Catalytic asymmetric cycloadditions

While Quinap (95) is an excellent and versatile ligand from which numerous developments in asymmetric catalysis have benefited,49 its synthesis is cumbersome, and hence its price remains high (R enantiomer 100 mg, 337 CHF). Carreira et al. showed that the synthetically readily accessible PEMAP ligand class is as versatile as 

TABLE 2.5. Yield and Enantioselectivity for Formation of 107 Using Ligand 96  

Zhou also reported a series of related P,S-ferrocenyl ligands and their use in the [3+2] cycloaddition of aryl-substituted azomethine ylides with A-phenylmalei-mide.52 While these silver complexes were able to efficiently catalyze the reaction, the enantioselectivity was lower than in the protocol described above. 

Most of the examples given in the preceding text relied on silver phosphine complexes as catalysts. The. Mrgensen group examined the use of cinchona-derived ligands in the silver fluoride-catalyzed reaction of aromatic iminoesters 103 with methylacrylate (27). Yields were excellent, but enantioselectivities were only in the 

While significant progress has been achieved in catalytic asymmetric cycloaddition of aryl iminoesters with dipolarophiles, the field is still in its infancy. Notably, 

---

Dochnahl M, Fu GC (2009) Catalytic asymmetric cycloaddition of ketenes and nitroso compounds enantioselective synthesis of a-hydroxycarboxylic acid derivatives. Angew Chem Int Ed 48 2391-2393... 

Various a,a,a, a -tetraaryl-l,3-dioxolane-4,5-dimethanols have been prepared from (R,R)-tartrate, which are called TADDOLs by Seebach et al. They studied the influence of the Ti catalyst preparation methods, the presence of molecular sieves, and the TADDOL structure in the enantioselective Diels-Alder reaction of acryloyl oxazolidinones [41] (Eq. 8A.22). Seebach also prepared polymer- and dendrimer-bound Ti-TADDOLates and used in catalytic asymmetric cycloadditions [42],... 

J0rgensen and Juhl reported the first organocatalytic enantioselective inverse-electron-demand hetero-Diels-Alder reaction of aldehydes (e.g., 71) and enones (e.g., 72) with excellent diastereo- and enantioselectivity. Scheme 3.26 [41], The reaction utilizes a chiral enamine intermediate as an alkene in catalytic asymmetric cycloaddition reactions. 

A few studies reporting an asymmetric Diels-Alder reaction involving vinyl-boronates have been hitherto published. A catalytic asymmetric cycloaddition has been developed using 3- 3-boronyl-propenoyl)-l,3-oxazolidin-2-ones as dienophiles and a chiral titanium catalyst in the presence of molecular sieves [57]. Adducts were obtained as single isomers in good yield and high enantioselectivity (>93% ee) (Scheme 9.25). Cyclopentadiene gave a mixture of endo and exo isomers (-95 5). 

Scheme 2.25 Dynamic one-pot, three-component catalytic asymmetric cycloaddition.

A catalytic asymmetric cycloaddition reaction between norbomadiene and methylenecyclopropane can also be achieved in the presence of a [Ni(cod)2]-(—)-benzylmethylphenylphosphine catalyst to give the cycloadduct (72) in an optically active form. This reaction may proceed via a metallocyclopentane intermediate. The reactions of methylenecyclopropane with [Ni(cod)2l-phosphine systems do not appear to involve cleavage of the three-membered ring. However, the bis(acrylonitrile)nickel-catalysed cycloaddition reaction of methylenecyclopropane with methyl acrylate, which yields 3-methoxy-carbonylmethylenecyclopentane (73), does involve C—C bond cleavage. Reaction with the deuterium-substituted compound CHD=CDC02Me gives the cyclopentane derivative (74). An intermediate of the type (75) may be involved in this reaction. 

Catalytic asymmetric Diels-Alder reactions are presented by Hayashi, who takes as the starting point the synthetically useful breakthrough in 1979 by Koga et al. The various chiral Lewis acids which can catalyze the reaction of different dieno-philes are presented. Closely related to the Diels-Alder reaction is the [3-1-2] carbo-cyclic cycloaddition of palladium trimethylenemethane with alkenes, discovered by Trost and Chan. In the second chapter Chan provides some brief background information about this class of cycloaddition reaction, but concentrates primarily on recent advances. The part of the book dealing with carbo-cycloaddition reactions is... 

See e.g. (a) W. Cahhuthehs, Cycloaddition Reactions in Organic Synthesis, Tetrahedron Organic Chemistry Series Vol. 8 Pergamon Press Elmsford, NY 1990 (b) I. OjiMA, Catalytic Asymmetric Synthesis, VCH Publishers. Inc. New York. 1993 ... 

This chapter focuses on some typical examples, starting with the usual cycloaddition reactions and then the catalytic asymmetric Diels-Alder reactions, hetero Diels-Alder reactions, retro Diels-Alder reactions, and intramolecular... 

Since then, optically active a-aminophosphonates have been obtained by a variety of methods including resolution, asymmetric phosphite additions to imine double bonds and sugar-based nitrones, condensation of optically active ureas with phosphites and aldehydes, catalytic asymmetric hydrogenation, and 1,3-dipolar cycloadditions. These approaches have been discussed in a comprehensive review by Dhawan and Redmore.9 More recent protocols involve electrophilic amination of homochiral dioxane acetals,10 alkylation of homochiral imines derived from pinanone11 and ketopinic acid,12 and alkylation of homochiral, bicyclic phosphonamides.13... 

Modifications to the architecture of the imidazolidinone catalyst provided the fnryl derivative (20) which proved to be a powerfnl catalyst for the catalytic asymmetric Diels-Alder cycloaddition of simple a,P-unsaturated ketones [50]. Although... 

The aza-Diels-Alder reaction is an important and versatile tool for the preparation of nitrogen-containing heterocycles present in numerous natural products and drug candidates. It involves the [4 + 2] cycloaddition of either an imine with an electron-rich diene or an azabutadiene with an electron-rich alkene (inverse electron demand). Catalytic asymmetric variants employing not only metal complexes, but also organic molecules were disclosed over the last few years. 

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. 

Many groups have tackled the development of catalytic asymmetric versions of nitrile oxide cycloaddition reactions using chiral Lewis acid catalysts. However, Ukaji is the first and the only chemist who has succeeded in the achievement of such processes involving nitrile oxide cycloaddition reactions. He studied reactions... 

---