Facile Benzo-Ring Construction via Palladium-Catalyzed Functionalization of Unactivated sp<sup>3</sup> C−H Bonds under Mild Reaction Conditions

Feng, Yuanming; Wang, Yuji; Landgraf, Bradley J.; Liu, Shi; Chen, G.

doi:10.1021/ol101220x

Cited by 147 publications

(62 citation statements)

References 52 publications

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“…[29,30] Based on the higher reactivity of the o-OMe donor compared to the other benzoate donors tested (9)(10)(11), we decided to carry on with 3. A reason for the lower reactivity of p-CN-o-OMe donor 11 could be a lower Lewis basicity of the carbonyl group and the methyl ether oxygen as a result of the electron-withdrawing effect of the cyano functionality.…”

Section: Resultsmentioning

confidence: 99%

Glycosyl ortho‐Methoxybenzoates: Catalytically Activated Glycosyl Donors with an Easily Removable and Recyclable Leaving Group

et al. 2016

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We describe the β‐ortho‐methoxybenzoate as a shelf stable and practical C‐1 nucleofuge for catalytic chemical glycosylation in which the benzoic acid by‐product can be easily removed, reisolated, and potentially recycled after the glycosylation reaction. This new type of glycosyl donor can be efficiently activated by a range of promoters, including Bi(OTf)3, Fe(OTf)3, TMSOTf (TMS = trimethylsilyl), and triflic acid, with low (<10 mol‐%) catalyst loadings. The donor shows higher reactivity than analogous benzoate, p‐methoxybenzoate and p‐cyano‐o‐methoxybenzoate donors. In glycosylation reactions with o‐methoxybenzoate donors, the yields of disaccharide products were good to excellent for various glycosyl acceptors, including a carbohydrate‐based secondary alcohol. Furthermore, β‐selective mannosylation was achieved with a Crich‐type donor at 0 °C to ambient temperature, without donor preactivation. The donor was also used for the first step of a one‐pot two‐step glycosylation to obtain a trisaccharide; the second coupling involved activation of a thioglycoside with NIS/TMSOTf (NIS = N‐iodosuccinimide). We believe that this offers a good alternative to current protocols.

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Section: Resultsmentioning

confidence: 99%

Glycosyl ortho‐Methoxybenzoates: Catalytically Activated Glycosyl Donors with an Easily Removable and Recyclable Leaving Group

et al. 2016

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“…We found dihydroxy alcohols can be used to furnish interesting ethers (7,8) and the free hydroxy groups can be further elaborated to provide useful bifunctional molecules. Delightfully, long linear carboxylic acid derivatives (13)(14)(15)(16) were efficiently alkoxylated as well.…”

Section: Methodsmentioning

confidence: 99%

“…To test our hypothesis, a model study was initiated with the butyramide derivative 1, which contains an 8-aminoquinoline-derived auxiliary (Q; Table 1). This specific auxiliary [14] (Q) was first reported by the group of Daugulis and has been developed as an effective directing group for the activation of C(sp3)ÀH bonds. At the beginning of our investigations, a variety of oxidants, such as PhI(OAc) 2 , PhI(TFA) 2 , K 2 S 2 O 8 , NaIO 4 , NaIO 3 , and selectfluor, were examined in the presence of Pd(OAc) 2 in a MeOH/xylene cosolvent system.…”

mentioning

confidence: 99%

An Efficient Palladium‐Catalyzed CH Alkoxylation of Unactivated Methylene and Methyl Groups with Cyclic Hypervalent Iodine (I³⁺) Oxidants

et al. 2013

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Over the last two decades, transition-metal-catalyzed direct functionalization of CÀH bonds has emerged as a valuable tool for organic synthesis. [1] Compared to C(sp2)ÀH bond activation, however, the catalytic functionalization of C(sp3)À H bonds, [2,3] especially unactivated methylene C(sp3) À H bonds, remains an important fundamental challenge. Because of steric hindrance and intrinsic inertness, methylene C À H bonds are significantly more difficult to cleave than primary CÀH bonds. In addition, the potential competing b-hydride elimination from cyclometallates also complicates the process. Therefore, only a few examples of C(sp3)ÀH bond activations of unactivated methylenes have been reported thus far. [4] Among these successful discoveries of methylene C(sp3) À H bond activation, the majority of studies were focused on CÀH arylation, acetoxylation, or amidation. In a recent C(sp3)ÀH amidation study, [4h] NFSI served as both an intriguing oxidant and nitrogen source, and further theoretical studies revealed a low-energy barrier for reductive C À N bond formation from a high-oxidation-state palladium catalyst. More recently, an elegant example of ligand-enabled C À H arylation of methylene C(sp3)ÀH bonds was reported by Yu and co-workers (Scheme 1). [5] However, to the best of our knowledge, C(sp3) À H alkoxylation [6,7] of unactivated methylene positions has not yet been achieved.Alkyl ethers serve as important structural motifs found in a diversity of pharmaceuticals and natural products. [8] The classic approaches [9] to alkyl ethers, such as Williamson and Mitsunobu reactions, suffer from shortcomings which have limited their applications in the synthesis of complex alkyl ethers. Although a number of new protocols [10] have been developed in recent years, new methods for alkyl ether synthesis are still in great demand. Direct transformation of readily available alkanes into valuable complex alkyl ethers by transition-metal-catalyzed C(sp3) À H functionalization of unactivated methylenes is arguably a highly efficient and atom-economic method toward these compounds.Herein, we report the first example of a palladium(II)catalyzed C(sp3)ÀH alkoxylation of an unactivated methylene with cyclic hypervalent iodine (I 3+ ) oxidants. Our preliminary mechanistic study revealed that either DMP [11] (I 5+ ) or 1-acetoxy-1,2-benziodoxole-3(1H)-one serve as intriguing precursors to the oxidant I 3+ for the C(sp3) À H alkoxylation.In our continuous studies of CÀO bond formation through palladium catalysis, [12] we envisioned that certain oxidative conditions [13] could promote palladium(II)-catalyzed C(sp3) À H bond activation through an orthometalation process by coordination with specific directing groups. In a subsequent step C(sp3)ÀO bond formation by the reductive elimination could afford the corresponding alkyl ether derivatives with suitable oxidants and alcohol partners (Scheme 1). To test our hypothesis, a model study was initiated with the butyramide derivative 1, which contains an 8-aminoquinoline-derived au...

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“…[1,2] Compared to the achievements in the area of C(sp 2 )ÀH alkylation, [3,4] catalytic alkylation of unactivated C(sp 3 )ÀH bonds, especially methylene C(sp 3 ) À H bonds, remains largely undeveloped. [5][6][7][8][9][10] In 2013, the group of Chen and our group independently reported the only two examples of (BnO) 2 PO 2 H-promoted, 8-aminoquinoline-directed [11,12] alkylation of b-methylene C(sp 3 )ÀH bonds with a-haloacetates and methyl iodide. [9] However, the scope with respect to the coupling partners was limited to these two classes of specific reagents, both of which do not contain b-hydrogen atoms.…”

mentioning

confidence: 99%

Sulfonamide‐Promoted Palladium(II)‐Catalyzed Alkylation of Unactivated Methylene C(sp³)H Bonds with Alkyl Iodides

Chen¹,

Shi²

2014

Angew Chem Int Ed

134

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The alkylation of unactivated β-methylene C(sp(3))-H bonds of α-amino acid substrates with a broad range of alkyl iodides using Pd(OAc)2 as the catalyst is described. The addition of NaOCN and 4-Cl-C6H4SO2NH2 was found to be crucial for the success of this transformation. The reaction is compatible with a diverse array of functional groups and proceeds with high diastereoselectivity. Furthermore, various β,β-hetero-dialkyl- and β-alkyl-β-aryl-α-amino acids were prepared by sequential C(sp(3))-H functionalization of an alanine-derived substrate, thus providing a versatile strategy for the stereoselective synthesis of unnatural β-disubstituted α-amino acids.

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Facile Benzo-Ring Construction via Palladium-Catalyzed Functionalization of Unactivated sp³ C−H Bonds under Mild Reaction Conditions

Cited by 147 publications

References 52 publications

Glycosyl ortho‐Methoxybenzoates: Catalytically Activated Glycosyl Donors with an Easily Removable and Recyclable Leaving Group

Glycosyl ortho‐Methoxybenzoates: Catalytically Activated Glycosyl Donors with an Easily Removable and Recyclable Leaving Group

An Efficient Palladium‐Catalyzed CH Alkoxylation of Unactivated Methylene and Methyl Groups with Cyclic Hypervalent Iodine (I³⁺) Oxidants

Sulfonamide‐Promoted Palladium(II)‐Catalyzed Alkylation of Unactivated Methylene C(sp³)H Bonds with Alkyl Iodides

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Facile Benzo-Ring Construction via Palladium-Catalyzed Functionalization of Unactivated sp3 C−H Bonds under Mild Reaction Conditions

Cited by 147 publications

References 52 publications

Glycosyl ortho‐Methoxybenzoates: Catalytically Activated Glycosyl Donors with an Easily Removable and Recyclable Leaving Group

Glycosyl ortho‐Methoxybenzoates: Catalytically Activated Glycosyl Donors with an Easily Removable and Recyclable Leaving Group

An Efficient Palladium‐Catalyzed CH Alkoxylation of Unactivated Methylene and Methyl Groups with Cyclic Hypervalent Iodine (I3+) Oxidants

Sulfonamide‐Promoted Palladium(II)‐Catalyzed Alkylation of Unactivated Methylene C(sp3)H Bonds with Alkyl Iodides

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Facile Benzo-Ring Construction via Palladium-Catalyzed Functionalization of Unactivated sp³ C−H Bonds under Mild Reaction Conditions

An Efficient Palladium‐Catalyzed CH Alkoxylation of Unactivated Methylene and Methyl Groups with Cyclic Hypervalent Iodine (I³⁺) Oxidants

Sulfonamide‐Promoted Palladium(II)‐Catalyzed Alkylation of Unactivated Methylene C(sp³)H Bonds with Alkyl Iodides