Oxidative amination of olefins

Oxidative aminations of olefins with sulfonamides also appear to occur by insertions of alkenes into Pd-N bonds in some cases. An example of the use of stereochemistry to probe for syn or anti addition of palladium and nitrogen aaoss an alkene during oxidative amination is shown in Equation 9.89b. The stereochemistry of the alkene unit indicates that the reactions occur by insertions of olefins into Pd-N bonds. As shown in Equation 9.89b, frie E-olefin containing a pendant sulfonamide would form the E-product if syn addition of the palladium and sulfonamido group occurs during the catalytic process, but it would form the Z-product if anti addition occurred. The product from syn addition is formed, and such syn stereochemistry is consistent with migratory insertion of the olefin into a palladium-sulfonamido intermediate. ... 

This chapter focuses on the subset of these reactions that have been studied most intensively and that draw from the stoichiometric reactions presented earlier in this text. Thus, the first sections of this chapter highlight certain aspects of hydrocyanation, hydrosilylation, disilylation, hydroboration, diboration, silylborations, and hydroami-nation. The last section presents aspects of palladium-catalyzed oxidation and metal-catalyzed oxidative amination of olefins. 

The oxidative aminations of olefins have been reported in parallel witfi the oxidations of olefins witii alcohols, phenols, and carboxylic acids. These reactions are generally conducted with amides or imides amines are tfiought to be protonated by the acidic medium or to bind the metal center too tightly to allow for the catalytic chemistry to occur. Some exceptions noted below have been observed with arylamines or with rhodium catalysts. These oxidations have been conducted botfi intermolecularly and intramolecularly The oxidations have been conducted with benzoquinone, with copper, or with alone as the... 

Some of the earliest oxidative aminations of olefins were reactions of lactams with electron-poor olefins reported by Murahashi. Examples of these reactions conducted with tiie combination of Oj and CuCl with HMPA as additive are shown in Equation 16.115. This type of oxidative amination of olefins can also be conducted with N-alkyl arylamines, as demonstrated by Hegedus (Equation 16.116). Like the oxidations of acrylates with alcohols, these reactions occur at the p-carbon of the acrylate. 

Intramolecular oxidative aminations of olefins have alsobeen studied, and many of these intramolecular processes were observed prior to the analogous intermolecular variants. The oxidative aminations of alkenes with arylamines and arylamine derivatives catalyzed by palladium complexes were shown by Hegedus to form indoles (Equation 16.120). These reactions were conducted with orf/io-allylaniline and ort/zo-allylaniline derivatives as substrate, Pd(NCMe)jCl2 as catalyst, and benzoquinone as oxidant. Intramolecular reactions of N-tosylated aliphatic amines were reported by Larock. ° For example, the tosylamide in Equation 16.121 imdergoes cyclization in high yield in the presence of dioxygen with Pd(OAc)j as catalyst in DMSO. A related reaction (Equation 16.122) was reported recently in toluene solvent with added pyridine. ... 

Hosokawa, Murahashi, and coworkers demonstrated the ability of Pd" to catalyze the oxidative conjugate addition of amide and carbamate nucleophiles to electron-deficient alkenes (Eq. 42) [177]. Approximately 10 years later, Stahl and coworkers discovered that Pd-catalyzed oxidative amination of styrene proceeds with either Markovnikov or anti-Markovnikov regioselectivity. The preferred isomer is dictated by the presence or absence of a Bronsted base (e.g., triethylamine or acetate), respectively (Scheme 12) [178,179]. Both of these reaction classes employ O2 as the stoichiometric oxidant, but optimal conditions include a copper cocatalyst. More recently, Stahl and coworkers found that the oxidative amination of unactivated alkyl olefins proceeds most effectively in the absence of a copper cocatalyst (Eq. 43) [180]. In the presence of 5mol% CUCI2, significant alkene amination is observed, but the product consists of a complicated isomeric mixture arising from migration of the double bond into thermodynamically more stable internal positions. 

Oxidative cleavage of olefins, terminal alkynes, or aromatic rings 9-11 Oxidation of aromatic side chains 9-21 Oxidation of amines 9-22 Oxidation of primary alcohols or ethers... 

The synthesis of N phthaloyl enamides has been reported by a remarkably general method for aerobic oxidative amination of unactivated alkyl olefins as shown in Scheme 9.6 [12]. From a practical synthesis point of view, the phthalimide can not only serve as a directing group for asymmetric hydrogenation but can also be removed under mild conditions. 

Furthermore, Stahl and coworkers reported the oxidative amination of cyclic olefin (such as cyclopentene, cycloheptene) to afford cyclic allylic amine product. However, this reaction proceeds via m-am inopal I adation//i-hydride elimination pathway, rather than allylic C-H activation (Scheme 16) [33]. 

Moreover, there are already two other oxidative amination processes on the horizon, namely allylic amination of olefins and 1,2-diamination of 1,3-dienes [14]. Could these useful, but stochiometric transformations be rendered catalytic and perhaps also asymmetric some day ... 

Thus, N-H bond cleavage in this system provides a foundation for the development of mild catalytic transformation of ammonia as in arene-oxidative amination and olefin hydroamination. 

Oxidative amination of aromatic amines which are less basic than aliphatic amines proceeds smoothly without protection of amines. The intramolecular reaction of aniline derivatives offers good synthetic methods for heterocycles. 2-Methylindole is obtained by 5-exo amination of 2-allylaniline [50]. As an application, A-methyl-2-methyl-3-siloxyindole 114 was prepared from A-methyl-2-(l-siloxyallyl)aniline 113. Without silyl protection, no reaction occurred [51]. If there is another olefinic bond in the same molecule, the aminopalladation product 116 of the amide 115 undergoes olefin insertion to give the tricyclic compound 117 [50]. 2,2-Dimethyl-1,2-dihydroquinoline (119) was obtained by 6-endo cyclization of 2-(3,3-dimethylallyl)aniline (118). 

Af-Substituted aziridines (55) can be synthesized by the palladium-promoted amination of olefins using primary amines followed by oxidation with bromine. ... 

As with the amine oxides, mixtures of olefins are obtained when more than one type of jS -hydrogen is present. In noncyclic compounds, the olefin composition often approaches that expected on a statistical basis from the number of each type of hydrogen. The tram olefin usually predominates over the cis for a given isomeric pair. In cyclic systems, conformational features, ring strain, and related factors usually distort the mixture from that expected on a statistical basis. Elimination in a direction in which the syn mechanism can operate is strongly preferred over elimination in a direction where this is impossible. 

The oxidative functionalization of olefins to generate aldehydes, ketones, vinyl ethers, vinyl acetates, allylic acetates, and allylic ethers, as well as enamides, allylic amines, and products containing new C-C bonds has been studied extensively in both industrial and academic... 

More recently, oxidative aminations of vinylarenes with amides and imides have been reported by Stahl. - In this case, the regioselectivity of the process depends on tiie presence or absence of a tertiary amine additive. As shown in Equation 16.117, the 1,1-disubsti-tuted olefin is formed in the presence of amine, but a 1,2-disubstitued olefin is formed in the absence of amine. This change in regioselectivity is proposed to arise from the degree of reversibility of the addition of the nucleophile to the coordinated vinylarene in the presence and absence of base. As shown in Scheme 16.31, the kinetic site of nucleophilic attack is proposed to be the internal carbon, but the thermodynamic site of attack is proposed to be the terminal carbon. The thermodynamic site of attack is proposed to be the terminal carbon because attack at this position forms an ti -benzyl complex. In the presence of base, the kinetic product is rapidly deprotonated, and the 1,1-disubstituted olefin is formed. In the absence of base, the deprotonation step is slow enough that the thermodynamic product of attack is generated. 

Stahl has also shown that the product from oxidative amination of simple alkenes forms in the presence of a Pd(II) complex and dioxygen without copper. The analogous reactions conducted in the presence of copper led to isomerization of the olefin by an unknown mechanism, and a mixture of products was formed. Thus, the reactions conducted with Oj as oxidant in the absence of copper are more selective. An example of the reaction with phthalimide as nitrogen donor in the absence of copper is shown in Equation 16.119. 

With Palladium In 1979, Diamond et al. [39] reported the first Pd-catalyzed chelation-assisted olefin arylation using aromatic amines as substrates. The Pd-cat2ilyzed oxidative direct vinylation of arenes is well known, and the Fujiwara [40] reaction, for example, is a method for the Pd-catalyzed oxidative arylation of olefins. 

In 2006, Stahl reported the activity of 78a and rac-78b in the intramolecular amination of olefins (Equation (9.9)). A variety of substituted heterocycles were generated in fair to very good yields. Interesting features of this reaction are the use of atmospheric O2 as oxidant and the potential for an asymmetric version. 

Rhodium catalysts have also found application in oxidative aminations of styrenes. Beller and co-workers observed that numerous styrenes reacted with various kinds of secondary aliphatic amines in the presence of the cationic rhodium complexe [Rh(cod)2]BF4 and PPhs. Regioselectively the corresponding anti-Markovnikov products ( -enamines) were formed [49], While the Markovnikov product was never observed under such conditions, the target enamine was mostly obtained along with hydrogenated olefin, and in some cases even small amounts of hydroaminated products were detected [50],... 

However, when the temperature is increased to 120°C, the principal reaction is the elimination to olefin. The thermal decomposition of dimethyl dodecyl amine oxide at 125°C in a sealed system, as opposed to a vacuum used by Cope and others, produces 2-methyl-5-decyhsoxa2ohdine, dimethyl dodecyl amine, and olefin (23). The amine oxide oxidi2es XW-diaLkylhydroxylainine to the nitrone during the pyrolysis and is reduced to a tertiary amine in the process. 

Organic Reagents. Amine oxides are used ia synthetic organic chemistry ia the preparation of olefins, or phase-transfer catalysts (47), ia alkoxylation reactions (48), ia polymerization, and as oxidizing agents (49,50). 

The kinetics of formation and hydrolysis of /-C H OCl have been investigated (262). The chemistry of alkyl hypochlorites, /-C H OCl in particular, has been extensively explored (247). /-Butyl hypochlorite reacts with a variety of olefins via a photoinduced radical chain process to give good yields of aUyflc chlorides (263). Steroid alcohols can be oxidized and chlorinated with /-C H OCl to give good yields of ketosteroids and chlorosteroids (264) (see Steroids). /-Butyl hypochlorite is a more satisfactory reagent than HOCl for /V-chlorination of amines (265). Sulfides are oxidized in excellent yields to sulfoxides without concomitant formation of sulfones (266). 2-Amino-1, 4-quinones are rapidly chlorinated at room temperature chlorination occurs specifically at the position adjacent to the amino group (267). Anhydropenicillin is converted almost quantitatively to its 6-methoxy derivative by /-C H OCl in methanol (268). Reaction of unsaturated hydroperoxides with /-C H OCl provides monocyclic and bicycHc chloroalkyl 1,2-dioxolanes. 

Reactions of enamines with aluminum hydrogen dichloride (540,541) (UAIH4 and AICI3) or aluminum hydrogen dialkyl compounds (542) led to organoaluminum intermediates which could be hydrolyzed to tertiary amines or oxidized to aminoalcohols. The formation of olefins by elimination of the tertiary amine group has also been noted in these reactions. 

The three steps 32-34 have been suggested77 to be equilibria, and the overall equilibrium must lie far to the left because no adduct 23 is found in the reaction mixture when the reaction of sulfonyl chloride with olefin is carried out in the absence of a tertiary amine. A second possible mechanism involving oxidative addition of the arenesulfonyl halide to form a ruthenium(IV) complex and subsequent reductive elimination of the ruthenium complex hydrochloride, [HRulvCl], was considered to be much less likely. 

Hegedus et al. have thoroughly studied the homogeneous hydroamination of olefins in the presence of transition metal complexes. However, most of these reactions are either promoted or assisted, i.e. are stoichiometric reactions of an amine with a coordinated alkene [98-101] or, if catalytic, give rise to the oxidative hydroamination products, as for example in the cyclization of o-allylanilines to 2-alkylindoles [102, 103], i.e. are relevant to Wacker-type chemistry [104]. 

---