Metal-Catalyzed Amination of Alcohols

This chapter focuses on the metal-catalyzed amination of alcohols and related compounds such as aminoalcohols, phenols and di- and polyhydroxy compounds. Details of the synthesis of amines with acidic catalysts, including zeolites, mixed oxides and metal phosphates, can be found elsewhere [3,5-7]. 

Method 2. Alcohol amination—metal catalyzed amination of an alcohol over a metal catalyst under reducing conditions. 

The metal-bound carbonyl ligand is readily subjected to the attack of not only carbanions but heteroatom nucleophiles such as alcohols and amines to form ligands useful for formation of compounds containing ester and amide functionalities. The ease with which the nucleophilic attack takes place at metal-coordinated alkenes and alkynes provides a basis for oxidation of these molecules in the presence of a transition metal complex catalyst [3,4a], as exemplified by the Wacker type alkene oxidation by the use of a Pd catalyst. Metal catalyzed addition of alcohols or amines to alkenes and alkynes also involve the analogous nucleophilic attack [4b-e]. The attack of carbanions and heteroatom nucleophiles... 

Some iV-alkylation reactions catalyzed by other noble metal catalysts have also been reported. In 2011, Gusev and co-workers reported an Osmium complex-catalyzed N-alkylation of amines at 200 °C with a low catalyst loading (0.1 mol%) [122]. In 2014, Zhu and co-workers disclosed a [ReH7(PCy3)2]-catalyzed amination of alcohols with anilines under CO atmosphere (Eq. 29) [123]. The authors proposed that coordination of CO with Re might lead to decomposition of ReH7(PCy3)2 to a rhenium carbonyl complex, which was believed to be the active... 

The synthesis of alcohols, ethers, and ketones by metal-catalyzed addition of water or alcohols to alkenes and alkynes is a well-established reaction in organic chemistry. Many regio- and stereoselective modifications of these reactions are known. In contrast, the analogous addition of ammonia or primary and secondary amines to nonactivated alkenes and alkynes has not had a comparable development, in spite of extensive efforts. In this section, we summarize the recent results of amination to unsaturated compounds. 

A significant part of the examples of transition metal catalyzed formation of five membered heterocycles utilizes a carbon-heteroatom bond forming reaction as the concluding step. The palladium or copper promoted addition of amines or alcohols onto unsaturated bonds (acetylene, olefin, allene or allyl moieties) is a prime example. This chapter summarises all those catalytic transformations, where the five membered ring is formed in the intramolecular connection of a carbon atom and a heteroatom, except for annulation reactions, involving the formation of a carbon-heteroatom bond, which are discussed in Chapter 3.4. 

In 1970 the transition metal catalyzed formation of alkyl formates from CO2, H2, and alcohols was first described. Phosphine complexes of Group 8 to Group 10 transition metals and carbonyl metallates of Groups 6 and 8 show catalytic activity (TON 6-60) and in most cases a positive effect by addition of amines or other basic additives [26 a, 54-58]. A more effective catalytic system has been found when carrying out the reaction in the supercritical phase (TON 3500) [54 a]. Similarly to the synthesis of formic acid, the synthesis of methyl formate in SCCO2 is successful in the presence of methanol and ruthenium(II) catalyst systems [54 b]. 

MTO has also been claimed to be the first transition metal complex to catalyze the direct, solvent-independent formation of ethers from alcohols [30]. Aromatic alcohols give better yields than aliphatic ones and reactions between different alcohols have been used to prepare asymmetric ethers. Also catalyzed by 1 is the dehydration of alcohols to form olefins at room temperature. When primary or secondary amines, respectively, are used as the limiting reagents, direct amination of alcohols gives the expected secondary or tertiary amines in yields of ca. 95 %. Disproportionation of alcohols to carbonyl compounds and alkanes is also observed for aromatic alcohols in the presence of MTO as catalyst. 

The mechanisms of uncatalyzed [431], tertiary amine catalyzed [432], metal-catalyzed [433, 434], and light-catalyzed additions of alcohols to isocyanates have been extensively investigated [142, 435-437]. 

The direct transformation of alcohols to the corresponding amines is of growing interest because alcohols are easily available or accessible by chemical means. Amination of alcohols is usually catalyzed by transition metals at high temperatures and elevated pressures. Unfortunately, there is no enzyme known today that allows this particular functional group interconversion (FGl) in one step. Consequently, a multi-enzyme cascade was set up for the amination of alcohols as demonstrated for various benzylic and cinnamic alcohols under physiological conditions [24] aerobic alcohol oxidation toward the aldehyde was performed via a galactose oxidase originating from Fusarium (NRRL 2903 [25]) followed by an in situ co-TA-catalyzed reductive amination step (Scheme 4.5). 

SCHEME 8 Transition metal catalyzed reactions of propargyl alcohols (10) with supercritical CO2 in the presence of primary amines. 

During the past few years, increasing numbers of reports have been published on the subject of domino reactions initiated by oxidation or reduction processes. This was in stark contrast to the period before our first comprehensive review of this topic was published in 1993 [1], when the use of this type of transformation was indeed rare. The benefits of employing oxidation or reduction processes in domino sequences are clear, as they offer easy access to reactive functionalities such as nucleophiles (e. g., alcohols and amines) or electrophiles (e. g., aldehydes or ketones), with their ability to participate in further reactions. For that reason, apart from combinations with photochemically induced, transition metal-catalyzed and enzymatically induced processes, all other possible constellations have been embedded in the concept of domino synthesis. 

Transition-metal- and enzyme-catalyzed alkylations of ammonia and amines with alcohols and diols have been reviewed59. RuCl2(PPh3)3 is a homogeneous catalyst for the reaction of long-chain terminal alcohols with secondary amines to give tertiary amines (equation 22)60. 

Tab. 10.6 summarizes the application of this transformation to a variety of racemic secondary allylic carbonates using the lithium anion of 4-methoxy-N-(p-toluidine)-benzene sulfonamide. The excellent regioselectivity obtained for this type of substitution provided an important advance in the synthesis of N-(arylsulfonyl)anihnes using the metal-catalyzed allyhc amination reaction. The allyhc alcohol derivatives examined... 

Many such activated acyl derivatives have been developed, and the field has been reviewed [7-9]. The most commonly used irreversible acyl donors are various types of vinyl esters. During the acylation of the enzyme, vinyl alcohols are liberated, which rapidly tautomerize to non-nucleophilic carbonyl compounds (Scheme 4.5). The acyl-enzyme then reacts with the racemic nucleophile (e.g., an alcohol or amine). Many vinyl esters and isopropenyl acetate are commercially available, and others can be made from vinyl and isopropenyl acetate by Lewis acid- or palladium-catalyzed reactions with acids [10-12] or from transition metal-catalyzed additions to acetylenes [13-15]. If ethoxyacetylene is used in such reactions, R1 in the resulting acyl donor will be OEt (Scheme 4.5), and hence the end product from the acyl donor leaving group will be the innocuous ethyl acetate [16]. Other frequently used acylation agents that act as more or less irreversible acyl donors are the easily prepared 2,2,2-trifluoro- and 2,2,2-trichloro-ethyl esters [17-23]. Less frequently used are oxime esters and cyanomethyl ester [7]. S-ethyl thioesters such as the thiooctanoate has also been used, and here the ethanethiol formed is allowed to evaporate to displace the equilibrium [24, 25]. Some anhydrides can also serve as irreversible acyl donors. 

In 1997, Sturmer highlighted the importance of the combination of enzymes and transition metals in one pot [36]. Since then, this concept has aroused much interest within the scientific community. In all the DKRs presented in this section, the enzyme catalyzes a transesterification process. Thus, enzyme- and metal-catalyzed DKRs are categorized according to the nature of the substrates as being allylic substrates, secondary alcohols, or primary amines. In the first case,... 

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