Alkynolates synthesis

It has been noted that the synthesis of pyrroles from ketoximes and acetylene in some case leads to tertiary a-acetylenic alcohols [4,5,7], It indicates a possibility of oxime involvement into the Favorsky alkynol synthesis. The conditions of acetylenic alcohols formation from ketoximes and acetylene have been investigated on the example of the reaction between cyclohexanone oxime and acetylene (Scheme 1.160) [175]. 

Addition of a hydroxy group to alkynes to form enol ethers is possible with Pd(II). Enol ether formation and its hydrolysis mean the hydration of alkynes to ketones. The 5-hydroxyalkyne 249 was converted into the cyclic enol ether 250[124], Stereoselective enol ether formation was applied to the synthesis of prostacyclin[131]. Treatment of the 4-alkynol 251 with a stoichiometric amount of PdCl2, followed by hydrogenolysis with formic acid, gives the cyclic enol ether 253. Alkoxypalladation to give 252 is trans addition, because the Z E ratio of the alkene 253 was 33 1. 

The palladium-catalyzed reaction of o-iodoanilides with terminal acetylenic carbinols provides a facile route to the synthesis of quinolines using readily available starting materials (93TL1625). When o-iodoanilide 126 was stirred with acetylenic carbinol 127 in the presence of bis-triphenyl phosphine palladium(ll) chloride in triethylamine at room temperature for 24 h, the substituted alkynol 128 was obtained in 65% yield. On cyclization of 128 with sodium ethoxide in ethanol, 2-substituted quinoline 129 was obtained in excellent yield. 

Rearrangement of acetylenic sulphenates to the allenic sulphoxides 151 was discovered when the synthesis of propargylic ester of trichloromethanesulphenic acid 152 was attempted (equation 86). This reaction is of general scope and gives very good yields of allenic sulphoxides (Table 14) from structurally diverse cohols and various sulphenyl chlorides Reaction of alkynols 153 with benzenesulphenyl chloride in the presence... 

Substituting the benzene ring with a double bond, Pd-catalyzed intramolecular alkoxylation of alkyne 122 also proceeded via an alkenyl palladium complex to form furan 123 instead of a benzofurans [99, 100]. In addition, 3-hydroxyalkylbenzo[fc]furans was prepared by Bishop et al via a Pd-catalyzed heteroannulation of silyl-protected alkynols with 2-iodophenol in a fashion akin to the Larock indole synthesis, [101]. 

Unsaturated lactones can be obtained from alkynols and according to the substrate and/or the catalyst as well as to the reaction conditions, the double bond can be endo- or exocyclic. Thus, we will distinguish the two modes of synthesis. 

E. Alcazar, J. M. Pletcher, and F. E. McDonald, Synthesis of seven-membered ring glycals via endo-selective alkynol cyclo-isomerization, Org. Lett., 6 (2004) 3877-3880. 

McDonald et al. applied their dihydropyran formation to the oligosaccharide synthesis featuring reiterative alkynol cycloisomerization [19c-f]. Dihydropyran 49 was prepared by the method described above and then NIS-promoted glycosyla-tion with the acyclic alkynol 50 followed by Ph3SnH-promoted dehalogenation and... 

Acetylenic precursors employed in the syntheses of sugars may be divided into three groups (a) aldehydes (usually in the form of acetals), (b) alkyl alkynyl ethers, and (c) alkynols or alkynediols. Some of them are commercially available (for example, 2-butyne-l,4-diol), and others are prepared by Grignard-type reactions between 1-alkynylmag-nesium halides or lithium alkynes and suitable aldehydes, ketones, or epoxides. In this way, the synthesis of substrates having the desired number of carbon atoms, as well as the necessary functional groups, can be achieved. The next step consists in partial saturation of the triple bond to afford the desired cis- or trans-alkene. ct.s-Alkene systems... 

F. E. McDonald and M. Wu, Stereoselective synthesis of L-oliose trisaccharide via iterative alkynol cycloisomerization and acid-catalyzed glycosylation, Org. Lett., 4 (2002) 3979-3981. 

McDonald, F. E. Gleason, M. M. Asymmetric synthesis of nucleosides via molybdenum-catalyzed alkynol cycloisomerization coupled with stereoselective glycosylations of deoxy-furanose glycals and 3-amidofuranose glycals. J. Am. Chem. Soc. 1996, 118, 6648-6659. 

Substituted maleic anhydrides have been directly exdted, but sensitization may also be used. In some cases the first method is better, and in some cases the second. In an approach to merrilactone A, which is closely related to the earlier-mentioned synthesis (Scheme 6.30), 2,3-dimethylmaleic anhydride was employed as a starting material in a sensitized [2 + 2]-photocydoaddition to 1,2-dichlorethene [114]. The reaction of tetrahydrophthalic anhydride (120) with alkenols and alkynols was conducted by direct irradiation in a Pyrex vessel. As an example, the reaction with allyl alcohol is depicted. The exo-product 121 was the preferred product with the endo-product cydizing spontaneously to lactone 122 (Scheme 6.43) [115]. Other alkenols reacted similarly. 

Allylmetallation of alkynes is a useful tool for the synthesis of 1,4-dienes. Various main group allylmetals, as well as allylic transition metals, have been utilized in such transformations. The reaction of allylindium reagents with terminal alkynols was first reported in 1992. The reaction proceeds in DMF giving 1,4-dienes, where the proximal... 

The bromohydrin is then quantitatively converted to the THP ether, which is added to LiC=CH-ethylenediamine complex in dimethyl sulfoxide to give VII in very high yield. No purification is required in either of these steps. A shorter synthesis of 9-decyn-l-ol (IX) was subsequently developed. An acetylene "zipper" isomerization (42) with sodio-1,3-diaminopropane is used to convert either 3-decyn-l-ol (VIII) or 2-decyn-l-ol into the terminal alkynol IX. Both of these starting alkynols are commercially available and the saving in labor is advantageous for moderate scale production. 

Reduction of la-alkynols to (E)-alkenols." This reaction is often one step in the synthesis of insect pheromones. Sodium in liquid ammonia is generally preferred for this reduction (5, 590). An alternative, general method is reduction with a large excess of lithium aluminum hydride in diglyme-THF. 

A review on ynolates, including the synthesis of p-lactones, has appeared <03S2275>. Morita-Baylis-Hillman-type adducts have been converted into a-alkylidene-p-lactones 65, which on reaction with dimethyltitanocene can be transformed into 3-alkylidene-2-methyleneoxetanes <03OL399>. Lactones 66 have been obtained via the cinchona alkaloid-catalyzed dimerization of monosubstituted ketenes <03OL4745>. The PdCh-promoted synthesis of P-lactones 67 have been achieved via cyclocarbonylation of 2-alkynols <03OL4429>. 

As discussed in Sect. 2, a-selanylalkyllithiums, generated from selenoacetals, can react with various electrophilic reagents, i. e. chloromethyl isopropyl ether for the synthesis of la-hydroxy vitamin D analogues [25] and with propargylic chloride derivatives for the preparation of alkynols [26]. A synthesis of vinyl-cyclopropane derivatives from l,4-dichloro-but-2-ene was achieved with trans stereoselectivity (>93%) in 68-89% yield. This one-pot cyclization, via an intramolecular allylic substitution, required the presence of two equivalents of u-BuLi [26] (Scheme 23). 

Besides the conventional methods, the metallo-carbene route to access cyclic compounds has become a versatile tool in sugar chemistry. Synthesis of stavudine 112, an antiviral nucleoside, from an allyl alcohol [101] is realized by a Mo(CO)5-mediated cyclization reaction (O Scheme 26). Molybdenum hexacarbonyl smoothly reacts with the triple bond of 113 to generate the intermediate Mo-carbene, which undergoes a clean cyclorearrangement to yield the furanoid glycal 114. Alkynol isomerization is effected by group-6 transition metal carbonyl complexes [102]. 

A similar approach had been reported earlier by Bestmann and coworkers" in their synthesis of hexadeuteriated leukotriene A4 methyl ester. C-alkylation of the tetrahy-dropyranyl ether of 3-butyn-l-ol with 2,2,3,3-tetradeuterio-l-iodopentane, prepared in 4 steps from propargyl alcohol, and subsequent protective group removal afforded the tetradeuteriated acetylenic alcohol 46 (equation 30). Semideuteriation of the alkynol and further transformation by known methods produced the labeled key reagent 3,4,6,6,7,7-hexadeuterio-(Z)-(3-nonen-l-yl)triphenylphosphonium iodide (47). Wittig olefination of epoxy dienal 45 with the labeled ylide generated from 47 completed the synthesis of... 

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