Propargylic alcohols alkylation

Allylic metals, in propargylic alcohol alkylation, 11, 129 ir-Allylic palladium complexes, and carbocyclization, 11, 426 Allylic position, alkenes, dienes, polyenes, metallation, 9, 6 Allylic selenides, [2,3]sigmatropic rearrangement, 9, 481 Allylic substitution reactions for C-N bonds via amination... 

The alkynylation of estrone methyl ether with the lithium, sodium and potassium derivatives of propargyl alcohol, 3-butyn-l-ol, and propargyl aldehyde diethyl acetal in pyridine and dioxane has been studied by Miller. Every combination of alkali metal and alkyne tried, but one, gives the 17a-alkylated products (65a), (65c) and (65d). The exception is alkynylation with the potassium derivative of propargyl aldehyde diethyl acetal in pyridine at room temperature, which produces a mixture of epimeric 17-(3, 3 -diethoxy-T-propynyl) derivatives. The rate of alkynylation of estrone methyl ether depends on the structure of the alkyne and proceeds in the order propar-gylaldehyde diethyl acetal > 3-butyn-l-ol > propargyl alcohol. The reactivity of the alkali metal salts is in the order potassium > sodium > lithium. 

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]. 

With 1-2 mol% of 64b, racemic mixtures of aryl-alkyl carbinols 86 [103], propargylic [104] and allylic alcohol [105] 88 and 87, respectively, were resolved (Fig. 43). The best selectivities were attained for aryl-alkyl-carbinols 86, where the unreacted isomer was obtained with excellent ees after 55% conversion, while propargyl alcohols 88 required clearly higher conversions for high ees in the remaining starting material [106]. 

When re-alkyl ethynyl ketones were tested as the substrate of LBADH, the preferred stereochemistry and optical purity of the resulting propargylic alcohol were dependent upon the size of the alkyl group (Figure 7.26) [71]. 

Reaction of propargylic alcohols 229 with alkyl diazoacetates entails competition between O/H insertion and cyclopropenation. 

The Cu(I)-catalyzed cyclization for the formation of ethyl ( )-tetrahydro-4-methylene-2-phenyl-3-(phenylsulfonyl)furan-3-carboxylate 82 has been accomplished starting from propargyl alcohol and ethyl 2-phenylsulfonyl cinnamate. Upon treatment with Pd(0) and phenylvinyl zinc chloride as shown in the following scheme, the methylenetetrahydrofuran 82 can be converted to a 2,3,4-trisubstituted 2,5-dihydrofuran. In this manner, a number of substituents (aryl, vinyl and alkyl) can be introduced to C4 <00EJO1711>. Moderate yields of 2-(a-substituted N-tosyIaminomethyl)-2,5-dihydrofurans can be realized when N-tosylimines are treated with a 4-hydroxy-cis-butenyl arsonium salt or a sulfonium salt in the presence of KOH in acetonitrile. The mechanism is believed to involve a new ylide cyclization process <00T2967>. 

Organocopper-Mediated Alkylation of Propargyl Alcohol Derivatives... 

Acid-catalyzed hydrolysis of S-allenylsulfinylamines 425, easily accessible from propargyl alcohols (cf. Scheme 7.8), provides the alkynes 427 (Scheme 7.56) [108, 109]. This transformation is postulated to proceed via the intermediate allenic sulfinic acid 426. However, in some cases with R1 = R2 = alkyl, more complicated products are formed instead of simple alkynes 427 [372]. 

These reactions are thought to proceed by initial formation of the lithio propargylic alcohol adduct, which undergoes a reversible Brook rearrangement (Eq. 9.14). The resulting propargyllithium species can equilibrate with the allenyl isomer and subsequent reaction with the alkyl iodide electrophile takes place at the allenic site. An intramolecular version of this alkylation reaction leads to cyclic allenylidene products (Eq. 9.15). 

In this review, we will initially describe the role of Bi(III) salts as activators for a-donors. In particular, benzyl and propargyl alcohols will be presented as mild electrophiles in alkylation reactions. In addition, we will show the versatility of Bi(III) salts and give a short overview of Bi(III)-catalyzed hydroarylation and hydroalkynylation reactions [23]. Besides our own results, which primarily focus... 

Scheme 27 Diastereoselective alkylation of propargyl alcohols with silyl enol ethers, allyl silanes and electron-rich arenes...

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,... 

As described in the previous section, the ruthenium-catalyzed propargylic alkylation of propargylic alcohols with acetone afforded the corresponding alkylated products in high yields with complete selectivity [27]. When an optically active 1 -phenyl-2 -propyn-1 -ol was treated with acetone at room temperature in the presence of la as catalyst, only a racemic alkylated product was obtained [27]. This result... 

Propargyl alcohol can be specifically alkylated at the triple bond by adding one equivalent of a... 

C-A]k vlation of Propargyl Alcohol with a Higher Alkyl Bromide... 

Stoichiometric Propargylic Alkylation of Propargylic Alcohols Assisted by Cobalt... 

In 1993, Nicholas and his co-worker developed the stereospecific propargylic alkylation of chiral propargylic alcohols 30 with enol silanes 31 by using a stoichiometric amount of [Co2(CO)5L] (L = phosphite), but separation procedures of the produced diastereoisomers are necessary twice on the way to obtain the compounds specifically alkylated at the propargylic position 32 (Scheme 5). In 2001, Montana and his co-worker reported the diastereo-selective Nicholas alkylation of propargylic acetal complexes 33 bearing a chiral auxiliary with various enol silanes 34 (Equation (14)). A high diastereoselectivity is observed, but unfortunately, only low to moderate enantioselec-tivities are achieved in all cases. 

Thus, a synthetic cycle for the formation of enantiomerically pure propargylic alkylated compounds from an achiral propargylic alcohol has been accomplished by starting from the ruthenium-BINAP complex 66 (Scheme 12). This stepwise reaction provides the first synthetic approach to highly enantioselective propargylic substitution reactions. 

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