The Acyloin Condensation as a Cyclization Method

!-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...

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“…Acyloin condensation 1 and aldol reaction 2 are well-known synthetic methods to obtain -hydroxy and -hydroxy ketones, respectively.…”

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confidence: 99%

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

Maeda

Obora

Sakaguchi

et al. 2008

Bulletin of the Chemical Society of Japan

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“…However, the results obtained using the cyclic acyloin reaction with diesters (eq. [2]) show that ring sizes from 4 to over 30 are formed in high yield without the need for high-dilution conditions ( l a ) . Even the highly strained 4-, 8-, 9-, and 10-membered rings are readily prepared and they are obviously the product of highly strained intermediates.…”

Section: Discussionmentioning

confidence: 99%

“…eq. [2]), with reported yields of 76 and 96% for the 12-and 18-membered tethers, respectively ( 1 a).…”

Section: + 'mentioning

confidence: 98%

“…This reaction is particularly useful in the case of diesters 2 where an intramolecular cyclization yields a cyclic acyloin product (eq. [2]) ( l a , 2). With the introduction of chlorotrimethylsilane (TMSC1) as an alkoxide scavenger, the usefulness of this methodology has been extendedconsiderablv (3).…”

Section: Traduit Par La Redaction]mentioning

confidence: 99%

“…With the introduction of chlorotrimethylsilane (TMSC1) as an alkoxide scavenger, the usefulness of this methodology has been extendedconsiderablv (3). Yields are increased and in some 2 …”

Section: Traduit Par La Redaction]mentioning

confidence: 99%

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The acyloin reaction using tethered diesters

Daynard¹,

Eby²,

Hutchinson³

1993

Can. J. Chem.

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A study of the intramolecular acyloin condensation using diesters tethered by their alkoxide groups was undertaken. The goal was to provide a method for optimizing the yield of mixed acyloin products from the reaction of two different esters by utilizing tethered dissimilar esters as substrates. The results of the study show that the yield of the acyloin condensation is dependant on the tether length. Tethers of 8 and 14 carbons in length give yields comparable to those obtained from an intermolecular control reaction while shorter tethers give reduced yields of product. However, the use of mixed tethered diesters and a crossover experiment between two different tethered substrates provides a statistical distribution of products. These observations have been interpreted as resulting from a fragmentation of the initially formed radical anion intermediate that destroys the tethered nature of the substrate(s).

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3-Benzyl-5-(2-hydroxyethyl)-4-methyl-1,3-thiazolium Chloride

Kuhlmann

2001

Encyclopedia of Reagents for Organic Synthesis

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The Acyloin Condensation as a Cyclization Method

Cited by 79 publications

References 85 publications

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

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

The acyloin reaction using tethered diesters

3-Benzyl-5-(2-hydroxyethyl)-4-methyl-1,3-thiazolium Chloride

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