Advances in Organic Synthesis: Volume 8

By Bentham Science Publishers

Advances in Organic Synthesis is a book series devoted to the latest advances in synthetic approaches towards challenging structures. It presents comprehensive articles written by eminent authorities on different synthetic approaches to selected target mo

• Language: English
• Publisher: Bentham Science Publishers
• Release date: Apr 10, 2018
• ISBN: 9781681085647

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Catalytic Tandem Reactions Triggered by the Introduction of a Carbonyl Function

Pascal D. Giorgi, Sylvain Antoniotti*

Université Côte d’Azur, CNRS, Institut de Chimie de Nice, France

Abstract

Catalysis has played a prominent role in recent decades allowing chemists to develop novel and efficient reactions in almost every class of chemical transformation. With the tuning of the catalysts’ steric and electronic properties, sophisticated reactions have been discovered, sometimes featuring several individual steps and resulting in one-pot formation of complex chemical structures with high atom-economy. With the increasing recognition of the importance of green and sustainable chemistry, the concept of step-economy has gained traction and one-pot multistep reactions have been developed. Current research in this area now focuses on the use of multiple catalysts within the same reactor to convert simple and available substrates into complex and valuable products. In this chapter, we review a selection of examples of catalytic tandem reactions triggered by the introduction of a carbonyl function either formed by oxidation of alcohols, hydroformylation, isomerisation or carbonylation. In particular, we emphasize nanocatalysis, the use of metal nanoparticles as catalysts. The in situ formation of reactive carbonyl electrophiles opens a wide array of possible subsequent reactions as illustrated in the following pages.

Keywords: Biocatalysis, Dual catalysis, Fine chemicals, Green chemistry, Metal nanoparticles, Multicatalysis, Nanocatalysis, One-pot reactions, Organocatalysis, Orthogonal multicatalysis, Oxidation, Sustainable chemistry, Tandem reactions.

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* Corresponding author Sylvain Antoniotti: Université Côte d’Azur, CNRS, Institut de Chimie de Nice, Parc Valrose, 06108 Nice cedex 2, France; Tel: [phone]; Fax: [phone]; E-mail: [e-mail]

Introduction

When green and sustainable chemistry principles were released in 1998 [1-3], a significant portion of the scientific community reacted with skepticism. Trendy science, useless chemistry, and inefficiency are examples of flaws attributed to green chemistry. About 20 years later, one can say that a significant shift has been made towards greener and more sustainable chemistry in most fields of the chemical sciences, both in academia and in industry. These efforts have been made around four pillars that are: 1) Waste diminution; 2) Resource management;

3) Safety and innocuity of chemicals; and 4) Energy consumption. In many instances, catalysis has been shown to improve sustainability profiles by addressing multiple aspects of green chemistry. Indeed, catalysis, which is one of the twelve principles substituting stoichiometric promoters by catalytic entities, could also contribute to resource management of metals, lowering of energy requirements and waste prevention with the design of highly efficient and selective chemical processes [4-6]. An important principle when dealing with synthetic method development in organic chemistry is the principle of atom economy [7, 8], which eventually contributes to the even more important principle of waste prevention. Atom economy (AE) compares the molecular weight of the target product with the sum of the molecular weights of all the chemicals involved in the reaction, i.e. starting material(s), reagent(s) and in theory even solvent(s). Ideal reaction would have an AE score of 100% such as a thermal Diels-Alder cycloaddition performed in neat conditions, while a Wittig olefination would have a much lower AE score (Scheme 1).

Scheme 1)

Comparison of Diels-Alder cycloaddition and Wittig olefination in terms of atom economy (solvents are not considered).

The recycling of solid or supported catalysts is also an important aspect of atom economy that is rarely considered.

The same type of calculations could be made for multistep synthesis, but the overall cost for isolation and purification of intermediates is rarely considered. To save both time and resources, and in some favorable cases, to benefit from synergistic effects, new methods have emerged with several consecutive reactions occurring in the same reactor, ideally using only individual catalytic reactions. Multicatalytic reactions are designed for the synthesis of complex molecules in one single operation (one-pot) from suitable starting material(s) with the intervention of two or more catalysts [9]. The terminology of cascade, domino, or tandem processes may apply, depending on whether the reaction is intra- or intermolecular (Scheme 2). If it is necessary to change the conditions during the reaction, or to add another reaction partner after a certain period of time, the term sequential one-pot reaction would then be preferred [10]. Tandem processes are the most commonly reported examples of cascade reactions, either intra- or intermolecular, where one single catalyst is involved in two or more elementary steps occurring sequentially [11, 12].

Scheme 2)

Examples of terminology applying in different examples of one-pot reactions.

In the case of multicatalytic processes, there are several classifications. In dual catalysis, two catalysts work together to activate the substrate molecule, while in cooperative dual catalysis, two catalysts independently activate two different substrate molecules, to allow for substrate coupling (Scheme 3). In other cases, a bifunctional catalyst could be used to activate two substrate molecules or two functional groups within the same substrate. Co-catalysis refers to processes where an ancillary catalyst is used to assist the recycling of the main catalyst, for example the Wacker process where copper salts are used to recycle palladium in its active. Finally, multicatalysis refers to one-pot processes where several catalysts work sequentially along a multistep reaction sequence without interfering with each other.

All these processes have several advantages, one of the most important being the reduction of waste generation and/or energy consumption by avoiding work-up and purification procedures of the intermediates. In some cases, synergistic effects are observed, such as a favorable equilibrium shift when a thermodynamic product is formed in the late stages of the sequence. The key to success for the development of such reactions is a good understanding of the reaction mechanism of each step, and for kinetically controlled reactions, an evaluation of their relative rates.

Scheme 3)

Different categories of multicatalytic reactions.

In this chapter, we present a selection of recent reports from the literature to illustrate multicatalytic processes that are based on the initial formation of a carbonyl functional group, with an emphasis on processes involving nanocatalysts, i.e. supported metal nanoparticles (NPs). Tandem processes where one or more reactions involve stoichiometric reagents or promoters, and flow chemistry multistep synthesis are outside the scope of this review. The reader might refer to previous review articles that specifically address the design of multifunctional nanocatalysts for tandem reactions [13], concurrent tandem catalysis [14], orthogonal tandem catalysis [15], tandem oxidative processes involving multimetallic nanoclusters [16], auto-tandem catalysis [17], enantioselective cooperative catalysis [18], asymmetric tandem catalysis [19], cascade reactions initiated by alcohols oxidation [20, 21], or biooxidation [22].

Oxidation/Heteronucleophile addition

Tandem and/or cascade reactions employing oxidation conditions for bi- or multicomponent heteronucleophile addition to in situ formed carbonyl compounds have been widely investigated in the past decade [23]. A key reason for the success of such one-pot multistep approaches is the generation of reactive intermediates that are immediately converted into complex products without requiring tedious and/or low yielding isolation procedures and avoiding degradation issues. These approaches result in very efficient and highly atom- and step-economical processes leading to the synthesis of valuable compounds, including esters, amides, and imines. Furthermore, metal NPs/O2 systems have been widely studied in the oxidation of alcohols, either bearing activating substituents (aryl, allyl) or relatively inert ones (alkyl), and generally allow primary alcohols to selectively lead to the corresponding aldehydes [24]. Catalytic protocols involving M NPs have thus been designed to oxidize various alcohols and convert them into diverse compounds in situ by heteronucleophile addition [25-30]. For example, a straightforward base-free oxidative esterification was proposed based on Au NPs-catalyzed oxidation of poorly reactive aliphatic octan- 1-ol to octyl octanoate, under a pressurized atmosphere of O2 [25]. It is worth noting that the selectivity of the reaction could be tuned towards acid or ester formation by changing the nature of the NPs’ support and changing the solvent from organoaqueous to aqueous. Thus, use of NiO as the support proved to be effective for the synthesis of octanoic acid with 97% selectivity, whereas replacing it with CeO2 produced the corresponding ester with a 66% yield and 79% selectivity (Scheme 4).

Scheme 4)

Selective oxidation and oxidative esterification of aliphatic 1-octanol catalyzed by Au NPs.

The recyclability was tested by recovering the catalysts by centrifugation after the addition of ethyl acetate, washing and drying. A gradual decrease was observed but 85– 91% yields were still obtained after the sixth run. Interestingly, no change in the size of Au NPs was observed by TEM analysis performed on the catalyst after six cycles.

In other instances, the Lewis acid-base character of the support was shown to be beneficial to the tandem process. For example, an Au-catalyzed oxidation/amine condensation/nucleophile addition protocol reported the synthesis of α-substituted phosphates involving aromatic alcohols, primary amines and hydrogenophosphates [31]. It is noteworthy that the amphoteric character of hydroxyapatite (HAP) support resulted in significant enhancements of the reaction efficiency. Subsequently, a tight cooperation was observed between Au NPs and the HAP surface in which the determining rate was optimized to limit side reactions. Thus, α–aminophosphonates were obtained with a yield up to 86%, in a one-pot three-component procedure in solvent-free conditions (Scheme 5).

Scheme 5)

One-pot three component cascade reaction for the synthesis of α-aminophosphate catalyzed by AuNPs supported on hydroxyapatite (HAP).

Au/HAP catalyst could be reused 5 times with similar performance (95% conversion, 98% selectivity).

In another example dealing with amide formation by oxidative amidation, the use of polymer-incarcerated carbon black-stabilized metal nanoparticles (PI/CB-M NPs) was the key to success [32]. The Au NPs-catalyzed oxidation of benzylic alcohols under O2 (1 bar) in the presence of a stoichiometric amount of NaOH was followed by the nucleophilic addition of the amine partner and further oxidation of the intermediate at the NP surface. The size of Au NPs appears to have a clear influence on the amide formation, and 18 examples were reported with up to 79% selectivity when using Au NPs with an average diameter of 7.2 nm (Scheme 6).

Scheme 6)

Selective oxidative amidation catalyzed by medium-sized incarcerated PI/CB-Au NPs.

By combining supported catalysis and biocatalysis, a one-pot procedure of aerobic oxidation/reductive amination/direct amidation has been proposed based on an integrated AmP-CPG/Pd(0)-catalyzed benzyl alcohol oxidation, followed by catalytic reductive amination and a lipase-catalyzed acylation with an aliphatic carboxylic acid (Scheme 7) [33].

Scheme 7)

General scheme of integrated heterogeneous oxidation/reductive amination/direct amidation via multiple relay catalysis.

The recycling of the catalyst could be performed 6 times for the reductive amination with conversion up to 90% at each cycle.

An Au-catalyzed reductive hydrogen transfer/hydrolysis/nucleophile addition/dehydration process was proposed, based on the self-condensation of benzyl amines for the synthesis of imines. Interpretations of kinetic studies based on a Hammett plot showed a hydrogen transfer from the amine to the NPs surface, followed by the oxidation of the Au-H bond. After hydration of the imine moiety and the release of a molecule of ammonia, the corresponding aldehyde was obtained, immediately followed by the condensation of a second amine to produce the desired imine with a yield up to 86% (Scheme 8) [34-36].

Scheme 8)

Tandem oxidation of benzyl amines to imines catalyzed by Au NPs.

The catalysts could be recycled 8 times with the imine yield remaining at 73% at 8th run.

The direct synthesis of quinoline derivatives from nitroarenes and aliphatic alcohols was proposed via an iridium-based reductive hydrogen transfer/condensation/dehydrogenation using sub-nanosized iridium clusters supported on TiO2 [37]. This protocol presented a high efficiency profile for the tandem reaction, allowing the catalyst to be recycled three times, while maintaining 100% activity. Mechanistic insights suggested that the dehydrogenation of the alcohol occurs first, followed by the hydrogen transfer generating the aminoarene and the aldehyde. Condensation of the amine with the aldehyde followed by ring closure with concomitant dehydration/dehydrogenation furnished the quinoline product. Surprisingly, the quality of TiO2 appeared to play an essential role in the condensation/cyclization, since more basic or more acidic supports did not produce similar product yields (Scheme 9).

Scheme 9)

Ir sub-nanosized clusters-catalyzed hydrogen transfer/condensation/dehydrogenation.

Carbohydrates represent promising renewable feedstock chemicals that are easily accessible in huge amounts from lignocellulosic materials. Since biomass conversion is highly desirable, it is important to develop efficient and scalable reductive processes to refine these raw materials. A synthesis of valuable products from biomass conversion was proposed with the reduction of carbohydrates into γ-valerolactone and pyrrolidone. Au-catalyzed reduction/cyclisation of carbonyl compounds afforded the corresponding pyrrolidone, based on formate-mediated transfer reduction between levulinic acid (LA) and benzylamine. The reaction was used for the synthesis of 5-methyl-2-pyrrolidone, obtained in 97% yield [38]. It was proposed that formate used as a sole hydrogen source could act as a reducing reagent, in the presence of LA and the amine. This protocol was applied to a large variety of carbohydrate derivatives such as glucose, fructose, sucrose, and even starch and cellulose. Au/ZrO2-VS catalyst (VS standing for very small NPs: ca. 1.8 nm diameter) showed superior activity with respect to other solid catalysts for the selective production of pyrrolidone derivatives with ZrO2 support appearing to be the most tolerant of harsh acidic media (Scheme 10).

Scheme 10)

Au-catalyzed pyrrolidone synthesis via biomass conversion.

Upon recycling experiments, results for the 5th run remained similar (95% yield, 99% selectivity).

Octahedral MnO2 molecular sieve (OMS) was investigated as catalyst in the one-pot tandem conversion of benzyl alcohol to 2-benzylidene-malononitrile, (E)-chalcone, and 2,3-dihydro-1,5-benzothiazepine [39]. For example, the latter was formed by action of OMS-2-U, a material formed by hydrothermal synthesis in the presence of urea, resulting in tunnels of 3 × 3 structures (Scheme 11). In the presence of urea, the material obtained exhibited different physico-chemical properties compared with the control such as increased surface area (150 vs. 116 m²/g BET), slightly higher total pore volume (0.60 vs. 0.47 cm³/g), a higher number of acid sites (1.07 vs. 0.32 mmol/g NH3-desorbed) and a significantly higher number of basic sites (0.33 vs. 0.069 mmol/g CO2-desorbed).

Scheme 11)

One-pot three-steps synthesis of 2,3-dihydro-1,5-benzothiazepine catalyzed by OMS-2-U under O2.

Recycling study showed that no significant decrease in the catalytic activity was observed even after five cycles.

The carbonyl group could also be created by oxidation of a methyl group with the introduction of an external oxygen atom. For example, an efficient oxidation/oxidative esterification has been proposed based on a Cu-catalyzed aerobic oxidation of the Csp3-H bond of quinaldine, followed by an oxidative esterification leading to N-heteroaryl esters in 90% yield [40]. It was found that the methyl group had to be located at the 2-position, indicating the prominent role of nitrogen atom. A plausible mechanism was proposed as depicted in Scheme (12), in which the N-heteroaryl methyl group is first oxidized to the corresponding aldehyde, before being oxidatively coupled with the alcohol partner to produce the final N-heteroaryl ester.

Scheme 12)

Copper-catalyzed oxidative esterification of activated methyl group in N-heteroaryl series.

Subsequently, an aryl ester synthesis catalyzed by Pd(II) salts was proposed via a double aromatic methyl oxidation/oxidative coupling (Scheme 13) [41]. As previously mentioned, the introduction of a directing group was essential to truly perform a cross-coupling reaction and to diminish homocoupling reactions. Notably, the reaction exhibited high selectivity upon the addition of Ag salts.

Scheme 13)

Direct functionalization aromatic methyl groups and aryl ester synthesis.

The corresponding intermediate could then be oxidized by a peroxide species and lead to Pd(III) or Pd(IV) and a carbaldehyde intermediate, followed by the reductive elimination to the second palladacycle (Scheme 14). Subsequently, both oxidized partners would undergo a Kornblum-DeLaMare rearrangement to the first oxygenated diaryl hemiacetal intermediate, the structure of which was confirmed by MALDI-TOF MS, followed by a β-hydrogen elimination and reductive elimination leading to Pd(0) and the aryl ester product in 71% yield. Pd(0) would then be reoxidized to Pd(II) under AgCO3/O2.

Scheme 14)

Plausible mechanism for tandem activation of aromatic methyl groups for benzyl ester synthesis (PA=2-pyridylacyl).

Oxidation/C-nucleophile addition

If heteronucleophile addition is known to be favored in the presence of lone pairs of electrons on the heteroatom (i.e. O, S, N), activated carbon atoms may also act as nucleophiles. Thus, the formation of C-C bonds can be envisaged, a valuable prospect for organic synthesis, using activated methylene, electron-rich arenes or other nucleophilic carbon atoms resulting in C-nucleophile addition.

A straightforward protocol for biobased chemical feedstock valorization has been proposed with a sequential one-pot oxidation/aldolization protocol, based on furfuryl alcohol oxidation, catalyzed by Pd-NPs supported on mesoporous silica nanoparticles (MSNs), followed by an aldolization/crotonization sequence [42]. Interestingly, the aldolization, involving a large excess of acetone, could be catalyzed by a modified version of the silica support bearing aminomethyl units (MAP-MSN) within the pore framework (Scheme 15).

Scheme 15)

Bicatalytic one-pot process for the oxidation/aldolization/crotonization of furfuryl alcohol with acetone catalyzed by Pd-MSNs & MAP-MSNs.

Upon recycling of the catalyst, an increase of the yield of furfural intermediate and a decrease of the yield of the final product were observed, suggesting a significant loss in activity of the second catalyst, possibly due to the oxidation of amine groups. This problem was solved by regeneration of the catalyst by using NaBH4, and a 73% conversion of furfuryl alcohol could be obtained, with a yield of 70% of product.

The oxidation of allylic alcohols could be combined with a Heck coupling under the sole catalysis of Pd(OAc)2 [43]. The sequential addition of aryl iodide electrophiles together with 1.1 equiv. of Et3N was sufficient to yield β-aryl-α,β-unsaturated carbonyl products (Scheme 16).

Scheme 16)

Oxidation/Heck coupling with aryl iodide of oct-1-en-3-ol catalyzed by Pd(OAc)2.

It is interesting to note that similar products could be obtained from allylic alcohols submitted to a Pd-catalyzed Heck reaction, the carbonyl group resulting from a β-hydride elimination furnishing an enol intermediate further isomerised to the corresponding carbonyl compound by keto-enol tautomerism, and not a direct initial oxidation of the alcohol functional group [44, 45].

An Ir-catalyzed domino borrowing-hydrogen transfer reaction/aldolization has been proposed for the direct double β-methylation of 1-phenylethanol derivatives with methanol as the primary source of carbon. Herein, the metal nanocluster catalyst presented a larger specific area and more corner sites where the catalyst activity is known to take place [46, 47]. Efficiency of the catalytic system in the presence of CsCO3 even allowed the alkylation to proceed with methanol as C1 source, which is typically a difficult material to handle owing to its high dehydrogenation energy, in comparison to other alcohols. Moreover, aggregation of nanoclusters was avoided thanks to an alternative procedure using DMF as a stabilizer with no additives, making photoluminescent Ir nanoclusters easily observable. Mechanistic insights showed the involvement of an iridium hydride intermediate upon alcohol oxidation. The following aldol reaction results in the enone formation, immediately followed by the hydrogenation/reduction sequence to give the corresponding β-substituted alcohol with a 94% yield (Scheme 17) [48].

Scheme 17)

Double β-methylation of 1-phenylethanol by methanol catalyzed by Ir nanoclusters.

Some strategies were proposed to implement more sophisticated reactions that rely on the initial oxidation of alcohols like a PCC oxidation/Wittig olefination of alcohols [49] or other stoichiometric oxidation processes as detailed in a recent review article [20]. Eventually, catalysis was introduced for the oxidation step for more powerful and sustainable one-pot processes. For example, a tandem oxidation/Wittig olefination sequence was described using manganese oxide octahedral molecular sieve (OMS) as heterogeneous catalyst (Scheme 18) [50]. The catalyst could be recycled four times, yet maintaining the conversion above 85%.

A tandem oxidation/olefination in the presence of a copper catalyst was further developed using diazo reagents as an olefination partner [51]. The reaction could be performed with primary