ABSTRACT
Catalytic oxidative cyclisation reactions have been employed for the synthesis of the E and F rings of the complex natural product target pectenotoxinâ 4. The choice of metal catalyst (cobalt- or osmium-based) allowed for the formation of THF rings with either trans or cis stereoselectivity. Fragment union using a modified Julia reaction then enabled the synthesis of an advanced synthetic intermediate containing the EF and G rings of the target.
Subject(s)
Alanine/analogs & derivatives , Bridged Bicyclo Compounds, Heterocyclic/chemical synthesis , Alanine/chemical synthesis , Alanine/chemistry , Bridged Bicyclo Compounds, Heterocyclic/chemistry , Catalysis , Crystallography, X-Ray , Cyclization , Models, Molecular , Molecular Conformation , Oxidation-Reduction , StereoisomerismABSTRACT
A novel osmium-catalysed oxidative cyclisation of 1,2-diols bearing a pendant vinyl silane affords THFs that contain silicon functionality at the ring junction. When the cyclisation occurs onto a vinyl benzyldimethylsilyl group, the resulting silyl group can act as a masked hydroxyl group and undergo a Fleming-Tamao type oxidation at a later stage to form the corresponding lactol. The scope of this reaction can also be extended beyond 1,2-diols and applied to the cyclisation of α-hydroxy-sulfonamides and α-hydroxy-amides.
Subject(s)
Silanes/chemistry , Cyclization , Oxidation-ReductionABSTRACT
Replacing trifluoroacetic acid with a catalytic amount of Lewis acid in the osmium mediated oxidative cyclization results in higher yielding reactions that can proceed nearly an order of magnitude faster. The osmium loading can also be reduced to as little as 0.2 mol %. Furthermore, these mildly acidic conditions are capable of tolerating a wide range of acid sensitive protecting groups that are incompatible with previous cyclization conditions.
