Catalytic asymmetric synthesis enantioselectivity

Hodous BL, Ruble JC, Fu GC (1999) Enantioselective addition of alcohols to ketenes catalyzed by a planar-chiral azaferrocene catalytic asymmetric synthesis of arylpropionic acids. J Am Chem Soc 121 2637-2638... 

The studies summarized above clearly bear testimony to the significance of Zr-based chiral catalysts in the important field of catalytic asymmetric synthesis. Chiral zircono-cenes promote unique reactions such as enantioselective alkene alkylations, processes that are not effectively catalyzed by any other chiral catalyst class. More recently, since about 1996, an impressive body of work has appeared that involves non-metallocene Zr catalysts. These chiral complexes are readily prepared (often in situ), easily modified, and effect a wide range of enantioselective C—C bond-forming reactions in an efficient manner (e. g. imine alkylations, Mannich reactions, aldol additions). 

In addition to its utility in the enantioselective formation of C-0 bonds (cf. Scheme 15), Trost s chiral ligand 102 has been used in the catalytic asymmetric synthesis of C-N bonds. An impressive application of this protocol is in the enantioselective total synthesis of pancrastatin by Trost (Scheme 17) H9i Thus, Pd-catalyzed desymmetrization of 112 leads to the formation of 113 efficiently and in > 95 % ee. The follow-up use of the N3 group to fabricate the requisite cyclic amide via isocyanate 117 demonstrates the impressive versatility of this asymmetric technology. 

The activation of C—H bonds and C—C bonds has attracted much attention in both academic and industrial laboratories because of their potential economic and ecological advantages. In the field of asymmetric synthesis, enantioselective catalytic C—X bond formation via the activation of C—H bonds and/or C—C bonds should have a great impact on asymmetric synthesis in both theory and practice. In theory, it is interesting to see how these very unreactive bonds can react preferentially in the presence of more reactive bonds with asymmetric control. In a practical sense, such C—H and C—C bonds are equivalent to the C M bonds in organometaUic reactions and would turn the corresponding stoichiometric amounts of metal into catalytic amounts. Conceptually, there are two fundamental ways to... 

The initial work on the asymmetric [4-1-2] cycloaddition reactions of A -sulfinyl compounds and dienes was performed with chiral titanium catalysts, but low ee s were observed <2002TA2407, 2001TA2937, 2000TL3743>. A great improvement in the enantioselectivity for the reaction of AT-sulfinyl dienophiles 249 or 250 and acyclic diene 251 or 1,3-cyclohexadiene 252 was observed in the processes involving catalysis with Cu(ll) and Zn(ii) complexes of Evans bis(oxazolidinone) (BOX) ligands 253 and 254 <2004JOC7198> (Scheme 34). While the preparation of enantio-merically enriched hetero-Diels-Alder adduct 255 requires a stoichometric amount of chiral Lewis acid complex, a catalytic asymmetric synthesis of 44 is achieved upon the addition of TMSOTf. 

Catalytic Asymmetric Synthesis, Ed. I. Ojima, VCH, New York (1993), Chpt 3 (enantioselective... 

Important extensions of proline catalysis in direct aldol reactions were also reported. Pioneering work by List and co-workers demonstrated that hydroxy-acetone (24) effectively serves as a donor substrate to afford anfi-l,2-diol 25 with excellent enantioselectivity (Scheme 11) [24]. The method represents the first catalytic asymmetric synthesis of anf/-l,2-diols and complements the asymmetric dihydroxylation developed by Sharpless and other researchers (described in Chap. 20). Barbas utilized proline to catalyze asymmetric self-aldoli-zation of acetaldehyde [25]. Jorgensen reported the cross aldol reaction of aldehydes and activated ketones like diethyl ketomalonate, in which the aldehyde... 

In this chapter, recent advances in asymmetric hydrosilylations promoted by chiral transition-metal catalysts will be reviewed, which attained spectacular increase in enantioselectivity in the 1990s [1], After our previous review in the original Catalytic Asymmetric Synthesis, which covered literature through the end of 1992 [2], various chiral Pn, Nn, and P-N type ligands have been developed extensively with great successes. In addition to common rhodium and palladium catalysts, other new chiral transition-metal catalysts, including Ti and Ru complexes, have emerged. This chapter also discusses catalytic hydrometallation reactions other than hydrosily-lation such as hydroboration and hydroalumination. 

In experimental studies on catalytic asymmetric synthesis, considerable attention has been paid to the interaction between chiral catalysts and the reactant(s) to achieve high enantioselectivity. However, very little attention has been paid to the interaction between the enantiomers of a chiral catalyst when this catalyst is not enantiomerically pure. 

The alkaloid-catalyzed addition of alcohols to prochiral ketenes is one of the very first examples of catalytic asymmetric synthesis. In pioneering work by Pracejus in the 1960s quite remarkable 76% ee was achieved and it was not until 1999 that substantial improvement of enantioselectivity in catalytic asymmetric addition of O- and N-nucleophiles to prochiral ketenes was reported. In particular, the chiral... 

The phase-transfer-catalyzed direct Mannich reaction of 28 with a-imino ester 64 was achieved with high enantioselectivity by using 32e as catalyst (Scheme 4.23) [63]. This method enables the catalytic asymmetric synthesis of differentially protected 3-aminoaspartate, a nitrogen analogue of dialkyl tartrate, the util-... 

This type of additive (or ligand) control of stereoselectivity has three advantages. First of all, after the reaction has been completed, the chiral additive can be separated from the product with physical methods, for example, chromatographically. In the second place, the chiral additive is therefore also easier to recover than if it had to be first liberated from the product by means of a chemical reaction. The third advantage of additive control of enantioselectivity is that the enantiomerically pure chiral additive does not necessarily have to be used in stoichiometric amounts catalytic amounts may be sufficient. This type of catalytic asymmetric synthesis, especially on an industrial scale, is important and will continue to be so. 

Sulfoximines are versatile reagents for diastereoselective and asymmetric synthesis. They continue to find many synthetic applications as both nucleophilic and electrophilic reagents. While the nucleophilic character of sulfoximine reagents has been well exploited,1 the use of the sulfoximine group as a nucleofuge is more recent and adds to the synthetic use of these compounds. The palladium(0)-catalyzed chemistry of allylic sulfoximines and the use of chiral sulfoximines as ligands in catalytic asymmetric synthesis are areas of recent development that have potentially useful applications. Further work is required to understand the factors that determine the diastereoselection and the stereochemical outcomes of these reactions. These studies will result in enhanced product diastereo- and enantioselectivities and make these reagents even more attractive to the wider synthetic chemistry community. 

With the enantioselective intramolecular benzoin reaction established as a synthetic tool, and in combination with our efforts in the synthesis of bioactive natural products bearing a quaternary a-hydroxy ketone unit (Davis and Weismiller 1990 Heller and Tamm 1981), such as the 4-chromanone derivative (S)-eucomol (Bohler and Tamm 1967 Crouch et al. 1999), a catalytic asymmetric synthesis of various 3-hydroxy-4-chromanones brought about by the chiral triazolium salts 127, 123b and 102 as pre-catalysts was investigated (Enders et al. 2006d). The sterically different pre-catalysts were chosen in order to adjust the catalyst system to the steric and electronic properties of the substrates 128. A screening of the reaction conditions indicated 10 mol% of the... 

Kadyrov R, Riermeier TH (2003) Highly enantioselective hydrogen-transfer reductive amination catalytic asymmetric synthesis of primary amines. Angew Chem Int Ed Engl 42 5472-5474 Kang Q, Zhao ZA, You SL (2007) Highly enantioselective Friedel-Crafts reaction of indoles with imines by a chiral phosphoric acid. J Am Chem Soc 129 1484-1485... 

An elegant example of a highly efficient catalytic asymmetric synthesis is the Takasago process [128] for the manufacture of 1-menthol, an important flavour and fragrance product. The key step is an enantioselective catalytic isomerisation of a prochiral enamine to a chiral imine (Fig. 1.44). The catalyst is a Rh-Binap complex (see Fig. 1.44) and the product is obtained in 99% ee using a sub-strate/catalyst ratio of 8000 recycling of the catalyst affords total turnover numbers of up to 300000. The Takasago process is used to produce several thousand tons of 1-menthol on an annual basis. 

Vol. I-III, Springer, Berlin, 1999 b) H. Brunner, W. Zetdmeier, Handbook of Enantioselective Catalysis with Transition Metal Compounds, Vol. I-II, VCH, Wein-heim, 1993 c) R. Noyori, Asymmetric Catalysis in Organic Synthesis, Wiley, New York, 1994 d) I. Ojima, (Ed.), Catalytic Asymmetric Synthesis, VCH, Weinheim, 1993 e) D. J. Berrisford, C. Bolm,... 

For reviews see (a) Ojima I (ed) (1993) In Catalytic asymmetric synthesis. VCH, New York (b) Noyori R (1994) In Asymmetric catalysis in organic synthesis. WUey, New York (c) Brunner H, Zettimeier W (1993) In Handbook of enantioselective catalysis with transition metal compounds. VCH, Weinheim (d) Jacobsen EN, Pfaltz A, Yamamoto H (eds) (1999) In Comprehensive asymmetric catalysis. Springer, Berlin Heidelberg New York... 

In this chapter, a concise catalytic asymmetric synthesis entry to alkaloids containing the l,2,3,4-tetrahydro-9a,4a-(iminoethano)-9F/-carbazole (4) ring is presented and the enantioselective total synthesis of minfiensine (1) is discussed in detail. 

The catalytic asymmetric synthesis of diarylmethylamines by a rhodium/phos phoramidite catalyzed addition of arylboronic adds to N,N dimethylsulfamoyl pro tected aldimines has been reported by de Vries and Feringa [118], The reaction produces very high yields and high enantioselectivities of the protected amine. Deprotection of the amine is achieved without any racemization upon heating the product in the microwave with 1,3 diaminopropane (Scheme 1.35). 

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