A mild, efficient method for the oxidation of α-diazo-β-hydroxyesters to α-diazo-β-ketoesters

Abstract

A wide variety of α-diazo-β-ketoesters can be prepared in good overall yields via a two-step sequence involving addition of ethyl lithiodiazoacetate to aliphatic, aromatic and conjugated aldehydes followed by mild oxidation with the Dess-Martin periodinane. Keywords ethyl diazoacetate; Dess-Martin periodinane; oxidationIn the course of some natural product syntheses currently ongoing in these labs, we needed to convert an aldehyde 1 into an α-diazo-β-ketoester 4 and two reasonable sequences seemed possible (Scheme 1). The most common methodology for this transformation would involve first homologating 1 to the corresponding β-ketoester 2, followed by a Regitz diazo transfer step to produce 4. 1 Alternatively, a potentially more attractive route would be to initially add ethyl lithiodiazoacetate to aldehyde 1 to produce an α-diazo-β-hydroxyester 3, which would be oxidized to the desired diazo compound 4. Although the addition of metallated ethyl diazoacetate to aldehydes is well precedented, 2 examples of the oxidation of adducts 3 to the corresponding ketones 4 are rare. In the few extant cases, the β-hydroxy-α-diazoesters 3 are derived only from aromatic or conjugated aldehydes. Moreover, the only reagents which have been used for alcohol oxidation in these few examples are limited to manganese dioxide, 3 IBX, 4 or barium permanganate. 5Since we were particularly interested in effecting this sequence starting with aliphatic aldehydes, and also required a mild oxidant for the second step which is compatible with sensitive functionality, we have explored this methodology further, particularly with regard to the oxidation process. Since there was good literature precedent that α-diazo-β-ketoesters are stable towards Dess-Martin periodinane (DMP), 6 we chose to investigate this reagent for oxidation of substrates like 3.As listed in Table 1, several α-diazo-β-hydroxyesters 3 were prepared from a variety of aliphatic, aromatic and unsaturated aldehydes and ethyl lithiodiazoacetate in THF using the experimental procedure of Padwa, et al. 2b It was found that exposure of these compounds to Dess-Martin periodinane in methylene chloride at room temperature indeed led to the formation of the corresponding α-diazo-β-ketoesters

Construction of Two Vicinal Quaternary Carbons by Asymmetric Allylic Alkylation: Total Synthesis of Hyperolactone C and (−)‐Biyouyanagin A

“…After treatment of 10 with TsN 3 in CH 3 CN, the corresponding α‐diazo‐β‐ketoester 11 was obtained in 88 % yield 9. Exposure of 11 to Dess–Martin periodinane in CH 2 Cl 2 at room temperature led to the formation of the corresponding α‐diazo‐β‐ketoesters 12 10. Then 12 was smoothly transformed into β‐ketoester 5 in the presence of a catalytic amount of [Rh 2 (OAc) 4 ] in CH 2 Cl 2 through a hydrogen migration process 11…”

Modern Organic Synthesis with α-Diazocarbonyl Compounds

“…48 Mild oxidation of the resulting α-diazo-β-hydroxycarbonyl adducts to the corresponding diazodicarbonyl compound has been reported with both IBX 49 and Dess−Martin periodinane. 50 The two-step sequence (Scheme 19) represents a useful alternative to the traditional diazo transfer of β-dicarbonyl compounds. It can also be conveniently carried out in one pot when DBU is employed as the base.…”

New Syntheses of Diazo Compounds

“…The aldol‐type synthesis of β‐hydroxy‐α‐diazocarboxylic acid esters followed by a mild and selective oxidation with Dess–Martin periodinane53a or o ‐iodoxybenzoic acid (IBX)53b constitutes a synthesis of 2‐diazo‐3‐oxocarboxylic esters 25 . This synthesis can also be applied to obtain more highly functionalized diazo compounds, for example, 25 a , b 53a. Even the one‐step preparation of 25 is possible (aldehyde, ethyl diazoacetate, DBU, IBX, DMSO) 53b…”