Henry reaction asymmetric

Scheme 3 62 is an example of an asymmetric Henry reaction reported by Sasai et al.116 in 1993. The catalyst acts in a bimetallic manner. This multifunctional effect is further discussed in Chapter 8. 

Scheme 3-63 gives another example in which an asymmetric Henry reaction is involved in the synthesis of the /i-receptor-blocking drug (S )-propranolol. 

Scheme 6.146 Representative adducts obtained from the asymmetric Henry reaction between nitromethane and (hetero)aromatic aldehydes under bifunctional catalysis of C6 -thiourea-functionalized cinchona alkaloid 131.

Scheme 6.168 Syntheses of 4-ep/-cytoxazone and cytoxazone utilizing guanidine-thioureas 183 and 186 for the initial asymmetric Henry reaction step.

The catalytic asymmetric Henry reaction has been reviewed.141,142... 

The catalytic asymmetric Henry reaction has been reviewed.42 Mild and efficient enantioselective nitroaldol reactions of nitromethane with various aldehydes have been catalysed by chiral copper Schiff-base complexes yielding the corresponding adducts with high yields and good enantiometric excess.43,44... 

The asymmetric catalytic nitroaldol reaction, also known as the asymmetric Henry reaction, is another example of an aldol-related synthesis of high general interest. In this reaction nitromethane (or a related nitroalkane) reacts in the presence of a chiral catalyst with an aldehyde, forming optically active / -nitro alcohols [122], The / -nitro alcohols are valuable intermediates in the synthesis of a broad variety of chiral building blocks, e.g. / -amino alcohols. A highly efficient asymmetric catalytic nitroaldol reaction has been developed by the Shibasaki group, who used multifunctional lanthanoid-based complexes as chiral catalysts [122-125],... 

Risgaard, T., Gotheif, K. V., Jorgensen, K. A. Cataiytic asymmetric Henry reactions of siiyi nitronates with aidehydes. Org. Biomol. Chem. 2003, 1, 153-156. 

Interesting metal-controlled reversal of enantioselectivity was observed in the asymmetric Henry reaction of a-keto esters catalyzed by tridentate bis(oxazoline) complexes of 172, by changing the Lewis acid center from Cu(II) to Zn(II) <05JOC3712>. 

First encouraging results for a stereoselective synthesis in general were reported by Seebach in 1982, who investigated the syn/anti-diastereoselectivity starting from achiral aldehydes and nitroalkanes [4,5]. Barrett et al. examined the influence of nonchiral Lewis acids on the syn/anti diastereoselectivity [6]. Stoichiometric amounts of an enantiomerically pure aldehyde were used in a di-astereoselective reaction with 3-nitropropionate by Hanessian et al. [7]. However, an approach to enantioselective synthesis of nitroalcohols via the route of the asymmetric Henry reaction could not be carried out until almost one hundred years after the discovery of the nitroaldol reaction. 

In 1992, Shibasaki et al. [8] reported for the first time on the use of recently developed chiral heterobimetallic lanthanoid complexes (LnLB) as chiral catalysts in the catalytic asymmetric Henry reaction (Scheme 1). In the following sections, this efficient concept of an asymmetric nitroaldol reaction, its scope and limitations, and its applications to complex stereoselective synthetic topics are described. 

However, structural modification of the BINOL ligand system also plays an important role with regard to stereoselection in the asymmetric Henry reaction. Improved enantioselectivites were obtained using a number of (P)-BINOL derivatives 8 (3 mol equiv) in which the 6,6 -positions were substituted [21 ]. Their utility as asymmetric catalysts was assessed using the nitroaldol reaction of ni-tromethane with hydrocinnamaldehyde 1. Enantioselectivities up to 88% ee accompanied by chemical yields up to 85% were obtained using 3.3 mol % of various catalysts 9 and 10 equiv of nitromethane (-40 °C, 91 h) (Scheme 4). 

The asymmetric Henry reaction is important because products are convertible to many other valuable bifunctional or polyfunctional compounds. Organocatalysts for the reaction containing a guanidine unit are represented by the C2-symmetric 76, which directs the addition of nitroalkanes to a-keto esters asymmetrically. 

Even though the three forms of magnesium oxide crystals catalyze the asymmetric Henry reaction, only NAP-MgO induces high enantioselectivity (Table 5.5). Spurred... 

TABLE 53. Asymmetric Henry Reaction Between Nitromethane and Benzaldehyde Catalyzed by NAP-MgO with Different Ligands at —78 °C... 

TABLE 5.5. Asymmetric Henry Reaction between a-Keto Esters and Nitromethane Cataiyzed by NAP-MgO at -78 °C... 

Example 4, A highly asymmetric Henry reaction catalyzed by chiral copper(ll)... 

Scheme 23.2 Asymmetric Henry reaction reported by Nagasawa and coworkers.

The asymmetric Henry reaction has been reviewed, " and a survey of organocat- 0 alytic enantioselective versions includes recent advances in the emergent domino Michael/Henry protocol. 0... 

Scheme 2.209 Asymmetric Henry-reaction catalyzed by (S)-hydroxynitrile lyase...

Scheme 3.27 Cyclophane-based bisthiourea-catalyzed asymmetric Henry reaction. (Data from Kitagaki, S. et al., Chem. Commun., 49,4030-4032,2013 Breugst, M. and Houk, K. N., /. Org. Chem., 79, 6302-6309, 2014.)...

Kitagaki, S. Ueda, T. Mukai, C. Planar Chiral [2.2]Paracyclophane-Based Bis(thiourea) Catalyst Application to Asymmetric Henry Reaction. Chem. Commun. 2013, 49, 4030-4032. 

Arai, T., Watanabe, M., and Yanagisawa, A. (2007). ftactical asymmetric Henry reaction catalyzed by a chiral diamine-Cu(OAc)2 complex. Org. Lett., 9, 3595-3597. 

The scope, limitations and mechanisms of asymmetric Henry reactions catalysed by transition metal complexes have been reviewed. ... 

Miscellaneous. An asymmetric Henry reaction involving combination of an aldehyde with a silyl nitronate, catalyzed by Cu(OTf)2 in the presence of TBAT and a chiral BOX ligand, gives the nitroaldol products in moderate yield and stereoselectivity. TBAT is effective in triggering desilylation of certain functionalized silyloximes, resulting in concomitant cyclization and nitrone formation (eq 9) ... 

A dinuclear zinc complex 26 of a novel chiral ligand is a very efficient chiral catalyst system to promote asymmetric Henry reaction. It is employed as the key step in the synthesis of (-)-denopamine, a selective Pi-adrenoceptor agonist, clinically effective in treating congestive cardiomyopathy. Aldehyde 27 condenses with nitromethane in the presence of 10% catalyst 26 in THF to afford vincinal nitroalcohol 28 in 88% yield with 90% ee. Hydrogenation of 28 catalyzed by palladium on carbon in ethanol furnishes aminoalcohol 29, which is then converted into the final product 30. 

The key step of making Amprenavir 35, an HIV protease inhibitor successfully marketed by Vertex, involves asymmetric Henry reaction... 

A typical asymmetric Henry reaction procedure using a chiral copper catalysi ... 

A series of mono- and dialkylated, chiral 1,2-amino-phosphinamide ligands (752) have been successfully applied in the chiral phosphinamide-Zn(ii) catalysed asymmetric Henry reaction between benzaldehyde and nitromethane (Scheme 210). The effects of the N-substituent sizes of chiral ligands (752) on the enantioselectivities in this reaction have been correlated using a predictive quantitative structure-activity relationship (QSAR) mathematical model. A quantitative correlation model has been also established based on subtractive Sterimol parameters. Ligand optimisation based on the QSAR model led to chiral 1,2-amino-phosphinamide ligand (752a), which produced (R)-p-nitroalcohol (753) in excellent yield (99%) and enantioselectivity (92% ee). ... 

Functionalization of the cinchona structure with a thiourea at the C6 position of the quinolone ring was demonstrated shortly after development of the C9 derivatives [69]. The transformation of the C6 methoxy group into a thiourea bearing a 3,5-di(trifluoromethyl)phenyl group, without affecting the stereochemistry at C9, resulted in a highly effective organocatalyst for the asymmetric Henry reaction of nitromethane with aromatic aldehydes (Scheme 6.28). 

The synthetic route to the structurally related bis-thioureas of type 32 from (R)-5,5, 6,6, 7,7, 8,8 -octahydro-l,T-binaphthyl-2,2 -diamine was reported by Shi. The effectiveness of the acid-base synergistic catalysis of parent 32a and N,N-diisopropylethylamine was verified by application to the asymmetric Henry reaction of nitromethane with aromatic aldehydes (Scheme 7.57) [86]. Moreover, the Morita-Bayhs-Hillman reaction between 2-cyclohexen-l-one or 2-cyclopenten-1-one and aromatic aldehydes was found to proceed with moderate to good levels of enantioselectivity under the catalysis of 32b, which has additional 3,5-bis(trifluoromethyl)phenyl groups at the 3,3 -positions of the octahydrobinaph-thyl backbone, and l,4-diazabicyclo[2.2.2]octane (DABCO) (Scheme 7.57) [87]. 

In 2007, Ooi and coworkers introduced chiral tetraaminophosphonium salts as a new class of Bronsted acids [166]. Similar to the guanidine/guanidinium case, these tetraaminophosphonium salts act as Bronsted bases in their neutral/ deprotonated (triaminoiminophosphorane) form, while they can also be used as mono-functional Bronsted acids in their protonated, phosphonium form. Phos-phonium salt 67, when neutralized in situ with KO Bu, was shown to be a highly effective catalyst in the enantioselective Henry reaction of nitroalkanes with various aromatic and aliphatic aldehydes (Scheme 10.65). The same strategy was further applied to the catalytic asymmetric Henry reaction of ynals [167] and hydrophosphonylation of ynones (Scheme 10.66) [168]. Brfunctional catalysis using this scaffold were also obtained using the carboxylate salts of tetraaminophosphoniums in the direct Mannich reaction of sulfonyl imines with azlactones (Scheme 10.67) [169]. 

The Henry reaction is a base-catalyzed C-C bond-forming reaction between nitroalkanes and aldehydes or ketones. It is similar to the aldol addition, and is also referred to as the nitroaldol reaction. Since its discovery in 1895 [1] the Henry reaction has become one of the most useful reactions for the formation of C-C bonds, and most particularly for the synthesis of P-nitroalcohol derivatives [2]. The general features of this reaction are (i) the potential offered by the nitro and hydroxyl groups on the products for transformation into other compound families such as P-amino alcohols, P-amino acids, or nitroalkenes (ii) only a catalytic amount of base is required (iii) up to two contiguous stereogenic centers may be created in a single step concomitantly to the C-C bond formation. Several recent reviews with a focus on the asymmetric Henry reaction and its applications have appeared [3j. 

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