Amines, homoallylic alkylation

Aldehydes, ketones, and acetals react with allyltrimethylsilane in the presence of a catalytic amount of BiX3 (X = C1, Br, OTf) to give homoallyl alcohols or homoallyl alkyl ethers (Equation (52)).91-93 The BiX3-catalyzed allylation of aldehydes and sequential intramolecular etherification of the resulting homoallylic silyl ethers are involved in the stereoselective synthesis of polysubstituted tetrahydropyrans (Equation (53)).94,95 Similarly, these Lewis acids catalyze the cyanation of aldehydes and ketones with cyanotrimethylsilane. When a chiral bismuth(m) catalyst is used in the cyanation, cyanohydrines are obtained in up to 72% ee (Equation (54)). a-Aminonitriles are prepared directly from aldehydes, amines, and cyanotrimethysilane by the BiCl3-catalyzed Strecker-type reaction. 

The carbopalladation is extended to homoallylic amines and sulfides[466. Treatment of 4-dimethylamino-l-butene (518) with diethyl malonate and Li2PdCl4 in THF at room temperature leads to the oily carbopalladated complex 519, hydrogenation of which affords diethyl 4-(dimethylamino) butylmalonate (520) in an overall yield of 91%. Similarly, isopropyl 3-butenyl sulfide (521) is carbopalladated with methyl cyclopentanonecarboxylate and Li2PdCl4. Reduction of the complex affords the alkylated keto ester 522 in 96% yield. Thus functionalization of alkenes is possible by this method. 

For example, N-(2-hydroxyphenyl)imines 9 (R = alkyl, aryl) together with chiral zirconium catalysts generated in situ from binaphthol derived ligands were used for the asymmetric synthesis of a-amino nitriles [17], the diastereo- and/or enantioselective synthesis of homoallylic amines [18], the enantioselective synthesis of simple //-amino acid derivatives [19], the diastereo- and enantioselective preparation of a-hydroxy-//-amino acid derivatives [20] or aminoalkyl butenolides (aminoalkylation of triisopropylsilyloxyfurans, a vinylogous variant of the Mannich reaction) [21]. A good example for the potential of the general approach is the diastereo- and enantioselective synthesis of (2R,3S)-3-phenylisoserine hydrochloride (10)... 

Treatment of a-alkyl and a,a-dialkyl homoallylic amines 209 with phenyl selenium halides (X = C1, Br, I) in acetonitrile containing sodium carbonate produced mixtures of azetidines and pyrrolidines <1997TL1393, 2002EJ0995>. The ratio of azetidine to pyrrolidine increased according to the steric hinderance around the cr-carbon and with the nature of the counterion X (PhSeCl < PhSeBr < PhSel). The mechanistic investigations led to the conclusion that seleniranium halide intermediates 210 were involved in ring closure to azetidines 211 (Scheme 41). 

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]. 

Another series of -alkyl-metal complexes that owe their stabilities to the formation of a five-membered chelate ring is those produced in the reaction of allylic and, homoallylic amine and sulfide complexes of Pd(II) with nucleophiles. Lithium tetra-chloropalladate reacts with N,N-dimethylallylamine in methanol to produce the methoxy- kalkylPd complex ... 

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. 

A closely related reaction has been developed on homoallylic amines and sulfides. These substrates undergo regiospecific carbopalladation in the presence of stabilized enolates and lithium tetrachloropalladate to provide stable five-membered paUadacycles. Reduction of the complexes 9 and 10, respectively, affords the alkylated diester 11 and keto ester 12 (Scheme 8). 

For multicomponent synthesis of homoallylic amines using all-yltributylstannane instead of allyltrimethylsilane and catalyzed hy different species, see Polymer-bound-Yb salts (polyfluoro-alkyl sulfonic acids) (a) Y. Yin, G. Zhao, G.-L. Li, Tetrahedron 2005, 61, 12042-12052. Synthesis of polystyrene-bound per-fluoroaUcyl sulfonic acids and the application of their ytterbium salts in multicomponent reactions (MCRs). (Bromodimethyl) suhbnium bromide (Me S BrBr) (b) B. Das, B. Ravikanth, P Thirupathi, B. Vittal Rao, Tetrahedron Lett. 2006, 47, 5041-5044. (Bromodimethyl)sulfonium bromide catalyzed efficient multicomponent one-pot synthesis of homoaUyhc amines. 

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