Catalytic enantioselective Diels-Alder reactions of furans and 1,1,1-trifluoroethyl acrylate

Catalytic enantioselective Diels-Alder reactions of furans and 1,1,1-trifluoroethyl acrylate in the presence of oxazaborolidium catalysts 2 or 3 provide 7-oxabicyclo[2.2.1]hept-5-enes with high endo-selectivity and excellent enantioselectivity.     

Broadly effective enantioselective Diels-Alder reactions of 1-amino-substituted-1,3-butadienes

[reaction: see text] A broad range of substituted 1-amino-1,3-butadienes undergo enantioselective Diels-Alder reactions with methacrolein in the presence of 5 mol % of Cr(III)-salen complex 1. The reactions are carried out conveniently, at room temperature, and they afford the cycloadducts in high yields and excellent ee's.     

Mechanistic studies of hydrazide-catalyzed enantioselective Diels-Alder reactions

The mechanism of the enantioselective, hydrazide-catalyzed Diels-Alder cycloaddition was investigated in detail. Both the formation of the reactive iminium species and the hydrolysis of the product iminium intermediates were found to be extremely rapid, leaving the cycloaddition as the kinetically significant step. Mechanistic studies using NMR showed that a retro-Diels-Alder reaction occurred during the catalytic cycle, suggesting a thermodynamic component to the reaction.     

N-alkoxyacrylamides as substrates for enantioselective Diels-Alder reactions

[reaction: see text] The use of N-alkoxyacrylamides as substrates for Lewis acid catalyzed Diels-Alder reactions has been examined. Enantioselectivities up to 92% ee have been achieved using very simple chiral Lewis acids prepared from triisobutylaluminum and 2,2-dimethyl-alpha,alpha,alpha',alpha'-tetra-1-naphthalenyl-TADDOL (1-NaphtTADDOL). The use of Yamamoto's Zn-BINOL, easily prepared from Et2Zn and 1,1'-bi-2-naphthol (BINOL), proved to be even more efficient, and enantioselectivities up to 96% ee were achieved.     

(1R,2R)-DPEN-derived triazolium salts for enantioselective oxodiene Diels-Alder reactions

Enantioselective oxodiene Diels-Alder reactions catalyzed by (1R,2R)-DPEN-derived triazolium salts were realized successfully. With 0.5 mol % of (1R,2R)-DPEN-derived triazolium salt C and 150 mol % of Et₃N, the reactions of various α-chloroaldehydes (α-bromoaldehyde) with substituted enones led to 3,4-dihydropyridinones and their derivatives in good yields, diastereoselectivities, and enantioselectivities (up to 97% ee).     

磺酰氨基酸钛配合物对Diels-Alder反应的对映选择性催化作用

研究了对甲苯磺酰基-L-缬氨酸、对甲苯磺酰基-L-苯丙氨酸、对甲苯磺酰基-L-亮氨酸、对甲苯磺酰基-L-异亮氨酸、对甲苯磺酰基-L-脯氨酸、1-萘磺酰基-L-缬氨酸、1-萘磺酰基-L-苯丙氨酸、1-萘磺酰基-L-亮氨酸和1-萘磺酰基-L-异亮氨酸与钛的配合物对环戊二烯与丙烯酸甲酯的环加成反应的对映选择性催化作用。萘磺酰基氨基酸钛配合物的对映选择性比对甲苯磺酰基氨基酸钛配合物好,氨基酸与钛比为2:1时比1:1要好得多。1-萘磺酰基-L-异亮氨酸与钛的2:1配合物的对映选择性最好,e.e.值为56%。     

C2-symmetric bissulfoximines as ligands in copper-catalyzed enantioselective Diels-Alder reactions

[reaction: see text] Bissulfoximines have been used as chiral ligands in copper-catalyzed enantioselective Diels-Alder reactions between acryloyl-2-oxazolidinones and cyclopentadiene. After optimizing the ligand structure, the metal source, the counterions, and the solvent, products with up to 93% ee have been obtained.     

Catalytic asymmetric synthesis of alpha-amino phosphonates using enantioselective carbon-carbon bond-forming reactions

We have developed highly enantioselelctive reactions of silicon enolates with N-acyl-alpha-iminophosphonates leading to optically active alpha-amino phophonates. A copper (II)-diamine complex was shown to be effective in this reaction, and high levels of yield and selectivity were achieved. It is noteworthy that this reaction opens a way to various biologically important, optically active alpha-amino phosphonate derivatives.     

Catalytic asymmetric aza Diels-Alder reactions of hydrazones using a chiral zirconium catalyst

Catalytic asymmetric aza Diels-Alder reactions of acylhydrazones with Danishefsky’s dienes have been developed. A chiral zirconium complex derived from zirconium propoxide and 3,3′,6,6′-I₄BINOL was found to be effective in this reaction, and the desired optically active 2,3-dihydro-4-pyridone derivatives were obtained with high enantioselectivities. Asymmetric formal synthesis of a natural product, coniine, was conducted using this catalytic asymmetric reaction as a key step.     

Catalytic, asymmetric trans-selective hetero Diels-Alder reactions using a chiral zirconium complex

[reaction: see text] The first catalytic, asymmetric 2,3-trans-selective hetero Diels-Alder reaction has been developed. The reactions of aldehydes with Danishefsky's dienes proceeded smoothly to afford the pyranone derivatives in high yields with high trans-selectivities and enantioselectivities in the presence of a chiral zirconium complex, which was prepared from zirconium tert-butoxide and (R)-3,3'-diiodobinaphthol or its derivatives, primary alcohol, and a small amount of water. This reaction was applied to the concise synthesis of (+)-prelactone C.     

A new class of C1-symmetric monosulfoximine ligands for enantioselective hetero Diels-Alder reactions

Quinoline-based C1-symmetric sulfoximines have been used as chiral ligands in copper-catalyzed asymmetric hetero Diels-Alder reactions leading to cycloadducts with up to 96% ee.     

Catalytic enantioselective Friedel-Crafts/Michael addition reactions of indoles to ethenetricarboxylates

[reaction: see text] The Friedel-Crafts reaction is an important reaction for the formation of new C-C bonds. Recently, catalytic enantioselective Friedel-Crafts reaction of alkylidene malonates has been reported. However, the substituents in alkylidene malonates are limited. To explore new substituents such as carboxyl and carbonyl groups, catalytic enantioselective Friedel-Crafts reactions of reactive ethenetricarboxylates and acyl-substituted methylenemalonates 1 were investigated. The reaction of 1 with indoles in the presence of catalytic amounts of chiral bisoxazoline copper(II) complex (10%) in THF at room temperature gave alkylated products in high yields and up to 95% ee. The enantioselectivity can be explained by the secondary orbital interaction on approach of indole to the less hindered side of the 1-Cu(II)-ligand complex.     

Highly enantioselective azadiene Diels-Alder reactions catalyzed by chiral N-heterocyclic carbenes

Highly enantioselective, N-heterocyclic carbene (NHC)-catalyzed aza-Diels-Alder reactions are described. A novel chiral triazolium salt based on the cis-1,2-aminoindanol platform serves as an efficient precatalyst for the NHC-catalyzed redox generation of enolate dienophiles that undergo LUMOdiene-controlled Diels-Alder reactions with N-sulfonyl-alpha,beta-unsaturated imines in good yields and with exceptional diastereo- and enantioselectivities (>99% ee). In contrast to uncatalyzed variants, this organocatalytic process proceeds at room temperature without stoichiometric reagents, producing synthetically valuable, enantiomerically pure cis-3,4-disubstituted dihydropyridinone products.     

Hetero Diels-Alder reactions of 1-amino-3-siloxy-1,3-butadienes under strictly thermal conditions

The hetero Diels-Alder reaction of 1-amino-3-siloxy-1,3-butadiene (1a) with a range of unactivated aldehydes proceeds readily under remarkably mild conditions: at room temperature and in the absence of Lewis acid catalysts. The cycloadducts are formed in good yields and can be converted directly to the corresponding dihydro-4-pyrones using acetyl chloride. Ketones and imines are also reactive in hetero Diels-Alder reactions with this diene.     

Catalytic, enantioselective, vinylogous aldol reactions

In 1935, R. C. Fuson formulated the principle of vinylogy to explain how the influence of a functional group may be felt at a distant point in the molecule when this position is connected by conjugated double-bond linkages to the group. In polar reactions, this concept allows the extension of the electrophilic or nucleophilic character of a functional group through the pi system of a carbon-carbon double bond. This vinylogous extension has been applied to the aldol reaction by employing "extended" dienol ethers derived from gamma-enolizable alpha,beta-unsaturated carbonyl compounds. Since 1994, several methods for the catalytic, enantioselective, vinylogous aldol reaction have appeared, with which varying degrees of regio- (site), enantio-, and diastereoselectivity can be attained. In this Review, the current scope and limitations of this transformation, as well as its application in natural product synthesis, are discussed.