Nitriles, asymmetric unsaturated nitrile

Abstract This chapter presents the latest achievements reported in the asymmetric hydroformylation of olefins. It focuses on rhodium systems containing diphosphites and phosphine-phosphite ligands, because of their significance in the subject. Particular attention is paid to the mechanistic aspects and the characterization of intermediates in the hydroformylation of vinyl arenes because these are the most important breakthroughs in the area. The chapter also presents the application of this catalytic reaction to vinyl acetate, dihydrofurans and unsaturated nitriles because of its industrial relevance. 

Rhodium-Catalyzed Asymmetric Hydroformylation of Unsaturated Nitriles... 

A more challenging example of an unsaturated nitrile reduction that lacks the carboxylate functional group is the asymmetric reduction of the nitrile shown in Figure 1.15. The product was required in the synthesis of chiral... 

DSM reported that the asymmetric hydroformylation of unsaturated nitriles (Scheme 12.72) to provide a potential route to (/ )-4-amino-2-methyl-l-ol (180), which is a key intermediate for TAK-637 (181), a new Tachykinin NK, receptor antagonist, developed by Takeda (Scheme 12.73). Rhodium-BINAPHOS (4 equiv) has catalyzed the asymmetric hydroformylation of but-3-enenitrile (allyl cyanide) with regioselectivity of 72/28 (b/1) and 66% ee at 73% conversions.227... 

Molybdenum carbene complexes. 17. 194-1 Olefin metathesis. Cross metathesis ( tZ)-a,P-unsaturated nitriles. Furthermore, era asymmetric allylboration provides fiinctionali... 

The asymmetric conjugate addition of activated methylenes is one of the most studied organocatalytic reactions. A wide variety of Michael acceptors such as enals, enones, a,P-unsaturated nitriles, nitroolefins, a,(i-unsaturated imides, and vinyl sulfones have been successfully employed as elechophiles with high degree of stereocontrol. 

The axially chiral dicarbo>g7lic acids 63 proved to be effective catalysts also in other classes of reactions. They were successfully used in the asymmetric addition of simple aza-enamines or vinylogous aza-enamines to imines (Scheme 24.22). In both cases, the optimisation of experimental parameters allowed products to be obtained with good yields and high ee values. Furthermore, the possibility to transform reaction products 70 and 73 respectively into a-aminoketones and y-amino a,p-unsaturated nitriles easily and without loss in ee gave additional value to the methodologies. 

A few other chiral NHCP systems have been reported, and their application in various palladium-catalyzed transformations such as hydroamination of a,P-unsaturated nitriles [32], asymmetric Suzuki-Miyaura coupling (see Section 10.2.1) [13n], and most frequently allylic substitution reactions have been studied [29, 33, 34]. Figure 10.3 summarizes the chiral NHCP systems not used in asymmetric hydrogenations, which we will present in the following. 

The asymmetric 1,3-dipolar cycloaddition of C,A(-cyclic azomethine imines with unsaturated nitriles yielded chiral cyanopyrazolidines in good to excellent yields and... 

In 2008, Yun et al. first reported the asymmetric p-boration of a,p-unsaturated nitriles and esters using Cu catalysts with chiral phosphine ligands [31, 32]. The phebox-Rh acetate complex 5 works as an effective catalyst for asymmetric boration of a,p-unsaturated esters (Scheme 29) [33]. The catalytic reaction of ethyl ( )-cinnamate with bis(pinacolato)diboron (B2pin2, l.leq) in the presence of 1 mol % of the scc-butyl phebox complex 5- Bu and 5 mol% of NaO Bu at 80 C afforded the borylated compound 46 in 86% yield. The product ee value of 97% was... 

As an alternative, iridium complexes show exciting catalytic activities in various organic transformations for C-C bond formation. Iridium complexes have been known to be effective catalysts for hydrogenation [1—5] and hydrogen transfers [6-27], including in enantioselective synthesis [28-47]. The catalytic activity of iridium complexes also covers a wide range for dehydrogenation [48-54], metathesis [55], hydroamination [56-61], hydrosilylation [62], and hydroalkoxylation reactions [63] and has been employed in alkyne-alkyne and alkyne - alkene cyclizations and allylic substitution reactions [64-114]. In addition, Ir-catalyzed asymmetric 1,3-dipolar cycloaddition of a,P-unsaturated nitriles with nitrone was reported [115]. 

Furthermore, the asymmetric catalysis of 27 could accommodate vinylogous aza-enamines as a source of an alkenyl unit, and the use of 27d bearing the 2,6-dimethyl-4-(l-adamantyl)phenyl groups as catalyst led to the establishment of the general and highly enantioselective formal alkenylation of N-benzoyl imines [77]. Since the oxidative transformation of an aza-enamine moiety of the product into a nitrile functionality appeared feasible as described above, this method offered facile access to optically active y-amino a,P-unsaturated nitriles (Scheme 7.50). 

Among the most successful classes of asymmetric acyl anion equivalents are the dioxane-containing a-amino nitriles 99 introduced by Enders and coworkers. These are deprotonated by EDA, and the resulting anions act as efficient equivalents of RCO for addition to a, (3-unsaturated esters [90AG(E)179],... 

However, most asymmetric 1,3-dipolar cycloaddition reactions of nitrile oxides with alkenes are carried out without Lewis acids as catalysts using either chiral alkenes or chiral auxiliary compounds (with achiral alkenes). Diverse chiral alkenes are in use, such as camphor-derived chiral N-acryloylhydrazide (195), C2-symmetric l,3-diacryloyl-2,2-dimethyl-4,5-diphenylimidazolidine, chiral 3-acryloyl-2,2-dimethyl-4-phenyloxazolidine (196, 197), sugar-based ethenyl ethers (198), acrylic esters (199, 200), C-bonded vinyl-substituted sugar (201), chirally modified vinylboronic ester derived from D-( + )-mannitol (202), (l/ )-menthyl vinyl ether (203), chiral derivatives of vinylacetic acid (204), ( )-l-ethoxy-3-fluoroalkyl-3-hydroxy-4-(4-methylphenylsulfinyl)but-1 -enes (205), enantiopure Y-oxygenated-a,P-unsaturated phenyl sulfones (206), chiral (a-oxyallyl)silanes (207), and (S )-but-3-ene-1,2-diol derivatives (208). As a chiral auxiliary, diisopropyl (i ,i )-tartrate (209, 210) has been very popular. 

The [2 + 3] cycloaddition reaction of nitrile oxides, easily accessible from corresponding aldoximes, with different alkenes is known as an excellent route to isoxazohne derivatives . The reactions of asymmetric addition ° or addition of unsaturated ger-manes and stannanes to nitrile oxides were reviewed in recent years. In this subsection only the main directions of the synthesis of isoxazole derivatives are briefly reported. 

N-Metalated azomethine ylides (44) are probably the most synthetically useful of these dipoles, since they can be generated from readily available N-alkylide-neamino esters or nitriles through a simple activation method. The resulting 1,3-dipoles show high reactivity with a,p-unsaturated carbonyl acceptors to provide excellent stereo- and regioselectivities. A variety of asymmetric versions have been reported. 

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