Intermolecular reactions alcohols/phenols

Transition metal-catalyzed allylic substitution with phenols and alcohols represents a fundamentally important cross-coupling reaction for the construction of allylic ethers, which are ubiquitous in a variety of biologically important molecules [44, 45]. While phenols have proven efficient nucleophiles for a variety of intermolecular allylic etherification reactions, alcohols have proven much more challenging nucleophiles, primarily due to their hard, more basic character. This is exemphfied with secondary and tertiary alcohols, and has undoubtedly limited the synthetic utihty of this transformation. 

If the oxidation is performed in the presence of an external dienophile, the respective products of [4+2] cycloaddition are formed [351-356]. Typical examples are illustrated by a one-pot synthesis of several silyl bicyclic alkenes 283 by intermolecular Diels-Alder reactions of 4-trimethylsilyl substituted masked o-benzoquinones 282 generated by oxidation of the corresponding 2-methoxyphenols 281 [351] and by the hypervalent iodine-mediated oxidative dearomatization/Diels-Alder cascade reaction of phenols 284 with allyl alcohol affording polycyclic acetals 285 (Scheme 3.118) [352]. This hypervalent iodine-promoted tandem phenolic oxidation/Diels-Alder reaction has been utilized in the stereoselective synthesis of the bacchopetiolone carbocyclic core [353]. 

The oxidative aminations of olefins have been reported in parallel witfi the oxidations of olefins witii alcohols, phenols, and carboxylic acids. These reactions are generally conducted with amides or imides amines are tfiought to be protonated by the acidic medium or to bind the metal center too tightly to allow for the catalytic chemistry to occur. Some exceptions noted below have been observed with arylamines or with rhodium catalysts. These oxidations have been conducted botfi intermolecularly and intramolecularly The oxidations have been conducted with benzoquinone, with copper, or with alone as the... 

Intermolecular hydroalkoxylation of 1,1- and 1,3-di-substituted, tri-substituted and tetra-substituted allenes with a range of primary and secondary alcohols, methanol, phenol and propionic acid was catalysed by the system [AuCl(IPr)]/ AgOTf (1 1, 5 mol% each component) at room temperature in toluene, giving excellent conversions to the allylic ethers. Hydroalkoxylation of monosubstituted or trisubstituted allenes led to the selective addition of the alcohol to the less hindered allene terminus and the formation of allylic ethers. A plausible mechanism involves the reaction of the in situ formed cationic (IPr)Au" with the substituted allene to form the tt-allenyl complex 105, which after nucleophilic attack of the alcohol gives the o-alkenyl complex 106, which, in turn, is converted to the product by protonolysis and concomitant regeneration of the cationic active species (IPr)-Au" (Scheme 2.18) [86]. 

More recently, Apeloig and Nakash have studied diastereoselectivity in the reaction of (E)-5 with p-methoxyphenol53. In both benzene and THF, the stereochemistry of the products was independent of the phenol concentration. The syn/anti ratios of the addition products were 90 10 in benzene and 20 80 in THF. They have suggested that intramolecular proton transfer after rotation of the Si—Si bond of the phenol-coordinated intermediate is responsible for the formation of the anti-addition rather than intermolecular proton transfer. This must be a special case due to much slower (by a factor of 109-1012) rates of addition of phenol to (E)-5. Since phenolic oxygen is definitely less basic than alkyl alcoholic oxygen, coordination of oxygen in the zwitterionic intermediate in the reaction of (E)-5 with phenol must be loose and hence the intermediates should have much chance of rotation around the Si—Si bond. 

Intermolecular additions of the O-H bonds of phenols and alcohols and the N-H bonds of sulfonamides and benzamide to alkenes catalysed by 1 mol% of triflic acid have been reported as tools for the synthesis of cyclic ethers and amines. This study contributed to defining the relationship between these reactions and those catalysed by metal triflates.36... 

Further efforts demonstrate that the reaction of triethyl phosphite occurs under quite mild conditions in a conjugate manner with a wide range of oc,p-unsaturated aldehydes provided that a proton source is present (Scheme 5.21). The use of protic solvents, such as alcohols or phenols, not only provides a source of proton for the anionic site of the zwitterionic adduct but also furnishes a nucleophile for the required dealkylation step. The simplest hypothesis consistent with all of these facts is that the protonation-valency expansion of the quasiphosphonium ion intennediate using a proton source proceeds at a rate greater than the intermolecular pathway to enol ether. ... 

The direct nucleophilic substitution of electron-rich phenol ethers using hypervalent iodine oxidants in the presence of Lewis acid or fluorinated alcohols and involving aromatic cation-radical intermediates was originally developed by Kita and coworkers in 1994 [362], Since then this procedure with some variations has been extensively applied by Kita and other researchers for various oxidative transformations. In the intermolecular mode, this reaction (Scheme 3.122) has been utilized for the preparation of the products 298 from N3, AcO , ArS, SCN , 3-dicarbony 1 compounds and other external nucleophiles [320]. The oxidative coupling reaction in the intramolecular mode provides a powerful synthetic tool for the preparation of various... 

The oxidations of olefins with many oxygen nucleophiles other than water have also been reported. These reactions include the s5mthesis of vinylic and allylic ethers from reactions of olefins with alcohols and phenols, and vinylic and allylic esters from reactions of olefins with carboxylic acids. These reactions have been conducted with both monoenes and 1,3-dienes. Both intermolecular and intramolecular versions of each of these processes have been developed. Some discussion of these reactions was included in Chapter 11 because of their connection to the nucleophilic attack of oxygen nucleophiles on coordinated olefins and dienes. 

A review describes the asymmetric epoxidation of allylic alcohols,369 another the role of metal oporphyrins in oxidation reactions.370 jhe TiiOPrMi, catalysed self-epoxidation of allylic peroxides proceeds via an intermolecular mechanism.371 Racemic allyl alcohols can be resolved by asymmetric epoxidation (eq.35).372 a Pd(II)/Mn02/benzoquinone system catalyses the oxidative ring-closure of 1,5-hexadienes (eq.36).373 propenyl phenols are oxidatively degraded to aryl aldehydes and MeCHO in the presence of Co Schiff-base catalysts.374 An Oppenauer-type oxidation with Cp2ZrH2/cyclohexanone converts primary alcohols selectively into aldehydes.375 co macrocycles catalyse the oxidation of aryl liydrazones to diazo compounds in high yields.376 similar Co complexes under CO oxidise primary amines to azo compounds.377 Arene Os complexes in the presence of base convert aldehydes and water slowly into carboxylic acids and H2.378... 

In addition to cross-coupling chemistry, one of the most direct routes to the formation of vinyl ethers entails the addition of alcohols and phenols to alkynes. This atom-efficient transformation is referred to as hydroalkoxylation and can be tuned to generate vinyl ethers in excellent yields under very mild conditions. Both intermolecular and intramolecular versions of this reaction are well known, and a vast array of catalysts and conditions has been used for the successful synthesis of vinyl ethers [111, 112]. The following sections will highlight a number of advances in this area with special attention paid to modifications such as the development of fast reactions, green processes, as well as the ability of the reactions to tolerate moisture or air. 

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