Propargylic alcohols methods

Pyrrole derivatives are prepared by the coupling and annulation of o-iodoa-nilines with internal alkynes[291]. The 4-amino-5-iodopyrimidine 428 reacts with the TMS-substituted propargyl alcohol 429 to form the heterocondensed pyrrole 430, and the TMS is removed[292]. Similarly, the tryptophane 434 is obtained by the reaction of o-iodoaniline (431) with the internal alkyne 432 and deprotection of the coupled product 433(293]. As an alternative method, the 2,3-disubstituted indole 436 is obtained directly by the coupling of the o-alky-nyltrifluoroacetanilide 435 with aryl and alkenyl halides or triflates(294]. 

Specifications and Analytical Methods. The commercial aqueous solution is specified as 34% minimum butynediol, as determined by bromination or refractive index. Propargyl alcohol is limited to 0.2% and formaldehyde to 0.7%. 

Sc(OTf)3, AcOH, p-nitrobenzoic anhydride or Sc(OTf)3, AC2O, 66- >95% yield. The lower yields are obtained with allylic alcohols propargylic alcohols give higher yields. Phenols are effectively acylated with this catalyst, but at a much slower rate than simple aliphatic alco-hols. The method was shown to be superior to most other methods for macrolactonization with minimum diolide formation. 

Previous syntheses of terminal alkynes from aldehydes employed Wittig methodology with phosphonium ylides and phosphonates. 6 7 The DuPont procedure circumvents the use of phosphorus compounds by using lithiated dichloromethane as the source of the terminal carbon. The intermediate lithioalkyne 4 can be quenched with water to provide the terminal alkyne or with various electrophiles, as in the present case, to yield propargylic alcohols, alkynylsilanes, or internal alkynes. Enantioenriched terminal alkynylcarbinols can also be prepared from allylic alcohols by Sharpless epoxidation and subsequent basic elimination of the derived chloro- or bromomethyl epoxide (eq 5). A related method entails Sharpless asymmetric dihydroxylation of an allylic chloride and base treatment of the acetonide derivative.8 In these approaches the product and starting material contain the same number of carbons. 

Furthermore, Jana et al. developed a FeCl3-catalyzed C3-selective Friedel-Crafts alkylation of indoles, using allylic, benzylic, and propargylic alcohols in nitromethane as solvent at room temperature. This method can also be used for the alkylation of pyrrole (Scheme 4). The reactions were complete within 2-3 h without the need of an inert gas atmosphere leading to the C-3-substitution product exclusively in moderate to good yields [20]. 

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 above two consecutive transformations provide straightforward access from propargyl alcohols to cyclopropene derivatives with an a- or /1-hydroxy group. This simple method is complementary to the access to 3-hydroxymethylcyclopropenes, via Rh2(OAc)4 catalyzed addition of diazoacetate to alkynes followed by reduction of the ester group, a route that is restricted to the access of primary cyclopropenyl alcohols [57], and is an alternative to the use of 2,2-dibromo-l-chlorocyclopropane via cyclopropenyl Uthium. 

Recently, reaction of a propargylic alcohol with diethyl chlorophos-phite in the presence of a tertiary amine has been found to be a facile method for the direct preparation of allenicphosphonates (Equation 4.37).167... 

Selective oxidation of allylic alcohols.1 This zircononcene complex when used in catalytic amount can effect an Oppenauer-type oxidation of alcohols, including allylic ones, in the presence of a hydrogen acceptor, usually benzaldehyde or cyclohexanone. This system oxidizes primary alcohols selectively in the presence of secondary ones. Thus primary allylic alcohols are oxidized to the enals with retention of the configuration of the double bond in 75-95% yield. The method is not useful for oxidation of propargylic alcohols. 

The use of chlorodiphenylphosphine to induce a [2,3]-sigmatropic rearrangement of enediynyl propargylic alcohols is one of the first synthetic methods adopted for the preparation of enyne-allenes. For instance, treatment of 108 with chlorodiphenylphosphine and triethylamine at -78 to 0°C afforded the enyne-allenylphosphine oxide 109 in 63% isolated yield (Scheme 20.23) [9]. Thermolysis of 109 at 37 °C in the presence of 1,4-CHD generated the biradical 110, leading to 111 and combina-... 

Despite the rich chemistry of 45 [18], the only method for accessing this compound is the oxidation of the corresponding alcohol derived from 2-methyl-2-propen-l-ol or other sources, which can be obtained through multi-step operations. In contrast to the known methods, 45 can be readily derived from 44 and 50 by a simple one-pot operation. Since the propargylic alcohol 50 a is readily accessed from a ketone or aldehyde, realization of the transformation of 50 to 45 through a one-pot procedure provides a novel method for carbonyl olefmation of ketones or aldehydes. 

Shortly after this work, Shibasaki and coworkers developed a useful method for the substitution of allyl and propargyl alcohols using Bi(OTf)3 [61]. Various amines such as tosylamine, carbamates, amides and cinnamylamide yielded allyl and propargyl amides 27a-h and 25g-h in excellent yields (Scheme 21). The addition of KPF6 was... 

This overview impressively demonstrates that Bi(III) salts are not only versatile Lewis acid catalysts for the activation of cr-donors, including benzyl and propargyl alcohols, but also efficient catalysts for the activation of Ji-donors such as styrenes or alkynes. In recent years, various environmentally benign bismuth-catalyzed methods have been developed for the alkylation of arenes, heteroarenes,... 

The present method is practical and efficient as it employs readily available enantioenriched propargylic alcohols as precursors to the allenylindium reagents. With achiral aldehydes the diastereoselectivity is high for branched aldehydes, moderate for unbranched aldehydes, and low for benzaldehyde (Table I). With cHral a-methyl aldehydes the additions proceed under effective reagent control to afford anti adducts of high ee and with excellent diastereoselectivity (eq. 1 and 2). Comparable results were obtained with 3 1 dimethyl sulfoxide-tetrahydrofuran (DMSO-THF) as the solvent. 

Catalytic transformations of alkynes have recently led to tremendous developments of synthetic methods with useful applications in the synthesis of natural products and molecular materials. Among them, the selective activations of terminal alkynes and propargylic alcohols via vinylidene- and allenylidene-metal intermediates play an important role, and have opened new catalytic routes toward anti-Markovnikov additions to terminal alkynes, carbocyclizations or propargylations, in parallel to the production of new types of molecular catalysts. 

Although the reaction of alkali acetylides with oxirane proceeds slowly in liquid ammonia 15], it is an excellent method for preparing "homo-propargylic alcohols in quantities of 1 mol or more [2). Since oxirane is very volatile, considerable losses could occur if it is allowed to be swept along with the escaping ammonia vapour. One solution is to carry out the reaction under reflux, using a special condenser filled with dry ice and acetone. This would require regular addition of dry ice over a period of at least 12 h. It is much simpler to mix the acetylide... 

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