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. 2023 Apr 12;145(14):8242-8247.
doi: 10.1021/jacs.3c01809. Epub 2023 Mar 30.

Allyl Alcohol as an Acrolein Equivalent in Enantioselective C-C Coupling: Total Synthesis of Amphidinolides R, J, and S

Cole C Meyer  1 , Katherine L Verboom  1 , Madeline M Evarts  1 , Woo-Ok Jung  1 , Michael J Krische  1
Affiliations

Allyl Alcohol as an Acrolein Equivalent in Enantioselective C-C Coupling: Total Synthesis of Amphidinolides R, J, and S

Cole C Meyer et al. J Am Chem Soc. .

Abstract

The first systematic study of catalytic enantioselective 1,2-additions to acrolein is described. Specifically, using allyl alcohol as a tractable, inexpensive acrolein proelectrophile, iridium-catalyzed acrolein allylation is achieved with high levels of regio-, anti-diastereo-, and enantioselectivity. This process delivers 3-hydroxy-1,5-hexadienes, a useful compound class that is otherwise challenging to access via enantioselective catalysis. Two-fold use of this method unlocks concise total syntheses of amphidinolide R (9 vs 23 steps, LLS) and amphidinolide J (9 vs 23 or 26 steps, LLS), which are prepared in fewer than half the steps previously possible, and the first total synthesis of amphidinolide S (10 steps, LLS).

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
Allyl alcohol as an acrolein equivalent in catalytic enantioselective carbonyl addition.
Figure 2.
Figure 2.
Catalytic cycle and stereochemical model.
Scheme 1.
Scheme 1.
Retrosynthetic analysis of amphidinolides R, J and S via catalytic enantioselective C−C coupling of allyl alcohol.
Scheme 2.
Scheme 2.
Synthesis of Fragments A–D.a aYields are of material isolated by silica gel chromatography. See Supporting Information for experimental details.
Scheme 3.
Scheme 3.
Total synthesis of amphidinolides R, J and S.a aYields are of material isolated by silica gel chromatography. See Supporting Information for experimental details.
See this image and copyright information in PMC

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