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. 2023 Dec 1;26(45):e202300982.
doi: 10.1002/ejoc.202300982. Epub 2023 Nov 9.

Cooperative Chiral Lewis Base/Palladium-Catalyzed Asymmetric Syntheses of Methylene-Containing δ-Lactams

Paul Zebrowski  1 , Uwe Monkowius  2 , Mario Waser  1
Affiliations

Cooperative Chiral Lewis Base/Palladium-Catalyzed Asymmetric Syntheses of Methylene-Containing δ-Lactams

Paul Zebrowski et al. European J Org Chem. .

Abstract

We herein report a two-step approach for the enantioselective synthesis of novel chiral δ-lactams. By using a cooperative chiral ITU/achiral Pd-catalyst system, this protocol proceeds via an asymmetric α-allylation of activated aryl esters first, followed by an acid-mediated lactam formation. A variety of differently substituted products could be obtained with usually high levels of enantioselectivities and in reasonable yields (16 examples, up to 98 : 2 er and 73 % yield over two steps). In addition, further utilizations of the products via transformations of the exocyclic double bond were successfully carried out as well.

Keywords: Lewis base catalysis; Pd-catalysis; asymmetric organocatalysis; cyclizations; lactams.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
General structures of lactams (A) and isothioureas (B), the general reactivity of activated aryl esters 1 under ITU catalysis (C), and the herein investigated synergistic ITU/Pd‐catalyzed synthesis of δ‐lactams 3 (D).
Scheme 2
Scheme 2
Asymmetric application scope (isolated and NMR (IST) yields over both steps).
Scheme 3
Scheme 3
Further manipulations of the exocyclic double bond.
See this image and copyright information in PMC

References

    1. None
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    1. Caruano J., Muccioli G. G., Robiette R., Org. Biomol. Chem. 2016, 14, 10134. - PubMed
    1. Puffr R., Kubanek V., Lactam Based Polyamides (Vol 1 and Vol 2), CRC Press, 1991.

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