Simple and efficient synthesis of highly functionalized cyclohexanes; formal total synthesis of ovalicin and fumagillin

Two chiral cyclohexanes 4 and 6, which are key intermediates for the total synthesis of ovalicin 1 and fumagillin 2, respectively, were synthesized from (2R,3S) 1,2-epoxy-4-penten-3-ol. The key steps involve an efficient construction of divinylalcohol 7 using methallyl Grignard reagent 9c, and an intramolecular olefin metathesis of 7.

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(3S,4R)-3-Methoxy-7-(4-methoxybenzyloxy)methyl-4-(triethylsilyloxy)octa-1,7-dieneC24H40O4Si[α]D24=+14.8 (c 0.80, CHCl3)Absolute configuration: (3S,4R)

(3S,4R)-3-Methoxy-1-(4-methoxybenzyloxy)methyl-4-(triethylsilyloxy)cyclohex-1-eneC22H36O4Si[α]D25=+70.0 (c 0.99, CHCl3)Absolute configuration: (3S,4R)

(3S,4R)-1-Hydroxymethyl-3-methoxy-4-(triethylsilyloxy)cyclohex-1-eneC14H28O3Si[α]D24=+112.5 (c 0.23, CHCl3)Absolute configuration: (3S,4R)

(3S,4R)-7-((4-Methoxybenzyloxy)methyl)octa-1,7-diene-3,4-diolC17H24O4[α]D24=+2.5 (c 0.33, CHCl3)Absolute configuration: (3S,4R)

(3S,4R)-3,4-Isopropylidendioxy-7-((4-methoxybenzyloxy)methyl)octa-1,7-dieneC20H28O4[α]D25=+2.2 (c 0.74, CHCl3)Absolute configuration: (3S,4R)

(3S,4R)-3,4-Isopropylidendioxy-1-((4-methoxybenzyloxy)methyl)cyclohex-1-eneC18H24O4[α]D24=-21.1 (c 0.23, CHCl3)Absolute configuration: (3S,4R)

(3S,4R)-1-Hydroxymethyl-3,4-(isopropylidendioxy)cyclohex-1-eneC9H13O3[α]D25=-18.4 (c 0.54, CHCl3)Absolute configuration: (3S,4R)