Recent advances in C(sp3)H bond carbonylation by first row transition metals

Carbonylation is one of the most valuable processes both in academia and industry. Direct functionalization of inert C(sp²)H bond into C(sp²)-carbonyl derivatives was actively pursued over decades using noble metals. But the corresponding C(sp³)H bond carbonylation is a challenging area and only few examples were known till now. Utilization of first row transition metals as an alternative to their noble partners is more sustainable. In this context, use of first row transition metals for direct C(sp³)H bond functionalization is burgeoning as an exciting area. This digest review covers some of the recent achievements in this regard especially using Ni, Co and Cu as first row transition metals. The reported approaches are categorized in two types: directed and non-directed activation/functionalization of C(sp³)H bonds using carbon monoxide gas or its surrogates as a C1 source.     

Photoredox catalyzed C(sp3)C(sp) coupling of dihydropyridines and alkynylbenziodoxolones

A visible light mediated deformylative alkynylation of aldehydes is presented. Under photo irradiation, 1,4-dihydropyridine (DHP), derived from an aldehyde, generated a C(sp³)- radical which couples with an alkynylbenziodoxolone to generate an alkyl substituted alkyne coupling product. This strategy is mild and easy to operate, a wide range of functional groups were tolerated, and 16 examples of products with 35–86% yields were obtained.     

Advances in amide and thioamide assisted C(sp3)H functionalization

CH activation is gaining substantial attention from synthetic and process chemists in recent years. Regio- and stereo-selective CH functionalization particularly facilitated by carboxylic acids and derivatives as directing groups has been progressing to an extent that this transformation could be conceived as one of the steps to assemble molecules in modern retrosynthetic analysis. This digest paper covers the most recent developments in C(sp³)H functionalization using carboxylic acid derivatives such as amides or thioamides as a directing group and highlights new reaction discoveries and applications. The content of this review is organized based on the types of directing groups and the mechanism by which the C(sp³)H bond is believed to be activated.     

Photoredox catalytic cascade radical addition/aromatization of methylene-2-oxazolines: Mild access to C(sp3)-difluoro-oxazole derivatives

Difluoroalkylated oxazoles were prepared from methylene-2-oxazolines (MOs) and difluoroalkylating reagents via a photoredox strategy. This reaction includes tandem radical addition and subsequent aromatization steps, resulting in 19 difluorinated oxazole derivatives with diverse functionalities and excellent reaction selectivity in the presence of multiple reactivity pathways.     

Visible light photoredox-catalyzed phosphorylation of quinoxalin-2(1H)-ones

A visible light photoredox-catalyzed C-3 phosphorylation of quinoxalin-2(1H)-ones with diphenylphosphine oxide has been developed. The reaction was effectively accelerated using an inexpensive eosin B as a photoredox catalyst under ambient air at room temperature without any other metal, oxidant, or additive. This approach offers a facile way to prepare 3-diphenylphosphorylated quinoxalin-2(1H)-one derivatives.     

A convenient stereoselective synthesis of 5-hydroxy-3-oxoesters and 3-hydroxy-5-oxoesters

A biocatalytic approach was employed for the asymmetric reduction of sterically demanding ketones to prepare 3-hydroxy-5-oxo-5-phenylpentanoates and 5-hydroxy-3-oxo-5-phenylpentanoates. Screening a collection of microorganisms led to the identification of stereocomplementary microbial strains that provide access to both enantiomers of 3-hydroxy-5-oxo-5-phenylpentanoates and 5-hydroxy-3-oxo-5-phenylpentanoates with high enantiomeric excess (up to 99% ee). Moreover, the application of Saccharomyces cerevisiae gave two diastereomers of 3,5-dihydroxy-5-phenylpentanoates with high enantiomeric excess (up to 99% ee). The applicability of the identified strains was demonstrated by transforming the obtained dihydroxy ester into the chemically valuable lactone (4S,6R)-tetrahydro-4-hydroxy-6-phenyl-pyran-2-one.     

Organocatalytic oxidative synthesis of C2-functionalized benzoxazoles,naphthoxazoles, benzothiazoles and benzimidazoles

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Cyclometallated 1,2,3-triazol-5-ylidene iridium(III) complexes: synthesis,structure, and photoluminescence properties

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The synthesis of chiral tridentate ligands from l-proline and their application in the copper(II)-catalyzed enantioselective Henry reaction

A series of chiral tridentate ligands derived from readily available enantiopure l-proline were designed and synthesized. The ligands together with Cu(OAc)₂ were successfully used in asymmetric Henry reactions. Various structurally divergent aldehydes and nitromethane were converted into versatile β-nitro alcohols in MeOH at room temperature with very good yields (up to 85%) and enantioselectivities (up to 86%).     

Enantioselective synthesis of chiral 4H-pyran derivatives through [3+3] tandem reaction over a squaramide catalyst

An efficient [3+3] tandem reaction between 1-phenyl-3-methyl-5-pyrazolones and 2-(1-alkynyl)-2-alken-1-ones over a tertiary amine–squaramide catalyst is described. The pyran fused pyrazolone derivatives were successfully obtained in 53–88% yields and with 62–84% ee by this synthetic methodology. This methodology involves easily accessible starting material, mild condition, satisfied yields and ee values. Additionally, when enynes were used as the substrates for the [3+3] cascade reaction, isomerized target products could be obtained directly.     

Deprotonation of 1,1′-methylenebis[4-tert-butyl-2-(diphenylphosphino)-benzene] and its analogues: synthesis and crystal structure of {5-But-2-[4-But-2-(Ph2P)C6H3(Ph)CH]C6H3P(Ph)K(OEt2)}2

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Dimericbiscognienynes B and C: New diisoprenyl-cyclohexene-type meroterpenoid dimers from Biscogniauxia sp.

Till now, only three diisoprenyl-cyclohexene/ane-type meroterpenoid dimers have been identified. The isolation of two new diisoprenyl-cyclohexene-type meroterpenoid dimers (dimericbiscognienynes B and C) from Biscogniauxia sp. 71-10-1-1 added new members to this family.     

Double electrooxidative C–H functionalization of (het)arenes with thiocyanate and 4-nitropyrazolate ions

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Activation of DMSO for Swern-type oxidation by 1,1-dichlorocycloheptatriene

A new dimethylsulfoxide activation method employing 1,1-dichlorocycloheptatriene has been developed for a mild Swern-type oxidation of a variety of alcohols. The carbonyl products can be obtained in good to excellent yields from this operationally simple and efficient method. This work is the first report of dimethylsulfoxide activation by a simple chlorinated hydrocarbon reagent, which has the unique ability of equilibrating to its reactive aromatic cationic form.     

A roadway of exploring polymer science,a lifetime of nurturing polymer scientists

正This special column is dedicated to Professor Shou-Kuan Fu on the occasion of his 80thbirthday.Prof. Shou-Kuan Fu, born in July, 1940 in Jiangsu Province. He obtained his B.S. in Chemistry from Department of Chemistry,Fudan University in 1962, then, he graduated from graduate school of Fudan University in 1966, under the supervision of Prof. TongYin Yu, a distinguished pioneer of polymer science in China and the founder of Department of Macromolecular Science at Fudan University.     

Asymmetric synthesis of 1,4-disubstituted 3-methylidenedihydroquinolin-2(1H)-ones

A series of enantiomerically pure or highly enriched (R)- or (S)-3-methylidenetetrahydroquinolin-2-ones was readily prepared by highly diastereoselective Michael additions of various Grignard reagents to quinolin-2(1H)-ones, containing an (R,R)- or (S,S)-di(1-phenylethylamino)phosphoryl group as chiral auxiliary, followed by Horner-Wadsworth-Emmons olefination of formaldehyde. An efficient synthesis of the starting (R,R)- and (S,S)-3-({di[(1-phenylethyl)amino]}phosphoryl)-1-alkyl-quinolin-2(1H)-ones is also described. The relative and absolute configurations of the intermediate adducts and final methylidenequinolinones were established by NMR and X-ray analysis.     

Stereoselective sulfoxidation catalyzed by achiral Schiff base complexes in the presence of serum albumin in aqueous media

Four coordination complexes ML derived from an achiral Schiff base ligand (H₂L?=?2,2′-[(1,2-ethanediyl)bis(nitrilopropylidyne)]bisphenol) have been synthesized and characterized. A method is described for the enantioselective oxidation of a series of aryl alkyl sulfides using the coordination complexes in the presence of serum albumins (SAs) in an aqueous medium at ambient temperature. The mixture of metal complexes with serum albumins is useful for inducing asymmetric catalysis. The complex, albumin source and substrate influence stereoselective sulfoxidation. At optimal pH with the appropriate oxidant, some of ML/SA systems are identified as very efficient catalysts, giving the corresponding sulfoxides in excellent chemical yield (up to 100%) and good enantioselectivity (up to 94% ee) in certain cases. UV–visible spectroscopic data provide evidence that stronger binding between the complex and serum albumin lead to higher enantioselectivity.     

New functional chiral P-based ligands and application in ruthenium-catalyzed enantioselective transfer hydrogenation of ketones

Metal-catalyzed asymmetric transfer hydrogenation is a powerful and practical method for the reduction of ketones to produce the corresponding secondary alcohols, which are valuable building blocks in the pharmaceutical, perfume, and agrochemical industries. Hence, a series of novel chiral β-amino alcohols were synthesized by chiral amines with regioselective ring opening of (S)-propylene oxide or reaction with (S)-(+)-2-hydroxypropyl p-toluenesulfonate by a straightforward method. The chiral ruthenium catalytic systems generated from [Ru(arene)(μ-Cl)Cl]₂ complexes and chiral phosphinite ligands based on amino alcohol derivatives were employed in asymmetric transfer hydrogenation of ketones to give the corresponding optically active alcohols; (2S)-1-{[(2S)-2-[(diphenylphosphanyl)oxy]propyl][(1R)-1-phenylethyl]amino}propan-2-yldiphenylphosphinitobis[dichol-oro(η⁶-benzene)ruthenium(II)] acts an excellent catalyst in the reduction of α-naphthyl methyl ketone, giving the corresponding alcohol with up to 99% ee. The substituents on the backbone of the ligands were found to have a remarkable effect on both the conversion and enantioselectivity of the catalysts. Furthermore, this transfer hydrogenation is characterized by low reversibility under these conditions.     

Synthesis of threo- and erythro-configured trihydroxy open chain lipophilic ketones as possible anti-mycobacterial agents

A series of threo- and erythro-configured open-chain trihydroxy ketones was synthesized starting from l- and d-ascorbic acid respectively as the starting material, through the use of Grignard reactions for the requisite CC bond formations. The lipophilic ketones were screened against Mycobacteriumtuberculosis for anti-proliferative activity. The lipophilic ketones with tetradecyl alkyl side chains were found to be moderately active against cell proliferation.     

Synthesis of a novel sterically hindered chiral cyclic phosphoric acid derived from l-tartaric acid and application to the asymmetric catalytic Biginelli reaction

A novel sterically hindered chiral cyclic phosphoric acid derived from l-tartaric acid was designed and synthesized based on highly regioselective cyclosulfitation of chiral 1,1,4,4-tetraphenylbutanetetraol. The asymmetric Biginelli reaction catalyzed by this newly synthesized chiral phosphoric acid was examined, and enantioselectivities up to 99% ee was obtained.