Nitrones oxime-olefin

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. 

Intramolecular cycloaddition of fV-benzyl-substituted 3-O-allylhexose nitrones furnishes chiral oxepane derivatives. The regioselectivity of the cycloaddition depends on several factors such as (1) the structural nature of the nitrone, (2) substitution and stereochemistry at 3-C of the carbohydrate backbone, and (3) substitution at the terminus of the O-allyl moiety. A mixture of an oxepane and a pyran is formed in the intramolecular oxime olefin cycloaddition of a 3-O-allyl carbohydrate-derived oxime <2003T4623>. The highly stereoselective synthesis of oxepanes proceeds by intramolecular nitrone cycloaddition reactions on sugar-derived methallyl ethers <2003TA3899>. 

Intramolecular oxime-olefin cycloaddition (lOOC) is a useM approach to iV-unsubstituted isoxazolidines. However, high temperatures are usually necessary to induce oxime tautomerization to nitrone. Tamura et al. reported the generation of iV-boranonitrones 107 by treatment of 0-/-butyldimethylsilyloximes 106 with two equiv of BF3.0Et2 at room temperature. Under the reaction conditions, the intermediate 107 smoothly underwent intramolecular cycloaddition to afford 108 after extractive work-up <05JOC10720>. 

BUzSnO catalyzes the formation of the nitrone 14 from benzaldehyde and the oxime 13. Addition of an olefin, followed by hydrolysis, gives a N-unsubstituted isoxazolidine (95CL357). 

The action of hydroxylamine on the dibromo-ketone (327) unexpectedly resulted in the isoxazoline (328)." The spiro-isoxazoline (330) is formed by anodic oxidation of the phenolic oxime (329)." Three novel reactiom leading to isoxazolines have been reported the nitrone PhCH=CHCPh=N-(CH2SMe)-0 undergoes 1,5-dipolar cyclization and elimination on heating, to yield compound (331)," silylation of secondary nitro-alkanes gives silyl-nitronates, which, in the presence of triethylamine, undergo 1,3-cyclo-addition to olefins thus sequential treatment of MejCHNOa with trimethyl-... 

Based on the enantioselective Michael addition/ISOC (intramolecular silyl nitronate olefin cycloaddition)/lragmentation sequence previously developed by the group of Rodriguez [33a], Shao and coworkers proposed an extrapolation for the construction of spirooxindoles catalyzed by a bifunctional tertiary amine-thiourea catalyst XV between 4-allyl-substituted oxindoles 63 and nitrostyrenes 64 (Scheme 10.21) [33b]. After the addition of TMSCl and EtgN at -30 C, the Michael adduct underwent an ISCX3 to afford the spiro oxime derivatives 65 in very good yields (85-85%), and excellent diastereo (up to >30 1) and enantioselectivities (94-99% ee) after the treatment with TBAF. 

---