Catalytic asymmetric hetero-Diels–Alder route to a key intermediate for the synthesis of calyxin L

A catalytic asymmetric formal synthesis of diarylheptanoid natural product calyxin L has been achieved by incorporating an enantio- and diastereoselective hetero-Diels–Alder (HDA) reaction, a Suzuki–Miyaura coupling, and a stereocontrolled catalytic hydrogenation of 2,4,6-trisubstituted dihydropyran as the key steps. The HDA reaction between 4-(4-benzyloxyphenyl)-2-triethylsilyloxy-1,3-butadiene and (4-benzenesulfonyloxyphenyl)propynal catalyzed by dirhodium(II) tetrakis[(R)-3-(benzene-fused-phthalimido)-2-piperidinonate], Rh2(R-BPTPI)4, provided cis-2,6-disubstituted tetrahydropyran-4-one in 91% yield with 91% ee.

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(2R,6S)-2-(4-Benzenesulfonyloxyphenylethynyl)-6-(4-benzyloxyphenyl)tetrahydropyran-4-oneC32H26O6S[α]D22=-2.9 (c 1.00, CHCl3)Source of chirality: asymmetric hetero-Diels–Alder reactionAbsolute configuration: (2R,6S)

(2S,6S)-2-(4-Benzenesulfonyloxyphenyl)-6-[2-(4-benzenesulfonyloxyphenyl)ethyl]tetrahydropyran-4-oneC31H28O8S2[α]D21=-45.5 (c 1.00, CHCl3)Source of chirality: asymmetric hetero-Diels–Alder reactionAbsolute configuration: (2S,6S)

(2S,4R,6S)-2-(4-Benzenesulfonyloxyphenyl)-6-[2-(4-benzenesulfonyloxyphenyl)ethyl]-4-{4-methoxy-2,6-bis-[2-(trimethylsilyl)ethoxymethoxy]phenyl}tetrahydropyranC50H64O12S2Si2[α]D24=-6.7 (c 1.05, CHCl3)Source of chirality: asymmetric hetero-Diels–Alder reactionAbsolute configuration: (2S,4R,6S)