Butyn-1-ol

The substituted phenylacetylenes (6) were all prepared by a modified (2-6) Stephens-Castro coupling (7) of an aryl halide (3) with a monoprotected acetylene [2-methyl-3-butyn-2-ol (4, R = -C(CH3)20H) or trimethylsilyla-cetylene (4, R -81(0113)3)] in a refluxing dialkylamine solvent, followed by a deprotection step (Scheme I). 

It should be noted that a considerable acceleration of the reaction for low-reactive 4-iodopyrazoles is observed for substrates in which acceptor substituents at the pyrazole nitrogen atom additionally play the role of protecting group. Thus, it has been shown (88M253) that iV-phenacyl- and iV-p-tosyl-4-iodopyrazoles interact with phenylacetylene, 2-methyl-3-butyn-2-ol, and trimethylsilylacetylene at room temperature for 3-24 h in 70-95% yields (Scheme 56). 

In 1988, Linstrumelle and Huynh used an all-palladium route to construct PAM 4 [21]. Reaction of 1,2-dibromobenzene with 2-methyl-3-butyn-2-ol in triethylamine at 60 °C afforded the monosubstituted product in 63 % yield along with 3% of the disubstituted material (Scheme 6). Alcohol 15 was then treated with aqueous sodium hydroxide and tetrakis(triphenylphosphine)palladium-copper(I) iodide catalysts under phase-transfer conditions, generating the terminal phenylacetylene in situ, which cyclotrimerized in 36% yield. Although there was no mention of the formation of higher cyclooligomers, it is likely that this reaction did produce these larger species, as is typically seen in Stephens-Castro coupling reactions [22]. 

Somei adapted this chemistry to syntheses of (+)-norchanoclavine-I, ( )-chanoclavine-I, ( )-isochanoclavine-I, ( )-agroclavine, and related indoles [243-245, 248]. Extension of this Heck reaction to 7-iodoindoline and 2-methyl-3-buten-2-ol led to a synthesis of the alkaloid annonidine A [247]. In contrast to the uneventful Heck chemistry of allylic alcohols with 4-haloindoles, reaction of thallated indole 186 with 2-methyl-4-trimethylsilyl-3-butyn-2-ol affords an unusual l-oxa-2-sila-3-cyclopentene indole product [249]. Hegedus was also an early pioneer in exploring Heck reactions of haloindoles [250-252], Thus, reaction of 4-bromo-l-(4-toluenesulfonyl)indole (11) under Heck conditions affords 4-substituted indoles 222 [250], Murakami described the same reaction with ethyl acrylate [83], and 2-iodo-5-(and 7-) azaindoles undergo a Heck reaction with methyl acrylate [19]. 

A. ( )-1-(Dimethylphenylsilyl)-1-buten-3-ol (2a). A solution of 10.0 g (0.143 mol) of racemic 3-butyn-2-ol (Note 1) dissolved in 255 mL of tetrahydrofuran (THF, Note 2) in a 1-L, round-bottomed flask equipped with a reflux condenser and nitrogen atmosphere is prepared. Dimethylphenylsilane (21.4 g, 0.157 mol) (Note 3) and a small piece of sodium metal (ca. 5 mg) (Note 4) are placed in the reaction mixture. The solution is stirred for 15 min and 12 mg (2.05 x 10 5 mol) of bis(q-divinyltetramethyldisiloxane)tri-tert-butylphosphineplatinum(O) (Note 5) is added. The reaction mixture is then heated under reflux for 12 hr. The orange solution is cooled to ambient temperature, and the solvent is removed under reduced pressure to yield a crude orange residue containing 2a. The oil is subjected to column chromatography on silica gel (Note 6) (gradient elution 5, 10, 20, 35% EtOAc/hexanes) providing 25.4 g (123.23 mmol, 86%) of pure 2a as a yellow oil (Note 7). 

The three-step procedure described for the preparation of the illustrated crotylsilanes is initiated with the hydrosilation of rac-3-butyn-2-ol. This procedure is significantly improved with respect to the positional selectivity of the hydrosilation resulting in exclusive formation of the racemic (E)-vinylsilane, and as a result the present procedure is much more amenable to scale-up than those previously described in the literature.8 The enzymatic resolution of the racemic secondary allylic alcohol (vinylsilane) has also been reported using commercially available lipase extracts. The use of a Johnson ortho ester Claisen rearrangement affords the (E)-crotylsilanes 4 in nearly enantiomerically pure form. 

See 4-Ethoxy-2-methyl-3-butyn-2-ol See other ACETYLENIC COMPOUNDS... 

An improved procedure for the synthesis of a-allenic alcohols in good yields and with approximately 90% e.e. was reported by Olsson and Claesson (56). (- )-(S)-3-Butyne-2-ol (25) was converted into the monotetrahydropyranyl derivatives 26a to c, which gave on reduction with LAH in ether or THF the chiral allenes 27a to c (Scheme 4). The absolute configurations of 27b and c were... 

A three-necked 500mL round-bottom flask was fitted with a reflux condenser, magnetic stir bar, stopper, and gas lnlet/outlet adapters. Under dry nitrogen the flask was charged with m-bromophenol (10.Og, 57.8 mmol), 2-methyl-3-butyn-2-ol (5.0g, 59.4 mmol) and 250 mL of distilled trlethylamlne resulting in a pale yellow solution. The mixture was heated at reflux for 15 min while... 

Methylethylldene)bis(4,l-phenyleneoxy-4,1-phenylene-sulf onyl-4,1-phenyleneoxy-3,1-phenylene)]bis[2-methyl-3-butyn-2-ol] IV... 

Ketones containing triple bonds in the a,)3-positions are reduced to the corresponding unsaturated alcohols with sodium cyanoborohydride or tetra-butylammonium cyanoborohydride in 64-89% yields [780]. Thus 4-phenyl-3-butyn-2-one gave 4-phenyl-3-butyn-2-ol [780]. If the same ketone was converted to its p-toluenesulfonylhydrazone and this was reduced with bis benzyloxy)borane, 1-phenyl-1,2-butadiene was obtained in 21% yield [786]. 

Procedure for KR of a propargylic iec-alcohol using catalyst 16 KR of ( )-4-phenyl-3-butyn-2-ol [83]... 

A vial containing ( )-4-phenyl-3-butyn-2-ol (73.0 mg, 0.500 mmol) and catalyst 16 (3.3 mg, 0.005 mmol) in tert-amyl alcohol (1.0 mL) was capped with a septum and sonicated to help dissolve the catalyst. The resulting purple solution was cooled to 0 °C, and Ac O (35.4 pL, 0.375 mmol) was added by syringe. After 49 h, the reaction mixture was quenched by the addition of a large excess of MeOH. After concentration in vacuo, the residue was purified by FC on sihca gel (EtOAc/hexanes, 1/9 — 1/1 then EtOAc/hexanes/ EtjN, 9/9/2) to afford the (l )-acetate (68.6% ee by chiral-GC) and the (5)-alcohol (96.0%ee by chiral-GC on the acetate obtained following esterification). The calculated selectivity value at 58.3% conversion was s = 20.2. 

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