Alcohols with acetylides

Ketones react with acetylide ion (Section 8.7) to give alcohols. For example, the reaction of sodium acetylide with 2-butauone yields 3-methy -l-pentyn-3-ol ... 

The addition of lithium acetylides can also be carried out enantioselectively in the presence of 22-24 ]vjucieophiiic addition of the unsubstituted lithium acetylide led to the alkynyl alcohol with lower enantioselectivity than the addition ofsilyl-substituted acetylides. The trimethylsilyl substituted acetylides gave the best results. 

C. In liquid ammonia the reaction with epoxybutane would be slower than in the case of oxiiane. However, the most important effect of the replacement of the NH3 by DMSO is, that the specific solvatarion of the metal ion by DMSO facilitates attack of the acetylide on the ring. The presence of this solvent does not give rise to difficulties during the aqueous woik-up of alcohols with a longer carbon chain (compare exp. 23). 

The propargylic alcohol group may be exploited as an allylic alcohol precursor (Eq. 6A.2) and may be generated by nucleophilic addition to an electrophile [25] or by addition of a formaldehyde equivalent to a preexisting terminal acetylene group [26], Once in place, reduction of the propargylic alcohol with lithium aluminum hydride or, preferably, with sodium bis(2-methoxyethoxy)aluminum hydride (Red-Al) [27] will produce the trans allylic alcohol. Alternately, catalytic reduction over Lindlar catalyst can be used to obtain the cis allylic alcohol [28]. The addition of other lithium acetylides to ketones produces chiral secondary alcohols, which also can be reduced by the preceding methods to the cis or trans allylic alcohols. Additional synthetic approaches to allylic alcohols may be found in the various references cited in this chapter. 

The main idea of these techniques lies in the interaction of the active hydrogen atom of the alcohols with the anions of metal hydrides, alkyls, acetylides, nitrides, amides, dialkylamides, bis(trialkylsilyl)amides, sulfides, etc., with formation of compounds where an H atom is bonded by a strong covalent bond (usually gaseous HX). Alkaline hydrides of the most active metals (K, Rb, Cs) are used to slow down the reaction of metal with alcohol sometimes it is necessary simply to avoid explosion. 

Other unsaturated substrates arylated by various diaryl iodonium salts included butenone, acrylic acid, methyl acrylate and acrylonitrile [46]. Allyl alcohols with diaryliodonium bromides and palladium catalysis were arylated with concomitant oxidation for example, from oc-methylallyl alcohol, aldehydes of the general formula ArCH2CH(Me)CHO were formed [47]. Copper acetylide [48] and phenyl-acetylene [49] were also arylated, with palladium catalysis. 

An acetylide adds to formaldehyde (H2C = 0) to give (after the protonation step) a primary alcohol with one more carbon atom than there was in the acetylide. 

Ketone functions on imidazole can be reduced to secondary alcohols by sodium borohydride, and converted into tertiary alcohols with lithium acetylides or Grignard reagents <88CPB22, 88H(27)457>. They form the usual carbonyl derivatives (e.g., oximes <82UC(B)1027>, and can be chain extended by aldol condensations <91JCS(P1)2691, 94H(38)503>. 

LAPIS INFERNALIS (7761-88-8) A powerful oxidizer. Forms friction- and shock-sensitive compounds with many materials, including acetylene, anhydrous ammonia (produces compounds that are explosive when dry), 1,3-butadiyne, buten-3-yne, calcium carbide, dicopper acetylide. Contact with hydrogen peroxide causes violent decomposition to oxygen gas. Violent reaction with chlorine trifluoride, metal powders, nitrous acid, phosphonium iodide, red or yellow phosphorus, sulfur. Incompatible with acetylides, acrylonitrile, alcohols, alkalis, ammonium hydroxide, arsenic, arsenites, bromides, carbonates, carbon materials, chlorides, chlorosulfonic acid, cocaine chloride, hypophosphites, iodides, iodoform, magnesium, methyl acetylene, phosphates, phosphine, salts of antimony or iron, sodium salicylate, tannic acid, tartrates, thiocyanates. Attacks chemically active metals and some plastics, rubber, and coatings. 

The reported synthesis for (5Z,9Z)-14-methylpentadeca-5,9-dienoic acid (14) started with commercially available 4-methylpentan-l-ol, which upon reaction with phosphorous tribromide afforded l-bromo-4-methylpentane [52], Commercially available pent-4-yn-l-ol was also protected as the tetrahydropyranyl ether as shown in Fig. (18). Formation of the lithium acetylide with n-BuLi in THF and subsequent addition of 1-bromo-4-methylpentane in hexamethylphosphoric acid triamide resulted in the isolation of the tetrahydropyranyl protected 9-methyldec-4-yn-l-ol. Hydrogenation of the alkyne with Lindlar s catalyst and quinoline in dry hexane afforded the cis hydropyranyl-protected 9-methyldec-4-en-l-ol. Deprotection of the alcohol with />-toluenesulfonic acid afforded (Z)-9-methyldec-4-en-l-ol. Pyridinium chlorochromate oxidation of the alcohol resulted in the isolation of the labile (Z)-9-methyldec-4-enal. Final Wittig reaction with (4-carboxybutyl) triphenylphosphonium bromide in THF/DMSO resulted in the desired (5Z,9Z)-14-methylpentadeca-5,9-dienoic acid (14). 

Brinkmeyer and Kapoor have now found that acetylenic ketones, RC= CCOR, are reduced by LiAlH4 and 1 at — 78° with the highest enantiomeric selectivity observed to date. Thus CH3Ce CCOCH2CH(CH3)2 is reduced to the corresponding (R)-alcohol with an enantiomeric excess of 827 . Similar asymmetric reductions were observed with seven other ketones of this type. Propargylic ketones are readily available by reaction of lithium acetylides with aldehydes followed by Jones oxidation of the propargylic alcohols. 

With the first three chiral auxiliaries, 8a-c, low to medium e.e.s of 7 were obtained, far from values needed to make the process operate on a large scale. Somewhat higher enantioselectivities were obtained when the reaction was performed at —40°C with an N-para-methoxybenzoyl (PMB)-protected substrate 9 (Scheme 13.3). Even more important for the research concept than just enhancement of e.e.s were the observations made in these experiments. First, 2 mol of the acetylide and 2 mol of the chiral auxiliary were needed for complete ketone alkynylation. Second, pyrolidino-ephedrine 8d proved to be the best auxiliary amino-alcohol. With this auxiliary, an e.e. of over 98% was achieved, with complete conversion of the ketone, but only when the acetylide-alkoxide solution was first warmed to 0°C then cooled down to —40°C before addition of the ketone 9 (Scheme 13.3). 

An enantioselective 1,2-addition of zinc acetylide to aryl aldehydes employing a catalytic amount of chiral BINOL ligand in combination with Ti(0/-Pr)4 is high yielding and allows as3mi-metric construction of chiral propargylic alcohols with excellent... 

Formation of alkyne dimers with a GO inserted was observed in the thermal reactions of Fe3(GO)i2 with isopropenyl-acetylene two isomeric open clusters 3a and 3b were isolated and characterized by X-ray diffraction. In contrast, the thermal reactions of internal propargylic alcohols with Fe3(GO)i2 led to pentanuclear acetylide derivatives, obtained upon elimination of aldehydes or chetones from the alkynes (Figure 1). ... 

ButinedioM. 4 is a cr> stalline compoiuid melting at 68 C and boiling at 125 127 C at 2 mru. It can also iDe produced by heating propargjd alcohol with. formaIdeli de in the presence of the acetylide catalysts described abo e ... 

Sodium acetylide and acetylenic Grignard reagents react with aldehydes and ketones to give alcohols of the type... 

The interaction of (10) with vinylmagnesiiim chloride yields, after hydrolysis of the ketal group, 46% of the 3a-vinyl-l7-ketone (11b) and 7% of the 3j5-vinyl-17-ketone (12b). Ethynylation of (10) with potassium acetylide in dimethylformamide or with acetylene and potassium t-amyloxide in t-amyl alcohol-ether gives only the 3a-ethynyl derivative (11c) in 63% and 74% yields, respectively. ... 

---