Alkenes morpholines

Hydroamination of activated alkenes has been reported with complexes 91-93 (Fig. 2.15). For example, 91 catalyses the hydroamination of methacrylonitrile (X = CN in Scheme 2.13) by a range of secondary amines (morpholine, thiomorpholine, piperidine, iV-methylpiperazine or aniline) in good to excellent conversions (67-99%) and anfi-Markovnikov regioselectivity (5 mol%, -80°C or rt, 24-72 h). Low enantioselectivies were induced ee 30-50%) depending on the amine used and the reaction temperature [79]. 

Fields et al. found one example of an alkene, 1,1-dimorpholino-ethylene, which did not give the expected cycloaddition product, the 12,12-dimorpholino-6,ll-dihydro-6,ll-ethanoacridizinium ion (10). They conjectured that the l-(2-pyridyl)-2-morpholinonaphthalene (12) isolated had been formed via the expected adduct (10) which had undergone loss of morpholine to form the enamine (11) which could undergo ring opening (via a retro-quaternization reaction) followed by loss of a proton to yield (12). 

Morpholine, piperidine and diethylamine were used as bases. The catalyst precursor was [Pd(OAc)2] (106) and P(o-tol)3 or a similar phosphine. The mechanism is thought to involve vinylation of the alkene as in Scheme 74 as the initial process. This leads to the formation of an i73-allylpalladium derivative, which is then trapped by the amine to give the final product. If dienes are used instead of monoenes, 2,5-dienylamines are produced (equation 193).651... 

The Heck-type reaction of vinylic bromides with alkenes in the presence of nucleophiles such as stabilized enolates or secondary amines (morpholine or piperidine) are efficient three-component reactions that were developed in the late 1970s... 

The Upjohn Dihydroxylation allows the sy/i-selective preparation of 1,2-diols from alkenes by the use of 0s04 as a catalyst and a stoichiometric amount of an oxidant such as NMO (N-methyl morpholine- JV-Oxide). 

Butadienes of this type are readily available by addition of morpholine to 3-alkene-l-ynes in the presence of Hg(OAc)2 (45-65% yield).1... 

IJ Trienes.1 These trienes can be prepared in moderate yield by Pd-cat-alyzed reaction of fumaryl chloride (1) with 1-alkenes in the presence of N-ethyl-morpholine (2), which is superior to Bu3N as the base. (E,E)-5-Phenyl-2,4-pentadienyl chloride (3) can also be used in the condensation (last example), but this reaction is not (E,E,E)-specific. 

A reversion of the addition direction has been observed in the case of electron rich alkenes such as enol ethers and enamines. For example, ethyl vinyl ether reacts with the mesoionic compound (9) to produce the cycloadduct (108) in 58% yield. Other examples are the reactions of mesoionic 1,3-dithiolones with cyclohexyl vinyl ether, cyclopenten-l-yl ethyl ether, ethyl isobuten-l-yl ether and /V-(isobuten-l-yl)morpholine. The observed regioselectivities have been also qualitatively discussed on the basis of MO perturbation theory (79LA360). 

The morpholine enamine of fra/i.s-2-decalone exists as a 1 4 mixture of A1- and A2-isomers DAD reacts with the former by equatorial attack and the latter by axial attack351 (Scheme 177). In contrast, less electrophilic alkenes, such as / -nitrostyrene and phenyl vinyl ketone, react only with the A2-isomer at C-3 by axial attack (see Section III.B), unless sterically impeded. 

Although 0s04 is thought of as a specific oxidant for cis alkenes there are a few examples of hydroxylation of trans alkenes, e.g. cis- and frans-cyclodecene can be hydroxylated to the respective cis and irons diols.597 The Os04-alkene-pyridine reaction can be made catalytic by the use of suitable secondary oxidants such as H202, C103 , Bu OOH, A-morpholine A-oxide, I04 , 02 and CIO-. S54... 

Strategy Reaction of an alkene with a catalytic amount of OSO4, in the presence of N-morpholine N-oxide (NMO), yields a diol product. To pick a starting material for these products, choose an alkene that has a double bond between the diol carbons. 

The regioselective amination of 2,3-dihydrofuran with morpholine catalyzed by palladium thiocyanate diphosphine complexes (45 turnovers)102, and the regioselective addition of aniline to acrylonitrile and analogous electron-poor alkenes catalyzed by dialkylpalladium(dmpe) complexes (hundreds of turnovers)103 have recently been reported, but the scope of the reactions is limited to the specific type of alkene. 

Another ruthenium-catalyzed oxidation uses tetrapropylammonium permthenate (TRAP) [24]. Being a ruthenium(VII) oxide, the permthenate ion is a less powerful oxidant than rutheni-um(VIII) oxide and more functional groups are stable to the oxidation conditions, including alkenes, alkynes, amines, amides, benzyl, trityl and silyl ethers [24]. However, alcohols and lactols still undergo oxidations in high yield with W-methyl-morpholine A-oxide (NMO) as the stoichiometric oxidant. The reactions are usually carried out in dichloromethane, acetonitrile, or mixtures of both in the presence of molecular sieves [24]. 

The shift values obtained in CDCb are at approximately 0.1 p.p.m. lower field. The large upfield shift of this proton from simple alkenes is, of course, the result of lone pair electron delocalization into the tt-system, resulting in an increase in electron density at the 3-carbon. The ease with which this delocalization can occur crudely correlates with the kinetic reactivity of the various enamines where the most reactive are generally the pyrrolidine enamines. A similar analysis of the proton spectra for enamines derived from 2-butanone and a variety of amines has also been made. Again, the pyrrolidine enamine absorption occurs upfield from both the piperidine and morpholine enamines. The vinylic... 

The use of a cooxidant can reduce the amount of osmium required for a complete reaction of an alkene from stoichiometric to catalytic some examples of oxidants that can achieve this are peroxides [20, 22, 35, 37, 42-44] including hydrogen peroxide [20, 42], chlorates [45], periodate [46, 47], hypochlorite [48], N-methyl-morpholine-N-oxide (NMMO) [22, 34, 35, 37, 49], potassium ferricyanide [50, 51], and even air [52, 53]. 

Finally the remaining alkene is dihydroxylated with catalytic Os04and stoichiometric iV-methyl-morpholine (NMO) as oxidant to give the diol 56 that cyclises to the THF 57 stereospecifically. The aldehyde 58 was used to make (-)-dysiherbane. 

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