Enantio- and diastereoselective hetero-Diels–Alder reactions between 4-methyl-substituted Rawal’s diene and aldehydes catalyzed by chiral dirhodium(II) carboxamidates: catalytic asymmetric synthesis of (−)-cis-aerangis lactone

The first catalytic asymmetric hetero-Diels–Alder (HDA) reaction between 3-tert-butyldimethylsilyloxy-1-dimethylamino-1,3-pentadiene (4-methyl-substituted Rawal’s diene) and aldehydes is described. With 3 mol % of dirhodium(II) tetrakis[N-benzene-fused-phthaloyl-(S)-piperidinonate], Rh2((S)-BPTPI)4, the cycloaddition reaction proceeded exclusively in an endo fashion and gave, after a novel sequential treatment with dimethyl acetylenedicarboxylate and acetyl chloride, the corresponding 2,3-cis-disubstituted dihydropyranones with up to 98% ee and perfect diastereoselectivity. The utility of this catalytic protocol was demonstrated by an asymmetric synthesis of the (−)-cis-aerangis lactone.

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(2R,3S)-3-Methyl-2-pentyl-2,3-dihydro-4H-pyran-4-oneC11H18O292% ee[α]D22=+139.6 (c 1.22, CHCl3)Source of chirality: Enantioselective hetero-Diels–Alder reactionAbsolute configuration: (2R,3S)

(2S,3S)-3-Methyl-2-phenyl-2,3-dihydro-4H-pyran-4-oneC11H12O294% ee[α]D21=-4.2 (c 1.12, CHCl3)Source of chirality: Enantioselective hetero-Diels–Alder reactionAbsolute configuration: (2S,3S)

(2S,3S)-Methyl 2-hydroxy-2-methyl-3-phenylpropionateC11H14O394% ee[α]D22=-18.4 (c 0.59, CHCl3)Source of chirality: Enantioselective hetero-Diels–Alder reactionAbsolute configuration: (2S,3S)

(2S,3R)-3-Methyl-2-pentyl-2,3-dihydro-4H-pyran-4-oneC11H18O292% ee[α]D22=-140.1 (c 1.03, CHCl3)Source of chirality: Enantioselective hetero-Diels–Alder reactionAbsolute configuration: (2S,3R)

(2S,3S,4S)-3-Methyl-2-pentyl-3,4-dihydro-2H-pyran-4-olC11H20O292% ee[α]D22=+6.3 (c 1.19, CHCl3)Source of chirality: Enantioselective hetero-Diels–Alder reactionAbsolute configuration: (2S,3S,4S)

(2S,3S)-3-Methyl-2-pentyl-2,3-dihydro-2H-pyran-6-oneC11H18O292% ee[α]D22=-180 (c 1.04, CHCl3)Source of chirality: Enantioselective hetero-Diels–Alder reactionAbsolute configuration: (2S,3S)

(−)-cis-Aerangis lactoneC11H20O292% ee[α]D22=-67.2 (c 1.06, CHCl3)Source of chirality: Enantioselective hetero-Diels–Alder reactionAbsolute configuration: (2S,3S)