Synthesis of β,γ-disubstituted-γ-lactones through a Johnson–Claisen rearrangement: a short route to xylobovide, nor-canadensolide, canadensolide, sporothriolide and santolinolide

The Johnson–Claisen rearrangement of allyl alcohols with chiral vicinal diol functionality was employed to access chiral β,γ-disubstituted-γ-lactones in high enantio- and diastereoselectivity. These were efficiently converted into nor-canadensolide, the advanced γ-(lactone–lactol) intermediate for xylobovide, canadensolide and sporothriolide and the lactone moiety of the santolinolides.

Figure optionsDownload as PowerPoint slide

(2S,3R)-Ethyl-2,3-dihydroxypentanoateC7H14O4Ee = 99% [Chiral HPLC][α]D25=-3.8 (c 0.4, CHCl3)Source of chirality: asymmetric dihydroxylationAbsolute configuration: (2S,3R)

(2S,3R)-Ethyl-2,3-dihydroxyheptanoateC9H18O4Ee = 99% [Chiral HPLC][α]D25=+11.2 (c 2.5, CHCl3)Source of chirality: asymmetric dihydroxylationAbsolute configuration: (2S,3R)

(2S,3R)-Ethyl-2,3-dihydroxynonanoateC11H22O4Ee = 99% [Chiral HPLC][α]D25=+12.8 (c 1, CHCl3)Source of chirality: asymmetric dihydroxylationAbsolute configuration: (2S,3R)

(2S,3R)-Ethyl-2,3-isopropylidenedioxypentanoateC10H18O4[α]D25=+12.6 (c 1.5, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (2S,3R)

(2S,3R)-Ethyl-2,3-isopropylidenedioxyheptanoateC12H22O4[α]D25=+15.2 (c 1.22, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (2S,3R)

(2S,3R)-Ethyl-2,3-isopropylidenedioxynonanoateC14H26O4[α]D25=+11.0 (c 1, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (2S,3R)

(4R,5R,2E)-Ethyl-4,5-isopropylidenedioxyhept-2-enoateC12H20O4[α]D25=-8.9 (c 1.8, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (4R,5R,2E)

(4R,5R,2E)-Ethyl-4,5-isopropylidenedioxynon-2-enoateC14H24O4[α]D25=+18.8 (c 1.38, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (4R,5R,2E)

(4R,5R,2E)-Ethyl-4,5-isopropylidenedioxyundec-2-enoateC16H28O4[α]D25=+25.5 (c 1.1, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (4R,5R,2E)

(4R,5R,2E)-4,5-Isopropylidenedioxyhept-2-ene-1-olC10H18O3[α]D25=+15.7 (c 0.7, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (4R,5R,2E)

(4R,5R,2E)-4,5-Isopropylidenedioxynon-2-ene-1-olC12H22O3[α]D25=+25.8 (c 1.16, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (4R,5R,2E)

(4R,5R,2E)-4,5-Isopropylidenedioxyundec-2-ene-1-olC14H26O3[α]D25=+8.7 (c 0.92, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (4R,5R,2E)

(4S,5R)-4-Vinyl-5-[(R)-1-hydroxypropyl]-4,5-dihydro-2(3H)-furanoneC9H14O3[α]D25=-54 (c 2, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (4S,5R,1′R)

(4R,5R)-4-Vinyl-5-[(R)-1-hydroxypropyl]-4,5-dihydro-2(3H)-furanoneC9H14O3[α]D25=-57.5 (c 1.2, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (4R,5R,1′R)

(4S,5R)-4-Vinyl-5-[(R)-1-hydroxypentyl]-4,5-dihydro-2(3H)-furanoneC11H18O3[α]D25=-48.4 (c 1.9, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (4S,5R,1′R)

(4R,5R)-4-Vinyl-5-[(R)-1-hydroxypentyl]-4,5-dihydro-2(3H)-furanoneC11H18O3[α]D25=-50.3 (c 0.6, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (4R,5R,1′R)

(4S,5R)-4-Vinyl-5-[(R)-1-hydroxyheptyl]-4,5-dihydro-2(3H)-furanoneC13H22O3[α]D25=-39.5 (c 0.38, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (4S,5R,1′R)

(4R,5R)-4-Vinyl-5-[(R)-1-hydroxyheptyl]-4,5-dihydro-2(3H)-furanoneC13H22O3[α]D25=-18.2 (c 0.2, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (4R,5R,1′R)

(3aS,4S,6R,6aR)-6-Ethyl-tetrahydro-4-hydroxyfuro [3,4-b]furan-2(3H)-oneC8H12O4[α]D25=-5.0 (c 2, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (3aS,4S,6R,6aR)

(3aS,4S,6R,6aR)-6-Butyl-tetrahydro-4-hydroxyfuro[3,4-b]furan-2(3H)-oneC10H16O4[α]D25=-13.5 (c 2, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (3aS,4S,6R,6aR)

(3aS,4S,6R,6aR)-6-hexyl-tetrahydro-4-hydroxyfuro [3,4-b]furan-2(3H)-oneC12H20O4[α]D25=-71.9 (c 1, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (3aS,4S,6R,6aR)

(3aS,6R,6aR)-6-Ethyl-tetrahydrofuro[3,4-b]furan-2,4-dioneC8H10O4[α]D25=-43 (c 1, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (3aS,6R,6aR)

(3aS,6R,6aR)-6-Butyl-tetrahydrofuro[3,4-b]furan-2,4-dioneC10H14O4[α]D25=-20.7 (c 1.4, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (3aS,6R,6aR)

(3aS,6R,6aR)-6-Hexyl-tetrahydrofuro[3,4-b]furan-2,4-dioneC12H18O4[α]D25=-31.7 (c 1.2, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (3aS,6R,6aR)

(2R,3R)-Tetrahydro-2-[(R)-1-hydroxyheptyl]-5-oxo furan-3-carbaldehydeC12H20O4[α]D25=-25 (c 1, CHCl3)Initial source of chirality: asymmetric dihydroxylationAbsolute configuration: (2R,3R,1′R)

(4S,5S,2E)-Ethyl-4,5-isopropylidenedioxyhex-2-enoateC11H18O4[α]D25=+7.2 (c 0.8, CHCl3)Initial source of chirality: asymmetric dihydroxylation or (R,R)-diethyl tartrateAbsolute configuration: (4S,5S,2E)

(4S,5S,2E)-4,5-Isopropylidenedioxyhex-2-ene-1-olC9H16O3[α]D25=-31.9 (c 0.5, CHCl3)Initial source of chirality: asymmetric dihydroxylation or (R,R)-diethyl tartrateAbsolute configuration: (4S,5S,2E)

(4S,5S)-4-Vinyl-5-[(S)-1-hydroxyethyl]-4,5-dihydro-2(3H)-furanoneC8H12O3[α]D25=+76.7 (c 0.6, CHCl3)Initial source of chirality: asymmetric dihydroxylation or (R,R)-diethyl tartrateAbsolute configuration: (4S,5S,1′S)

(4R,5S)-4-Vinyl-5-[(S)-1-hydroxyethyl]-4,5-dihydro-2(3H)-furanoneC8H12O3[α]D25=+125.7 (c 0.7, CHCl3)Initial source of chirality: asymmetric dihydroxylation or (R,R)-diethyl tartrateAbsolute configuration: (4R,5S,1′S)

(4R,5S)-5-Acetyl-4-vinyl-4,5-dihydrofuran-2(3H)-oneC8H10O3[α]D25=-50.0 (c 0.2, CHCl3)Initial source of chirality: asymmetric dihydroxylation or (R,R)-diethyl tartrateAbsolute configuration: (4R,5S)

(4R,5S)-5-Isoprenyl-4-vinyl-4,5-dihydrofuran-2(3H)-oneC9H12O2[α]D25=+35.0 (c 0.4, CHCl3)Initial source of chirality: asymmetric dihydroxylation or (R,R)-diethyl tartrateAbsolute configuration: (4R,5S)