Total Synthesis of (+)-Cochlearol B by an Approach Based on a Catellani Reaction and Visible-Light-Enabled [2+2] Cycloaddition.

Angew Chem Int Ed Engl 2022 08 23;61(31):e202201213. Epub 2022 Jun 23.

Department of Chemistry, University of Michigan, Willard Henry Dow Laboratory, 930 North University Ave., Ann Arbor, MI 48109, USA.

A 14-step synthesis of (+)-cochlearol B is reported. This renoprotective meroterpenoid features a unique core structure containing a densely substituted cyclobutane ring with three stereocenters. Our strategy employed an organocatalytic Kabbe condensation in route to the key chromenyl triflate. A subsequent Catellani reaction incorporated the remaining carbon atoms featured in the skeleton of cochlearol B. An ensuing visible-light-mediated [2+2] photocycloaddition closed the cyclobutane and formed the central bicyclo[3.2.0]heptane core. Notably, careful design and tuning of the Catellani and photocycloaddition reactions proved crucial in overcoming undesired reactivity, including cyclopropanation reactions and [4+2] cycloadditions.
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http://dx.doi.org/10.1002/anie.202201213DOI Listing
August 2022

Origin of enantioselectivity reversal in Lewis acid-catalysed Michael additions relying on the same chiral source.

Chem Sci 2021 Nov 4;12(42):14133-14142. Epub 2021 Oct 4.

Willard Henry Dow Laboratory, Department of Chemistry, University of Michigan 930 North University Avenue Ann Arbor Michigan 48109 USA

Enantiodivergence is an important concept in asymmetric catalysis that enables access to both enantiomers of a product relying on the same chiral source as reagent. This strategy is particularly appealing as an alternate approach when only one enantiomer of the required chiral ligand is readily accessible but both enantiomers of the product are desired. Despite the potential significance, general catalytic methods to effectively reverse enantioselectivity by changing an achiral reaction parameter remain underdeveloped. Herein we report our studies focused on elucidating the origin of metal-controlled enantioselectivity reversal in Lewis acid-catalysed Michael additions. Rigorous experimental and computational investigations reveal that specific Lewis and Brønsted acid interactions between the substrate and ligand change depending on the ionic radius of the metal catalyst, and are key factors responsible for the observed enantiodivergence. This holds potential to further our understanding of and facilitate the design of future enantiodivergent transformations.
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http://dx.doi.org/10.1039/d1sc03741bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8565382PMC
November 2021

Synthesis of azetidines by aza Paternò-Büchi reactions.

Chem Sci 2020 Aug 12;11(29):7553-7561. Epub 2020 Jun 12.

Willard Henry Dow Laboratory , Department of Chemistry , University of Michigan , Ann Arbor , MI 48109 , USA . Email:

The [2 + 2] photocycloaddition reaction between an imine and an alkene component, the aza Paternò-Büchi reaction, is one of the most efficient ways to synthesize functionalized azetidines. However, the application of the aza Paternò-Büchi reaction has been met with limited success due to the inherent challenges associated with this approach. This review covers the current scope and limitations of reported examples of aza Paternò-Büchi reactions in organic synthesis. An outlook is provided, which highlights recent improvements and the discovery of new reaction protocols that have overcome some long-standing challenges within this field of research.
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http://dx.doi.org/10.1039/d0sc01017kDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408364PMC
August 2020

Tetrahydropyridines via FeCl-Catalyzed Carbonyl-Olefin Metathesis.

Org Lett 2020 04 23;22(7):2844-2848. Epub 2020 Mar 23.

Department of Chemistry, Willard Henry Dow Laboratory, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109, United States.

Herein we describe the application of Lewis-acid-catalyzed carbonyl-olefin metathesis toward the synthesis of substituted tetrahydropyridines from commercially available amino acids as chiral pool reagents. This strategy relies on FeCl as an inexpensive and environmentally benign catalyst and enables access to a variety of substituted tetrahydropyridines under mild reaction conditions. The reaction proceeds with complete stereoretention and is viable for a variety of natural and unnatural amino acids to provide the corresponding tetrahydropyridines in up to 99% yield.
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http://dx.doi.org/10.1021/acs.orglett.0c00918DOI Listing
April 2020

Eight-Step Enantiodivergent Synthesis of (+)- and (-)-Lingzhiol.

Org Lett 2020 01 19;22(1):290-294. Epub 2019 Dec 19.

Department of Chemistry , University of Michigan , Willard Henry Dow Laboratory, 930 North University Avenue , Ann Arbor , Michigan 48109 , United States.

An eight-step enantioselective synthesis of lingzhiol is described herein. The sense of an asymmetric Michael reaction is reversed by the choice of metal source, enabling facile access to both enantiomers. A spontaneous semipinacol ring contraction enables mild construction of the lingzhiol core, and radical-mediated benzylic oxidation proceeds in the presence of an unprotected secondary alcohol. This represents the shortest enantioselective synthesis of lingzhiol to date and the only enantiodivergent approach to both enantiomers of this meroterpenoid natural product.
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http://dx.doi.org/10.1021/acs.orglett.9b04322DOI Listing
January 2020

Functionalized azetidines via visible light-enabled aza Paternò-Büchi reactions.

Nat Commun 2019 11 8;10(1):5095. Epub 2019 Nov 8.

Willard Henry Dow Laboratory, Department of Chemistry, University of Michigan, Ann Arbor, MI, 48109, USA.

Azetidines are four-membered nitrogen-containing heterocycles that hold great promise in current medicinal chemistry due to their desirable pharmacokinetic effects. However, a lack of efficient synthetic methods to access functionalized azetidines has hampered their incorporation into pharmaceutical lead structures. As a [2+2] cycloaddition reaction between imines and alkenes, the aza Paternò-Büchi reaction arguably represents the most direct approach to functionalized azetidines. Hampered by competing reaction paths accessible upon photochemical excitation of the substrates, the current synthetic utility of these transformations is greatly restricted. We herein report the development of a visible light-enabled aza Paternò-Büchi reaction that surmounts existing limitations and represents a mild solution for the direct formation of functionalized azetidines from imine and alkene containing precursors.
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http://dx.doi.org/10.1038/s41467-019-13072-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6841681PMC
November 2019
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