Alcohol carbonylations, transition-metal-catalyzed

Hydrogen transfer reactions from an alcohol to a ketone (typically acetone) to produce a carbonyl compound (the so-caUed Oppenauer-type oxidation ) can be performed under mild and low-toxicity conditions, and with high selectivity when compared to conventional methods for oxidation using chromium and manganese reagents. While the traditional Oppenauer oxidation using aluminum alkoxide is accompanied by various side reactions, several transition-metal-catalyzed Oppenauer-type oxidations have been reported recently [27-29]. However, most of these are limited to the oxidation of secondary alcohols to ketones. 

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. 

Mechanistic Aspects of Transition-Metal-Catalyzed Alcohol Carbonylations... 

This chapter focuses on the application of transition metal catalysts and enzymes for the formation of carbon-carbon bonds. Transition metal-catalyzed carbon-carbon bond formations are not always very green but they often replace even less favorable conventional approaches. The key to making them really green is that they have to be easily separable and reusable. Several of these reactions, such as the hydroformylation, oligomerisation, carbonylation of alcohols and the metathesis, are therefore also treated in Chapter 1, Section 1.8 and Chapter 7, since their greener variations are performed in novel reaction media. 

Transition-metal-catalyzed carbonylation of an iodide in the presence of an alcohol or water gives the ester or acid, respectively. Bis(triphenylphosphanyl)palladium dichloride and octa-carbonyldicobalt are efficient catalysts. Starting from diiodidc 16, dicarboxylic ester 17 or dicarboxylic acid 18 are obtained in good to excellent yield.The formation of 18 is a good alternative to the hydrolysis of an ester to an acid. ... 

Transition metal catalyzed hydrosilylation of a, -unsaturated ketones and aldehydes (78) proceeds in a 1,4- and/or 1,2-fashion to give enol silyl ethers (79) (or the saturated carbonyl compounds 80 after acidic work-up) and/or allyl silyl ethers (81) (or allyl alcohols 82), respectively (equation 54). Monohydrosilanes combined with a Pt or Rh catalyst prefer 1,4-addition. This reaction is an alternative meth for the preparation of enol silyl ethers (79). Diphenylsilane with [RhCl(PPh3)3] catalyst reduces the car-... 

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]. 

The a-C—C bonds adjacent to carbonyls, alcohols, and nitriles are often the targets for activation [92]. This section focuses on recent developments of transition metal-catalyzed C—CN bond cleavage. 

Hydrocarboxylation is the formal addition of hydrogen and a carboxylic group to double or triple bonds to form carboxylic acids or their derivatives. It is achieved by transition metal catalyzed conversion of unsaturated substrates with carbon monoxide in the presence of water, alcohols, or other acidic reagents. Ester formation is also called hydroesterification or hydrocarb(o)alkoxylation . The transition metal catalyst precursors are nickel, iron or cobalt carbonyls or salts of nickel, iron, cobalt, rhodium, palladium, platinum, or other metals4 5. 

It is generally agreed that Roelen s discovery of the hydroformylation reactiont was the birth of the transition metal-catalyzed carbonylation. Initially, Co catalysts were most extensively used, but the Rh-based processes have since been developed as a superior methods. Although Pd may have been tested along with several other metals, such as Fe, Ru, and Ni, it has never been shown to be very useful in the hydroformylation reaction, sometimes called the oxo process. A publication in 1963 by Tsuji et al. on a related but clearly different reaction of alkenes with CO and alcohols in the presence of a Pd catalyst producing esters was one of the earliesL if not the earliesL reports describing a successful and potentially useful Pd-catalyzed carbonylation reaction. This was soon followed by the discovery of another Pd-catalyzed carbonylation reaction of allylic electrophiles with CO and alcohols ° (Scheme 7). 

In the following ten chapters we wiU look at the details of the transitional metal-catalyzed carbonylative activation of C-X bonds. Depending on the nucleophiles used, their reactions mechanisms are different and have their own term as well. For example, alkoxycarbonylation refers to using alcohols as nucleophiles, aminocarbonylation means using amines as nucleophiles, and so on. Each type of reaction will be discussed separately and end with a personal prediction. 

There is an impressive number of publications on the application of transition metal-catalyzed carbonylation reactions in total synthesis. In 1980 Tsuji and colleagues applied palladium-catalyzed alkoxycarbonylation in the synthesis of Zearalenone [22] and Curvularin [23]. Starting from the corresponding aryl iodides or benzyl chlorides and alcohols, the parent molecules for Zearalenone and Curvularin were prepared in good yields and finally transferred to the target products by a few more steps (Scheme 10.1). 

Some of the most commonly reported C-alkylation methods involving the transition-metal-catalyzed transfer hydrogenation of alcohols can be described as follows (1) the a-alkylation of ketones and carbonyl compounds (2) alcohol-alcohol coupling reactions to afford ketones and (3) P-alkylation by alcohol dimerization, which is also referred to as a Guerbet reaction. 

The alcohol-alcohol coupling reaction involves the following steps (Schemes 3, 4) (1) the initial simultaneous transition-metal-catalyzed dehydrogenation of the two different alcohols to afford the corresponding carbonyl compounds and metal halide and (2) the aldol condensation of the carbonyl compounds and the subsequent hydrogenation of the resulting unsaturated carbonyl compounds in a similar manner to that described above for the ketone a-alkylation reaction (Schemes 3, 4) to give the C-alkylated ketone product. 

Silanes And Base. In the presence of bases, certain silanes can selectively reduce carbonyls. Epoxy-ketones are reduced to epoxy-alcohols, for example with (MeO)3SiH and LiOMe. ° Controlling temperature and solvent leads to different ratios of syn- and anti- products.Silanes reduce ketones in the presence of BF3-OEt2 ° and transition metal compounds catalyze this reduction. ... 

Several examples of transition metal catalysis for the synthesis of piperidines appeared this year. Palladium catalyzed intramolecular urethane cyclization onto an unactivated allylic alcohol was described as the key step in the stereoselective synthesis of the azasugar 1-deoxymannojirimycin . A new synthetic entry into the 2-azabicyclo[3.3.1]nonane framework was accomplished through a palladium mediated intramolecular coupling of amine tethered vinyl halides and ketone enolates in moderate yields . A palladium catalyzed decarboxylative carbonylation of 5-vinyl... 

Transition metal carbonyls and their derivatives are remarkably effective and varied in their ability to catalyze reactions between unsaturated molecules (e.g., CO and olefinic compounds) or between certain saturated and unsaturated molecules (e.g., olefins and H2 or H20). The carbonyl derivatives of cobalt are particularly active catalysts for such reactions and have been put to use in the industrial synthesis of higher aliphatic alcohols. In fact, much of the growth in knowledge concerning catalysis by metal carbonyls has been stimulated by the industrial importance of the Fischer-Tropsch synthesis, and by the economically less important, but chemically more tractable, hydroformylation reaction. 

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