Nitrogen stereoselective cycloadditions

Epoxidations of chiral allenamides lead to chiral nitrogen-stabilized oxyallyl catioins that undergo highly stereoselective (4 + 3) cycloaddition reactions with electron-rich dienes.6 These are the first examples of epoxidations of allenes, and the first examples of chiral nitrogen-stabilized oxyallyl cations. Further elaboration of the cycloadducts leads to interesting chiral amino alcohols that can be useful as ligands in asymmetric catalysis (Scheme 2). 

Intramolecular nitrone cycloadditions often require higher temperatures as nitrones react more sluggishly with alkenes than do nitrile oxides and the products contain a substituent on nitrogen which may not be desirable. Conspicuously absent among various nitrones employed earlier have been NH nitrones, which are tautomers of the more stable oximes. However, Grigg et al. [58 a] and Padwa and Norman [58b] have demonstrated that under certain conditions oximes can undergo addition to electron deficient olefins as Michael acceptors, followed by cycloadditions to multiple bonds. We found that intramolecular oxime-olefin cycloaddition (lOOC) can occur thermally via an H-nitrone and lead to stereospecific introduction of two or more stereocenters. This is an excellent procedure for the stereoselective introduction of amino alcohol functionality via N-0 bond cleavage. 

Hassner and coworkers have developed a one-pot tandem consecutive 1,4-addition intramolecular cycloaddition strategy for the construction of five- and six-membered heterocycles and carbocycles. Because nitroalkenes are good Michael acceptors for carbon, sulfur, oxygen, and nitrogen nucleophiles (see Section 4.1 on the Michael reaction), subsequent intramolecular silyl nitronate cycloaddition (ISOC) or intramolecular nitrile oxide cycloaddition (INOC) provides one-pot synthesis of fused isoxazolines (Scheme 8.26). The ISOC route is generally better than INOC route regarding stereoselectivity and generality. 

The stereoselectivity of these cycloaddition reactions is influenced by the steric hindrance of both, the IV- and C -substituent of the nitrone, that is, the selectivity increases as the nitrogen substituent of the nitrone becomes bulkier. As shown in Table 2.17, the highest diastereoselectivity in these reactions was observed with A-benzyl nitrones (479b) and (480). 

Wilcox and co-workers (145) reported that the stereoselectivity of 1,3-dipolar cycloaddition reactions can be controlled in a predictable manner when ion pairs are located at a proper position near the reaction site (Scheme 11.40). He has employed an A-phenylmaleimide substrate having a chiral center in the substituent at ortho position of the phenyl group. Due to serious steiic hindrance, this phenyl group suffers hindered rotation around the aryl-nitrogen bond (rotation barrier 22 kcal/mol). Four diastereomeric cycloadducts are possible in the cycloaddition step with a nitrile oxide. When the cycloaddition reaction is carried out in... 

The 1,3-dipolar cycloaddition of nitrones to alkenes has been shown to be very useful in the field of synthesis of alkaloids. The reaction is normally efficient and the inherent features of carbon-carbon bond formation, oxygen transfer and nitrogen incorporation have been joined by high regioselectivity and even stereoselectivity (79ACR396). The... 

Chiral alkoxy allenes derived from 1,3-alkylidene-L-erythritol and -D-threitol have been used in cycloaddition reactions to provide the 4-substituted /3-lactams 418 (R = Me, Ph). Intramolecular alkylation at nitrogen was achieved by the action of potassium carbonate and tetrabutylammonium bromide in dry acetonitrile. The absolute stereochemistry of the product 419 (R = Me, Ph) was assigned on the basis of the CD helicity rule (see Section 2.04.3.5) and NMR spectroscopy. The [2+2] cycloaddition of CSI to threitol vinyl ethers was found to have low stereoselectivity in contrast to the findings with erythritol derivatives <2004CH414, 2005EJ0429>. 

The photodimerization of 2-pyridones is an efficient, regiospecific, and stereoselective [4+ 4]-cycloaddition [56] that converts two achiral aromatics into a highly functionalized tricyclic cyclooctadiene with four stereogenic centers (Scheme 9.34). For tethered pyridones, the trans isomer is usually the major product when one or both pyridine nitrogens are methylated. By contrast, in the unsubstituted systems,... 

Dipolar cycloaddition of nitrones to alkenes has been widely utilized for the synthesis of many nitrogen-containing natural products. Indeed, in this process, up to three stereogenic centers are built up in a single step, often in a highly stereoselective manner. Louis and Hootele recently reported the first highly selective 1,3-dipolar cycloaddition between an a,P-unsaturated sulfoxide and a cyclic ni-... 

A-Boc protected oxazolidines found application in the enantioselective synthesis of aminosugars <030L3001>. Oxazolidin-2-ones were also used as tethers for the stereoselective [4+3] cycloadditions of nitrogen-stabilised oxyallyl cations via epoxidation of allenamides <03JA12694>. 

N-Alkyl- and N-aryl-ketenimines are poor electrophilic partners and do not react with benzylidene-aniline or dicyclohexylcarbodiimide." The introduction of an electron-withdrawing substituent (tosyl or cyano ) on the nitrogen atom enhances the electrophilic character of the cumulene and cycloadditions to imines occur under very mild conditions (Scheme 42). In most cases, the reactions are trans stereoselective. 

The 1,3-dipolar cycloaddition of 7V-benzyl-C-ethoxycarbonylnitrone with (5)-5-hydroxymethyl-(577)-fiiran-2-one is regio- and stereo-selective. The intramolecular 1,3-dipolar cycloaddition of sugar ketonitrones (50) provides a convenient method for the stereoselective formation of carbohydrate derivatives (51) possessing nitrogenated quaternary centres. This methodology has been successfully used to prepare synthetic precursors of (—)-tetrodotoxin (52) (Scheme 18). The hydrophobic effect has been shown to influence the rate and selectivity of 1,3-dipolar cycloaddition reactions of C,iV-diphenylnitrone with electron-deficient dipolarophiles. ... 

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