Dehydrogenative [4 + 2] Cycloaddition of Formamides with Alkynes through Double C−H Activation

Nakao, Yoshiaki; Morita, Eiji; Idei, Hiroaki; Hiyama, Tamejiro

doi:10.1021/ja1102037

Cited by 154 publications

(80 citation statements)

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“…27 Prior to our discovery, to the best of our knowledge, nickel-catalyzed C(sp 3 )H bond functionalization had been limited to only one example, namely, the Ni(0)-catalyzed cycloaddition of formamides with alkynes. 28 After the determining the optimized reaction conditions, it was found that 157 afforded the desired product 162 in 83% yield with Ni(OTf) 2 as the precatalyst with the aid of a sterically bulky carboxylic acid (MesCO 2 H) and a base (Na 2 CO 3 ) in DMF at 140°C for 24 h (Scheme 9). As described in our previous reports where the 8-aminoquinoline was used as directing group, 22 the present system also showed a high catalytic activity when other Ni(II) and Ni(0) sources were used.…”

Section: C(spmentioning

confidence: 99%

Nickel Catalysts/N,N′-Bidentate Directing Groups: An Excellent Partnership in Directed C–H Activation Reactions

2015

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, working on the use of molecular defined iron complexes as catalysts for the selective hydrosilylation of carbonyl compounds. From January 2013, he has been a postdoctoral fellow in the research group of Prof. Naoto Chatani at Osaka University (Japan), where he is focused on the directed CH bond functionalization and CC or Cheteroatom bond formation reactions with transition-metal catalysis. AbstractThis review focuses on chelation-assisted regioselective CH activation with CC or/and CN bond formation using nickel(0) or -(II) as the catalysts, where bidentate directing groups play a key role in the successful transformation. A 2-pyridinylmethylamine or an 8-aminoquinoline moiety are the more powerful auxiliaries among the directing groups examined.

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Section: C(spmentioning

confidence: 99%

Nickel Catalysts/N,N′-Bidentate Directing Groups: An Excellent Partnership in Directed C–H Activation Reactions

2015

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“…To our delight, the desired carbazoles 6a-h could be obtained in good yields in the presence of 4equivalents of DDQ in chorobenzene at 110 8 8C( entries [1][2][3][4][5][6][7][8]. It is noteworthy that this novel process consists of four C(sp 3 )ÀHb ond functionalizations and two C(sp 2 )ÀHb ond functionalizations in as ingle operation.…”

Section: Methodsmentioning

confidence: 99%

“…[4m] Despite this progress in C(sp 3 ) À Hb ond functionalizations for the formation of either C À Co rC À Xb onds,t ot he best of our knowledge,t he metal-free dehydrogenative Diels-Alder (DDA) reaction with the formation of two C À Cb onds in asingle operation by aDDQ-mediated direct C(sp 3 ) À Hbond functionalization has not been explored so far. [5] Herein, we report anovel DDQ-mediated direct DDAreaction between 2-methyl-3-arylmethylindolesa nd electron-deficient olefins to provide facile access to tetrahydrocarbazoles,c arbazoles, and poly-heteroacenes (Scheme 1b).…”

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confidence: 99%

“…Different aryl groups (R 1 )w ere compatible under the reaction conditions,t hus delivering the desired products 3a-h in 91-98 %y ields with moderate diastereoselectivities (entries [1][2][3][4][5][6][7][8]. Notably,the substrate 2c, with an easily removable protecting group (4-methoxybenzyl), was compatible with the oxidative DDQ conditions and thus delivered the corresponding product 3i in excellent yield (entry 9).…”

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confidence: 99%

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Metal‐Free Dehydrogenative Diels–Alder Reactions of 2‐Methyl‐3‐Alkylindoles with Dienophiles: Rapid Access to Tetrahydrocarbazoles, Carbazoles, and Heteroacenes

Zhou

Zhang

2015

Angewandte Chemie

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An unprecedented strategy for in situ generation of indole-based ortho-quinodimethanes (oQDMs) from 2-methyl-3-alkylmethylindoles by either am etal-free DDQ-or BQ-mediated dehydrogenative process was developed. These oQDMs were trapped by electron-deficient dienophiles to provideafacile approach to synthetically valuable tetrahydrocarbazoles,c arbazoles,a nd hetereoacenes.T he salient features of this transformation include direct C(sp 3 )ÀHb ond functionalizations,r eadily available starting materials,m etalfree conditions,high efficiency,operational simplicity,and ease of scale-up.Metal-free DDQ-mediated cross-dehydrogenative coupling (CDC) reactions have received much attention during the past years,and have become one of the efficient strategies for addressing the direct functionalization of C(sp 3 ) À Hbonds (Scheme 1a). [1][2][3][4] In 2006, Li and co-workers reported the first example of DDQ-mediated direct CDC reactions between benzyl ether and simple ketones and the cross-coupling products were obtained in moderate yields under neat conditions at 100 8 8C.[4a] As eries of elegant DDQ-mediated CDC reactions between allylic/propargylic/benzylic C(sp 3 ) À H bonds and diverse coupling partners were then developed by the groups of Bao, [4b-c] Floreancig, [4d-g] Jiao, [4h] and Li [4i] Recently,several enantioselective versions of CDC reactions, through the combination of DDQ and either ac hiral metal catalyst or organocatalyst, have been developed by the groups of Cozzi, [4j] Hayashi, [4k] Liu, [4l] and Wang.[4m] Despite this progress in C(sp 3 ) À Hb ond functionalizations for the formation of either C À Co rC À Xb onds,t ot he best of our knowledge,t he metal-free dehydrogenative Diels-Alder (DDA) reaction with the formation of two C À Cb onds in asingle operation by aDDQ-mediated direct C(sp 3 ) À Hbond functionalization has not been explored so far.[5] Herein, we report anovel DDQ-mediated direct DDAreaction between 2-methyl-3-arylmethylindolesa nd electron-deficient olefins to provide facile access to tetrahydrocarbazoles,c arbazoles, and poly-heteroacenes (Scheme 1b).Te trahydrocarbazole scaffolds are frequently found in natural products and as building blocks in organic synthesis. [6] Meanwhile,carbazoles and derivatives have received considerable attention because of their frequent occurrence in biologically active natural and unnatural products,a nd in organic functional materials (Figure 1). [7,8] To advance organic materials science,t he design of novel scaffolds and improvements in synthetic methods for these compounds are critically important. Obviously,t hose methodologies which are based on direct CÀHf unctionalization have advantages over the classic reactions as they do not require the prefunctionalization of starting materials.H owever,d espite the progress made in the synthesis of extended p systems by direct C(sp 2 ) À Ha ctivation, [9] thed evelopment of novel methodologies through direct C(sp 3 ) À Hf unctionalization still remain ac onsiderable challenge.D uring our r...

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“…4,5 Thus, the hydroalkylation of carboncarbon unsaturated bonds via unactivated sp 3 CH bond activation has not yet been challenged. We have found that alkynoxy groups (OC¸C) work as a directing group for the activation of adjacent CH bond and as an addition partner.…”

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confidence: 99%

Intramolecular Hydroalkylation via Activation oftert-Butyl C–H Bond in Silylethynyl Aryl Ethers

Minami¹,

Noguchi²,

Yamada³

et al. 2016

Chem. Lett.

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The title reaction of silylethynyl 2,6-(tBu) 2 phenyl ethers took place in the presence of a palladium catalyst and pivalic acid to give 2-silylmethylenechromanes. The initial products were converted by treatment with acetic acid to thermodynamically stable 4H-chromenes, which were further reacted with activated aldehyde and ketone. Addition of a carbonhydrogen bond to a carboncarbon unsaturated bond is an ideal transformation in green chemistry, as by-products are not generated. Efforts so far have been focused mainly on sp 2 CH bond activation followed by insertion of unsaturated bonds. On the other hand, the corresponding sp 3 CH activation is almost limited to benzylic and allylic positions or to the sites next to a heteroatom such as oxygen and nitrogen and to carbonyl and imino groups.1,2 Typical examples are the nickelcatalyzed additions of unactivated sp 3 CH bonds to alkynes or alkenes using 8-aminoquinoline as the directing group.3 Additional examples involve sp 3 CH bond activation followed by addition to alkenes or alkynes to achieve annulation reaction.4,5 Thus, the hydroalkylation of carboncarbon unsaturated bonds via unactivated sp 3 CH bond activation has not yet been challenged. We have found that alkynoxy groups (OC¸C) work as a directing group for the activation of adjacent CH bond and as an addition partner. 68 In the course of this study, we disclosed that palladium-catalyzed hydrobenzylation reaction of alkynyl ortho-tolyl ethers occurs via benzylic sp 3 CH activation. 6a We envisaged that this alkynoxy group strategy might be applicable to hydroalkylation via aliphatic sp 3 CH activation. Herein, we report the intramolecular hydroalkylation reaction of alkynyl ethers via aliphatic sp 3 CH activation in the presence of palladium(0)/pivalic acid dual catalysis.We first exposed tert-butyldimethylsilylethynyl 2,6-(tBu) 2 -4-Me-phenyl ether (1a) to 5 mol % of Pd(OAc) 2 and PCy 3 , the standard hydrobenzylation conditions, 6a at 120°C, but no reaction occurred. We assumed that bulky phosphines are not suitable for steric reason at the target reaction center. Accordingly, we switched to less bulky trialkylphosphines and were pleased to find that PBu 3 was effective for the desired hydroalkylation. As a result, syn-adduct 2a was obtained via CH bond cleavage in a tBu group, albeit with a low yield (Table 1, Entry 1). Replacing Pd(OAc) 2 by Pd(dba) 2 was totally futile (Entry 2), suggesting that zero-valent palladium complexes do not show any catalytic activity. Then, considering the catalytic conditions for previous hydrobenzylation reactions, a catalytic amount of pivalic acid was added to the reaction in Run 2. This results in the formation of 2a in 77% yield as a Z/E mixture (95:5) along with an endo-isomer 3a (14%) (Entry 3), a thermodynamically more stable isomer of 2a. On the other hand, use of 10 mol % of PBu 3 suppressed the reaction (Entry 4). Since Pd(OAc) 2 can be reduced by triorganophosphine, 9 we examined catalytic conditions using Pd(OAc) 2 and 2 equiv of PBu 3 in the presence of ...

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Dehydrogenative [4 + 2] Cycloaddition of Formamides with Alkynes through Double C−H Activation

Cited by 154 publications

References 25 publications

Nickel Catalysts/N,N′-Bidentate Directing Groups: An Excellent Partnership in Directed C–H Activation Reactions

Nickel Catalysts/N,N′-Bidentate Directing Groups: An Excellent Partnership in Directed C–H Activation Reactions

Metal‐Free Dehydrogenative Diels–Alder Reactions of 2‐Methyl‐3‐Alkylindoles with Dienophiles: Rapid Access to Tetrahydrocarbazoles, Carbazoles, and Heteroacenes

Intramolecular Hydroalkylation via Activation oftert-Butyl C–H Bond in Silylethynyl Aryl Ethers

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