Reactions with Oxygen Nucleophiles

Oxidation of ethylene in alcohol with PdCl2 in the presence of a base gives the acetal of acetaldehyde and vinyl ether [39,40]. The reaction of alkenes with alcohols 

The syntheses of brevicomin (36) [42,43] and lfontalin [44,45] have been achieved as an elegant application of the intramolecular acetal formation from the double bond with the diol in 35 in dry DME. 

The oxidation of terminal alkenes with an EWG in alcohols or ethylene glycol affords acetals of aldehydes chemoselectively. Acrylonitrile is converted to 3,3-dimethoxypropionitrile (38), which is produced commercially as an intermediate of vitamin Bi in MeOH using methyl nitrite (37) as a unique reoxidant of Pd(0). Methyl nitrite (37) is regenerated by oxidation of NO with oxygen in MeOH. Methyl nitrite is a gas, which can be separated easily from water formed by the oxidation [la], 

Oxypalladation of vinyl ether, followed by alkene insertion, is an interesting synthetic route to functionalized cyclic ethers. In prostaglandin synthesis, the oxypalladation of ethyl vinyl ether (40) with the protected cyclopentenediol 39 generates 41 and its intramolecular alkene insertion generates 42. The intermolecular insertion of the alkene 43, and /1-elimination of 44 occurred as one-pot reaction at room temperature, giving the final product 45 in 72% yield [46], The stereochemistry of the product shows that the alkene insertion (carbopalladation of 41) is syn. It should be noted that the elimination of /1-hydrogen from the intermediate 42 is not possible, because there is no /1-hydrogen syn coplanar to the Pd and, instead, the insertion of alkene 43 occurs. 

The direction of elimination of the /1-hydrogen to give either enol ethers or allylic ethers from alkenes can be controlled by using DMSO as a solvent. Formation of the allylic ether 47 was utilized in the synthesis of the tetronomycin precursor 47 from 46 [47], The oxidation of optically active 3-alkene-l,2-diol 48 afforded the 2,5-dihydrofuran 50 with high ee. It should be noted that /1-OH in 49 is eliminated to 

Y (carbanion stabilizing group) = S02Ph, SO2P-T0I, S02NMc2, 

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Displacement reactions with oxygen nucleophiles are of potential commercial interest. Alkaline hydrolysis provides 2-fluoro-6-hydroxypyridine [55758-32-2], a precursor to 6-fluoropyridyl phosphoms ester insecticides (410—412). Other oxygen nucleophiles such as bisphenol A and hydroquinone have been used to form aryl—pyridine copolymers (413). 

Reaction with Oxygen Nucleophiles. In the presence of strong acids, eg, H2SO4, HBF, or BF, aziridines react with alcohols to form P-amino ethers (93) ... 

Sulfur compounds " are better nucleophiles than their oxygen analogs (p. 439), so in most cases these reactions take place faster and more smoothly than the corresponding reactions with oxygen nucleophiles. There is evidence that some of these reactions take place by SET mechanisms. ... 

C. Palladium-catalyzed reactions with oxygen nucleophiles. 

Both dienyl- and 7r-allylmetal complexes of Fe,492 Mo,493,494 and W374 have also been prepared and undergone similar reactions with oxygen nucleophiles. One pertinent example is the reaction of 7r-allylmolybdenum complexes with internal alcohols leading to THFs (Equation (128)) 493 additional examples of this chemistry have appeared in a... 

Reaction with oxygen nucleophiles provides a simple route for the oxidation (Fig. 88) [229] and alkoxylation [230] (Fig. 89) of pyridine and related heteroaromatics. 

Most reactions with oxygen nucleophiles that have been reported have involved displacement of a 4-halogen substituent. 

Reactions with Oxygen Nucleophiles. The hist report of the reaction of oxygen nucleophiles was for the deracemization of cyclic allylic ethers, for example, the palladium(0)-catalyzed reaction of 2-cyclohexeny 1-1 -methyl carbonate with sodium pivalate afforded the pivalate ester in 94% yield and 92% ee. This reaction was extended to other cyclic allylic carbonates. 

An intramolecular ring-opening reaction with oxygen nucleophiles was discovered by Jacobsen to be catalyzed by the Co(salen)OAc catalyst 12 [22]. The... 

The second set of examples involves the use of thionium ions as electrophiles in inter- and intramolecular processes to obtain a-substituted sulfides (see 24 25, Scheme 20.7T which is the most common type of Pummerer reaction. Applications of this classical Pummerer rearrangement are exemplified in the synthesis of trans-solamin, the synthesis of indolizidine alkaloids, and the synthesis of the CDE ring of erinacine E. The first exanple fScheme 20.10 uses Pummerer chemistry in the generation of a thionium ion, which reacts in an intermolecular tin-mediated ene reaction the second one fScheme 20.11 uses Pummerer chemistry to introduce a nitrogen-containing heterocycle by intramolecular addition to form the coniceine core and the third example fScheme 20.12 is an intramolecular silicon-induced Pummerer reaction with oxygenated nucleophiles applied to the synthesis of a precursor of erinacine. Details of these Pummerer-based strategies are discussed below. 

Brooke G, Chambers R, Drury C, Bower M (1993) Remarkable orientationeil effects in the displacement of the fluorine from heptafluoro-isoquinoline and -quinoline towards sitlfur nucleophiles. Further reactions with oxygen nucleophiles. J Chem Soc, Perkin Trans I 1993 2201-2209... 

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