Synthesis of Diamino Carboxylic Esters by Palladium‐Catalyzed Oxidative Intramolecular Diamination of Acrylates

Abstract

Unligated palladium(II) salts catalyze the oxidative diamination of acrylic esters to yield 2,3-diamino carboxylic esters. The reaction employs copper(II) bromide as oxidant and proceeds with good to excellent stereoselectivities and complete chemoselectivity. Preliminary mechanistic studies provide evidence for the involvement of a direct amination of the C--Pd bond in the alpha position relative to the ester group. This protocol significantly broadens the overall scope of the palladium-catalyzed diamination of alkenes and represents the first direct diamination of functionalized nonterminal substrates. The reaction yields readily protected 2,3-diamino acid derivatives, which can be considered as highly functionalized building blocks for subsequent synthesis. The use of one of these new diamination products as a suitable starting material in a short synthesis of the alkaloid absouline is demonstrated as an example.

Methods for direct alkene diamination, new & old

“…For example, cyclization of E- styrene derivative 345 proceeds with overall retention of alkene stereochemistry, while reaction of E- acrylate 350 takes place with inversion to yield the cis -configuration 351 . 232 In the former case, initial syn- aminopalladation is thought to be followed by anti- bromination/depalladation, giving rise to alkyl bromide 348 . C-N bond formation then takes place through an intramolecular S N 2-type displacement to generate both the anti- configured urea 346a and isourea 346b .…”

Oxidative Functionalization of Alkenes

“…For ureas, the observed stereochemistry suggests a sequence of syn-aminopalladation followed by anti-C-N bond formation within the scenario of a transient oxidation state, leading to the observed cis-stereochemistry of the diamine product 146 [101]. In contrast, the corresponding sulfamates give rise to products 148 with the opposite trans-stereochemistry [102].…”

Synthetic Strategies towards the Azabicyclo[3.3.0]-Octane Core of Natural Pyrrolizidine Alkaloids. An Overview

“…Thus an intramolecular reaction of the ester with an NH-unprotected pyrrolidine generates a PA-core as an amide in the first step, and is generally followed by reductive removal of the oxygen atom of the amide bond in the second stage followed usually by deprotection steps to deliver the final PAs (Scheme 9). This route provided PAs from the hyacinthacine family 120,152-162 as well as absouline, [163][164][165] isoretronecanol, 166,167 pyrrolam A, 168,169 trachelanthamidine, 170,171 casuarine, 158,172,173 heliotridane, 175 turneforcidine 175 and a fungi PA -7a(S)-phydroxyphenopyrrozin. 176 Typical yields for the cyclization step were in the range from 22% to quantitative.…”