Asymmetric synthesis of (+)-stagonolide C and (−)-aspinolide A via organocatalysis

A new enantioselective synthesis of two important fungal metabolites, (+)-stagonolide C and (−)-aspinolide A, has been described from readily available raw materials. Proline catalyzed asymmetric α-aminooxylation and Jorgensen’s epoxidation of aldehydes are the key reactions employed in the introduction of chirality. The formation of the 10-membered lactone core structure was finally accomplished via Steglich esterification and ring closing metathesis reactions.

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(R)-tert-Butyldimethyl(pent-4-en-2-yloxy)silaneC11H24OSi[α]D25=-9.8 (c 2.0, CHCl3)Source of chirality: Brown’s asymmetric allylationAbsolute configuration: (R)

(R,E)-Ethyl 5-(tert-butyldimethylsilyloxy)hex-2-enoateC14H28O3Si[α]D25=-15.8 (c 1.0, CHCl3)Source of chirality: Brown’s asymmetric allylationAbsolute configuration: (R)

(R,E)-5-(tert-Butyldimethylsilyloxy)hex-2-enalC12H24O2Si[α]D25=-1.2 (c 0.3, CHCl3)Source of chirality: Brown’s asymmetric allylationAbsolute configuration: (R)

((2S,3S)-3-((R)-2-(tert-Butyldimethylsilyloxy)propyl)oxiran-2-yl)methanolC12H26O3Si[α]D25=-17.0 (c 0.3, CHCl3)Source of chirality: Brown’s asymmetric allylation/Jorgensen’s asymmetric epoxidationAbsolute configuration: (2S,3S,5R)

(3S,5R)-5-(tert-Butyldimethylsilyloxy)hex-1-en-3-olC12H26O2Si[α]D25=-30.1 (c 1.0, CHCl3)Source of chirality: Brown’s asymmetric allylation/Jorgensen’s asymmetric epoxidationAbsolute configuration: (3S,5R)

(5S,7R)-7,9,9′,10,10′-Pentamethyl-5-vinyl-2,4,8-trioxa-9-silaundecaneC14H30O3Si[α]D25=-13.7 (c 0.6, CHCl3)Source of chirality: Brown’s asymmetric allylation/Jorgensen’s asymmetric epoxidationAbsolute configuration: (5S,7R)

(S)-5-(tert-Butyldimethylsilyloxy)pentane-1,2-diolC11H26O3Si[α]D25=-2.3 (c 1.0, CHCl3)Source of chirality: Asymmetric α-aminooxylationAbsolute configuration: (S)

(S)-tert-Butyldimethyl(3-(oxiran-2-yl)propoxy)silaneC11H24O2Si[α]D25=-2.9 (c 0.4, CHCl3)Source of chirality: Asymmetric α-aminooxylationAbsolute configuration: (S)

(S)-6-(tert-Butyldimethylsilyloxy)hex-1-en-3-olC12H26O2Si[α]D25=-0.7 (c 0.6, CHCl3)Source of chirality: Asymmetric α-aminooxylationAbsolute configuration: (S)

(S)-10,10′,11,11′-Tetramethyl-5-vinyl-2,4,9-trioxa-10-siladodecaneC14H30O3Si[α]D25=-34.1 (c 0.64, CHCl3)Source of chirality: Asymmetric α-aminooxylationAbsolute configuration: (S)

(S)-4-(Methoxymethoxy)hex-5-en-1-olC8H16O3[α]D25=-114.0 (c 0.2, CHCl3)Source of chirality: Asymmetric α-aminooxylationAbsolute configuration: (S)

((2R,3R)-3-(4-(tert-Butyldimethylsilyloxy)ethyl)oxiran-2-yl)methanolC13H28O3Si[α]D25=-16.5 (c 1.7, CHCl3)Source of chirality: Jorgensen’s asymmetric epoxidationAbsolute configuration: (2R,3R)

(R)-7-(tert-Butyldimethylsilyloxy)hept-1-en-3-olC13H28O2Si[α]D25=+7.1 (c 2.4, CHCl3)Source of chirality: Jorgensen’s asymmetric epoxidationAbsolute configuration: (R)

(R)-2,2′,3,3′,11,11′,12,12′-Octamethyl-5-vinyl-4,10-dioxa-3,11-disilatridecaneC19H42O2Si2[α]D25=+6.0 (c 2.0, CHCl3)Source of chirality: Jorgensen’s asymmetric epoxidationAbsolute configuration: (R)

(R)-5-(tert-Butyldimethylsilyloxy)hept-6-en-1-olC13H28O2Si[α]D25=-9.2 (c 1.3, CHCl3)Source of chirality: Jorgensen’s asymmetric epoxidationAbsolute configuration: (R)