Stereoselective synthesis of (+)-boronolide and (−)-5-epi-boronolide

Stereoselective synthesis of boronolide and 5-epi-boronolide was achieved from d-(−)-tartaric acid. The key step involves the reduction of a keto Weinreb amide for the synthesis of boronolide, and a single pot construction of a diketone from the bis-Weinreb amide of tartaric acid and subsequent reduction with L-Selectride for 5-epi-boronolide.

Figure optionsDownload as PowerPoint slide

(4S,5S)-N-Methoxy-N,2,2-trimethyl-5-pentanoyl-1,3-dioxolane-4-carboxamideC13H23NO5[α]D = −7 (c 1, CHCl3)Source of chirality: d-(−)-tartaric acidAbsolute configuration: (2S,3S)

(4S,5R)-5-((S)-1-Hydroxypentyl)-N-methoxy-N,2,2-trimethyl-1,3-dioxolane-4-carboxamideC13H25NO5[α]D = +6.1 (c 1.2, CHCl3)Source of chirality: d-(−)-tartaric acidAbsolute configuration: (2S,3R,4S)

(4S,5R)-4-(Hex-5-enoyl)-5-((S)-1-hydroxypentyl)-2,2-dimethyl-1,3-dioxolaneC16H28O4[α]D = −28 (c 1, CHCl3)Source of chirality: d-(−)-tartaric acidAbsolute configuration: (7S,8R,9S)

(4S,5S)-5-((S)-1-tert-Butyldimethylsilyloxypentyl)-4-(hex-5-enoyl)-2,2-dimethyl-1,3-dioxolaneC22H42O4Si[α]D = −9.7 (c 1.6, CHCl3)Source of chirality: d-(−)-tartaric acidAbsolute configuration: (7S,8S,9S)

(4R,5S)-5-((S)-1-tert-Butyldimethylsilyloxypentyl)-4-((R)-1-hydoxyhex-5-enyl)-2,2-methyl-1,3-dioxolaneC22H44O4Si[α]D = −13.1 (c 1.3, CHCl3)Source of chirality: d-(−)-tartaric acidAbsolute configuration: (6R,7R,8S,9S)

(6S)-6-((4S,5R)-5-((R)-1-tert-Butyldimethylsilyloxypentyl)-2,2-dimethyl-1,3-dioxolan-4-yl)-tetrahydro-2H-pyran-2-oneC21H40O5Si[α]D = +3.5 (c 4.6, CHCl3)Source of chirality: d-(−)-tartaric acidAbsolute configuration: (5R,6S,7S,8S)

(6R)-6-((1S,2R,3S)-1,2,3-Trihydroxyhept-1-yl)-tetrahydro-2H-pyran-2-oneC12H22O5[α]D = −25.4 (c 2.4, CHCl3)Source of chirality: d-(−)-tartaric acidAbsolute configuration: (5R,6S,7R,8S)

1-((4S,5S)-5-Pentanoyl-2,2-dimethyl-1,3-dioxolan-4-yl)-hex-5-en-1-oneC16H26O4[α]D = −14.3 (c 1.2, CHCl3)Source of chirality: d-(−)-tartaric acidAbsolute configuration: (7S,8S)

(S)-1-((4R,5R)-5-(S)-(1-Hydroxypentyl)-2,2-dimethyl-1,3-dioxolan-4-yl)hex-5-en-1-olC16H30O4[α]D = −8.3 (c 1.2, CHCl3)Source of chirality: d-(−)-tartaric acidAbsolute configuration: (6S,7R,8R,9S)

(6S)-6-((4R,5R)-5-(S)-(1-Hydroxypentyl)-2,2-dimethyl-1,3-dioxolan-4-yl)-tetrahydro-2H-pyran-2-oneC15H26O5[α]D = −28 (c 3.4, CHCl3)Source of chirality: d-(−)-tartaric acidAbsolute configuration: (5S,6R,7R,8S)

(6S)-6-((4R,5R)-5-(S)-(1-Hydroxypentyl)-2,2-dimethyl-1,3-dioxolan-4-yl)-5,6-dihydro-pyran-2-oneC15H24O5[α]D = −27.1 (c 1.6, CHCl3)Source of chirality: d-(−)-tartaric acidAbsolute configuration: (5S,6R,7R,8S)

5-epi-BoronolideC18H26O8[α]D = −66 (c 0.7, CHCl3)Source of chirality: d-(−)-tartaric acidAbsolute configuration: (5S,6R,7R,8S)