General strategy towards chiral methylene bis-pyrans: synthesis of the C2–C16 fragment of phorboxazole A

A chiral methylene bis-pyran fragment was synthesized by making efficient use of an oxy-anion intramolecular Michael addition, Brown’s asymmetric allylation and Grubb’s ring closing metathesis reactions in a stereoselective manner.

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(2R,4S)-5-Hexene-1,2,4-triolC6H12O3[α]D25=-5.6 (c 0.75, CHCl3)Source of chirality: glucoseAbsolute configuration: (2R,4S)

1-[2,2-Dimethyl-(4R)-1,3-dioxolan-4-yl]-(2S)-3-buten-2-olC9H16O3[α]D25=-7.6 (c 2.35, CHCl3)Source of chirality: glucose

4-[2-Benzyloxy-(2S)-3-butenyl]-2,2-dimethyl-(4R)-1,3-dioxolaneC16H22O3[α]D25=-32.9 (c 3.15, CHCl3)Source of chirality: glucose

3-Benzyloxy-4-[2,2-dimethyl-(4R)-1,3-dioxolan-4-yl]-(3R)-butan-1-olC16H24O4[α]D25=+18.1 (c 0.85, CHCl3)Source of chirality: glucose

Ethyl 5-benzyloxy-6-[2,2-dimethyl-(4R)-1,3-dioxolan-4-yl]-(E,5R)-2-hexenoateC20H28O5[α]D25=-20.1 (c 2.7, CHCl3)Source of chirality: glucose

Ethyl 5-benzyloxy-7,8-dihydroxy-(E,5R,7R)-2-octenoateC17H24O5[α]D25=-16.2 (c 0.4, CHCl3)Source of chirality: glucoseAbsolute configuration: (5R,7R)

Ethyl 2-[4-benzyloxy-6-hydroxymethyl-(2S,4R,6R)-dihydro-4H-2-pyranyl]acetateC17H24O5[α]D25=-9.5 (c 1.15, CHCl3)Source of chirality: glucose

Ethyl2-[4-benzyloxy-6-methoxymethoxymethyl-(2S,4R,6R)-dihydro-4H-2-pyranyl]acetateC19H28O6[α]D25=-7.6 (c 0.3, CHCl3)Source of chirality: glucose

1-[4-Benzyloxy-6-methoxymethoxymethyl-(2R,4R,6R)-dihydro-4H-2-pyranyl]-(2R)-4-penten-2-olC20H30O5[α]D25=-9.8 (c 1.0, CHCl3)Source of chirality: glucose

1-[4-Benzyloxy-6-methoxymethoxymethyl-(2S,4R,6R)-dihydro-4H-2-pyranylmethyl]-(1R)-3-butenyl acrylateC23H32O6[α]D25=-14.6 (c 1.0, CHCl3)Source of chirality: glucose

6-[4-Benzyloxy-6-methoxymethoxymethyl-(2S,4R,6R)-2H,3H,4H,5H-2-pyranylmethyl]-(6R)-2H,5H-2-pyranoneC21H28O6[α]D25=-10.7 (c 1.0, CHCl3)Source of chirality: glucose

6-[4-Benzyloxy-6-methoxymethoxymethyl-(2S,4R,6R)-2H,3H,4H,5H-2-pyranylmethyl]-(6R)-2H,5H-2-pyranolC23H34O6[α]D25=-1.7 (c 0.75, CHCl3)Source of chirality: glucose

C24H30O44-Benzyloxy-2-[2-ethoxy-(2S,6R)-2H,5H-6-pyranylmethyl]-6-methoxymethoxymethyl-(2R,4R,6R)-2H,3H,4H,5H-pyran[α]D25=-8.2 (c 1.15, CHCl3)Source of chirality: glucose