Oximes intramolecular oxime-olefin cycloaddition

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>. 

Isoxazoles and isoxazolidines fused with sugar systems are found to show biological activity. In a continuation of our studies on the utilization of a variety of protocols on the sugar-derived chirons we embarked onto the 1,3-dipolar cycloaddition reactions. Accordingly, intramolecular oxime olefin cyclo-addition (lOOC) reactions on the chiron (91 X=NOH) gave an isoxazolidine-fused saccharide (92) (Scheme 22.21). 

Intramolecular nitrile oxide—olefin cycloaddition of oxazolidine and thiazoli-dine oximes 407 (R = H, Me R1 =H, Me X = 0, S n = 1,2) proceed stereose-lectively, yielding tricyclic fused pyrrolidines and piperidines. Thus, 407 (n =2 R = H R1 =Me X=S) has been oxidized to the nitrile oxides with sodium hypochlorite, in the presence of triethylamine in methylene chloride, to give the isoxazolothiazolopyridine 408 in 68% yield. Reduction of 408 with lithium aluminum hydride affords mercaptomethylmethylpiperidine 409 in 24% yield (448). 

A total synthesis of the sesquiterpene ( )-illudin C 420 has been described. The tricyclic ring system of the natural product is readily quickly assembled from cyclopropane and cyclopentene precursors via a novel oxime dianion coupling reaction and a subsequent intramolecular nitrile oxide—olefin cycloaddition (463). 

Similar intramolecular cycloaddition of TBDMS-protected oximes, tethered with olefin moieties, in the presence of boron trifluoride-ether generated A-nonsubstituted isoxazolidines in moderate to good yield (eq 52). The olefin geometry of the substrate was retained under the reaction conditions and the cycloaddition proceeded with high diastereoselectivity. 

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. 

A derivative of enantiomeric calystegine Bj, bearing a hydroxymethyl group at the 7-position (40), has been synthesized stereo selectively through a protected polyhydroxy aminocydoheptanone (38) and the corresponding azide (39) obtained by intramolecular cycloaddition of an olefinic oxime (37) derived from D-glucose [53]. 

Another synthesis of (-)-allosamizoline (8) was also carried out using the glucoseamine derivative 44 by an intramolecular cycloaddition of a nitrile oxide to an olefin as a key step (Scheme 5). ° lodination of 44 followed by reductive 3-elimination using zinc in THF afforded the 5-enofuranose 46, whose reaction with ethanethiol in cone. HCl followed by silylation with TBSOTf afforded 47. Dethioacetalization of 47 with HgCl2-CaC03 followed by treatment of the resulting aldehyde with NH2OH afforded the oxime 50, which underwent intramolecular cycloaddition to produce the isoxazoline 51. Alternatively, treatment... 

The ability of the intramolecular nitrile oxide-olefin [3 + 2] cycloaddition reaction to furnish isoxazolines suitable for further elaboration is illustrated in Scheme 34 utilizing (Ry mandelic acid (2). Chiral oxime 142, prepared in four steps from 2, is oxidized to a nitrile... 

The enantioselective intramolecular formal 2+4-cycloaddition of acrylates and a, -unsaturated imines (99) catalysed by chiral phosphines (100), derived from amino acids, produced A-heterocycles (101) (Scheme 31). Chiral dirhodium(II) carboxamidates (102) catalysed the hetero-Diels-Alder reactions between 2-aza-3-silyloxy-l,3-butadienes and aldehydes to yield all cw-substituted l,3-oxazinan-4-ones in high yields and high enantioselectivity (98% ee)P The nickel-catalysed 4 + 2-cycloaddition of a, -unsaturated oximes with alkynes yielded 2,3,4,6-tetrasubstituted pyridine derivatives. The reaction of isoquinoline, an activated alkyne, and 4-oxo-4//-l-benzopyran-3-carboxaldehyde (103), in ionic solvents, produced 9a//,15//-benzo[a][l]benzopyrano[2,3-/t]quinolizine derivatives (105) via the zwitterion (104) selectively and in good yields (Scheme 32).The Diels-Alder cycloaddition of ethyl 3-(tetrazol-5-yl)-l,2-diaza-l,3-butadiene-l-carboxylates with -rich heterocycles, nucleophilic olefins, and cumulenes formed 3-tetrazolyl-l,4,5,6-tetrahydropyridazines regioselectively. The silver-catalysed formal inverse-electron-demand Diels-Alder... 

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