Synthesis of Diketones and ω-Hydroxy Ketones from Methyl Ketones and α,ω-Diols by an [IrCl(cod)]2/PPh3/KOH System

Abstract

!-Hydroxy ketones and diketones, which are important starting materials for the synthesis of cycloalkanones and heterocyclic compounds, were prepared by the one-step reaction of methyl ketones with ,!-diols under the influence of an iridium complex and a base. The selectivity of !-hydroxy ketones and diketones could be controlled by varying the starting ratio of methyl ketones to ,!-diols. For example, reaction using acetophenone (5 equiv) with respect to 1,6-hexanediol (1 equiv) in the presence of [IrCl(cod)] 2 , PPh 3 , and KOH without solvent gave 1,10-diphenyl-1,10-decanedione in almost quantitative yield, while reaction using acetophenone (1 equiv) to 1,6-hexanediol (4 equiv) led to 8-hydroxy-1-phenyl-1-octanone in 92% yield. This methodology was successfully extended to the reaction of arylacetonitriles with ,!-diols leading to diaryldinitriles.Hydroxy ketones and diketones are a very important class of compounds which are ubiquitous in nature and represent a basic key structure in organic synthesis. Acyloin condensation 1 and aldol reaction 2 are well-known synthetic methods to obtain -hydroxy and -hydroxy ketones, respectively.On the other hand, a variety of synthetic methods for the preparation of diketones have been disclosed, 3 since diketones are important starting materials for the synthesis of cycloalkanones and heterocyclic compounds. To the best of our knowledge, however, there have been few methods reported so far for the preparation of hydroxy ketones and diketones via the same methodology. Therefore, it seems very attractive to explore a facile synthetic route to diketones from readily available starting materials. In the course of our study to extend iridium-catalyzed synthetic reactions, 4 we have found that -alkylation of ketones with alcohols leading to higher alkylated ketones is efficiently promoted by iridium complexes like [IrCl(cod)] 2 . 5 Many groups have also reported related work on iridium-or ruthenium-catalyzed -alkylations using alcohols as alkylating agents. 6,7 If our strategy could be extended to the reaction between ketones and ,!-diols, the reaction would provide a very convenient synthetic tool for preparing !-hydroxy ketones and diketones. In this paper, we would like to report a novel synthetic method for preparing !-hydroxy ketones and diketones from methyl ketones and ,!-diols by the action of iridium complexes (eq 1).In order to confirm optimum reaction conditions, the reaction of acetophenone (1a) with 1,6-hexanediol (2a) was chosen and examined in the presence of several Ir complexes and KOH under various reaction conditions (Table 1).The reaction of 1a (10.0 mmol) with 2a (2.0 mmol) in the presence of [IrCl(cod)] 2 (0.1 mmol), PPh 3 (0.4 mmol), and KOH (0.4 mmol) without any solvent at 100 C for 15 h (standard conditions) gave a homogeneous solution and was found to produce double-alkylated product, 1,10-diphenyl-1,10-decanedione (7aa), in almost quantitative yield (>99%) (86% isolated yield) along with a small amount of aldol condensate of 1a, 1,3-diphenyl-2-bute...

Iridium-Catalyzed Reactions Involving Transfer Hydrogenation, Addition, N-Heterocyclization, and Alkylation Using Alcohols and Diols as Key Substrates

“…48 The selectivity to give w-hydroxy ketones by monoalkylation or diketones by double alkylation was found to be controlled by varying the starting ratio of methyl ketone to a,w-diol.…”

“…Our strategy was successfully extended to the reaction between ketones and a,w-diols which provides a very convenient synthetic tool for preparing w-hydroxy ketones and diketones. 48 The selectivity to give w-hydroxy ketones by monoalkylation or diketones by double alkylation was found to be controlled by varying the starting ratio of methyl ketone to a,w-diol.…”

“…[56][57][58] The synthesis of CPDL (48) from 2-cyano-15-hydroxypentadecanoate (46) was carried out as follows: Substrate 46 was refluxed with KOH (4 equiv) in ethylene glycol for 6 hours to give CPDA (47) in 72% yield according to the literature method. 59 Subsequently, CPDA (47) was allowed to react with a fluoroalkyl-containing distannoxane catalyst (Otera's catalyst) 60 in a mixed solvent of FC-72 and decane, employing Otera's method for the synthesis of lactones, 58 which led to CPDL (48) in 30% yield (Scheme 17).…”

“…51 We successfully extended this strategy to the double alkylation of arylacetonitriles with a,w-diols. 48 For instance, phenylacetonitrile (39) (10 mmol) was allowed to react with pentane-1,5-diol ( 40 ). The reaction is highly chemoselective and no monoalkylation product was detected at all under these conditions.…”

Production of 1,3-Propanediol from Pure and Crude Glycerol Using Immobilized Clostridium butyricum

“…The bulk chemical demand of this compound is following the growing trend discussed in [5]; 1,3-PD has been investigated as a substrate for chemocatalysis, in particular with the aim of developing ecofriendly, halogenated, reagent-free syntheses of valuable chemicals, with the minimization of waste. Iridium and ruthenium catalyzed reactions of 1,3-PD with nitrogen containing compounds, such as aminoarenes, naphtylamines, piperidine, tetrahydroquinoline, diethylamine, and phenylacetonitrile, have afforded quinolones [6,7], 7,8-benzoquinolines [8], julolidines [9], along with 1,3-dipiperidine [10], diaryldinitrile [11], and also monoaminated [12] 1,3-PD derivatives. 1,3-PD has also been used as a substrate in the C-C bond-forming hydrogen transfer (HT).…”