2- Methyl-3-butyn synthesis

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]. 

Synthesis of the End-Capping Agent 4- (m-Hydroxyphenyl) -2-methyl-3-butyn-2-ol 1 ... 

A key step in one route to the synthesis of hexamethyl Dewar benzene is the cycloaddition of 2-butyne to tetramethylcyclobutadiene (stabilized by A1 cation). Using the parent compounds (no methyls), develop a Woodward-Hoffmann orbital correlation diagram for the reaction and determine whether the reaction is thermally allowed. 

Under flash vacuum thermolysis (FVT) the 1,2,3-triazine (32) was readily thermolyzed to an alkyne, a nitrile, and nitrogen in high yields. For unsymmetrically substituted 1,2,3-triazines as FVT substrates, fragmentation proceeded selectively a bulky substituent at C-4(6) made the adjacent C—N bond break more easily than the opposite C—N bond. The FVT method was applied to the synthesis of the fluorinated alkynes, perfluoro-3-methyl-l-butyne and difluoroethyne [(33), R = (CF3)2CF, F] (Equation (1)) (89CC1657, 91CC456). It has been claimed, however, that tris(dimethylamino)-1,2,3-triazine forms the monocyclic azete. 

A very elegant, simple, versatile and high yielding synthesis of fused l,3-dithiol-2-ones has been described recently. In a representative example, treatment of 4-benzoyloxy-l-bromo-2-butyne with potassium O-methyl xanthate in methanol gave the expected xanthate ester in excellent yield. Refluxing of this ester in chlorobenzene for one hour in the presence of dimethyl fumarate gave 1 in quantitative yield. 

A number of alternative multi-step procedures for the synthesis of a-tert-alkyl ketones are known, none of which possess wide generality. A previous synthesis of 2-tert-pentylcyclopentanone Involved reaction of N-l-cyclopentenylpyrrol idine with 3-chl oro-3-methyl-l-butyne and reduction of the resulting acetylene (overall yield 46%). However, all other enamines tested afford much lower yields. Cuprate addition to unsaturated ketones may be useful in certain cases.9 Other indirect methods have been briefly reviewed. ... 

The FVT method can be applied for the synthesis of the fluorinated alkynes, perfluoro-3-methyl-l-butyne and difluoroethyne 40 (R = (CF3)2CF, F) (Scheme 3) <1989CC1657, 1991CC456>. It has been claimed, however, that tris (dimethylamino)-l,2,3-triazine forms the monocyclic azete. 

Fowler, J. S 2-Methyl-3-butyn-2-ol as an acetylene precursor in the Mannich reaction. A new synthesis of suicide inactivators of monoamine oxidase, J. Org. Chem., 42,26.37, 1977. 

We are mainly concerned here with general processes but two specific reactions are of some interest. Fragmentation occurs in the pyrolysis of CFBrs, giving perfluorobenzene (Figure 9.3) [3-5] this was probably the first synthesis of this compound, although it was not reported for some time. Trimerisation of hexafluoro-2-butyne leads to hexakis(trifluoro-methyl)benzene [6,7], areaction that was referred to in Chapter 7, Section lllB, Subsection 1. 

The stereoselective synthesis of unsaturated oxetanes has recently been achieved by Feigenbaum and coworkers.Previous studies have indicated that photochemical cis-trans isomerization of enals is rapid and results in the formation of equivalent amounts of stereoisomeric alkene adducts. " For example, irradiation of rran.r-crotonaldehyde and 2,6-dimethylfuran produced a 1 1 mixture of alkenic isomers (174) and (175) in 64% yield. Irradiation of 4-trimethylsilylbutyn-2-one and furan provided with S 1 stereoselectivity the bicyclic oxetane (176) in which the methyl group occupies the exo position, presumably because of the small steric requirement of the triple bond. Desilyation of the protected al-kyne produced an alkynic oxetane which was hydrogenated under Lindlar conditions to bicyclic vinyl-oxetane (177) attempts to use the unprotected butyn-2-one gave low isolated yields of oxetane because of extensive polymerization. The stereochemical outcome thus broadens previous alkynyloxetane syn-theses and makes possible the preparation of new oxetane structures that may be synthetically useful. 

The sp -sp coupling reaction can be extended to the synthesis of terminal alkynes by use of protected alkynes such as trimethylsilylacetylene (28 TMSA) or 2-methyl-3-butyn-2-ol (29), followed by subsequent removal of the protecting group (Schemes 17, 18 and 20). - - Thus, commercially available TMSA (28) reacts with aryl bromides or iodides in the presence of a palladium complex and copper(I) iodide, followed by treatment with dilute aqueous potassium hydroxide in methanol or a P source, such... 

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... 

Some effected the coupling of phenyl-, 2-fuiyl-. and 1-hexenylboronic acids with 4-thallated indole-3-carboxaldehyde (Pd(OAc),/DMF) to give 4-substituted 3-formylin-doles [148]. Regioselective thallation of indole-3-carboxaldehyde is achieved using thallium tris-trifluoroacetate in 77% yield. Indole 129, which is available by the Buchwald zirconium indoline synthesis, was used by Buchwald to synthesize 130 via a Suzuki protocol [149]. Boronate ester 130 is prepared by the hydroboration of3-methyl-1-butyne with catechol borane. Indole 131 had been used in earlier studies to synthesize the clavicipitic acids. 

However, such precautions are not invariably necessary, and fair yields (20-63%) are observed in the synthesis of a number of heterocycle-containing ethynylphosphonic esters, even in CgHg at 80°C on reaction of the corresponding bromoacetylenic alcohols Likewise, the reaction between diethyl phosphite and 4-chloro-2-methyl-3-butyn-2-ol in dry ElO at room temperature in the presence of a catalytic amount of CuCl and diethylamine gives good yields (60-72%) of dialkyl... 

The reagent has also been used for the synthesis of acetylenic diols.4 Thus 3-methyl-l-butyne-3-ol (6) is heated with two moles of the reagent to form the dilithio derivative. Cyclohexanone is added and the diol (7) is obtained in 60% yield. The reaction can also be carried out with acetylene and two different ketones. 

Ethynyl-2-nitrophenol (Attempted Alternate Synthesis). To a stirred solution of 4-iodo-2-nitrophenol (14.Og, 0.053 mole)(7) in 150 ml of tetrachloroethylene was added bis(triphenylphosphine) palladium dichloride (0.74g, 0.001 mole), cuprous iodide (0.40g, 0.002 mole), triphenyl phosphine (0.03g, 0.001 mole), and 50 ml of dry triethylamine. After the reactants were thoroughly mixed, 2-methyl-3-butyn-2-ol (5.4g, 0.064 mole) was added. The stirred reaction mixture was heated slowly to 70-75°C and maintained at that temperature for 16 hours. The tetrachloroethylene and triethylamine were removed under reduced pressure and the red gumlike residue was extracted with hot heptane. The heptane solution was treated with charcoal and the heptane was stripped off to give a yellow solid (9.5g). The solid was dissolved in benzene and was placed in a silica gel column. Elution with 1 1 benzene/hexane yielded 1.8g of product. The remainder of the product was removed... 

A one-step synthesis of this alkaloid is consequent upon the reaction of thallous salts of nonchelated j8-diketones with alkyl halides. In the present instance the thallous salt of 4-hydroxyquinolone (93) reacted with 3-chloro-3-methyl-l-butyne to generate flindersine (94) in 28% yield 111). 

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