Catalytic Asymmetric Dihydroxylation of Enamides and Application to the Total Synthesis of (+)‐Tanikolide

Abstract

Asymmetric dihydroxylation of β,β′‐ disubstituted enamides afforded chiral tertiary‐alcohol‐containing α‐hydroxyaldehydes and 1,2‐diols with high enantioselectivity (see scheme). This method was applied to the total synthesis of the antifungal natural product (+)‐tanikolide, as well as the synthesis of an intermediate en route to (S)‐oxybutynin.

Silver Triflate/N‐Fluorobenzenesulfonimide‐Catalyzed Cycloisomerization of Tryptamine‐Ynamide to Spiro[indoline‐3,4′‐piperidine] Induced by Cation‐π‐π Interactions between Substrate and Metal Ligand

“…The chelation of sulfonamide and silver catalyst enabled the regioselective addition of the indole nucleophile to the β-carbon of ynamide to provide the α-metalated spiroindoleninium intermediate 1-2 b. [8] The stabilization of the spiroindoleninium intermediate by the phenyl group on the NFSI allowed the capture of Hantzsch ester or indole to form the intermediate 1-3 or 1-4. The cationπ-π interaction enabled the phenyl ring and NFSI sheilded the Si face of the spiroindoleninium ion, therefore favoring the approach of the nucleophiles from the Re face of the spiroindoleninium ion to access the product 2 or 4 a after a protodemetalation.…”

“…In this system, a cation-π-π interaction between the substrate and the metal ligand on the catalyst was identified to stabilize the substrate-metal ligand complex, leading to the acceleration of the reaction or improvement in the yields (Figure 1, d). This cycloisomerization proceeded via an intramolecular umpolung-type addition [8] followed by an intermolecular trapping of the persistent spiroindoleninium intermediates by strong nucleophiles such as hydride donors [9][10][11] and indole derivatives [12] to interrupt the high propensity to undergo the rapid Wagner-Meerwein rearrangement of the spiroindoleninium intermediates. Herein, we described our research on the AgOTf/NFSI-catalyzed cycloisomerization of tryptamine-ynamide to spiro[indoline-3,4'-piperidine] derivatives.…”

Asymmetric Synthesis of the β-Methyl-Substituted Analogues of (+)-Tanikolide and (–)-Malyngolide

“…Domino reactions of epoxy alcohols with hypervalent iodine reagents [14,19] and asymmetric dihydroxylation of enamides have also been investigated [20]. The asymmetric synthesis of (−)-malyngolide was first reported by Mukaiyama [21].…”

Asymmetric Synthesis of (+)‐Tanikolide and the β‐Methyl‐Substituted Analogues of (+)‐Tanikolide and (–)‐Malyngolide

“…A number of different strategies have been employed in previous syntheses of (+)‐tanikolide,3 including Sharpless asymmetric epoxidation/dihydroxylation of allylic alcohols,4 the use of the enantiopure starting materials D ‐erythrulose5a and D ‐erythrose,5b stereospecific C–H insertion of dichlorocarbene with a chiral secondary alcohol,5c asymmetric α‐alkylation of a β‐keto ester and subsequent Bayer–Villiger oxidation,5d α‐metalation of ketones, and ring‐closing metathesis 4b,5a,6. Domino reactions of epoxy alcohols with hypervalent iodine reagents7 and asymmetric dihydroxylation of enamides have also been investigated 8. The asymmetric synthesis of (–)‐malyngolide was first reported by Mukaiyama 9.…”