Ethynyl-0-ionol

Acetylene passed slowly into a soln. of Li-naphthalene in tetrahydrofuran to give Li-acetylide quantitatively, then j -ionone added ethynyl-/ -ionol. Y 90%. - This is a convenient procedure for the ethynylation of a,y -unsatd. ketones under very mild conditions. F. e. s. K. Suga, S. Watanabe, and K. Takahashi, Chem. Ind. 1967, 1748 Can. J. Chem. 46, 3041 (1968) 2-acetylene-1,4-diols s. Chem. Ind. 1968, 1489. 

In another study, Bienayme [65] obtained retinal in three steps from P-ionone, involving a Pd-catalyzed rearrangement of a mixed carbonate, derived from ethynyl-retro-ionol. 

Thus, the (3-ionone was smoothly deconjugated and ethynylated to give ethynyl-retro-ionol as a mixture of E/Z stereoisomers. Formation of the carbonate and its Pd-catalyzed rearrangement produced straightforward a mixture of aldehydes and a allene compound. After silica-gel chromatography, the allenic-aldehyde was conjugated with a catalytic amount of HBr in acetone. Retinal was obtained as a mixture of E and Z isomers (75/25), which could be converted into the all E isomer by simple equilibration, Fig. (33). 

A similar route was patented by Ancel and Meilland [66], The ethynyl-retro-ionol was acetylated (Ac20-DMAP-Et3N) and this propargylic acetate was reacted with methyl butadiene acetate in the presence of BF3-Et20. The allenic-retinal, obtained in 61% yield was isomerised in retinal by HBr in acetone (yield 50%), Fig. (34). 

Ethynyl-p-ionol Dimethyl sulfoxide Ethyl bromide Copper chloride Alumina (Alcoa F-20)... 

Ethynyl-beta-ionol has been converted to its lower alkyl ethers by use of alkyl sulfates, using an aprotic solvent such as dimethyl sulfoxide (DMSO) or dimethyl formamide (DMF) in a basic medium, using a base such as NaOH or Ba(OH)2.The yields around 90%. In one example, the following components were used ethynyl-p-ionol 65.7 g (0.3 mole) ethyl sulfate 138.6 g (0.9 mole) sodium hydroxide (97%) pellets 37.0 g (0.9 mole) dimethyl sulfoxide 200 ml. 

The reaction of acetylenes with a,/3-unsaturated ketones to give the corresponding acetylenic carbinols can be carried out conveniently with naphthalene-lithium.5 An example is the reaction of /3-ionone with lithium acetylide to give ethynyl-/3-ionol. 

There are numerous applications of acetylides in the preparation of a-hydroxyalkynes, the following being illustrative of the general procedures. For the preparation of ethynyl-p-ionol (2), a key carotenoid building block, P-ionone (i) is condensed with ethynyl magnesium bromide (4) in ether [2], or with lithium acetylide (5) in liquid ammonia [7], in 87% and 75% yields, respectively (Scheme 1). The lower yield obtained with lithium acetylide probably reflects the propensity of P-ionone (3) to enolize under the reaction conditions. 

The units 49 and 50 used in the synthesis of vitamin A are also used in many ways in carotenoid syntheses and are produced industrially in large scale. p-Ionone (17) can be converted into vinyl-p-ionol (51) by ethynylation to 52 and partial hydrogenation [42]. This conversion is also achieved in one step by 1,2-addition of vinylmagnesium chloride 55[43]. The two routes are, in principle, equivalent, and which one is used in practice is decided by conditions on site. In this example, the main considerations are the availability of acetylene (4) and vinyl chloride, operating experience, and permits for handling these materials. The Ci5-phosphonium salt 49 is formed directly from 51 by the action of triphenylphosphine and acid [44,45]. A step involving labile P-ionylidene-ethyl halide is thus avoided. Crystalline (lE,9E)-49 is obtained in excellent yield by reaction of 51 with triphenylphosphine and sulphuric acid in isopropanol/heptane [46]. 

The reaction of -ionone with vinylmagnesium chloride gives vinyl-)S-ionol directly, which could also be accessed via ethynylation and partial hydrogenation. The allyl alcohol is converted immediately with triphenylphosphane under acidic conditions to the corresponding ) -ionylideneth)dtriphenylphosphonium salt. [55]... 

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