Littérature scientifique sur le sujet « Chemoselective Transformation »

AbstractEfficient chemoselective transfer hydrogenation of the C=C bond of α,β-unsaturated ketones has been developed, using the iridium complexes containing pyridine-imidazolidinyl ligands as catalysts and formic acid as a hydrogen source. In comparison with organic solvents or H2O as solvent, the mixed solvents of H2O and MeOH are critical for a high catalytic chemoselective transformation. This chemoselective transfer hydrogenation can be carried out in air, which is operationally simple, allowing a wide variety of α,β-unsaturated substrates with different functional groups (electron-donating and electron-withdrawing substituents) leading to chemoselective transfer hydrogenation in excellent yields. The practical application of this protocol is demonstrated by a gram-scale transformation.

A gold(i)-catalysed highly chemoselective three-component reaction of phenols, α-diazocarbonyl compounds and allenamides is presented. This transformation features mild reaction conditions, high functional group tolerance, and broad applicability.

A chemoselective synthesis of novel 1,4-benzodiazepin-2-ones and dienyl thiazolidin-4-one carboxylates in excellent yields by ring transformation reactions of functionally decorated 2-azetidin-3-thiazolidin-4-ones is reported.

A novel chemoselective one-pot transformation of acetals to silyl ethers is reported. Free hydroxyls, double bonds and triple bonds are unaffected in optimal reaction conditions. This practical, inexpensive protocol allows the selective replacement of acetal-forming protecting groups with silyl groups in a single step under mild conditions.

Triazole–Au (TA–Au) catalysts were employed in several transformations involving propargyl ester rearrangement. Good chemoselectivity was observed, which allowed the effective activation of the alkyne without affecting the reactivity of the allene ester intermediates. These results led to the investigation of the preparation of allene ester intermediates with TA–Au catalysts under anhydrous conditions. As expected, the desired 3,3-rearrangement products were obtained in excellent yields (generally >90% yields with 1% loading). Besides the typical ester migrating groups, carbonates and carbamates were also found to be suitable for this transformation, which provided a highly efficient, practical method for the preparation of substituted allenes.

The thesis entitled “Copper-Catalyzed Novel Oxidative Transformations: Construction of Carbon-Hetero Bonds” is divided into two main sections. Section A deals with the utility of azide as a nitrogen source for C-N bond formation, which is further divided into 4 chapters, and section B presents decarboxylative radical coupling reaction for C-heteroatom bond formation which is further divided in to two chapters. Section A Chapter 1 describes an approach for the direct synthesis of nitrile from the corresponding alcohols using azide as a nitrogen source. Nitrile functionality is a versatile and ubiquitous which occurs in a variety of natural products. Nitrile functionality can be easily transformed into a variety of functional groups and products such as aldehydes, ketones, acids, amines, amides and nitrogen-containing heterocycles, such as tetrazoles and oxazoles. In this chapter a successful attempt for developing a novel methodology to oxidize benzylic and cinnamyl alcohols to their corresponding nitriles in excellent yields has been described. This strategy uses DDQ as an oxidant and TMSN3 as a source of nitrogen in the presence of a catalytic amount of Cu(ClO4)2·6H2O. A few representative examples are highlighted in Scheme 1.1 Scheme 1. Oxidative conversion of alcohols to nitriles Second chapter represents a protocol for the synthesis of 1,5-disubstituted tetrazoles from the corresponding secondary alcohols. Among heterocyles, tetrazole and its derivatives are important class of nitrogen containing molecules. Due to their well-known biological activities as well as vast applications in pharmaceuticals and material science, they are potential targets for synthetic organic chemists. Therefore, a simple and user-friendly method for the synthesis of tetrazole is desirable. In this chapter, a mild and convenient method to synthesize 1,5-disubstituted tetrazoles using easily accessible secondary alcohols by employing TMSN3 as a nitrogen source is developed. This reaction is performed in the presence of a catalytic amount of Cu(ClO4)2·6H2O using DDQ as an oxidant under ambient conditions (Scheme 2).2 Scheme 2. Oxidative conversion of secondary alcohols to tetrazoles Third chapter presents a method for synthesizing amides from their corresponding secondary alcohols. Amide functionality is a crucial backbone in peptide chemistry, it also serve as an important precursor or intermediate for variety of organic transformations. In this contention, a mild and convenient method to synthesize amides using easily accessible secondary alcohols by employing TMSN3 as a nitrogen source is developed. This reaction is performed in the presence of a catalytic amount of Cu(ClO4)2·6H2O using DDQ as an oxidant under ambient conditions (Scheme 3).3 Scheme 3. Oxidative conversion of secondary alcohols to amides Additionally, the application of this methodology has also been revealed for the synthesis azides directly from their alcohols. Some of the representative examples are shown in the Scheme 4.3 Scheme 4. Direct conversion of alcohols to their azides. Fourth chapter describes highly chemoselective Schmidt reaction. The classical Schmidt reaction involves the formation of new carbon-nitrogen bonds in a reaction of a carbon-centred electrophile with hydrazoic acid followed by loss of nitrogen, which usually occurs via a rearrangement. It is well known that under the Schmidt reaction conditions, ketones and carboxylic acids are converted into their corresponding amides and amines respectively, whereas aldehydes furnish a mixture of formanilides and nitriles. In this chapter, Schmidt reaction of aldehydes to obtain their nitriles without formation of the corresponding formanilide is presented (Scheme 5).4 It was also observed that aromatic ketones and acids functionalities were intact under the reaction condition, unlike the conventional Schmidt reaction. Scheme 5. Highly chemoselective Schmidt reaction Section B It is divided into two chapters, describes a copper catalyzed decarboxylative radical coupling for the synthesis of vinyl sulfones and nitroolefins (Scheme 6). Scheme 6. General strategy for the second part First chapter narrates a strategy for synthesizing nitroolefins from the α,β-unsaturated carboxylic acids. Nitroolefins represent a unique class of nitro compounds, which have multifaceted utility in organic synthesis. They possess antibacterial, rodent-repelling, and antitumor activities. They serve as important intermediates in organic synthesis. Nitroolefins also react with a variety of nucleophiles, and their electron-deficient character renders them as a powerful dienophiles in Diels-Alder reactions. In our attempt to use the decarboxylative strategy, this chapter describes a method for the nitrodecarboxylation of substituted cinnamic acid derivatives to their corresponding nitroolefins. This nitrodecarboxylation reaction is performed using catalytic amount of CuCl in the presence of air using TBN as a nitrating source (Scheme 7).5 Besides, the reaction provides a useful method for the synthesis of β,β-disubstituted nitroolefin derivatives which are generally difficult to access from other conventional methods. Scheme 7. Decarboxylative nitration Second chapter presents a new protocol for the synthesis of vinyl sulfones from the α,β-unsaturated carboxylic acid. Vinyl sulfones are versatile building blocks, which find their utility as Michael acceptors and used in cycloaddition reactions. This functional group has also been shown to potently inhibit a variety of enzymatic processes, and thus provides unique properties for drug design and medicinal chemistry. Vinyl sulfones are prominent in medicinal chemistry owing to their wide presence in pharmaceutically active molecules, such as enzyme inhibitors and biological activity. In this chapter, we report a method for the construction of C-S bonds via ligand promoted decarboxylative radical sulfonylation of ,-unsaturated carboxylic acids to synthesize vinyl sulfones using Cu catalysis (Scheme 8).6 This is the first report for this particular conversion. Scheme 8. Decarboxylative sulfonation

The thesis entitled “Copper-Catalyzed Novel Oxidative Transformations: Construction of Carbon-Hetero Bonds” is divided into two main sections. Section A deals with the utility of azide as a nitrogen source for C-N bond formation, which is further divided into 4 chapters, and section B presents decarboxylative radical coupling reaction for C-heteroatom bond formation which is further divided in to two chapters. Section A Chapter 1 describes an approach for the direct synthesis of nitrile from the corresponding alcohols using azide as a nitrogen source. Nitrile functionality is a versatile and ubiquitous which occurs in a variety of natural products. Nitrile functionality can be easily transformed into a variety of functional groups and products such as aldehydes, ketones, acids, amines, amides and nitrogen-containing heterocycles, such as tetrazoles and oxazoles. In this chapter a successful attempt for developing a novel methodology to oxidize benzylic and cinnamyl alcohols to their corresponding nitriles in excellent yields has been described. This strategy uses DDQ as an oxidant and TMSN3 as a source of nitrogen in the presence of a catalytic amount of Cu(ClO4)2·6H2O. A few representative examples are highlighted in Scheme 1.1 Scheme 1. Oxidative conversion of alcohols to nitriles Second chapter represents a protocol for the synthesis of 1,5-disubstituted tetrazoles from the corresponding secondary alcohols. Among heterocyles, tetrazole and its derivatives are important class of nitrogen containing molecules. Due to their well-known biological activities as well as vast applications in pharmaceuticals and material science, they are potential targets for synthetic organic chemists. Therefore, a simple and user-friendly method for the synthesis of tetrazole is desirable. In this chapter, a mild and convenient method to synthesize 1,5-disubstituted tetrazoles using easily accessible secondary alcohols by employing TMSN3 as a nitrogen source is developed. This reaction is performed in the presence of a catalytic amount of Cu(ClO4)2·6H2O using DDQ as an oxidant under ambient conditions (Scheme 2).2 Scheme 2. Oxidative conversion of secondary alcohols to tetrazoles Third chapter presents a method for synthesizing amides from their corresponding secondary alcohols. Amide functionality is a crucial backbone in peptide chemistry, it also serve as an important precursor or intermediate for variety of organic transformations. In this contention, a mild and convenient method to synthesize amides using easily accessible secondary alcohols by employing TMSN3 as a nitrogen source is developed. This reaction is performed in the presence of a catalytic amount of Cu(ClO4)2·6H2O using DDQ as an oxidant under ambient conditions (Scheme 3).3 Scheme 3. Oxidative conversion of secondary alcohols to amides Additionally, the application of this methodology has also been revealed for the synthesis azides directly from their alcohols. Some of the representative examples are shown in the Scheme 4.3 Scheme 4. Direct conversion of alcohols to their azides. Fourth chapter describes highly chemoselective Schmidt reaction. The classical Schmidt reaction involves the formation of new carbon-nitrogen bonds in a reaction of a carbon-centred electrophile with hydrazoic acid followed by loss of nitrogen, which usually occurs via a rearrangement. It is well known that under the Schmidt reaction conditions, ketones and carboxylic acids are converted into their corresponding amides and amines respectively, whereas aldehydes furnish a mixture of formanilides and nitriles. In this chapter, Schmidt reaction of aldehydes to obtain their nitriles without formation of the corresponding formanilide is presented (Scheme 5).4 It was also observed that aromatic ketones and acids functionalities were intact under the reaction condition, unlike the conventional Schmidt reaction. Scheme 5. Highly chemoselective Schmidt reaction Section B It is divided into two chapters, describes a copper catalyzed decarboxylative radical coupling for the synthesis of vinyl sulfones and nitroolefins (Scheme 6). Scheme 6. General strategy for the second part First chapter narrates a strategy for synthesizing nitroolefins from the α,β-unsaturated carboxylic acids. Nitroolefins represent a unique class of nitro compounds, which have multifaceted utility in organic synthesis. They possess antibacterial, rodent-repelling, and antitumor activities. They serve as important intermediates in organic synthesis. Nitroolefins also react with a variety of nucleophiles, and their electron-deficient character renders them as a powerful dienophiles in Diels-Alder reactions. In our attempt to use the decarboxylative strategy, this chapter describes a method for the nitrodecarboxylation of substituted cinnamic acid derivatives to their corresponding nitroolefins. This nitrodecarboxylation reaction is performed using catalytic amount of CuCl in the presence of air using TBN as a nitrating source (Scheme 7).5 Besides, the reaction provides a useful method for the synthesis of β,β-disubstituted nitroolefin derivatives which are generally difficult to access from other conventional methods. Scheme 7. Decarboxylative nitration Second chapter presents a new protocol for the synthesis of vinyl sulfones from the α,β-unsaturated carboxylic acid. Vinyl sulfones are versatile building blocks, which find their utility as Michael acceptors and used in cycloaddition reactions. This functional group has also been shown to potently inhibit a variety of enzymatic processes, and thus provides unique properties for drug design and medicinal chemistry. Vinyl sulfones are prominent in medicinal chemistry owing to their wide presence in pharmaceutically active molecules, such as enzyme inhibitors and biological activity. In this chapter, we report a method for the construction of C-S bonds via ligand promoted decarboxylative radical sulfonylation of ,-unsaturated carboxylic acids to synthesize vinyl sulfones using Cu catalysis (Scheme 8).6 This is the first report for this particular conversion. Scheme 8. Decarboxylative sulfonation

Amide bond formation is one of the most important reactions in organic chemistry. Amides occur in a wide variety of pharmaceuticals and other biologically active compounds, including peptides and proteins. In living cells, amide bonds are formed by ribosomes in very specific circumstances, which are not possible in organic chemistry. This chapter looks at the conventional mechanism, solid-phase peptide synthesis and chemoselective amide-forming ligation before discussing some of the problems associated with these reactions and approaches towards greener reactions.

This chapter evaluates chemoselectivity and protecting groups. In a chemoselective reaction, one functional group within the molecule reacts, leaving further potentially reactive functionality unaffected. Many of the principal transformations involved in functional group interconversions (FGIs) were introduced in the third chapter of this text. The reactions may involve addition, substitution, elimination, reduction, and oxidation. There are now a plethora of mild and selective reagents available to effect specific transformations. As a general rule, when there are two functional groups of unequal reactivity within a molecule, the more reactive can be made to react alone. However, it may not be possible to react the less reactive functional group selectively.

Paul J. Chirik at Princeton University reported (Science 2012, 335, 567) an iron catalyst that hydrosilylates alkenes with anti-Markovnikov selectivity, as in the conversion of 1 to 2. A regioselective hydrocarbamoylation of terminal alkenes was developed (Chem. Lett. 2012, 41, 298) by Yoshiaki Nakao at Kyoto University and Tamejiro Hiyama at Chuo University, which allowed for the chemoselective conversion of diene 3 to amide 4. Gojko Lalic at the University of Washington reported (J. Am. Chem. Soc. 2012, 134, 6571) the conversion of terminal alkenes to tertiary amines, such as 5 to 6, with anti-Markovnikov selectivity by a sequence of hydroboration and copper-catalyzed amination. Related products such as 8 were prepared (Org. Lett. 2012, 14, 102) by Wenjun Wu at Northwest A&F University and Xumu Zhang at Rutgers via an isomerization-hydroaminomethylation of internal olefin 7. Seunghoon Shin at Hanyang University (experimental work) and Zhi-Xiang Yu at Peking University (computational work) reported (J. Am. Chem. Soc. 2012, 134, 208) that 9 could be directly converted to bicyclic lactone 11 with propiolic acid 10 using gold catalysis. A nickel/Lewis acid multicatalytic system was found (Angew. Chem. Int. Ed. 2012, 51, 5679) by the team of Professors Nakao and Hiyama to effect the addition of pyridones to alkenes, such as in the conversion of 12 to 13. Radical-based functionalization of alkenes using photoredox catalysis was developed (J. Am. Chem. Soc. 2012, 134, 8875) by Corey R.J. Stephenson at Boston University, an example of which was the addition of bromodiethyl malonate across alkene 14 to furnish 15. Samir Z. Zard at Ecole Polytechnique reported (Org. Lett. 2012, 14, 1020) that the reaction of xanthate 17 with terminal alkene 16 led to the product 18. The radical-based addition of nucleophiles including azide to alkenes with Markovnikov selectivity (cf. 19 to 20) was reported (Org. Lett. 2012, 14, 1428) by Dale L. Boger at Scripps La Jolla using an Fe(III)/NaBH4-based system. A remarkably efficient and selective catalyst 22 was found (J. Am. Chem. Soc. 2012, 134, 10357) by Douglas B. Grotjahn at San Diego State University for the single position isomerization of alkenes, which effected the transformation of 21 to 23 in only half an hour.