An organocatalytic route to the synthesis of (6S)-5,6-dihydro-6-[(2R)-2-hydroxy-6-phenylhexyl]-2H-pyran-2-one and ravensara lactones

An organocatalytic enantioselective synthesis of the title compounds has been achieved. The stereogenic centers were generated by the iterative use of proline catalyzed α-aminoxylations and HWE olefination of aldehydes while the lactone ring was constructed by ring closing metathesis.

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(2R,4R)-4-((tert-Butyldimethylsilyloxy)-8-phenyloctane-1,2-diolC20H36O3Si[α]D25=+6.4 (c 0.5, CHCl3)Source of chirality: proline catalyzed α-aminoxylation of aldehyde followed by diol formationAbsolute configuration: (2R,4R)

tert-Butyldimethyl((R)-1-((R)-oxiran-2-yl)-6-phenylhexan-2-yloxy)silaneC20H34O2Si[α]D25=+4.8 (c 1.0, CHCl3)Source of chirality: proline catalyzed reactionAbsolute configuration: (2R,4R)

(S)-Methyl-4-hydroxy-6-phenyloctanoateC15H22O3[α]D25=+12.55 (c 1, CHCl3)Source of chirality: proline catalyzed α-aminoxylation of aldehydeAbsolute configuration: (4S)

(S)-Methyl 4-((tert-butyldimethylsilyloxy)-8-phenyloctanoateC21H36O6Si[α]D25=+17.0 (c 0.9, CHCl3)Source of chirality: proline catalyzed α-aminoxylation of aldehyde followed by TBS protection of aldehydeAbsolute configuration: (4S)

(4S,6R)-Ethyl 4,6-bis(tert-butyldimethylsilyloxy)-10-phenyldecanoateC29HO54Si2[α]D25=+22.2 (c 0.1, CHCl3)Source of chirality: proline catalyzed α-aminoxylation of aldehydeAbsolute configuration: (4S,6R)

(2R,4S,6R)-4,6-bis(tert-Butyldimethylsilyloxy)-10-phenyldecane-1,2-diolC28H54O4Si2[α]D25=-7.8 (c 1.0, CHCl3)Source of chirality: proline catalyzed α-aminoxylation of aldehyde followed by diol formationAbsolute configuration: (2R,4S,6R)

((5R,7S)-2,2,3,3,9,9,10,10-Octamethyl-5-((S)-oxiran-2-ylmethyl)-7-(4-phenylbutyl)-4,8-dioxa-3,9-disilaundecaneC28H52O3Si[α]D25=-2.5 (c 1.5, CHCl3)Source of chirality: proline catalyzed reactionsAbsolute configuration: (5R,7S,5’S)

(4R,6R,8S)-6,8-Bis(tert-Butyldimethylsilyloxy)-12-phenyldodec-1-en-4-olC30H56O2Si2[α]D25=+8.7 (c 1,CHCl3)Source of chirality: proline catalyzed reactionsAbsolute configuration: (4R,6R,8S)

(4R,6R,8S)-6,8-bis(tert-Butyldimethylsilyloxy)-12-phenyldodec-1-en-4-yl acrylateC33H58O4Si2[α]D25=+4.7 (c 1,CHCl3)Source of chirality: proline catalyzed reactionsAbsolute configuration: (4R,6R,8S)

(4S,6R)-4-Allyl-2,2-dimethyl-6-(4-phenylbutyl)-1,3-dioxaneC19H28O2[α]D25=-11.7 (c 0.6, CHCl3)Source of chirality: proline catalyzed reactionsAbsolute configuration: (4S,6R)

(4S,6R)-10-Phenyldec-1-ene-4,6-diolC16H24O2[α]D25=-32.6 (c 1.0, CHCl3)Source of chirality: proline catalyzed reactionsAbsolute configuration: (4S,6R)

(R)-6-((2R,4S)-2,4-Bis(tert-Butyldimethylsilyloxy)-8-phenyloctyl)-5,6-dihydro-2H-pyran-2-oneC31H54O24Si2[α]D25=+10.2 (c 0.45, CHCl3)Source of chirality: proline catalyzed reactionsAbsolute configuration: (2R,4S,6R)