Propargyl alcohol stoichiometric reaction

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]. 

Stoichiometric reactions of the isolated allenylidene complexes, which can be almost quantitatively prepared by treatment of la vdth propargylic alcohols vdth various nucleophiles, except thiols, gave the corresponding propargylic substituted products [15, 21] (Scheme 7.11). Here, the addition of either NH4CI or another terminal... 

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 Section 6.3.6, it was emphasized that C02 and secondary amines could add to terminal alkynes in the presence of ruthenium catalysts to afford carbamates. Under comparable conditions (393-413 K, 5 MPa Ru-catalysts), primary amines will afford symmetrical disubstituted ureas in moderate yield [131]. It is worth noting that although the final urea does not contain the starting alkyne, its catalytic formation requires, besides the Ru-catalyst, the presence of a stoichiometric amount of a 1-alkyne (e.g., a propargylic alcohol). A possible mechanism (Scheme 6.32) for this catalytic reaction may involve activation of the alkyne at the metal center, a nucleophilic addition of the carbamate to the activated alkyne to produce... 

The new reactivity mode for the in-situ generation of metal alkynylides was exploited in addition reactions to aldehydes. Stoichiometric quantities of Zn(OTf)2 and NEt3 or Hiinig s base effected deprotonation of a number of alkynes which underwent smooth addition to various aldehydes to furnish the corresponding propargylic alcohols (Eq. 5) [13]. Subsequent studies revealed that apart from Zn(OTf)2 other zinc sources such as ZnCl2 and ZnC03 could be used in this reaction (Eq. 6) [14]. 

Shortly after this initial success, the isolation of optically active propargyl alcohols in up to 99 % ee could be effected by the use of stoichiometric amounts of (-i-)-N-methyl ephedrine (1) (Eq. 7). A wide range of aldehydes and acetylenes participate in this addition reaction affording the product alcohols in generally high yields, especially when using aldehydes that are Ca-branched (Eq. 8). Of additional importance, the reaction can be performed with functionalized alkynes, which... 

Jiang has expanded the Carreira method of alkyne addition to aldehydes to include other ligands and Zn(II) salts (Eq. 13) [17]. Thus use of stoichiometric quantities of Zn(II) difluoromethane sulfonate salt and (lS,2S)-3-(tert-butyldi-methylsilyloxy)-2-N,N-dimethylamino-l-(p-nitrophenyl)propane-l-ol (3) in the addition reaction can afford propargylic alcohols in high ee. Difluoromethanesul-fonic acid is prepared from 3,3,4-,4-tetrafluoro[1.2]oxathietane the amino alcohol has been used in the synthesis of chloramphenicol and is also readily accessible. Application of a combination of this same amino alcohol ligand with Zn(OTf)2 has also been shown to afford products in high yield and ee in addition reactions (Eq. 14) [18]. 

We have tested AuC13 and BF3 etherate in comparison. Merely 0.3 % of the gold catalyst is sufficient to obtain 96 % isolated yield of the mono-substitution product 17 [5]. The reaction is performed at room temperature with two equivalents of propargylic alcohol 16, thus demonstrating both outstanding reactivity and remarkable selectivity for the mono-substitution. Application of the classical Friedel-Crafts catalyst BF3 etherate in stoichiometric amounts or in excess necessitates cooling, and results in rather clean formation of the sterically crowded bis-substi-tution product 18 as a mixture of the two diastereoisomers in the ratio 1 1. 

Stoichiometric reactions of isolated allenylidenes such as [Cp RuCl(p-SMe)2Ru -( -( -( ( I l iPh Cp ] [BF4] or [Cp RuCl(p-SMe)2Ru =C=C=C(/z-MeCf,H4 >2 Cp ] [BF4], prepared by treatment of 105a with propargylic alcohols in the presence of NH4BF4, gave the corresponding propargylic substituted products confirming the involvement of allenylidene-ruthenium intermediates in these catalytic... 

A most useful application of this process is the invention of a highly atom economic synthesis of pyridines, wherein the only stoichiometric by-product is water. Cycloisomerization of diyne 22 followed by reaction with hydroxylamine provides the tricyclic pyridine 23 with only water as the stoichiometric by-produd (Equation 1.26) [24]. The Ru-catalyzed cycloisomerization of propargyl alcohols can also generate six membered rings, which then form tetrahydroisoquinolines as shown in Equation 1.27. 

Hydrocarboxylation can also be used in the synthesis of heterocycles if the heterofunction is introduced at an appropriate position within the substrate. Thus, preparation of 2,4-disub-stituted 2-buten-4-olides can be achieved via stoichiometric transformation of a protected optically active propargyl alcohol without loss of optical activity30. Sequential treatment with zirconocene chloride hydride (Schwartz s reagent), carbon monoxide, and iodine gives a 55% yield of (S)-2-ethyl-4-isobutyl-2-buten-4-olide30. This reaction resembles the intramolecular hydrocarboxylation of allylic alcohols. 

The homobimetallic, ethylene-ruthenium complex 15, which contains three chloro bridges, was readily obtained from the reaction of [RuCl2(/ -cymene)]2 with 1 atm of ethylene [34]. In 2009, Demonceau and Delaude [34] showed that complex 15 could be a useful precursor to allow subsequent access to the diruthenium vinylidene complex 16, allenylidene complex 17, and indenylidene complex 18 (Scheme 14.8). Upon reaction with propargylic alcohol, complex 15 afforded vinylidene complex 16, which converted into the allenylidene complex 17 in the presence of molecular sieves [34]. As shown in the acid-promoted intramolecular rearrangement of mononuclear ruthenium allenylidene complexes [19, 20, 32], the addition of a stoichiometric amount of TsOH to complex 17 at -50 °C led to the indenylidene binuclear complex 18 [34]. Complex 18 has been well... 

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