Enantiospecific Total Synthesis of (+)-Tanikolide via a Key [2,3]-Meisenheimer Rearrangement with an Allylic Amine N-Oxide-Directed Epoxidation and a One-Pot Trichloroisocyanuric Acid N-Debenzylation and N-Chlorination

Abstract

The enantiospecific total synthesis of the δ-lactonic marine natural product (+)-tanikolide (1), isolated from Lyngbya majuscula , was achieved using a [2,3]-Meisenheimer rearrangement as the key reaction. During this rearrangement, we discovered that the allylic amine N-oxide could direct the m-CPBA double-bond epoxidation to the syn position. The resulting syn product 8 underwent epoxide ring opening under the m-CBA conditions to give the five- and six-membered cyclic ether amine N-oxides, which we further treated with Zn and conc. HCl to obtain the reduced bisbenzyl tertiary amines 23 and 22, respectively. When 23 and 22 were treated with trichloroisocyanuric acid (TCCA) in dichloromethane, oxidation at the benzyl position occurred, forming iminium ions. These intermediates were trapped by intramolecular reaction with the hydroxyls, and the resulting intermediates were then oxidized or shifted to afford 25 and 24, respectively. The entire one-pot process involves N-debenzylation, N-chlorination, and hemiacetal oxidation. The amine N-oxide-directed epoxidation complements Davies' ammonium-directed epoxidation. Thus, TCCA N-debenzylation is described for the first time and might be a useful N-debenzylation technique.

One‐Pot Synthesis of O‐Allylhydroxylamines through the Organocatalytic Oxidation of Tertiary Allylic Amines Followed by a [2,3]‐Meisenheimer Rearrangement

“…Having in hand the ideal reaction conditions, we turned our focus to exploring the substrate scope of this method (Table 2). There is a literature report in which, depending on the oxidation system and the substrate utilized, a mixture of oxidation of amine ( N ‐oxide) and alkene (epoxide) is obtained 3i. Although our oxidation protocol can perform both the oxidation of tertiary amines7b and alkenes,7c in all substrates utilized in this study, no epoxide was detected, thus providing excellent selectivity for the oxidation of tertiary amines (see also the Supporting Information).…”

A new outlook in oxidative transformations and coupling reactions via in situ generation of organic chloramines

“…Yang et al developed a methodology for the synthesis of enantiospecific (+)‐tanikolide 13 , a marine natural product via [2,3]‐Meisenheimer rearrangement (Scheme 7). [ 24 ] In the process of developing compound 13 , they found a novel synthetic route for the synthesis of novel N ‐chloramine compounds 17 and 18 in high yields. For the first time, they reported TCCA‐associated N ‐debenzylations of tertiary amines 15 and 16 followed by the N ‐chlorination.…”

“…are widely used as synthetic intermediates for the synthesis of functionalized organic compounds [ 22 ] and natural products like flustramine C [ 23 ] and tanikolide. [ 24 ] There are primarily five to six mechanisms directing the synthesis of multi‐heteroatom heterocycles via in situ generation of organic chloramines through C–Cl, C–N, (C=O)N, and S–N bond formation. Using N–Cl reagents and N ‐chloramines as substrates and oxidants, one can achieve C–H to C–Cl transformations with good to excellent yield.…”

Enantioselective Synthesis of a Tricyclic, sp3‐Rich Diazatetradecanedione: an Amino Acid‐Based Natural Product‐Like Scaffold

“…[9] Borane reduction of the carboxylic acid yielded alcohol 9 in 68 %y ield. Parikh-Doehring oxidation [10] delivered an a-amino aldehyde, which was directlys ubjected to Ta kai olefination conditions to give vinyl iodide 10 as as ingle E-isomer in 46 %o ver 2steps. Reduction of the methyl ester with DIBAL (diisobutylaluminium hydride) in toluene at À78 8C afforded the desired aldehyde 12 in 74 %y ield along with the corresponding alcohol 11,w hichc ould be reoxidized to the aldehydei n8 3% yield using IBX (2-iodoxybenzoic acid) in DMSO.F inally,aHorner-Wadsworth-Emmons (HWE) reaction with methyld iethylphosphonoacetate delivered advanced vinyl iodide 3 in 79 %y ield.…”