Synthesis of α‐Aminocyclopropyl Ketones and 2‐Substituted Benzoimidazoles from 2‐Hydroxycyclobutanones and Aryl Amines

Abstract

We have developed one-step protocols for the preparation of a large selection of α-aminocyclopropyl ketones or benzo[d]imidazoles, by reacting 2-substituted-2-hydroxycyclobutanones with aryl amines or o-phenylenediamines, respectively. In most case the reactions proceed at room temperature and are catalyst-free. The formation of benzo[d]imidazoles is rationalized in terms of an unusual ring-closure/ring-fission process followed by aromatization.

Tandem Baeyer–Villiger/Wittig/oxa-Michael addition: One-step to 5-substituted γ-lactones

“…Over the last few years, our group has explored the reactivity of α-hydroxy cyclobutanones with electrophiles [19][20] and nucleophiles [21][22][23] leading to the enantioselective synthesis of other functionalized cyclobutanone derivatives. Hence, further transformations useful for constructing diverse functionalized heterocycles [24][25][26][27] and cyclopropane carboxaldehydes [27][28][29] have also been developed. Continuing with our interest in exploiting new reactivities of α-hydroxy cyclobutanone and bearing in mind that 5-hydroxydihydrofuran-2(3H)-ones could be used efficiently as substrates in Wittig olefination reactions with stabilized phosphonium ylides (Scheme 1a), [15][16] we wondered whether it was possible to generate γ-lactol 3 (in mixture with its corresponding acyclic oxoacid) in situ from α-hydroxy cyclobutanone 1 and H2O2 (via a Baeyer-Villiger reaction), and trap it to undergo a tandem Wittig/oxa-Michael addition reaction to access γ-lactones such as 5 (Scheme 1c).…”

Synthesis of 1-[1-(Amino)cyclopropyl]ketones by Tandem Reaction Involving Vinyl Selenium Salt

“…(Simeprevir Sodium)、阿舒瑞韦(Asunaprevir)、伐尼瑞韦 (Vaniprevir)、格位瑞韦(Grazoprevir Hydrate)、达诺瑞韦 钠(Danoprevir Sodium)等抗菌药物, 盐酸安罗替尼 (Anlotinib Dihydrochloride)、紫杉醇类似物(Taxol analogue)、 大肠杆菌素类似物(Colibactin analogue)等抗肿瘤 分子和一些杀虫剂中均具有 1-[1-(胺基)环丙基]酮(或羧 酸衍生物)的结构单元; 在绿色植物中广泛存在的 1-氨 基环丙烷羧酸是植物激素乙烯的前体 [8] , 具有 α,α'-环化 的 P1 基团的甘氨酸 α-酮酰胺以及 HCV NS3 蛋白酶抑制 剂 BILN 2061 对丙型肝炎病毒(HCV)有良好的治疗效 果 [9] 等(Figure 1). 虽然有关合成环丙烷衍生物的方法有 很多 [21] , 但是到目前为止, 国内外合成 1-[1-(胺基)环丙 基]酮化合物的研究报道依旧很少, 其合成方法主要包 括邻胺基苯甲酸和 α-溴代-γ-丁内酯的多步环合 [10] , 1-乙 酰基-1-胺基环丙烷盐酸盐与双烯酮的酰胺化反应 [11] , 羟基环丁酮与芳胺的重排反应 [12] , 以及高价硫试剂参 与的串联反应 [13] (Scheme 1, a～d). 但这些方法仍存在 反应步骤多、总产率低、原料不易得等缺点.…”