Lewis acids 1,3-dipolar cycloaddition synthesis

Dipolar cycloaddition. Arylthiomethyl chlorides (1) in the presence of a Lewis acid can undergo a [4 + 2]cycloaddition to a tetrasubstituted alkene. They can be prepared by reaction of thiophenol with BrCH2Cl in the presence of DBU in CH,CN. C2H5A1C12 is preferred over A1C1, SnCl4, or TiCl4 as the Lewis acid. This reaction provides a short synthesis of cuparene (2). 

The dipolar cycloaddition of nitronates has been applied to the synthesis of several natural products in the context of the tandem [4+2] / [3 + 2] nitroalkene cycloaddition process. All of these syntheses have focused on the construction of pyrrolidine, pyrrolizidine, and indolizidine alkaloids. For example, the synthesis of ( )-hastanecine (316), a necine alkaloid, involves the elaboration of a p-benzoy-loxynitroalkene 311 via [4 + 2] cycloaddition with a chiral vinyl ether (312) in the presence of a titanium based Lewis acid, to provide the nitronate 313 with high diastereo- and facial selectivity (Scheme 2.30) (69). The dipolar cycloaddition of... 

Dipolar cycloaddition of alkenes with carbonyl ylides generated in situ is a versatile method for tetrahydrofuran synthesis. The synthetic potential of such transformations has been reviewed <2005JOM(690)5533, 2003BMI6-253>. In addition, the stereoselective [3 + 2] annulation of allyl silanes has become a reliable protocol for the synthesis of tetrahydrofurans as demonstrated in several total syntheses . Such a [3 + 2] annulation, for example, affords the tetrahydrofuran product 11 as a single stereoisomer (Scheme 15) <2002OL2945>. Lanthanide salts serve as efficient Lewis acid catalysts in similar [3 + 2] cycloaddition reactions . 

The importance of 1,3-dipolar cycloadditions (1,3-DC) in the realm of heterocyclic synthesis is widely documented and recent results concerning the intramolecular version of this methodology, including reactions with nitrile oxides and nitrones for access to isoxazole derivatives, have been reviewed <07T12247>. A quantum chemical study of the Lewis acid effect on the cycloaddition of benzonitrile oxide to propyne has been reported evidencing a small influence on the outcome of the reaction <07T5251>. 

Menthol [(—)-l] has been used as a chiral ligand for aluminum in Lewis acid catalyzed Diels-Alder reactions with surprising success2 (Section D.l.6.1.1.1.2.2.1). The major part of its application is as a chiral auxiliary, by the formation of esters or ethers. Esters with carboxylic acids may be formed by any convenient esterification technique. Esters with saturated carboxylic acids have been used for the formation of enolates by deprotonation and subsequent addition or alkylation reactions (Sections D.l.1.1.3.1. and D.l.5.2.3.), and with unsaturated acids as chiral dienes or dienophiles in Diels-Alder reactions (Section D. 1.6.1.1.1.), as chiral dipolarophiles in 1,3-dipolar cycloadditions (Section D.l.6.1.2.1.), as chiral partners in /(-lactam formation by [2 + 2] cycloaddition with chlorosulfonyl isocyanate (SectionD.l.6.1.3.), as sources for chiral alkenes in cyclopropanations (Section D.l.6.1.5.). and in the synthesis of chiral allenes (Section B.I.). Several esters have also been prepared by indirect techniques, e.g.,... 

Abstract This review is devoted to the stereoselectivity of intermolecular (intramolecular cycloadditions are not included) 1,3-dipolar cycloadditions of sugar-derived nitrones. Stereoselective cycloaddition (transformation of isoxazolidine followed by reduction of the N O bond to produce both an amino and a hydroxy function) allows the synthesis of tailor-made products of possible biological interest such as pol>4iydroxylated pyrrolidines, pyrrolizidines, indolizidines, fi-aminocarbonyl compounds, and disaccharides. Attention is focused on the preparation of isoxazolidinyl nucleosides and to the catalysis of the cycloaddition by Lewis acids. This review has concentrated on the new developments achieved from 1999 to February 2007. 

Kerr and coworkers developed an elegant access to optically active 3,6-cis disubstituted oxazine ring system via a homo-l,3-dipolar cycloaddition reaction of an aldehyde, a hydroxylamine, and a cyclopropane in the presence of a Lewis acid (Scheme 16). To emphasize the usefulness of this reactivity, it was first applied to the synthesis of phyllanthidine (7) (vide infra. Scheme 33). A modified version of this reaction provided access to 2,5-disubstituted pyrroloisoxazohdines, which upon N—O bond cleavage efficiently furnished the corresponding 2,5-cis pyrrofidine ring system (Scheme 16). 

Very recently, Maruoka reported an alternative catalytic asymmetric [3 + 2] cycloaddition reaction between various nitrones and acrolein catalyzed by the x-oxo-type chiral bis-Ti(IV) oxide, giving rise to the corresponding isoxazolidine derivatives in good yields and high enantioselectivities [177]. This type of titanium Lewis acid has also been used in enantioselective 1,3-dipolar cycloaddition of diazoacetates to various substituted acroleins, affording 2-pyrazolines with a chiral quarternary carbon center (Scheme 14.78) [178]. The products obtained with these methodologies have been applied to the synthesis of natural product and biologically important molecules. 

The versatile utility of transition-metal Lewis acids in catalytic organic synthesis has been thereby demonstrated in this decade to show high synthetic performance in a variety of reactions with high stereoselection and enantioselection, for example, for asymmetric Diels-Alder reactions, 1,3-dipolar cycloadditions, and other carbon-carbon or hetero atom bond-formation reactions. We hope that this review will stimulate further developments of this category Lewis acid catalyst and its application in a truly efficient chemical process in the future. 

Copper(I) catalysis has demonstrated its long-held reputation in asymmetric synthesis over the past decade. The moderate Lewis acidity and coordination property of Cu(l) salts make it a versatile metal center in various metal-ligand complex systems and thereby have broad applications in the area of organic chemistry, especially in the asymmetric catalysis field. This chapter summarizes the recent developments of Cu(l)-catalyzed asymmetric cycloaddition and cascade addition-cyclization reactions since 2010. A wide range of asymmetric transformations catalyzed by chiral Cu(l) complexes are discussed, such as the 1,3-dipolar cycloadditions, including [3+2], [3+3], and [3+6] cycloadditions. Other cycloadditions and cascade addition-cyclization reactions are also discussed. 

Christie and Jones first demonstrated in 2004 that appropriately substituted cyclopropanes adjacent to cobalt-alkyne complexes react with Lewis acids to yield 1,3-dipoles that are poised to participate in dipolar cycloadditions. Reaction of cyclopropane 21 with benzaldehyde and boron trifluoride provides tetrahydrofuran 22 in 83% yield. Kerr subsequently applied this strategy to the synthesis of tetrahydro-l,2-oxazines upon combination of cyclopranes like 21 with a variety of nitrones. ... 

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