Synthesis of Acetylenic Alcohols

The first organometallic compounds we encountered were compounds of the type RC=CNa obtained by treatment of terminal alkynes with sodium amide in liquid ammonia (Seetion 9.5)  

These compounds are sources of the nucleophilic anion RC=C , and their reaction with primary alkyl halides provides an effective synthesis of alkynes (Section 9.6). The nucleophilicity of acetylide anions is also evident in their reactions with aldehydes and ketones, which are entirely analogous to those of Grignard and organofithium reagents. 

These reactions are normally carried out in liquid ammonia because that is the solvent in which the sodium salt of the alkyne is prepared. 

Acetylenic Grignard reagents of the type RC CMgBr are prepared, not from an acetylenic halide, but by an acid-base reaction in which a Grignard reagent abstracts a proton from a terminal alkyne. 

The corresponding acetylenic organolithium reagents are prepared by the reaction of terminal alkynes with methyUithium or butyllithiuna. 

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Synthesis of acetylenic alcohols (Section 14.8) Sodium acetylide and acetylenic Grignard reagents react with aldehydes and ketones to give alcohols of the type... 

Favorskii-Babayan synthesis. Synthesis of acetylenic alcohols from ketones and terminal acetylenes in the presence of anhydrous alkali. 

Asymmetric synthesis of acetylenic alcohols is possible by reduction of the corresponding ketones with lithium aluminium hydride complexed with sugar derivatives the optical yields are 4—1%. The trimethylether of the naturally occurring robustol (30), from the leaves of Grevillea robusta A. Cunn., has been synthesized in 55 % yield via cupric acetate oxidative cycliza-tion of the diacetylene (31). ... 

Using this hydrogenation as the final step simplifies the problem to a synthesis of this acetylenic alcohol. We know how to form carbon-carbon bonds next to triple bonds, and we have seen the formation of acetylenic alcohols (Section 9-7B). 

Metal- and alloy-containing membranes are currently applied mainly in ultrapure hydrogen production. Pilot plants with palladium alloy tubular membrane catalyst were used in Moscow for hydrogenation of acetylenic alcohols into ethylenic ones. In the Topchiev Institute of Petrochemical Synthesis, a laboratory-scale reactor of the same type was tested... 

The reactions involving the generation of acetylenic bonds or extension of unsaturated bonds are extremely useful in chemical synthesis of unsaturated alcohols, carboxylic acids, and poly-yne acetals [Eq. (47) 125]. For the preparation of essential fatty acids, extension of propargyl units, followed by hydrogenation in the presence of Lindlar catalyst, will result in the efficient formation of ail c/x-type fatty acids [Eqs. (48) and (49) 126,127]. 

A brand-new methodology for synthesizing glycals from noncarbohydrate precursors, one based on cyclization of acetylenic alcohols, has emerged from the field of metalorganics. Molybdenum pentacarbonyl-trialkylamine complexes have been found to efficiently catalyze cyclization of l-alkyn-4-ols to substituted dihydrofurans [233,234]. This same transformation has been successfully carried out on asymmetrically substituted alcohols the furanoid glycals 132, 134, and 135 (O Scheme 45) so obtained have in turn been used as intermediates in the synthesis of nucleosides [235]. 

Depending on the catalytic species, palladium-catalyzed mono- and dicarbonyl-ation of alkynes may be achieved. Monocarbonylation of acetylenic alcohols in the presence of thiourea is an elegant route to a-methylene-7-butyrolactone 202, the structure of which is widely distributed in certain natural products98,99). The synthesis of a vernolepine derivative (203) has been attempted by this method 100l Pro-... 

Based on the elimination reaction, Pericas and coauthors" have developed a method for the synthesis of acetylenic ethers, derived from tertiary alcohols with a bulky alkyl group such as r -butyl and adamantyl. The key step in this synthesis is the dehydrobromination of l-bromo-2-alkoxyethylene 67 with sodium amide in ammonia or lithium diisopropylamide in a hexane-THF solution (equation 39)". ... 

Pale, P. and Chnche, J. 2000. Silver-catalyzed cyclization of acetylenic alcohols Synthesis of functionalized 2-methylene-oxolanes. Eur. J. Org. Chem. 2000 1019-1025. 

In the synthesis of propargylic alcohols, we saw the reaction of an alkynyl nucleophile (either the anion RC=CNa or the Grignard RC CMgBr, both prepared from the alkyne RC CH) with a carbonyl electrophile to give an alcohol product. Such acetylide-type nucleophiles will undergo Sn2 reactions with alkyl halides to give more substituted alkyne products. With this two-step sequence (deprotonation followed by alkylation), acetylene can be converted to a terminal alkyne, and a terminal alkyne can be converted to an internal alkyne. Because acetylide anions are strong bases, the alkyl halide used must be methyl or 1° otherwise, the E2 elimination is favored over the Sn2 substitution mechanism. 

In a protocol, similar to synthesis of homopropargylic alcohol, allenylborane derived from 3-(tert-butyldimethylsilyl)-l-(trimethylsilyl)-l-propyne affords, on condensation with conjugated acetylenic aldehydes (R = -BuC=C and Ph-C=C), the diynic alcohols with high diastereoselectivities. The SR/RS RR/SS ratio is >98 2 (Scheme 6.19) [1] with both aldehydes. 

A catalytic synthesis of a-methylenelactones by the pressure carbonylation of acetylenic alcohols, which gives a useful trans junction, has been described. The... 

In a paper discussing strategies for the synthesis of the macrocyclic diterpene jatrophone, brief comment is made disclosing that chromous sulphate can cleanly effect the stereospecific reduction of a-oxoacetylenes to the corresponding E-enone, analogous to the reduction of acetylenic alcohols." ... 

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