Organocatalytic Syntheses of Bioactive Natural Products
133
Four recent developments in reaction methodology—two of them
being organocatalytic reactions—now allow for a very efficient access
to UCS1025A. Hoye’s soft enolization cyclization (Hoye et al. 2006),
our oxa-Michael lactonization/trituration (de Figueiredo et al. 2007),
MacMillan’s organocatalytic Diels–Alder reaction (Wilson et al. 2005)
and Danishefsky’s BEt 3 -mediated coupling (Lambert and Danishefsky
2006) have made UCS1025A available in gram scale for biological
studies.
3
Lepidopteran Sex Pheromones
During the past decade, the horse chestnut leafminer Cameraria ohridella (Deschka and Dimic 1986) has spread from Macedonia over Europe and infested most of the horse chestnut trees (Aesculus hippocastanum). The insect’s life cycle begins with oviposition onto the leaf
surface. The larva then eats itself through the leaf which leads to brown
spots, giving the tree an autumnal appearance. The cycle repeats several
times per year. Lepidoteran sex pheromones are rather simple straightchain hydrocarbons terminated by hydroxyl, aldehyde or acetate groups.
The hydrocarbon chain is often decorated with different degrees of unsaturation with the E,Z-diene moiety being a frequent motif. We have
developed a divergent approach to 8E,10Z-tetradeca-8,10-dienal (20)
(Cameraria ohridella) and other members of this class of lepidopteran
pheromones, which takes advantage of the recently discovered organocatalytic transfer hydrogenation of enals (Scheme 8) (Yang et al. 2004,
2005; Ouellet et al. 2005).
A double Wittig homologation of the hexanedial 21 (López et al.
2005) with the phosphonium salt 18 affored decadienedial 22 (Iriye
et al. 1988) in good yield. It is noteworthy that the isomerization to
thermodynamically more stable E-enal occurs upon acidic hydrolysis.
A subsequent Wittig reaction with one equivalent of butyltriphenylphosphonium bromide afforded trienal 23 in good selectivity (Z:E>9:1) albeit in low yield. This material was subjected to the conjugate reduction
protocol developed by List to afford 8E,10Z-tetradeca-8,10-dienal 20.
Our strategy can be easily extended to the synthesis of other lepidopteran pheromones just by altering the chain length of starting alde-
133
Four recent developments in reaction methodology—two of them
being organocatalytic reactions—now allow for a very efficient access
to UCS1025A. Hoye’s soft enolization cyclization (Hoye et al. 2006),
our oxa-Michael lactonization/trituration (de Figueiredo et al. 2007),
MacMillan’s organocatalytic Diels–Alder reaction (Wilson et al. 2005)
and Danishefsky’s BEt 3 -mediated coupling (Lambert and Danishefsky
2006) have made UCS1025A available in gram scale for biological
studies.
3
Lepidopteran Sex Pheromones
During the past decade, the horse chestnut leafminer Cameraria ohridella (Deschka and Dimic 1986) has spread from Macedonia over Europe and infested most of the horse chestnut trees (Aesculus hippocastanum). The insect’s life cycle begins with oviposition onto the leaf
surface. The larva then eats itself through the leaf which leads to brown
spots, giving the tree an autumnal appearance. The cycle repeats several
times per year. Lepidoteran sex pheromones are rather simple straightchain hydrocarbons terminated by hydroxyl, aldehyde or acetate groups.
The hydrocarbon chain is often decorated with different degrees of unsaturation with the E,Z-diene moiety being a frequent motif. We have
developed a divergent approach to 8E,10Z-tetradeca-8,10-dienal (20)
(Cameraria ohridella) and other members of this class of lepidopteran
pheromones, which takes advantage of the recently discovered organocatalytic transfer hydrogenation of enals (Scheme 8) (Yang et al. 2004,
2005; Ouellet et al. 2005).
A double Wittig homologation of the hexanedial 21 (López et al.
2005) with the phosphonium salt 18 affored decadienedial 22 (Iriye
et al. 1988) in good yield. It is noteworthy that the isomerization to
thermodynamically more stable E-enal occurs upon acidic hydrolysis.
A subsequent Wittig reaction with one equivalent of butyltriphenylphosphonium bromide afforded trienal 23 in good selectivity (Z:E>9:1) albeit in low yield. This material was subjected to the conjugate reduction
protocol developed by List to afford 8E,10Z-tetradeca-8,10-dienal 20.
Our strategy can be easily extended to the synthesis of other lepidopteran pheromones just by altering the chain length of starting alde-