Late alkene substrates catalysts

Key contributions in the development of late transition metal catalysts toward alkene hydroamination, which precede the 2008 comprehensive review [10], focus on contributions using group 9 and 10 metals. Preferred substrates for these transformations include aminoalkenes [230] for intramolecular reactivity or the use of activated alkenes such as styrene [93, 109, 113, 245] or alkenes substituted with electron-withdrawing substituents to generate hydroamination products via aza-Michael-type reactions [246-249]. Au has also been applied to the hydrofunctionalization of alkenes, although these reactions have demanded the use of protected amine substrates such as ureas [250], tosylamides [251], and carbamates [252]. 

Protected nitrogen substrates in combination with late transition metal catalysts have proven exceptionally useful for addressing the aforementioned substrate scope problems when trying to mediate hydroamination with unactivated alkene substrates. In asymmetric variants of this reaction, early work by Yamamoto showed that protected aminoalkynes could be used as cydohydroamination substrates to yield chiral heterocydes with vinyl substituents [108, 225). Here the chiral chelating phosphine ligand 66 ((J ,J )-RENOPHOS) in combination with a Pd(0) precursor and benzoic acid yielded the desired products in good yield with up to 91% ee (Table 15.26). Unfortunately, to obtain these optimized enantiomeric excesses,... 

As in the P(III) chemistry above, both late metal (Pd) and lanthanide catalysts have been used for P(V)-H additions to alkynes, alkenes, aldehydes, and imines. In addition, titanium, aluminum, and zinc catalysts have been employed. Typical P(V) substrates include dialkyl phosphites P(0R)2(0)H and phosphine oxides PR2(0)H. 

Palladium-catalyzed, Wacker-type oxidative cycHzation of alkenes represents an attractive strategy for the synthesis of heterocycles [139]. Early examples of these reactions typically employed stoichiometric Pd and, later, cocat-alytic palladium/copper [140-142]. In the late 1970s, Hegedus and coworkers demonstrated that Pd-catalyzed methods could be used to prepare nitrogen heterocyles from unprotected 2-allylanilines and tosyl-protected amino olefins with BQ as the terminal oxidant (Eqs. 23-24) [143,144]. Concurrently, Hosokawa and Murahashi reported that the cyclization of allylphenol substrates can be accomplished by using a palladium catalyst with dioxygen as the sole stoichiometric reoxidant (Eq. 25) [145]. 

As already mentioned, there has been significant progress in the development of chiral catalysts for asymmetric hydroamination reactions over the last decade. However, significant challenges remain, such as asymmetric intermolecular hydro aminations of simple nonactivated alkenes and the development of a chiral catalyst, which is applicable to a wide variety of substrates with consistent high stereochemical induction and tolerance of a multitude of functional groups as well as air and moisture. Certainly, late transition metal based catalysts show promising leads that could fill this void, but to date, early transition metal based catalysts (in particular, rare earth metals) remain the most active and most versatile catalyst systems. 

The development of catalytic methods for the hydroamination of nonactivated alkenes, allenes, and alkynes has received considerable attention in recent years [1]. These highly atom-economical processes allow direct access to industrially and biologically relevant classes of compounds such as amines, enamines, and imines from cheap and readily available starting materials. This has recently led to an ever-increasing range of molecular compounds that have been identified as catalysts for these transformations (Scheme 13.1). Whereas rare-earth catalysts have been found to be mainly active in intramolecular hydroamination, other catalysts - in particular those of the late transition metals - are frequently limited to the addition of weakly basic substrates (aniline, sulfonamides, carboxamides, etc.) to alkenes, alkynes, and allenes. 

Compared with late metals, oxophilic (f metals are less tolerant of functional groups in their reaction with organic compounds. Tliese groups, present in any complex organic compound, either block open sites at the metal needed for catalysis or produce undesired side reactions. This helps explain why organic reactions (Chapters 9 and 14) where most substrate functionality must remain untouched. Early metals can still be good catalysts for hydrocarbons lacking heteroatom functionality, as in alkene polymerization (Chapter 12), typically catalyzed by (fTi and Zr. 

As one of the earliest appUcatiOTis of RCM for macrocyclization in natural product synthesis, the Hoveyda group reported in 1995 that Schrock catalyst catalyzed Z-selective formation of the macrocycle in Fig. 24 as a single alkene stereoisomer, which is a late stage intermediate for the total synthesis of Fluvirucin B [54]. While the conformational control of the substrate was believed to be crucial for the selectivity, recent stodies showed that catalyst cmitrol also played a key role in the reaction outcome, as Ru-catalyzed RCM of a very similar substrate yielded a 1 1 mixture of Z E isomers [55]. 

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