Oximes, conjugate addition

The sequential intramolecular conjugate addition of the oxime followed by intramolecular dipolar cycloaddition of the intermediate nitrone affords a... 

Tandem processes mediated by triethylborane involving conjugate addition to enones followed by aldol reaction are reported (Scheme 52, Eq. 52a). More recently, a tandem process involving addition of an isopropyl radical to an o ,/3-unsaturated oxime ether afforded an azaenolate intermediate that reacts with benzaldehyde in the presence of trimethylaluminum. The aldol product cyclizes to afford an isopropyl substituted y-bulyroloaclonc in 61% overall yield (Scheme 52) [116]. In these reactions, triethylborane is acting as a chain transfer reagent that delivers a boron enolate or azaenolate necessary for the aldolization process. 

Whereas the reactions of allenephosphonates 171 (R2 = OEt) with primary aliphatic and aromatic amines 172 and the reactions of the phosphane oxides 171 (R2 = Ph) with aliphatic amines 172 afford the conjugated addition products 173 always in good yields, the addition of anilines to 171 (R2 = Ph) leads to an equilibrium of the products 173 and 174 [231]. However, treatment of both phosphane oxides and phos-phonates of type 171 with hydroxylamines 172 (R3 = OR4) yields only the oximes 174 [232, 233]. The analogous reaction of the allenes 171 with diphenylphosphinoylhy-drazine furnishes hydrazones of type 174 [R3 = NHP(0)Ph2] [234],... 

One exception is the reaction of acetone oxime with divinyl ketone in the presence of an equimolar amount of zinc(II) bromide (162). Acetone oxime reacts with divinyl ketone on heating in THE at reflux, leading to both conjugate addition and nitrone cycloaddition, producing a 5 1 mixture of regioisomers with 8-oxa-l-azabicyclo[3.2.1]octan-4-one as the major isomer (Scheme 11.42). On the other hand, in the presence of an equimolar amount of zinc(II) bromide, 7-oxa-l-azabicyclo[3.2.1]octan-4-one is the major isomer (97 3) in a total yield of 97%, indicating that the Lewis acid has controlled the regioselectivity of the second step, namely, the cycloaddition. 

Regioselective alkylative opening of a,(1-epoxy ketone oxime [40] and tosylhydra-zones [41] with organocopper reagents is initiated by the generation of unsaturated azo compounds which undergo conjugate addition. 

Although the transformation is not an oxidation, Eric N. Jacobsen of Harvard University has developed (J. Am. Chem. Soc. 2004,126, 14724) an elegant route to enantiomerically-pure alcohols, based on the conjugate addition of an oxime such as 13 to an a.fi-unsaturated imide such as 14. 

Gawlcy and co-workers2 report that KDA is superior to LDA and to n-BuLi for deprotonation of dimethylhydrazones (7, 126-130) or of oxime ethers. The reaction is generally complete in THF at —78° in 15 minutes or less. The potassium counterion does not interfere with cuprate formation or conjugate addition. 

With hydroxylamine, the pyrylium salt (86) undergoes ring opening to an intermediate 1,5-enedione oxime (87) conjugate addition of the a,(3-unsaturated ketone gives (88), which in the presence of acid forms the isoxazole (89). 

Pyrans-4-ones and their monobenzo derivatives are easily attacked by nucleophiles via 1,4-conjugate additions which result in subsequent ring opening. Reactivity of this type makes it difficult to convert the carbonyl groups to acetals, oximes, and hydrazones by conventional methods. Since their reactivity toward nucleophiles provides a useful route for the preparation of a variety of rearranged products and new heterocyclic systems, their versatility as reactive intermediates is well documented. 

Zinc in acetic acid (Chapter 24) reduces the oxime to the amine and we can start the synthesis by doing the conjugate addition and then reducing the oxime in the presence of the keto-diester. 

Addition to alkynoic esters. Conjugate addition of oximes to alkynoic esters to provide ( j-alkenyl oxime ethers is catalyzed by PhjP. Interestingly, a-addition by phthalimide is observed. Such adducts are useful precursors of dehydro-a-amino acids. ... 

OXIMES AND SEMICARBAZONES Ceric ammonium nitrate. CLEMMENSEN REDUCTION Zinc dust. COMPLEX OF BENZYNE. Nickel carbonyl. n-COMPLEXES Diiron nonacarbonyl. CONDENSING AGENT Calcium carbide. CONJUGATE ADDITION Dimethylcop-perlithium. Nickel carbonyl. Tetrakisjiodo-(tri-ff-butylphosphine)copper(I)]. CONVERSION OF PHENOLS TO ARYL BROMIDES Triphenylphosphine dibromide. 

Oxazines can also be synthesized by intramolecular addition of oximes to carbon-carbon double bonds. These reactions are not general nitrones and other products can be formed in competition with oxazines. There are examples of conjugate addition to activated alkenes <81TL2557, 91CPB2830> and of acid or Lewis acid-catalyzed addition to simple alkenes <88TL6805> or allenes <89JCS(P1)2415>. 3-Methyl-6-vinyl-5,6-dihydro-4//-1,2-oxazine was isolated in moderate yield from... 

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