The first total synthesis of brasilicardins A and C, novel diterpenoid–saccharide–amino acid hybrid metabolites with unique immunosuppressive activity, is described. The key step is a Diels–Alder/reductive angular methylation sequence capitalizing on a trans-fused bicyclic α-cyano-α,β-enone as its precursor to construct the 8,10-dimethyl-trans/syn/trans-perhydrophenanthrene skeleton. Other notable features include an anti-selective aldol reaction, a stereocontrolled glycosylation of a C2 alcohol, and a one-pot, two-step global deprotection sequence that did not damage these sensitive molecules.

The first enantio-and diastereoselective construction of fused bicyclic ring systems via intramolecular C–H insertion reaction of σ-symmetric α-alkyl-α-diazoesters is described. With dirhodium(II) tetrakis[N-phthaloyl-(S)-tert-leucinate], Rh2(S-PTTL)4, the C–H insertion proceeded in a chemoselective manner to give methyl bicyclo[3.3.0]oct-7-ene-2-carboxylate and methyl bicyclo[4.3.0]nonane-7-carboxylate derivatives with up to 99% ee and perfect cis diastereoselectivity. The utility of this protocol was demonstrated by the catalytic asymmetric synthesis of a key intermediate in Whitesell's synthesis of udoteatrial hydrate.

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.(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)

The first catalytic asymmetric hetero-Diels–Alder reaction between 2-aza-3-silyloxy-1,3-butadienes and aldehydes is described. With dirhodium(II) tetrakis[N-benzene-fused-phthaloyl-(S)-piperidinonate], Rh2(S-BPTPI)4, the cycloaddition reaction proceeded exclusively in an endo mode to give all-cis-substituted 1,3-oxazinan-4-ones in high yields with up to 98% ee.

The first catalytic asymmetric hetero-Diels–Alder reaction between 2-aza-3-silyloxy-1,3-butadienes and aldehydes is described. With dirhodium(II) tetrakis[N-benzene-fused-phthaloyl-(S)-piperidinonate], Rh2(S-BPTPI)4, the cycloaddition reaction proceeded exclusively in an endo mode to give all-cis-substituted 1,3-oxazinan-4-ones in high yields with up to 98% ee.