Propargylic alcohols catalytic reactions

Friedel-Crafts reaction remains unexplored, possibly due to the difficulty of the cycloalkyne formation. A mild, versatile, and efficient method for the one-step synthesis of substituted dihydro- and tetrahydroisoquinolines has been developed by the FeCl3-6H20-catalyzed intramolecular allenylation/cyclization reaction of benzylamino-substituted propargylic alcohols, representing the first example of the intramolecular Friedel-Crafts reaction of propargylic alcohols (Scheme 8) [24, 25]. FeCls, InCls, and Yb(OTf)3 also exhibit good catalytic activity for the reaction. 

The heterogeneous catalytic system iron phthalocyanine (7) immobilized on silica and tert-butyl hydroperoxide, TBHP, has been proposed for allylic oxidation reactions (10). This catalytic system has shown good activity in the oxidation of 2,3,6-trimethylphenol for the production of 1,4-trimethylbenzoquinone (yield > 80%), a vitamin E precursor (11), and in the oxidation of alkynes and propargylic alcohols to a,p-acetylenic ketones (yields > 60%) (12). A 43% yield of 2-cyclohexen-l-one was obtained (10) over the p-oxo dimeric form of iron tetrasulfophthalocyanine (7a) immobilized on silica using TBHP as oxidant and CH3CN as solvent however, the catalyst deactivated under reaction conditions. 

Substituted propargylic alcohols were found to undergo direct carbonylation to the corresponding butenolides in 67-98% yield (Eq. 9.120) [86]. This reaction requires a catalytic amount of Pd2(dba)3-CHC13 (4%) and l,4-bis(diphenylphosphi-no)butane (8%) in CH2C12 under an atmosphere of CO (600 psi) and H2 (200 psi) at 95 °C for 36 h. The cyclocarbonylation reaction is believed to proceed via an allenyl-palladium intermediate, which is formed by initial insertion of Pd(0) into the C-O bond of the alkynol followed by rearrangement (Scheme 9.25). 

The virtue of performing the PKR in an enantioselective manner has been extensively elaborated during the last decade. As a result, different powerful procedures were developed, spanning both auxiliary-based approaches and catalytic asymmetric reactions. For instance, the use of chiral N-oxides was reported by Kerr et al., who examined the effect of the chiral brucine N-oxide in the intermolecular PKR of propargylic alcohols and norbornadiene [59]. Under optimized conditions, ee values up to 78% at - 60 °C have been obtained (Eq. 10). Chiral sparteine N-oxides are also able to induce chirality, but the observed enantioselectivity was comparatively lower [60]. 

Metal-catalyzed substitution reactions involving propargylic derivatives have not been studied in much detail until recently [311, 312]. In this context, the ability shown by transition-metal allenylidenes to undergo nucleophilic additions at the Cy atom of the cumulenic chain has allowed the development of efficient catalytic processes for the direct substitution of the hydroxyl group in propargylic alcohols [313]. These transformations represent an appealing alternative to the well-known and extensively investigated Nicholas reaction, in which stoichiometric amounts of [Co2(CO)g] are employed [314-317]. 

Highly reactive organic vinylidene and allenylidene species can be stabilized upon coordination to a metal center [1]. In 1979, Bruce et al. [2] reported the first ruthenium vinylidene complex from phenylacetylene and [RuCpCl(PPh3)2] in the presence of NH4PF6. Following this report, various mthenium vinylidene complexes have been isolated and their physical and chemical properties have been extensively elucidated [3]. As the a-carbon of ruthenium vinylidenes and the a and y-carbon of ruthenium allenylidenes are electrophilic in nature [4], the direct formation of ruthenium vinylidene and ruthenium allenylidene species, respectively, from terminal alkynes and propargylic alcohols provides easy access to numerous catalytic reactions since nucleophilic addition at these carbons is a viable route for new catalysis (Scheme 6.1). 

In the presence of a catalytic amount of methanethiolate-bridged diruthenium complex (la abbreviated as met-DIRUX), reactions of propargylic alcohols (2) with a variety of heteroatom-centered nucleophiles such as alcohols, thiols, amines, amides, and diphenylphosphine oxide gave the corresponding propargylic substituted... 

Quite recently, some mononuclear ruthenium complexes such as [(p-cymene)RuX-(CO)(PR3)]OTf (X = Cl, OTf, R = Ph, Cy) have been found to work as catalysts for the propargylation of aromatic compounds such as furans, where some ruthenium complexes were isolated as catalytically active species from the stoichiometric reactions of propargylic alcohols (Scheme 7.27) [31]. The produced active species promoted the propargylation of furans vdth propargylic alcohols bearing not only a terminal alkyne moiety but also an internal alkyne moiety, indicating that this propargylation does not proceed via allenylidene complexes as key intermediates. 

In order to obtain some information on the reaction mechanism, the reaction of propargylic alcohol with acetone in the presence of a catalytic amount of 5a was monitored. The result indicated that the catalytic formation of the hexadienone proceeded via the initial isomerization of propargylic alcohol to dnnamaldehyde followed by aldol condensation between the produced aldehyde and acetone, and then dehydration. In fad, heating of propargylic alcohol in the presence of a catalytic amount of 5a gave only dnnamaldehyde (Scheme 7.41), and the separate reaction ofcinna-... 

Scheme 7.41). It seems to be reasonable to presume that the isomerization of propargylic alcohol to cinnamaldehyde proceeds via an intramolecular nucleophilic attack of coordinated water on an electropositive a-carbon of the allenylidene ligand (Scheme 7.42). Then, dicationicdiruthenium complexes work as Lewis acids to promote the aldol condensation between cinnamaldehyde and acetone. Thus, the dual catalytic activity of dicationic chalcogenolate-bridged diruthenium complexes is essential to promote the present novel reaction between propargylic alcohols and acetone. 

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