Abstract:Reaction of nonracemic allylic hydroxy phosphonates, prepared by the asymmetric phosphonylation of unsaturated aldehydes, with methyl chloroformate in pyridine yields the corresponding carbonates. The carbonates are excellent substrates for the palladium-catalyzed addition of nucleophiles. Addition of the nucleophile is highly regioselective, resulting in γ -substituted vinyl phosphonates. The reaction of the allylic carbonates with aryl stannanes and malonates has been investigated. Progress in the applicatio… Show more
“…These nonracemic hydroxy phosphonates should be useful building blocks for asymmetric synthesis, provided that appropriate stereoselective or stereospecific transformations can be discovered. Having demonstrated that the palladium (0)-catalyzed addition of amines to nonracemic allylic hydroxy phosphonate derivatives proceeded with complete chirality transfer, our attention turned to the exploration of reactions with carbon-based nucleophiles …”
Reaction of the (1S)-allylic hydroxy phosphonate 1(S) with methyl chloroformate in pyridine yields the corresponding carbonate 3(S). The carbonate 3(S) undergoes a palladium-catalyzed arylation with p-tolyl tributylstannane to give both the 1E and 1Z vinyl phosphonates 6 (85:15). The E and Z vinyl phosphonates 6 were shown to have the opposite configuration at C-3. The major vinyl phosphonate isomer (3S,1E), was converted to (3S)-3-(p-tolyl)-butanal 8(S), completing a formal total synthesis of (S)-ar-turmerone 5a.
“…These nonracemic hydroxy phosphonates should be useful building blocks for asymmetric synthesis, provided that appropriate stereoselective or stereospecific transformations can be discovered. Having demonstrated that the palladium (0)-catalyzed addition of amines to nonracemic allylic hydroxy phosphonate derivatives proceeded with complete chirality transfer, our attention turned to the exploration of reactions with carbon-based nucleophiles …”
Reaction of the (1S)-allylic hydroxy phosphonate 1(S) with methyl chloroformate in pyridine yields the corresponding carbonate 3(S). The carbonate 3(S) undergoes a palladium-catalyzed arylation with p-tolyl tributylstannane to give both the 1E and 1Z vinyl phosphonates 6 (85:15). The E and Z vinyl phosphonates 6 were shown to have the opposite configuration at C-3. The major vinyl phosphonate isomer (3S,1E), was converted to (3S)-3-(p-tolyl)-butanal 8(S), completing a formal total synthesis of (S)-ar-turmerone 5a.
“…It has been shown that allylic hydroxy phosphonates can serve as useful intermediates in the synthesis of γ-substituted phosphonates by 1,3-transposition of functionality and that the steric and electronic influence of the phosphorus moiety can enhance the stereochemical and regiochemical outcome of the reactions. , In a nice illustration of the effect of the phosphonate on regioselectivity, Zhu and Lu demonstrated that the palladium-catalyzed addition of nucleophiles (amine and malonate) to the acetate derivatives 2 of racemic allylic hydroxy phosphonates 1 (Scheme ) takes place exclusively at the 3-position to give the γ-substituted vinyl phosphonates 4 in high yield . Palladium-catalyzed additions of nitrogen and carbon nucleophiles to racemic allylic phosphonates were later employed in the successful synthesis of fosfomycin and ω-phosphono amino acids. 5c-f Having demonstrated that the palladium (0)-catalyzed intermolecular addition of amines to nonracemic allylic hydroxy phosphonate derivatives proceeds with complete chirality transfer, we turned our attention to the exploration of reactions with carbon-based nucleophiles. , 1 Palladium(0)-Catalyzed Reactions of Allylic Hydroxy Phosphonate Derivatives…”
A combination of cross-metathesis and malonate addition was applied to a formal synthesis of the mammalian lignan enterolactone 5. The cross-metathesis of alkene 6 and phosphonate 3a gave the substituted allylic phosphonate 3d. The palladium-catalyzed addition of malonate 10d to the allylic phosphonate 3d was stereospecific and highly regioselective and yielded the vinyl phosphonate 11d. The vinyl phosphonate 11d was converted in two steps into the lactone 14, a known intermediate in the synthesis of enterolactone 5.
An FeCl3‐mediated regio‐ and stereoselective Friedel–Crafts‐type arylation of α‐hydroxy phosphonates with unactivated arenes has been developed in which the unstable allylphosphonate cations generated are stabilized by extended conjugation. The approach provides a simple, efficient and economic approach to highly demanding stereoselective γ‐aryl‐substituted vinylphosphonates and dialkyl (diarylmethyl)phosphonates with good regioselectivity. These reactions proceed under mild conditions and proceed in the absence of any additional solvent.
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