Butyn-2-ol, 4- Trimethylsilyl

Michael Rathke Robert Elghanian Michigan State University, East Lansing, MI, USA 

Solubility highly soluble in all standard organic solvents (hexanes, toluene, CH2CI2, EtOAc, alcohols, ethers). Partially soluble in water. 

Form Supplied in colorless to light yellow liquid racemic compound is commercially available. Nonracemic material must be prepared. 

Handling, Storage, and Precaution limited data are available for 4-TMS-3-butyn-2-ol. Prudent laboratory practices for handling chemicals should be followed. Use in a fume hood with adequate ventilation. 

More recently, Mulzer has reported use of the corresponding allenylsilane drived from4-TMS-3-butyn-2-ol for use in the synthesis of the C13-C18 fragment of branimycin (eq 2).  

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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]. 

Enzymatic reduction of 23a with recLBADH and CPCR resulted in unsatisfactory results (60% and 49% ee) as well. The results mentioned above indicate that a bulky substituent at the alkyne moiety results in a higher selectivity of the reduction. Furthermore, Bradshaw et al. reported that Lactobacillus kefir ADH, an enzyme highly homologous to LB ADH, affords (R)-4-trimethylsilyl-3-butyn-2-ol [(R)-25j with an ee of 94% in 25% yield [39bj. In our investigations ketone 23b was reduced by recLBADH with almost quantitative conversion. The enantiomeric excess and absolute configuration of the product were determined by desi-lylation with borax converting alcohol (R)-25 into enantiopure (R)-3-butyn-2-ol [(R)-24j (Scheme 2.2.7.14). 

Article previously published in the electronic Encyclopedia of Reagents for Oigenic Synthesis as 4-Trimethylsilyl-3-butyn-2-ol. DOI 10.1002/ 047084289X. m01324. 

J.A. Marshall, H. Chobanian, Lipase-catalyzed resolution of 4-trimethylsilyl-3-butyn-2-ol and conversion of the (R)-enantiomer to (R)-3-butyn-2-yl mesylate and (P)-l-tributylstannyl-l, 2-butadiene, Org. Synth. 82 (2005) 45-54. 

With telluronium salt (d) (typical procedure) A solntxon of n-BuLi (1.5 mmol) in hexane is added to a solution of the telluronium salt (0.65 g, 1.5 mmol) in dry THF (10 mL) at -78°C under N2. After 30 min, a solution of p-chlorobenzaldehyde (0.168 g, 1.2 mmol) in THF (2 mL) is added dropwise at -78°C and the reaction mixture is allowed to warm at room temperature. After the reaction is complete (monitored by TLC), H2O (1 mL) is added and the solution is stirred for another 1 h. The mixture is then extracted with ether (3x5 mL). The combined extracts are washed with brine, dried (Na2S04), filtered and concentrated under vacuum. Flash chromatography on an SiOj column gives l-(p-chlorophenyl)-4-(trimethylsilyl)-3-butyn-l-ol (0.265 g (87%) (98% GC purity)). 

The combined organic phases are washed with two 200-mL portions of water, four 200-mL portions of saturated sodium bicarbonate solution, and two 200-mL portions of saturated sodium chloride. The organic phase is dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure at room temperature using a rotary evaporator. The crude product is distilled through a short-path distillation apparatus under reduced pressure to give 45.2 g (0.318 mol, 71% yield) of 4-(trimethylsilyl)-3-butyn-l-ol, bp 78-79°C (10 mm), as a colorless liquid (Notes 4 and 5). 

Butyllithium (1.5 M in hexane) added to a soln. of phenylacetylene in THF at 0°, warmed to room temp., solvent removed in vacuo, cooled to —50°, the obtained Li-acetylide dissolved in THF, treated with 1 eq. ClTi(OPr-/)3 (1.59 Min THF), a 1 M soln. of styrene oxide in THF added at —50°, warmed to room temp, within 2 h, stirred for 3 days, and hydrolyzed with 1 AHCl - 2,4-diphenyl-3-butyn-l-ol. Y 70%. Alkyloxiranes gave only 10% of the expected product. F.e. inch ring opening of alkenyl-, alkynyl-, and trimethylsilyl-oxiranes, s. N. Krause, D Seebach, Chem. Ber. 121, 1315-20 (1988). 

In a similar manner, allenylborane derived from 3-(tert-butyldimethylsilyl)-l-(trimethylsilyl)-propyne gives mainly (lS,2i )-2-(fert-butyldimethylsilyl)-l-[2-(3-methyl-3-buten-l-ynyl)-l-cyclopentenyl]-4-(trimethylsilyl)-3-butyn-l-ol (54%) and (lS,2i )-2-(ferf-butyldimethylsilyl)-l-[2-l-cyclohexenylethynyl)-l-cyclopentenyl]-4-(trimethyl silyl)-3-butyn-l-ol (55%) (Chart 6.17) [1]. 

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