New Synthetic Methodology toward Macrolides/Macrolactams via Palladium-Catalyzed Carbon-Heteroatom Bond-Forming Reactions

Abstract

A concise and versatile syntheses of 11-16-membered macrolides and 13-15-membered macrolactams have been achieved using a Tsuji-Trost type reaction. This approach is composed of intramolecular cyclization employing ethyl carbonate with carboxylic acids and catalytic amount of Pd(PPh₃)₄ to form carbon-heteroatom covalent bonds with no use of stoichiometric reagents.

Key words

macrolactones - macrolactams - palladium-catalyzed ­reaction - carbon-heteroatom bond formation

References and Notes

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10

We observed that the reaction with the isolated single (E)-α-7c under the same reaction conditions afforded a 90:10 mixture of E/Z-isomers without production of γ-7c (Scheme  [4] ).

Scheme 4

11

This would be attributed to the strain based on the ring size.

13

The macrolactamization of 9c in the absence of KOt-Bu resulted in α-12c in 44% yield (Scheme  [5] ).

Scheme 5