Alkenes intermolecular hydroamination

Fig. 2.16 Copper-amido complexes as catalysts for the intermolecular hydroamination of electron-deficient alkenes...

The well-defined copper complexes 94 and 95 (Fig. 2.16) have been used as catalysts for the intermolecular hydroamination of electron-deficient alkenes [Michael acceptors, X=CN, C(=0)Me, C(=0)(0Me)] and vinyl arenes substituted... 

Organometallic complexes of the /-elements have been reported that will perform both intra-and intermolecular hydroamination reactions of alkenes and alkynes, although these lie outside of the scope of this review.149-155 Early transition metal catalysts are not very common, although a number of organometallic systems exist.156-158 In these and other cases, the intermediacy of a metal imido complex LnM=NR was proposed.159,160 Such a species has recently been isolated (53) and used as a direct catalyst precursor for N-H addition to alkynes and allenes (Scheme 35).161,162... 

Alkene hydroamination has been known for many years, but has been little used as a method in organic synthesis. Tobin Marks of Northwestern recently published a series of three papers that will make this transformation much mote readily accessible. In the first (J. Am. Chem. Soc. 125 12584,2003) he describes the use of a family of lanthanide-derived catalysts for intermolecular hydroamination of alkynes (to make imines, not illustrated) and alkenes. With aliphatic amines, the branched (Markownikov) product is observed, 1 — 2. With styrenes, the linear product is formed. When two alkenes are present, the reaction can proceed (3 —> 4) to form a ring, with impressive regioselectivity. 

Rare-earth metal complexes have proven to be very efficient catalysts for intramolecular hydroamination reactions involving aminoalkenes, aminoalkynes, aminoallenes, and conjugated aminodienes [88, 97]. They are significantly less efficient in intermolecular hydroamination reactions and only a limited number of examples are known [98-102]. The difficulties in intermolecular hydroamination reactions originate primarily from inefficient competition between strongly binding amines and weakly binding alkenes for vacant coordination sites at the catalytically active metal center. 

Organolanthanide-catalyzed intermolecular hydrophosphination is a more facile process than intermolecular hydroamination. The reaction of alkynes, dienes, and activated alkenes with diphenylphosphine was achieved utilizing the ytterbium imine complex 9 (Fig. 8) as catalyst [185-188]. Unsymmetric internal alkynes react regioselectively, presumably due to an aryl-directing effect (48) [186]. 

While intermolecular hydroamination of simple alkenes remains a great challenge as of now, addition of amines to alkynes, allenes, and dienes proceeds more easily. However, the addition of an amine to a polyene moiety may not necessary result in the formation of a new stereocenter, if an imine is generated (Scheme 11.18). 

Scheme 22 Intermolecular hydroamination of alkenes using mono- and bimetallic La complexes (61-63)...

More recently, reactivity investigations have explored the scope of reactivity of previously developed catalysts. With respect to advances in group-lO-catalyzed allene hydroamination, Widenhoefer [229] explored Pt(II) neutral and cationic species for the intermolecular hydroamination of allenes with secondary alkylamines to make aUylamine products with excellent regioselectivity and diastereoselectivity (E/Z) (Scheme 15.43). This work builds upon a 2005 report for neutral Pt(II) compleiKs for the intermolecular hydroamination of alkenes with secondary amines [230, 231]. In the 2010 report, a variety of cyclic and acyclic alkylamines can be used as substrates, although neither arylamines nor primary amines are disclosed as substrates. This system is also limited to monosubstituted allenes. Consistent with long-standing proposals [231], outer-sphere addition of the amine to a cationic Pt(II) It-allene complex is proposed [229]. 

Other Pt(II) catalysts in ionic solvent have been disclosed for alkene hydroamina-tion, including ethylene hydroamination (Section 15.3.2) by Brunet and coworkers [109, 112]. This same catalyst system can promote intermolecular hydroamination of unactivated 1-hexene to give a mixture of products, with the Markovnikov product being formed preferentially (Scheme 15.50) [109]. Even in this specialized reaction medium, elevated temperatures and long reaction times are required with these challenging unactivated substrates. 

The success of simple Au(I) PPhj systems for catalysis inspired the development of less strongly donating phosphine hgands in order to enhance it-acidity to improve reactivity with protected amines. Using triphenyl phosphite as a hgand, intermolecular hydroamination of alkenes with sulfonamides can be accomphshed with low catalyst loadings (Scheme 15.63) [263]. 

The first chiral rare earth metal-based hydroam-ination catalysts were reported in 1992 using chiral lanthanocene. Organolanthanide complexes catalyze regios-elective intermolecular hydroamination of alkenes, alkynes. 

INTERMOLECULAR HYDROAMINATION OF ACTIVATED ALKENES CATALYZED BY CHARGE-NEUTRAL HETEROLEPTIC COMPLEXES OF LARGE ALKALINE EARTHS... 

For a recent example of enantioselective intra- and intermolecular hydroaminations of terminal amino-alkenes and styrene derivatives with heteroleptic chiral magnesium-phenolate complexes, see Emge, T. J. Hultzsch, K. C. Angew. Chem. Int. Ed 2012, 51, 394. 

Neutral group 4 metal complexes appear to possess a relatively broad scope for catalytic hydroaminations. They have been employed for the intramolecular as well as the intermolecular hydroaminations of alkenes, alkynes, and allenes. Catalytic hydroaminations (and hydrohydrazinations) of alkynes have been exploited as key steps in catalytic multicomponent reactions, giving rise to highly functionalized substrates, in particular to several types of N-heterocycles. Chapter 13 by Gade focuses, inter alia, on two case histories involving hydrohydrazinations which exemplify key challenges and the way they may be addressed in practice. 

In the hydroamination of unsaturated carbon-carbon bonds, gold catalysts play an important role. Intermolecular hydroamination of alkenes [177], 1,3-dienes [204], terminal and internal alkynes [205], and allenes [206] are known to proceed smoothly in the presence of PhsP AufI) or AuCls catalyst. In addition, amino olefins also efficiently undergo intramolecular hydroamination using similar gold catalysts. He and coworkers have developed the catalytic cycloaddition of tosylated amino olefins [207], A representative example is shown in Scheme 18.35. When N-tosylated y-amino olefin (97) is exposed to a mixture of PhsP AuCl and AgOTf (5 mol% each) in toluene at 85 °C, pyrrolidine (98) is obtained in 96% yield. The gold(I)-catalyzed intramolecular hydroamination is applicable to N-alkenyl carbamates [208], N-alkenyl carboxamides [209], and N-alkenyl ureas [210], The use of microwave irradiation results in completing the hydroamination in a much shorter time than that required under thermal reaction conditions [211], The... 

The catalytic activity of 4 in intermolecular hydroamination of alkynes by anilines as well as in the intramolecular alkene and alkyne hydroamination has been reported [40]. The results show that in the presence of ]PhNMe2H+][B(CgF5) ], 4 could catalyze these reactions very efficiently (2.5 mol% catalyst, 20 - 80 °C). It was su ested that the Cp moiety was protonolyzed to give Cp H, which was identified by NMR. In most cases, excellent yields were achieved, indicating a possible high potential of Zn-Zn-bonded complexes for catalytic organic transformations. As the presumed mechanism is not discussed further, it is hitherto unclear whether a Zn species is prevalent in the catalytic cycle. 

Although efficient for the intramolecular hydroamination/cyclization (abbreviated IH below) of aminoalkenes (see below), organolanthanides exhibit a much lower catalytic activity for the intermolecular hydroamination of alkenes, as exemplified by the reaction of n-PrNH2 with 1-pentene catalyzed by a neodymium complex (Eq. 4.17) [127]. 

Iridium The intermolecular hydroamination of unactivated C=C bonds in ct-olefins (RCH=CH2) and bicycloalkenes (norbornene and norbornadiene) with arylamides (ArCONH2) and sulfonamides has been attained upon catalysis by chiral iridium complexes (PP)IrHCl(NHCOAr)(NH2COAr) [PP = chiral bidentate diphosphine]. Mechanistic studies identified the product of N-H bond oxidative addition and coordination of the amide as the resting state of the catalyst. Rapid, reversible dissociation of the amide precedes reaction with the alkene, but an intramolecular, kinetically significant rearrangement of the species occurs before the reaction with alkene. ... 

Multiple efficient catalysts were reported for the intramolecular process, while the intermolecular process has been studied predominantly for alkynes. The reactivity of the unsaturated fragment decreases in the order alkyne > allene diene > vinyl arene unactivated alkene with the intermolecular hydroamination of simple alkenes representing the most difficult transformation. The hydroamination of all types of carbon-carbon unsaturated fragments will be covered in this chapter. 

The intermolecular hydroamination of xmactivated alkenes with alkali metal catalysts has been known for a long time and a comprehensive review is available [7]. Reactions with ammonia or primary amines catalyzed by elemental lithium [140], sodium [141-144], potassium [141], alkali metal hydrides [141], and amides [145, 146] with ethylene typically require high reaction temperatures (250-500°C) and pressures (up to 1000 bar) and result in mixtures of mono-, di- and triethy-lamine in moderate yields. 

Although alkali metal amides cannot catalyze intermolecular hydroamination of higher unactivated alkenes, allylbenzene derivatives react smoothly via base-catalyzed isomerization into p-methyl styrene derivatives, which are active enough to form hydroamination products (22) [170]. 

Although detailed mechanistic studies have not yet been performed, it is noteworthy that the reaction exhibits first order rate with respect to the concentration of catalyst and both reagents. This feature remarkably contrasts lanthanide-catalyzed intermolecular hydroamination of alkynes [20] and base-catalyzed intermolecular hydroamination of ethylene with secondary amines [152], which were both first order with respect to the concentration of the alkene/alkyne and the catalyst, but zero order in amine. 

The intermolecular hydroamination reactions of alkynes and alkenes occur with Markovnikov or anti-Markovnikov selectivity. The nucleophilic addition to aUenes occurs at terminal carbon of allenes not at central one. 

Due to its marked atom economy, the intramolecular hydroamination of alkenes represents an attractive process for the catalytic synthesis of nitrogen-containing organic compounds. Moreover, the nitrogen heterocycles obtained by hydroamination/cyclisation processes are frequently found in numerous pharmacologically active products. The pioneering work in this area was reported by Marks et al. who have used lanthanocenes to perform hydroamination/cyclisation reactions in 1992. These reactions can be performed in an intermolecular fashion and transition metals are by far the more efficient catalysts for promotion of these transformations via activation of the... 

Enantioselective, multiple centers 153, 166,189 Hydroamination Intermolecular Alkene 30 Alkyne 1 Intramolecular Alkene 30 Alkyne 13,170 Hydrogen peroxide Oxidation of alcohols 26, 86 Hydrogenolysis of epoxide 1 Hydrozirconation 32... 

Addition of ammonia and amines to alkenes (hydroamination) is thermodynamically feasible, but kinetically hindered, hence it requires activation of either of the reactants1,2,51. The intramolecular reaction is generally more easily accomplished than the intermolecular reaction and allows the stereochemistry to be controlled to a certain degree. 

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