Some Observations on the Dakin--West Reaction

Cleland, George H.; Niemann, Carl

doi:10.1021/ja01171a022

Cited by 40 publications

(10 citation statements)

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“…According to the currently accepted mechanism, [6] the reaction of an amino acid with the anhydride leads to the Nacetyl derivative 1 and subsequently to the mixed anhydride 2 (Scheme 2). Cyclization of 2 provides the oxazol-5(4H)-one (azlactone) 3.S uch azlactones are acidic owing to the formation of resonance stabilized enolate 4 upon deprotonation.…”

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The Enantioselective Dakin–West Reaction

et al. 2016

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Here we report the development of the first enantioselective Dakin-West reaction, yielding a-acetamido methylketones with up to 58 %eewith good yields.T wo of the obtained products were recrystallized once to achieve up to 84 %ee. The employed methylimidazole-containing oligopeptides catalyze both the acetylation of the azlactone intermediate and the terminal enantioselective decarboxylative protonation. We propose ad ispersion-controlled reaction path that determines the asymmetric reprotonation of the intermediate enolate after the decarboxylation.Even though the Dakin-West (DW) reaction dates back to 1928, [1] it is still one of the most effective synthetic procedures to prepare a-acylamido ketones from primary a-amino acids. [2] Generally,t he treatment of an amino acid with an acid anhydride and base,t ypically pyridine,a te levated temperature provides the desired product upon liberation of CO 2 (Scheme 1). Numerous modifications of the original reaction conditions were developed, [2] including catalytic variants, [3] broadening its scope and applicability.U nsurprisingly,the DW reaction found application in the preparation of a-acylamido ketones as valuable precursors for various biologically active compounds, [4] and even in Woodwards fundamental total synthesis of strychnine. [5] Remarkably,n o asymmetric variant has been developed to date,thus restricting the use of this important reaction in modern synthetic chemistry.

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The Enantioselective Dakin–West Reaction

et al. 2016

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“…Since pyridine and triethylamine are poor catalysts for this transformation, it is assumed that DMAP and the isocyanate are in equilibrium with the dipole (81) which is converted by protonation into the more reactive N-carbamoylpyridinium ion (82). (82) reacts readily with carboxylates, phenolates, and alkoxides (with loss of COz) to yield amides or urethanes.…”

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4‐Dialkylaminopyridines as Highly Active Acylation Catalysts. [New synthetic method (25)]

Höfle

Steglich

Vorbrüggen³

1978

Angew. Chem. Int. Ed. Engl.

1,196

376

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and Helmut V o r b r i i g g e n [ * ] New synthetic methods (25)The synthesis of 4-dialkylaminopyridines can be accomplished in two steps starting from pyridine. Compared to pyridine, these derivatives are approximately lo4 times more active when used as acylation catalysts. Dialkylaminopyridines are being used with ever-increasing frequency for acylation reactions which proceed either incompletely or not at all in pyridine. This article reviews the various possible applications of 4-dialkylaminopyridines in terpene, steroid, carbohydrate and nucleoside chemistry as well as in the transformation of amino acids into a-acyl aminoketones and polymerization of isocyanates. In addition, N-substituted 4-dialkylaminopyridinium salts can be used for the transfer of sensitive groups to nucleophiles in aqueous medium. The exceptional catalytic effect of these derivatives, even in non-polar solvents, is due, in part, to the formation of high concentrations of N-acylpyridinium salts which are present in solution as loosely-bound, highly reactive ion pairs. DMAP PPY[*] Priv.-Doz.

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“…Even though the Dakin-West reaction can hardly be considered well-known, there is quite a lot of published work including some very detailed mechanistic investigations particularly by Steglich [5]. It is generally accepted that the mechanism involves dehydrative formation of an azlactone (oxazolinone) which is then Cacylated (in equilibrium with O-acylation), and then undergoes ring-opening hydrolysis followed by decarboxylation to form the acylamino ketone (Scheme 3) [6].…”

Section: Pyrrole Synthesismentioning

confidence: 99%