Homoallylic amines, oxidation

Scheme 1). Introduction of a jt bond into the molecular structure of 1 furnishes homoallylic amine 2 and satisfies the structural prerequisite for an aza-Prins transform.4 Thus, disconnection of the bond between C-2 and C-3 affords intermediate 3 as a viable precursor. In the forward sense, a cation ji-type cyclization, or aza-Prins reaction, could achieve the formation of the C2-C3 bond and complete the assembly of the complex pentacyclic skeleton of the target molecule (1). Reduction of the residual n bond in 2, hydro-genolysis of the benzyl ether, and adjustment of the oxidation state at the side-chain terminus would then complete the synthesis of 1. 

An electroreductive Barbier-type allyla-tion of imines (434) with allyl bromide (429) also occurs inaTHF-PbBr2/Bu4NBr-(Al/Pt) system to give homoallyl amine (436) (Scheme 151) [533]. The combination of Pb(II)/Pb(0) redox and a sacrificial metal anode in the electrolysis system plays a role as a mediator for both cathodic and anodic electron-transfer processes. The metals used in the anode must have a less positive anodic dissolution potential than the oxidation potentials of the organic materials in order to be present or to be formed in situ. In addition, the metal ion plays the role of a Lewis acid to form the iminium ion (437) by associating with imine (435) (Scheme 151). 

One of the first reports dealing with the carbozincation of alkenes by allylic organozinc reagents was the addition of allylzinc bromide to the homoallylic amine 118 which occurred in refluxing THF. A secondary organozinc 119 was regioselectively produced and provided the amine 120 after hydrolysis. A small amount of aminoalcohol 121, resulting from oxidation of 119, was also isolated when the reaction mixture was exposed to air (equation 52)80,81. 

Acetals result from oxidative coupling of alcohols with electron-poor terminal olefins followed by a second, redox-neutral addition of alcohol [11-13]. Acrylonitrile (41) is converted to 3,3-dimethoxypropionitrile (42), an intermediate in the industrial synthesis of thiamin (vitamin Bl), by use of an alkyl nitrite oxidant [57]. A stereoselective acetalization was performed with methacrylates 43 to yield 44 with variable de [58]. Rare examples of intermolecular acetalization with nonactivated olefins are observed with chelating allyl and homoallyl amines and thioethers (45, give acetals 46) [46]. As opposed to intermolecular acetalizations, the intramolecular variety do not require activated olefins, but a suitable spatial relationship of hydroxy groups and the alkene[13]. Thus, Wacker oxidation of enediol 47 gave bicyclic acetal 48 as a precursor of a fluorinated analogue of the pheromone fron-talin[59]. 

Oxidation of homoallylic amines results in cw-fused bicyclic amines via an im-inium ion (a). 

There are several well-known transformations of 3,6-dihydrothiazine oxides and 3,6-dihydrothiazine imines. In most of these reactions, either the cyclic sulfinamide moiety and/or the carbon-carbon double bond is involved. For example, a 3,6-dihydrothiazine oxide can be hydrolyzed under either acidic or basic conditions to afford a homoallylic amine derivative [Eq. (17)]. 

The cycloadducts of sulfur diimides exhibit hydrolytic behavior very similar to that of dihydrothiazine oxides (Scheme 1-XI). Alkaline hydrolysis of a dihydrothiazine imine affords an intermediate sulfinamide which, on treatment with aqueous acid, yields a homoallylic amine, presumably via a retro-ene process. A homoallylic amine is formed directly from a cycloadduct on acidic hydrolysis. ... 

Allylic diphenylphosphine oxides undergo 1,3-dipolar cycloadditions with nitrile oxides to give A -isoxazolines (70) with ann -preferred stereoselectivities of up to 5 1.37 Separate reduction of y -and anti-(70) to the hydroxy amines (71), followed by Wittig-Horner elimination provides stereoselective syntheses of the homoallylic amines (72) (Scheme 9). A study of the effect of substituents on phosphorus on the diastereoselectivity in the cycloaddition of nitrones to vinylphosphine oxides (73) and sulphides (74) has been reported.38 In certain cases diastereoselectivities of >90% were achieved. 

Ruthenium catalyzed oxidation of alcohols. Primary and secondary alcohols are oxidized by this amine oxide in the presence of various ruthenium compounds. This particular amine oxide is superior to a number of others. Acetone, DMF, and HMPT are the most satisfactory solvents. Only ruthenium compounds can function as catalysts. RuCla is the cheapest catalyst, but is poorly soluble in acetone. RuCl52[P(CeH5)3] and Ru3(CO)ia do not suffer from this limitation. Saturated primary and secondary alcohols are oxidized in high yield allylic alcohols are generally oxidized in satisfactory yields, but homoallylic alcohols arc inactive and tend to give low conversions. Cholesterol is not oxidized. There is little discrimination between axial and equatorial hydroxyl groups. ... 

The cycloaddition of 7V-sulfinyl compounds with dienes gives dihydrothiazine oxides, which are precursors of homoallyl amines or pyrroles. Reactions of these reactive dienophiles in the presence of SnCU or TiCU yield the adducts diastereoselectively under mild reaction conditions. 

Ammonium-directed metal-free oxidation of cyclic allylic and homoallylic amines has been reviewed. Such reactions yield all four diastereoisomers of the corresponding 3-amino-1,2-diols, and have featured in recent syntheses of ( )-l-deoxynojirimycin and ( )-l-deoxyaltronojirimycin. ... 

Scheme 4. Palladacycle from the Pd-mediated oxidation of a homoallylic tertiary amine.

Ally lie amination. 1-Alkenes can be functionalized with double bond migration that results in derivatives of l-amino-2-alkenes, when they are treated with TsNHCOOR and catalytic amounts of Pd(OAc)2 under O2. Maleic anhydride, 4A-molecular sieves and NaOAc are the proper additives for this reaction. Alternatively, the same transformation is accomplished with benzoquinone as the oxidant, together with l,2-bis(benzenesulfinyl)-ethane and (salen)Cr tl. A heterobimetallic catalytic system is involved. However, only the Pd(II) catalyst is needed for oxidative cyclization of homoallylic A-tosylcarbamates. ... 

In numerous synthetic studies it has been demonstrated that DMP can be used for a selective oxidation of alcohols containing sensitive functional groups, such as unsaturated alcohols [297,1215-1218], carbohydrates and polyhydroxy derivatives [1216, 1219-1221], silyl ethers [1222,1223], amines and amides [1224-1227], various nucleoside derivatives [1228-1231], selenides [1232], tellurides [1233], phosphine oxides [1234], homoallylic and homopropargylic alcohols [1235], fluoroalcohols [1236-1239] and boronate esters [1240]. Several representative examples of these oxidations are shown below in Schemes 3.349-3.354. Specifically, the functionalized allylic alcohols 870, the Baylis-Hillman adducts of aryl aldehydes and alkyl acrylates, are efficiently oxidized with DMP to the corresponding a-methylene-p-keto esters 871 (Scheme 3.349) [1217]. The attempted Swern oxidation of the same adducts 870 resulted in substitution of the allylic hydroxyl group by chloride. 

Scheme 14.21 Enantio- and diastereoselective synthesis of homoallylic fragments. CHAPTER 15 [2,3]-REARRANGEMENTS OF AMMONIUM ZWITTERIONS Scheme 15.1 Sigmatrnpic 12.31-rearrangements of reactive ammonium zwitterioas. Scheme 15.2 Meisenheimer s original report of an amine N-oxide rearrangement. Scheme 15.3 12.31- and ri.21-Meisenheimer rearrangements of amine jV-oxides.

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