Synthesis of benzo-fused lactams and lactones via Ru(<scp>ii</scp>)-catalyzed cycloaddition of amide- and ester-tethered α,ω-diynes with terminal alkynes: electronic directing effect of internal conjugated carbonyl group

Yamamoto, Yoshihiko; Kinpara, Keisuke; Saigoku, Tomoaki; Nishiyama, Hisao; Itoh, Kenji

doi:10.1039/b402649g

Cited by 62 publications

(30 citation statements)

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“…We previously found that such an unsymmetrical diyne reacted with terminal alkynes, electron-deficient nitriles, and isocyanates to give the corresponding cycloadducts with moderate to high regioselectivity. [5,10] In striking contrast, no regioselectivity was observed for the cycloadditions of 2h with malononitrile (3a) or chloroacetonitrile (3e), indicative of the cycloaddition with these nitriles proceeding via a different mechanism from the other examples. Moreover, we found that the similar cycloaddition of dichloroacetonitrile (3j) exhibited considerable regioselectivity, and the corresponding products 6hj and 7hj were obtained in a ratio of 80 : 20.…”

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confidence: 72%

Synthesis of 2‐Haloalkylpyridines via Cp*RuCl‐Catalyzed Cycloaddition of 1,6‐Diynes with α‐Halonitriles. Unusual Halide Effect in Catalytic Cyclocotrimerization

et al. 2005

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In the presence of 2 -5 mol % Cp*RuCl (cod), various 1,6-diynes reacted with a-monohaloand a,a-dihalonitriles at ambient temperature to afford 2-haloalkylpyridines in 42 -93% isolated yields. The failure of acetonitrile, N,N-dimethylaminoacetonitrile, phenylthioacetonitrile, and methyl cyanoacetate as nitrile substrate clearly showed that the a halogen substitution is essential for the present cycloaddition under mild conditions. The cycloaddition of unsymmetrical diynes bearing a substituent on one alkyne terminal gave 2,3,4,6-substituted pyridines exclusively.Keywords: alkynes; cyanides; cyclotrimerization; pyridines; rutheniumThe transition-metal-mediated [2 þ 2 þ 2] cyclocotrimerization of two alkynes and a nitrile is a powerful and straightforward route to substituted pyridines.[1] Although the catalytic cyclocotrimerization is becoming increasingly important as an environmentally benign process, the pair-and regio-selectivity as well as reaction conditions have remained to be largely improved compared to stoichiometric protocols. [2] In this context, mild and selective catalytic cycloadditions of a,w-diynes with nitriles were recently achieved by means of a chiral indenylcobalt complex and a nickel N-heterocyclic carbene complex.[3] In particular, the former catalyst proved to be effective toward the asymmetric synthesis of axially chiral pyridines. In addition, novel intramolecular protocols were recently developed to synthesize pyridine-containing macrocycles or 2-aminopyridines. [4] We have also developed independently the Cp*RuClcatalyzed cycloadditions of a,w-diynes with carbon-heteroatom multiple bonds, [5] and found that the dicyanides are exceptional nitrile substrates capable of undergoing cycloaddition even at ambient temperature.[6] In fact, in the presence of 5 mol % Cp*RuCl(cod) 1 (Cp* ¼ h 5 -C 5 Me 5 , cod ¼ 1,5-cyclooctadiene), the cycloaddition of dimethyl dipropargylmalonate (2a) with malononitrile (3a; R¼ CN) proceeded even at room temperature for 2.5 h to afford bicyclic pyridine 4aa (R ¼ CN) in 95% yield (Scheme 1). Although one of the two cyano groups remained intact after the reaction, the complete incompetence of acetonitrile provides the possibility of one cyano moiety as a coordinating group. To expand the scope of the nitrile substrate, other nitriles possessing a coordinating group a to the cyano group were further screened (Figure 1). Consequently, methyl cyanoacetate (3b; R ¼ CO 2 Me), N,N-dimethylaminoacetonitrile (3c; R¼ NMe 2 ), and phenylthioacetonitrile (3d; R¼ SPh) were found to be totally ineffective. In striking contrast, chloroacetonitrile (3e; R ¼ Cl) underwent cycloaddition with 2a in the presence of 2 mol % 1 at ambient temperature for 2 h to give rise to chloromethylpyridine 4ae in 93% isolated yield. [7] This result was quite surprising because trichloroacetonitrile, which underwent cycloaddition with 2a at 60 8C in our previous study, [5] failed to react at ambient temperature. These facts indicate that the observed reactivity enhancement is not ascribed...

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confidence: 72%

Synthesis of 2‐Haloalkylpyridines via Cp*RuCl‐Catalyzed Cycloaddition of 1,6‐Diynes with α‐Halonitriles. Unusual Halide Effect in Catalytic Cyclocotrimerization

et al. 2005

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“…The [2 + 2 + 2] cyclotrimerization of alkynes to benzene derivatives is well-documented and reviewed earlier. [57] …”

Section: Synthesis Of Substituted Pyrone Pyran and Cyclohexadiene Dmentioning

confidence: 97%

[2+2+2] Cycloaddition Reactions Catalyzed by Transition Metal Complexes

2006

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Recent progress in the synthesis of benzene and 1,3-cyclohexadiene derivatives, and heterocyclic compounds such as pyridines, pyridones, pyrans, pyrimidine diones, etc, has been reviewed. The general mechanistic aspects of the [2 + 2 + 2] cycloaddition reaction are discussed. The asymmetric variants of these reactions are also discussed along with the proposed models of asymmetric induction. Keywords: arenes; catalysis; cycloaddition; heterocycles; metallacycles; transition metals IntroductionThe significance and increasing popularity of [2 + 2 + 2] cycloaddition reactions is evident from the number of reviews that have recently appeared in the literature. [1][2][3] The [2 + 2 + 2] cycloaddition reaction is remarkable in terms of its ability to utilize various unsaturated substrates such as alkynes, diynes, alkenes, imines, isocyanates, isothiocyanates, and CO 2 in the synthesis of a broad variety of highly substituted cyclic molecules such as benzenes, pyridines, pyridones, 1,3-cyclohexadienes, pyrones, thiopyridones and cyclohexanes. Multisubstituted benzenes and pyridines have traditionally been synthesized by aromatic electrophilic substitution (AES) reactions and a variety of metal-mediated coupling reactions. Although, these reactions are extremely efficient, they generally involve multistep syntheses. The application of AES reactions in the synthesis of polysubstituted aromatic rings is limited by the effect of the substituent groups and, hence, it may be very difficult or even impossible to add various functionalities at a specific position on the aromatic ring. On the other hand, [2 + 2 + 2] cycloaddition reactions are extremely atom-efficient and involve the formation of several C À C bonds in a single step. Another important feature of the [2 + 2 + 2] cycloaddition reaction is tolerance of a myriad of functional groups such as alcohols, amines, alkenes, ethers, esters, halogens, and nitriles. Moreover, the availability of numerous catalytic systems that have Adv. Synth. Catal. 2006, 348, 2307 -2327 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 2307 REVIEWS been efficient in tedious syntheses highlights the applicability of the [2 + 2 + 2] cycloaddition reaction. These are important requirements for the [2 + 2 + 2] cycloaddition reaction to become a universal synthetic tool for the synthesis of benzene, pyridine, and other cyclic derivatives. An important problem with the [2 + 2 + 2] cycloaddition reaction is the lack of chemoand regioselectivity observed in earlier reported reactions. However, significant effort has been focused on attaining a high degree of chemo-, regio-and even enantioselectivity with considerable success as evident from recent reports. Excellent reviews on [2 + 2 + 2] cycloaddition reactions are available. Kotha and co-workers have reviewed the synthesis of benzene derivatives by the cyclotrimerization of three alkyne functionalities utilizing transition metal systems as catalysts.[1] Their review is divided into: (a) intermolecular reactionsin which the three pi (alkyn...

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“…They have started from anhydrides, [14] phthalimides, [15] β-hydroxy or β-phenylsulfanyl lactams [16,17] or 2-formylbenzoic acids. [18] Alternative methods such as condensations of imines with acetylene [19] or with an ester function [20] and treatment of an enamine with an aryl iodide [21] have also been reported. Whereas most of the previous strategies led easily to bis-aromatic fused heterocycles, synthetic pathways to design compounds of type V immediately appeared to be critical.…”

Section: Introductionmentioning

confidence: 98%

New Efficient Route to Fused Aryltetrahydroindolizinones via N‐Acyliminium Intermediates

et al. 2009

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Synthesis of benzo-fused lactams and lactones via Ru(ii)-catalyzed cycloaddition of amide- and ester-tethered α,ω-diynes with terminal alkynes: electronic directing effect of internal conjugated carbonyl group

Abstract: In the presence of a catalytic amount of Cp*RuCl(cod), 1,6- and 1,7-diynes connected by an amide or an ester tether underwent cycloaddition with terminal alkynes at room temperature to give rise to cycloadducts in 40-93% yields with 63 : 37-83 : 17 regioisomer ratios.

Cited by 62 publications

References 23 publications

Synthesis of 2‐Haloalkylpyridines via Cp*RuCl‐Catalyzed Cycloaddition of 1,6‐Diynes with α‐Halonitriles. Unusual Halide Effect in Catalytic Cyclocotrimerization

Synthesis of 2‐Haloalkylpyridines via Cp*RuCl‐Catalyzed Cycloaddition of 1,6‐Diynes with α‐Halonitriles. Unusual Halide Effect in Catalytic Cyclocotrimerization

[2+2+2] Cycloaddition Reactions Catalyzed by Transition Metal Complexes

New Efficient Route to Fused Aryltetrahydroindolizinones via N‐Acyliminium Intermediates

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