Oxidation propargylic

Clark et al. (113) extended this chemistry to the propargylic oxidation of al-kynes. These substrates proved to be less reactive than the corresponding alkenes, and generally require an excess of the oxidant to achieve satisfactory yields, Eq. 97. Enantioselectivities are modest, at best. 

Hu S, Hager LP (1998) Unusual Propargylic Oxidations Catalyzed by Chloroperoxidase. Biochem Biophys Res Commun 253 544... 

Propargylic oxidation. o,a -Dioxygenation is the normal pattern observed in oxidation of alkynes with t-butyl hydroperoxide catalyzed by selenium dioxide. The reactivity sequence is CHj = CH > CHj. Alkynes with one CH2 and one CH group afford cnynones as the major product. ... 

Cu catalyzed allylic or propargylic oxidation with t-butyl peresters (see 1st edition). 

Propargylic oxidation of the acyclic alkyne (5.126) can be achieved with moderate enantioselectivity. It is noteworthy that in this case, the quoted yield is based on the starting material (rather than being based on the perester).One drawback with this procedure is the very slow reaction rate. It has been discovered that the rate of the oxidation can be enhanced using phenylhydrazine as an additive, to aid in the reduction of Cu(II) to Cu(I), and Cu-PYBOX ligand (5.127) as catalyst. 

To a mixture of 100 ml of dry dichloromethane, 0.10 mol of propargyl alcohol and 0.11 mol of triethylamine was added a solution of 0.05 mol of Ph2PCl in 75 ml of dichloromethane in 3 min between -80 and -90°C. The cooling bath was removed, and when the temperature had reached 10°C, the reaction mixture was poured into a solution of 2.5 ml of 362 HCl in 100 ml of water. After vigorous shaking the lower layer was separated and the aqueous layer was extracted twice with 25-ml portions of dichloromethane. The combined solutions were washed twice with water, dried over magnesium sulfate and then concentrated in a water-pump vacuum, giving almost pure allenyl phosphine oxide as a white solid, m.p. 98-100 5, in almost 1002 yield. 

Aconitatc was obtained as a minor product in the carbonylation of propar-gyl alcohol[479]. However, in the two-step synthesis of methyl aconitate (536) from propargyl alcohol in 70% overall yield, the first step is the oxidative carbonylation under CO and air using Pdli and KI to giNe dimethyl hydro-xymethylbutenedioate (535), which is carbonylated further to give trimethyl aconitate (536) by u.sc of [Pd(Tu)4jl2 as a catalyst[480]. 

As an application of maleate formation, the carbonylation of silylated 3-butyn-l-ol affords the 7-butyrolactone 539[482], Oxidative carbonylation is possible via mercuration of alkynes and subsequent Lransmetallation with Pd(II) under a CO atmosphere. For example, chloromercuration of propargyl alcohol and treatment with PdCF (1 equiv.) under 1 atm of CO in THF produced the /3-chlorobutenolide 540 in 96% yield[483]. Dimethyl phenylinale-ate is obtained by the reaction of phenylacetylene, CO, PdCU, and HgCl2 in MeOH[484,485]. 

Acetylene is also protected as propargyl alcohol (300)[2H], which is depro-tected by hydrolysis with a base, or oxidation with MnOi and alkaline hydrolysis. Sometimes, propargyl alcohols are isomerized to enals. Propargyl alcohol (300) reacts with 3-chloropyridazine (301) and EtiNH to give 3-diethylami-noindolizine (303) in one step via the enal 302[2I2]. Similarly, propargyl alcohol reacts with 2-halopyridines and secondary amines. 2-Methyl-3-butyn-2-ol (304) is another masked acetylene, and is unmasked by treatment with KOH or NaOH in butanol[205,206,213-2l5] or in situ with a phase-transfer cata-lyst[2l6]. 

With two equivalents of an organomagnesium hahde, a Gtignard reagent is formed, capable of use in further syntheses (35,36). Cuprous salts cataly2e oxidative dimerization of propargyl alcohol to 2,4-hexadiyne-l,6-diol [3031-68-3] (37). 

The reactors were thick-waked stainless steel towers packed with a catalyst containing copper and bismuth oxides on a skiceous carrier. This was activated by formaldehyde and acetylene to give the copper acetyUde complex that functioned as the tme catalyst. Acetylene and an aqueous solution of formaldehyde were passed together through one or more reactors at about 90—100°C and an acetylene partial pressure of about 500—600 kPa (5—6 atm) with recycling as required. Yields of butynediol were over 90%, in addition to 4—5% propargyl alcohol. 

Isoxazole-5-carbaldehyde was prepared by the manganese dioxide oxidation of 5-hydroxymethylisoxazole (67T4697), the latter being formed from sodium fulminate and propargyl alcohol in greater than 90% yield. 

The procedure described is that of Wille and Saffer. Propiolaldehyde has also been prepared by the oxidation of propargyl alcohol using ammonium dichromate or manganese dioxide in 10% sulfuric acid. Propiolaldehyde has also been prepared by warming the dimethyl or diethyl acetal with dilute sulfuric acid. ... 

Compounds with triple bonds, i.e. acetylenic compounds, continue to receive attention. Patents have been filed for mixtures of propargyl alcohol with, for example, cellosolve + a phenol formaldehyde resin + tar bases heterocyclic nitrogen compounds + acetylenic + dialkylthiourea or a quaternary + antimony oxide . 

Giacomelli et al. constructed 3-propylisoxazole-5-yl-methanol via a [3-1-2] cycioaddition (Fig. 15) [158]. Nitrobutane was converted to nitrile oxide in the presence of 4-(4,6-dimethoxy [1,3,5]triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) and catalytic 4-dimethylaminopyridine (DMAP). Trityl chloride resin-bound propargyl alcohol was employed as the dipolarophile to trap the nitrile oxide, forming the cyclo adduct isoxazole ring under unusually mild conditions (i.e., microwave irradiation at 80 °C for five times 1 min). Disappearance of the starting material was monitored by FT-IR. 

A family of interesting polycychc systems 106 related to pyrrolidines was obtained in a one-pot double intermolecular 1,3-dipolar cycloaddition, irradiating derivatives of o-allyl-sahcylaldehydes with microwaves in toluene for 10 min in presence of the TEA salt of glycine esters [71]. A very similar approach was previously proposed by Bashiardes and co-workers to obtain a one-pot multicomponent synthesis of benzopyrano-pyrrolidines 107 and pyrrole products 108 (Scheme 37). The latter cycloadducts were obtained when o-propargylic benzaldehydes were utihzed instead of o-allyhc benzalde-hydes, followed by in situ oxidation [72]. 

R = Me, R = H) with cyclohexenol in the presence of F ion followed by NaOCl oxidation gave the tricyclic ether 61 in 65% yield (Scheme 9) [29]. The use of propargyl alcohol and propargyl thiol led, via the acetylenic oximes, to fused tetrahydrofuranoisoxazoles 62 a and 62 b, and tetrahydrothiopheno[3,4-c]isoxa-zole 62 c, respectively. Reaction of l-butyn-4-ol with 0-trimethylsilyl a-bro-moaldoxime 52e (R = R = Me) led to the tetrahydropyranoisoxazole 62 d. 

The homogeneous, anaerobic, oxidation of propargyl alcohol by cupric acetate in buffered pyridine solution is an example of a general reaction... 

The methanolic cupric bromide oxidation of propargyl alcohol to trans-BrCH-CBrCH20H (30%) and Br2C=CBrCH20H (18%) and, under other reaction conditions, Br2C-CBr-CH20H (93 %) follows simple second-order kinetics with a rate coefficient of 1.5 x 10 l.mole . sec at 64 °C. A mechanism of ligand-transfer in a 7t-complex is proposed. ... 

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