Application of the Aza-Achmatowicz Oxidative Rearrangement for the Stereoselective Synthesis of the Cassia and Prosopis Alkaloid Family

Abstract

Abstractcis-2-Methyl-6-substituted piperidin-3-ol alkaloids of the Cassia and Prosopis species are readily prepared by a combination of an aza-Achmatowicz oxidative rearrangement, dihydropyridone reduction followed by a Stereoselective allylsilane addition to a N-sulfonyliminium ion. The stereochemical outcome of the reduction reaction can be attributed to steric hindrance between the pseudoaxially oriented 2,6-substituents and the equatorially approaching hydride reagent which explains the exclusive formation of the cis-alcohol by axial approach of the hydride. The unsaturation present in the (E)-methyl-pent-3-enoate side chain was removed by catalytic reduction and the remaining ester group was converted to the corresponding Weinreb's amide. This key intermediate was utilized for the synthesis of azimic acid, deoxocassine, cassine and spicigerine. The facile preparation of (S)-N-tosylamidofuran 16 and its conversion to the chiral Achmatowicz oxidation product 18 provides a formal chiral synthesis of these alkaloids.

The 3‐Hydroxypiperidine Skeleton: Key Element in Natural Product Synthesis

“…Padwa and co‐workers developed a method for the total synthesis of (+)‐deoxocassine ( ent ‐ 14 ) starting from 2‐acetylfuran (Scheme ) 75. To construct an enantiopure tosylaminofuran, they made use of the elegant sulfinimine chemistry that was developed previously 76…”

A N,N′‐Dioxide–Copper(II) Complex as an Efficient Catalyst for the Enantioselective and Diastereoselective Mannich‐Type Reaction of Glycine Schiff Bases with Aldimines

“…[7] Optically active dihydropyridones are important synthetic intermediates used in the asymmetric synthesis of polyhydroxylated piperidine alkaloids. [15] This reaction offers a convenient approach to the synthesis of such compounds. Therefore, hydrolysis of the corresponding a,b-diamino acid ester 3 w [16] with 2n HCl, followed by protection with Boc 2 O gave adduct 4 in 89 % yield.…”

Achmatowicz reaction and its application in the syntheses of bioactive molecules

“…104-107 The issues related to the use of bromine and poor water solubility of pyran-3-ones, prompted the development of new non-bromine-based oxidizing agents such as m -CPBA in a variety of solvents. 108-113 This alternative furylcarbinol ring expansion was nicely employed in natural product total syntheses. 114-117 …”