Synthesis of chiral oxa- and azacycle-fused anthraquinone derivatives

A convenient protocol for the synthesis of chiral pyran and piperidine ring-fused anthraquinone derivatives has been developed from (R)-2,3-O-cyclohexylidene-glyceraldehyde using sequential applications of enyne metathesis, Diels–Alder reaction and aromatization as key steps.

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(1S)-1-[(2R)-1,4-Dioxaspiro[4.5]dec-2-yl]-3-butenyl (2-propynyl) etherC15H22O3[α]D = +24 (c 0.13, CHCl3)Source of chirality: d-mannitolAbsolute configuration : (1S,2′R)

(2R)-2-[(2S)-5-Vinyl-3,6-dihydro-2H-2-pyranyl]-1,4-dioxaspiro[4.5]decaneC15H22O3[α]D = +12 (c 0.09, CHCl3)Source of chirality: d-mannitolAbsolute configuration : (2R,2′S)

(2S)-2-[(2R)-1,4-Dioxaspiro[4.5]dec-2-yl]-1,4,7,12-tetrahydro-2Hnaphtho[2,3-f]isochromene-7,12-dioneC25H24O5[α]D = −19 (c 0.12, CHCl3)Source of chirality: d-mannitolAbsolute configuration : (2 S,2′R)

(2S)-2-[(1R)-1,2-Dihydroxyethyl]-1,4,7,12-tetrahydro-2H-naphtho[2,3-f]isochromene-7,12-dioneC19H16O5[α]D = −6 (c 0.75, DMF)Source of chirality: d-mannitolAbsolute configuration : (2 S,1′R)

(1S)-1-[(2R)-1,4-Dioxaspiro[4.5]dec-2-yl]-3-butenyl methanesulfonateC13H22O5S[α]D = +19 (c 0.12, CHCl3)Source of chirality: d-mannitolAbsolute configuration : (1S,2′R)

(1R)-1-[(2S)-1,4-Dioxaspiro[4.5]dec-2-yl]-3-butenyl azideC12H19N3O2[α]D = −25 (c 0.1, CHCl3)Source of chirality: d-mannitolAbsolute configuration : (1R,2′S)

(1R)-1-[(2S)-1,4-Dioxaspiro[4.5]dec-2-yl]-3-butenyl-4-methyl-1-benzene-sulfonamideC19H27NO4S[α]D = +3.3 (c 0.5, CHCl3)Source of chirality: d-mannitolAbsolute configuration : (1R,2′S)

N1-{(1R)-1-[(2S)-1,4-Dioxaspiro[4.5]dec-2-yl]-3-butenyl-N1-(2-propynyl)-4-methyl-1-benzenesulfonamideC22H29NO4S[α]D = +27 (c 0.1, CHCl3)Source of chirality: d-mannitolAbsolute configuration : (1R,2′S)

(2R)-2-[(2S)-1,4-Dioxaspiro[4.5]dec-2-yl]-1-[(4-methylphenyl)sulfonyl]-5-vinyl-1,2,3,6-tetrahydropyridineC22H29NO4S[α]D = −41 (c 0.15, CHCl3)Source of chirality: d-mannitolAbsolute configuration : (2R,2′S)

(2R)-2-[(2S)-1,4-Dioxaspiro[4.5]dec-2-yl]-3-[(4-methylphenyl)sulfonyl]-1,2,3,4,7,12-hexahydro-naphtho[2,3-f]isoquinolin-7,12-dioneC32H31NO6S[α]D = +1.0 (c 0.1, CHCl3)Source of chirality: d-mannitolAbsolute configuration : (2R,2′S)

(2R)-2-[(1S)-1,2-Dihydroxyethyl]-3-[(4-methylphenyl)sulfonyl]-1,2,3,4,7,12-hexahydro-naphtho[2,3-f]isoquinolin-7,12-dioneC26H23NO6S[α]D = +22 (c 0.1, CHCl3)Source of chirality: d-mannitolAbsolute configuration : (2R,1′S)