Addition of Alcohols and Amines

Hydroalkoxylation of alkynes, or the addition of alcohol to alkynes, is a fundamental reaction in organic chemistry that allows the preparation of enol ethers and a variety of oxygen-containing heterocycles such as furan, pyran, and benzofuran derivatives. Bergbreiter et al. found that a Mnear poly-(A-isopropylacrylamide) (PNIPAM) polymer exhibited inverse temperature solubility in water (i.e., soluble in cold water but insoluble in hot water). A recoverable homogeneous palladium catalyst was prepared based on the polymer. The PNIPAM-bound Pd(0) catalyst was effective for the reaction of 2-iodophenol with phenylacetylene in aqueous THE media to give the target product 

2-phenylbenzofuran (Eq. 4.41). This catalyst can be recovered simply by heating the water or by adding hexane (in aqueous THE). The catalyst could be reused up to 15 times with only a very modest loss of activity. Later, Uozumi et al. showed that an amphiphihc polystyrene-poly(ethylene glycol) (PS-PEG) resin-supported palladium-phosphine 

Pal et al. explored an efficient Pd/C-catalyzed reaction of 2-iodophenols with terminal alkynes in water without the use of any organic cosolvents in the presence of PPha, Cul, and proMnol to give the expected benzofuran products (Eqs. 4.42, 4.43). The hydroxyl group was well tolerated during reactions. When used as a base, prolinol afforded better yields of products than triethylamine, a common organic base, possibly due to its better miscibility with water. 

Hydroamination of alkynes offers a straightforward preparation of a variety of amines, enamines, and imines. Numerous reports have appeared in the literature on this process. However, almost all these reactions have been carried out in organic solvents, which usually require the protection of functional groups or harsh conditions. Recently, MarinelM et al. have reported an Au(III)-catalyzed hydroamination of alkynes in 

Vasudevan et al. have reported a microwave-promoted hydroami-nation of alkynes. Heating a mixture of l-ethynyl-4-methoxybenzene and 4-bromoaniline in water at 200°C in a microwave reactor for 20 minutes without any catalyst gave an imine product in 87% yield (Eq. 4.45). i 

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Additions of Alcohols and Amines to Platinum(II) and Palladium(II) Complexes... 

Schneider, C. Sreekanth, A. R. Mai E. (2004) Scandium-bipyridine-catalyzed enantioselective addition of alcohols and amines to meso-epoxides., Chem., Int. Ed. Engl, 43 5691-5694. 

R and = Alkyl. Aryl or H Scheme 16 Nucleophilic addition of alcohols and amines to Group 6 allenylidene complexes... 

The previous sections described synthetic methods involving palladium- and nickel-catalyzed additions of alcohols and amines to aryl halides and triflates. The development of procedures and catalysts used in these processes has occurred hand-in-hand with mechanistic analysis of the amination chemistry. The following sections describe the current understanding of why these procedures and catalysts are effective, and how this understanding led to some of the breakthroughs described above. 

Knochel, P. Cesium Hydroxide Catalyzed Addition of Alcohols and Amine Derivatives to Alkynes and Styrene. Tetrahedron Lett. 40 6139, 1999. 

The majority of gold(I) carbene complexes are pure organometallic compounds and the are out of the scope of this work. Some halide or triphenylphosphine carbene complexes are known and they will be considered here. Nucleophilic addition of alcohols or amines to gold-coordinated isocyanides is one of the best-established methods to obtain gold carbene derivatives. The reaction of H[Au(CN)2] with propene oxide and estirene oxide yields (cyano)carbene complexes (380) avoiding the intermediate step.2257 A cyclic carbene compound is obtained by reaction of a dinuclear isocyanide with amine (Scheme 32).2258... 

In summary, the research effort aimed towards active, chemoselective hydrogenations of certain C=0 and C=N bonds have delivered several catalysts that approach the level of activity required for use in the synthesis of alcohols and amines. However, other classes of substrate require considerable additional investigations to be conducted before homogeneous catalysts may be considered for this purpose. 

Arylazirines are carbonylated by [Rh2Cl2(CO)4] (96) to give isocyanates under mild conditions.462 The reaction can be carried out at normal pressure and at room temperature or below. Vinyl isocyanates are produced (equation 98). By addition of alcohols or amines, carbamates or ureas were obtained. 

Additional reactions which need to be highlighted are the reductive alkylation of alcohols and amines with aldehydes leading to the green synthesis of ethers and amines. These reactions are generally catalyzed by palladium [35]. This reaction can replace the classical Williamson s synthesis of ethers which requires an alcohol and an alkyl halide together with a base, and always results in the concomitant production of salt. The choice of Pd/C as catalyst is due to the low efficiency of this metal for the competitive carbonyl reduction. Analysis of the... 

Since alcohols and carbohydrates readily form equilibrium concentrations of alkyl nitrites which are themselves inactive as direct nitrosating agents (see below), it is to be expected that the addition of alcohols and carbohydrates will inhibit N-nitrosation of amines. This has been shown to be the case for aniline derivatives, and the reduction in the measured first order rate constants can be accounted for quantitatively by such equilibria (Aldred and Williams, 1982). But since alkyl nitrite formation is a rapid equilibrium process, it is not possible, at least for the aniline derivatives studied, to suppress N-nitrosation completely this way. This is in contrast to the effect of thiols discussed in Section 9. In another study (Kurechi et al., 1980), the same effect was observed at pH 3 for the nitrosation of dialkylamines, whereas at pH 5 there was claimed to be a rate enhancement on addition of alcohols, an effect which was not explained. 

Trichloromethyl-l,2-oxathietane 2,2-dioxide is a catalyst for the acylation of alcohols and amines under mild conditions.It also catalyzes the polymerization of (NPCl2)3. It is suggested that six-membered cyclic sultones are derived from /3-sultones transiently formed in the addition of sulfur trioxide to alkenes. Ring-expansion of 3,4,4-trifluoro-3-trifluorovinyl-l, 2-oxathietane 1-oxide occurs at 100°C to give 4,4,5,6,7,7-hexafluoro-l,3-dioxa-2-thiacyclohept-5-Halogenation of 3,3,4,4-tetrafluoro-l,2-oxathietane 2,2-dioxide in... 

Acyl azides (61) and (62) ° and isocyanate (63), the reaction intermediates of the modified Curtius reaction using DPPA, have been isolated in a pure state, since they are relatively thermally stable, and further converted to urethanes or ureas by the addition of alcohols or amines respectively. 

The alkoxydi(sulfonyl)methane shown in Scheme 128 (entry b) has been used as a useful carbonyl 1,1-dipole synthon ( C°-0). Its alkylation with alkyl halides is best achieved using CS2CO3 in DMF at 50 °C, and its palladium-catalyzed allylation requires the use of phase-transfer conditions (Scheme 128, entry b). The unmasking of the carbonyl group was then achieved by reacting the resulting disulfone with boron trichloride (-78 C, CH2CI2) followed by the addition of alcohols or amines to provide esters or amides respectively (Scheme 128, entry b). ... 

Evidence for sulfene formation is obtained by carrying out the reaction in the presence of suitable trapping agents, namely substrates which undergo nucleophilic additions, like alcohols and amines (Scheme 66). 

The oxidative addition of alcohols and primary amines to 2-alkyl (or aryl) -... 

Formation of the tetrahedral intermediate carbinolamine and subsequent elimination of water are amenable to acid-base catalysis and do not require a metal surface. The relative rates of adduct formation and subsequent dehydration to imine or enamine depend on the structure of alcohol and amine, and on the nature and strength of acidic and basic sites on the catalyst surface. It must be stressed that several side-reactions (e. g. dimerization and oligomerization, dehydration) are also acid or base-catalyzed, and good selectivity for the desired product requires proper tuning of the redox and acid-base properties of the catalyst. This is crucial in catalyst development when choosing a suitable support, additive, or modifier. Even traces of impurities remaining on the surface from the catalyst precursor can strongly influence product distribution [10]. 

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