Stereoselective synthesis of a C1–C6 fragment of pinnatoxin A via a 1,4-addition/alkylation sequence

A C1–C6 fragment of pinnatoxin A, (5S,6R)-5,6-dimethyl-3-methyleneoxepan-2-one, which features a γ,δ-trans-dimethyl-substituted α-methylene lactone, has been synthesized in an enantiomerically pure form from ethyl (E)-4-benzyloxy-2-butenoate through an auxiliary-based conjugate addition and alkylation reaction. The excellent diastereoselectivity (98:2) observed in the alkylation reaction is the result of stereocontrol from both the adjacent stereocenter and the chiral oxazolidinone.

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[4R,3(2E)]-3-(4-Benzyloxy-2-butenoyl)-4-phenyl-2-oxazolidinoneC20H19NO4[α]D26=-67.3 (c 2.07, CHCl3)Source of chirality: d-phenylglycineAbsolute configuration: (R)

[4R,3(3R)]-3-(4-Benzyloxy-3-methylbutanoyl)-4-phenyl-2-oxazolidinoneC21H23NO4[α]D22=-52.8 (c 2.08, CHCl3)Source of chirality: d-phenylglycineAbsolute configuration: [4R,3(3R)]

[4S,3(3R)]-3-(4-Benzyloxy-3-methylbutanoyl)-4-phenyl-2-oxazolidinoneC21H23NO4[α]D18=+43.5 (c 1.08, CHCl3)Source of chirality: d-phenylglycineAbsolute configuration: [4S,3(3R)]

[4R,3(2R,3R)]-3-(4-Benzyloxy-2,3-dimethylbutanoyl)-4-phenyl-2-oxazolidinoneC22H25NO4[α]D20=-82.0 (c 2.01, CHCl3)Source of chirality: d-phenylglycineAbsolute configuration: [4R,3(2R,3R)]

(2R,3R)-4-Benzyloxy-2,3-dimethyl-1-butanolC13H20O2[α]D21=+6.2 (c 2.00, CHCl3)Source of chirality: d-phenylglycineAbsolute configuration: (2R,3R)

(2R,3R)-4-Benzyloxy-2,3-dimethylbutanalC13H18O2[α]D21=-39.8 (c 2.16, CHCl3)Source of chirality: d-phenylglycineAbsolute configuration: (2R,3R)

Ethyl (2E,4S,5R)-6-benzyloxy-4,5-dimethyl-2-hexenoateC17H24O3[α]D22=-46.2 (c 2.09, CHCl3)Source of chirality: d-phenylglycineAbsolute configuration: (4S,5R)

Ethyl (2Z,4S,5R)-6-benzyloxy-4,5-dimethyl-2-hexenoateC17H24O3[α]D24=+22.6 (c 1.99, CHCl3)Source of chirality: d-phenylglycineAbsolute configuration: (4S,5R)

Ethyl (4S,5R)-6-hydroxy-4,5-dimethylhexanoateC10H20O3[α]D22=-10.6 (c 2.40, CHCl3)Source of chirality: d-phenylglycineAbsolute configuration: (4S,5R)

(5S,6R)-5,6-Dimethyloxepan-2-oneC8H14O2[α]D21=-43.1 (c 2.02, CHCl3)Source of chirality: d-phenylglycineAbsolute configuration: (5S,6R)

(5S,6R)-5,6-Dimethyl-3-methyleneoxepan-2-oneC9H14O2[α]D21=-6.7 (c 2.01, CHCl3)Source of chirality: d-phenylglycineAbsolute configuration: (5S,6R)