A highly diastereoselective oxa-Pictet-Spengler approach to (+)-astropaquinone B and (+)-astropaquinone C and the formation of astropaquinone B dimer

A concise and highly diastereoselective synthesis of (+)-astropaquinone B and (+)-astropaquinone C is reported. The synthetic strategy is based on an efficient combination of Dötz benzannulation using a chiral alkyne to construct the naphthalene unit and a highly diastereoselective oxa-Pictet-Spengler reaction to install the trans-configured pyran ring as the key steps.

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(2S)-tert-Butyldimethyl(pent-4-yn-2-yloxy)silaneC11H22OSie.e.=99%[α]D25=+3.6 (c 0.9, CHCl3)Initial source of chirality: (S)-ethyl 3-hydroxybutanoateAbsolute configuration: (2S)

(S)-7-(tert-Butyldimethylsilyloxy)-2-[2-(tert-butyldimethylsilyloxy)propyl]-4,5-dimethoxynaphthalen-1-olC27H46O5Si2[α]D25=-10.6 (c 1.2, CHCl3)Initial source of chirality: (S)-ethyl 3-hydroxybutanoateAbsolute configuration: (2S)

(S)-tert-Butyldimethyl[1-(1,4,5,7-tetramethoxynaphthalen-2-yl)propan-2-yloxy]silaneC23H36O5Si[α]D25 = +24.6 (c 0.25, CHCl3)Initial source of chirality: (S)-ethyl 3-hydroxybutanoateAbsolute configuration: (2S)

(S)-1-(1,4,5,7-Tetramethoxynaphthalen-2-yl)-propan-2-olC17H22O5[α]D25=+26.7 (c 0.4, CHCl3)Initial source of chirality: (S)-ethyl 3-hydroxybutanoateAbsolute configuration: (2S)

(1R,3S)-1,5,7,9,10-Pentamethoxy-3-methyl-3,4-dihydro-1H-benzo[g]isochromeneC19H24O6[α]D25=-89.7 (c 0.64, CHCl3)Initial source of chirality: (S)-ethyl 3-hydroxybutanoateAbsolute configuration: (1R,3S)

(+)-Astropaquinone BC17H18O6[α]D25=+42.3 (c 0.12, CHCl3)Initial source of chirality: (S)-ethyl 3-hydroxybutanoateAbsolute configuration: (1R,3S)

(1R,1′R,3S,3′S)-1,1′,7,7′,9,9′-Hexamethoxy-3,3′-dimethyl-3,3′,4,4′-tetrahydro-1H,1′H-6,6′-dibenzo[g]isochromene-5,5′,10,10′-tetraoneC34H34O12[α]D25=+19.6 (c 0.2, CHCl3)Initial source of chirality: (S)-ethyl 3-hydroxybutanoateAbsolute configuration: (1R,1′R,3S,3′S)

(+)-Astropaquinone CC16H16O6[α]D25=+44.0 (c 0.1, CHCl3)Initial source of chirality: (S)-ethyl 3-hydroxybutanoateAbsolute configuration: (1R,3S)