Article ID Journal Published Year Pages File Type
1347122 Tetrahedron: Asymmetry 2014 9 Pages PDF
Abstract

The stereoselective total synthesis of pectinolide B has been accomplished for the first time along with total syntheses of pectinolides A and C. MacMillan α-hydroxylation and Sharpless asymmetric dihydroxylation reactions are involved in generating the three stereogenic centers. Other important transformations in the synthesis are Z-selective Still–Gennari olefination, selective benzylation of the homoallylic alcohol, and a one-pot MOM deprotection followed by lactonization leading to all three pectinolides A–C being synthesized from a common intermediate. Pectinolides A, B, and C were synthesized from n-hexanal in 19, 20, and 18 steps with overall yields of 8.8%, 6.72%, and 9.2%, respectively.

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(S)-Hexane-1,2-diolC6H14O2[α]D25 = −24.8 (c 1.3, EtOH)Source of chirality: d-proline/MacMillan α-hydroxylationAbsolute configuration: (S)

(S)-5-Butyl-2,2,3,3,8,8,9,9-octamethyl-4,7-dioxa-3,8-disiladecaneC18H42O2Si2[α]D25 = −11.9 (c 2.6, CHCl3)Source of chirality: d-proline/MacMillan α-hydroxylationAbsolute configuration: (S)

(S)-2-(tert-Butyldimethylsilyloxy)hexan-1-olC12H28O2Si[α]D25 = +8.8 (c 3.4, CHCl3)Source of chirality: d-proline/MacMillan α-hydroxylationAbsolute configuration: (S)

(S,Z)-Methyl 4-(tert-butyldimethylsilyloxy)oct-2-enoateC15H30O3Si[α]D25 = +70.4 (c 2.8, CHCl3)Source of chirality: d-proline/MacMillan α-hydroxylationAbsolute configuration: (S,Z)

(S,2E,4Z)-Ethyl 6-(tert-butyldimethylsilyloxy)deca-2,4-dienoateC18H34O3Si[α]D25 = +43.3 (c 1.1, CHCl3)Source of chirality: d-proline/MacMillan α-hydroxylationAbsolute configuration: (S,2E,4Z)

(S,2E,4Z)-6-(tert-butyldimethylsilyloxy)deca-2,4-dien-1-olC24H38O3Si[α]D25 = +10.6 (c 1.5, CHCl3)Source of chirality: d-proline/MacMillan α-hydroxylationAbsolute configuration: (S,2E,4Z)

tert-Butyl((S,6Z,8E)-10-(4-methoxybenzyloxy)deca-6,8-dien-5-yloxy)dimethylsilaneC24H40O3Si[α]D25 = −26.4 (c 2.2, CHCl3)Source of chirality: d-proline/MacMillan α-hydroxylationAbsolute configuration: (S,6Z,8E)

(2S,3S,6S,Z)-6-(tert-Butyldimethylsilyloxy)-1-(4-methoxybenzyloxy)dec-4-ene-2,3-diolC24H42O5Si[α]D25 = +5.8 (c 2.3, CHCl3)Source of chirality: d-proline/MacMillan α-hydroxylation, Sharpless asymmetric dihydroxylationAbsolute configuration: (2S,3S,6S,Z)

(2S,3S,6S,Z)-2-(Benzyloxy)-6-(tert-butyldimethylsilyloxy)-1-(4-methoxybenzyloxy)dec-4-en-3-olC31H48O5Si[α]D25 = +25.9 (c 2.2, CHCl3)Source of chirality: d-proline/MacMillan α-hydroxylation, Sharpless asymmetric dihydroxylationAbsolute configuration: (2S,3S,6S,Z)

(5S,8S,Z)-5-((S)-1-(Benzyloxy)-2-(4-methoxybenzyloxy)ethyl)-8-butyl-10,10,11,11-tetramethyl-2,4,9-trioxa-10-siladodec-6-eneC33H56O6Si[α]D25 = +74.3 (c 1.4, CHCl3)Source of chirality: d-proline/MacMillan α-hydroxylation, Sharpless asymmetric dihydroxylationAbsolute configuration: (5S,8S,Z,S)

(2S,3S,6S,Z)-2-(Benzyloxy)-6-(tert-butyldimethylsilyloxy)-3-(methoxymethoxy)dec-4-en-1-olC25H44O5Si[α]D25 = +48.1 (c 1.9, CHCl3)Source of chirality: d-proline/MacMillan α-hydroxylation, Sharpless asymmetric dihydroxylationAbsolute configuration: (2S,3S,6S,Z)

(2Z,4S,5S,6Z,8S)-Methyl 4-(benzyloxy)-8-(tert-butyldimethylsilyloxy)-5-(methoxymethoxy)dodeca-2,6-dienoateC28H50O6NSi[α]D25 = +80.2 (c 1.9, CHCl3)Source of chirality: d-proline/MacMillan α-hydroxylation, Sharpless asymmetric dihydroxylationAbsolute configuration: (2Z,4S,5S,6Z,8S)

(5S,6S)-5-(Benzyloxy)-6-((S,Z)-3-hydroxyhept-1-enyl)-5,6-dihydro-2H-pyran-2-oneC19H24O4[α]D25 = +100 (c 0.5, CHCl3)Source of chirality: d-proline/MacMillan α-hydroxylation, Sharpless asymmetric dihydroxylationAbsolute configuration: (5S,6S,S,Z)

(5S,6S)-5-(Benzyloxy)-6-((S,Z)-3-(methoxymethoxy)hept-1-enyl)-5,6-dihydro-2H-pyran-2-oneC21H28O5[α]D25 = +55.2 (c 1.6, CHCl3)Source of chirality: d-proline/MacMillan α-hydroxylation, Sharpless asymmetric dihydroxylationAbsolute configuration: (5S,6S,S,Z)

(5S,6S)-5-Hydroxy-6-((S,Z)-3-(methoxymethoxy)hept-1-enyl)-5,6-dihydro-2H-pyran-2-oneC14H22O5[α]D25 = +8.6 (c 0.7, CHCl3)Source of chirality: d-proline/MacMillan α-hydroxylation, Sharpless asymmetric dihydroxylationAbsolute configuration: (5S,6S,S,Z)

(2S,3S)-2-((S,Z)-3-(Methoxymethoxy)hept-1-en-1-yl)-6-oxo-3,6-dihydro-2H-pyran-3-yl acetateC16H24O6[α]D25 = +66.2 (c 1.2, CHCl3)Source of chirality: d-proline/MacMillan α-hydroxylation, Sharpless asymmetric dihydroxylationAbsolute configuration: (2S,3S,S,Z)

(2S,3S)-2-((S,Z)-3-Hydroxyhept-1-enyl)-6-oxo-3,6-dihydro-2H-pyran-3-yl acetateC14H20O5[α]D25 = +84.9 (c 0.4, MeOH)Source of chirality: d-proline/MacMillan α-hydroxylation, Sharpless asymmetric dihydroxylationAbsolute configuration: (2S,3S,S,Z)

(S,Z)-1-((2S,3S)-3-(Benzyloxy)-6-oxo-3,6-dihydro-2H-pyran-2-yl)hept-1-en-3-yl acetateC21H26O5[α]D25 = +102.5 (c 0.6, CHCl3)Source of chirality: d-proline/MacMillan α-hydroxylation, Sharpless asymmetric dihydroxylationAbsolute configuration: (S,Z,2S,3S)

(S,Z)-1-((2S,3S)-3-Hydroxy-6-oxo-3,6-dihydro-2H-pyran-2-yl)hept-1-en-3-yl acetateC14H20O5[α]D25 = +75.0 (c 0.4, MeOH)Source of chirality: d-proline/MacMillan α-hydroxylation, Sharpless asymmetric dihydroxylationAbsolute configuration: (S,Z,2S,3S)

(S,Z)-1-((2S,3S)-3-Acetoxy-6-oxo-3,6-dihydro-2H-pyran-2-yl)hept-1-en-3-yl acetateC16H22O6[α]D25 = +194.5 (c 0.5, CHCl3)Source of chirality: d-proline/MacMillan α-hydroxylation, Sharpless asymmetric dihydroxylationAbsolute configuration: (S,Z,2S,3S)

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