Butynol

The method used is described by Drysdale, Stevenson, and Sharkey.4 The methyl ester of butadienoic acid has not been described previously, but the free acid contaminated by 2-bu-tynoic acid has been prepared by Wotiz, Matthews, and Lieb 5 by carbonation of propargylmagncsium bromide. Ethyl butadienoate has been prepared by Eglinton, Jones, Mansfield, and Whiting by alkali-catalyzed isomerization of ethyl 3-butynoate prepared from 3-butynol by chromic acid oxidation and esterification. 

Based on the extraordinary selectivity in hydrosilylation reactions when an alkyne competes with other groups for a silicon-bonded active hydrogen, further derivatisation can be carried out. The hydrosilylation of 2-methyl-3-butynol, which works very well with polymeric siloxanes, gives hydroxyal-kenylsilicon compounds - a l-silylalkenyl/2-silylalkenyl mixture from cis-addition across the triple bond. Elimination of water from the tert. alcohol produced, catalyzed by traces of a strong acid, results in isoprenylic siloxanes in more than 90 % overall yield (Eq. 8). 

Synthesis of the dihydrothiophene derivatives was described by Flynn et al. [70] (depicted in Scheme 23) and involved the conversion of 3-butynol 92 to benzyl 3-butynal sulfide 93. Sonogashira coupling of the sulfide 93 with acetic acid 5-iodo-2-methoxyphenyl ester 94, produced the intermediate 95. Treatment of compound 95 with iodine resulted in a rapid and... 

In 1985, Dbtz et al. reported during a study on the reaction of Fischer-type carbene complexes with alkynes [10] that 2-oxacyclopentylidene chromium complex 24 was obtained as a side product. Thus, treatment ofmethyl(methoxy)carbene complex with 3-butynol at 70 °C in dibutyl ether gave the cyclic carbene complex 24 in 23% yield along with the desired metathesis product 23. The authors briefly commented that the cyclic carbene complex 24 might be obtained through the vinylidene complex 25, generated by the reaction of the alkyne with the liberated pentacarbonylchromium species (Scheme 5.7). 

Then, in 1987, Dotz reported an improved procedure for this transformation, for which the use of Et20 as solvent improved the yield of the cyclic carbene complexes considerably [12]. For example, the five-membered Fischer-type carbene complex 29 (n=l) was prepared in 58 66% yield by the reaction of preformed M(CO)5(L) (M = Cr, W, L = Et20) and 3-butynol in Et20 at room temperature. The six-membered cyclic carbene complex could also be prepared by this method. This method has been applied to the preparation of functionalized cyclic Fischer-type carbene complexes from the corresponding alkynols. For example, Dotz et al. reported the preparation of various carbohydrate-functionalized cyclic Fischer-type carbene complexes, one of which is shovm in Scheme 5.9. 

Scheme 5.12 3-Butynol cyclization leading to dihydrofuran derivatives.

Asymmetric synthesis of stavudine and cordycepin, anti-HIV agents, and several 3 -amino-3 -deoxy-P-nudeosides was achieved utilizing this cycloisomerization of 3-butynols to dihydrofuran derivatives [16]. For example, Mo(CO)6-TMNO-promoted cyclization of the optically active alkynyl alcohol 42, prepared utilizing Sharpless asymmetric epoxidation, afforded dihydrofuran 43 in good yield. Iodine-mediated introduction of a thymine moiety followed by dehydroiodination and hydrolysis of the pivaloate gave stavudine in only six steps starting from allyl alcohol (Scheme 5.13). 

In 1994, Quayle et al. reported the application of this cyclic Fischer-carbene synthesis from 3-butynols to spirolactone synthesis, although the process was stepwise and a stoichiometric amount of the complex was employed [17]. The key transformation was the chromium or tungsten carbene complex formation followed by the CAN oxidation of the complex to give y-lactone. The reaction was further applied to the synthesis of andirolactone and muricatacin, the former being shown in Scheme 5.14. 

Schmidt et al. reported similar reactions of 3-butynols with Cr(CO)5(L) and Mo(CO)5(L) [18]. In most cases, a similar tendency to that reported by McDonald was observed, that is, five-membered cyclic carbene complexes were obtained when Cr(CO)5(OEt2) was employed, while dihydrofurans were obtained when Mo(CO)5 (NEt3) was employed, however, in one specific case, a unique difference of the reaction pathway was observed. Thus, when hemiacetal 44 was treated with Cr (CO)5(OEt2), the corresponding carbene complex 45 was obtained, which was further converted to dihydrofuran by treatment with DM AP. On the other hand, when 44 was... 

Heterocycle synthesis. Arylhydrazines and 1-alkynes react to form A-heterocycles. l-Aiyl-2-pyrazolene are produced from 3-butynol, whereas 2-methyl-3-aIkylindoles are obtained from other 1-alkynes." ... 

PyrazoHnes can also be prepared using the late-transition-metal, functional-group-tolerant Zn(OTf)2 as a catalyst [349]. Beller and coworkers showed that when 3-butynol is used as a hydrohydrazination substrate, rather than the formation... 

Pyne et al. were the first to use RCM in the synthesis of a tetrahydropyrrolizidine, namely, 1-epi-australine 93. Ring opening of epoxide 97, readily obtained from 3-butynol, with an enantiopure allyhc amine provided the desired diallylamine in moderate selectivity (Scheme 2.23). Conversion of the diallylamine into oxazolidi-none 98 opened the door to the first RCM cyclization. Portionwise addition of [Ru]-I catalyst (30mol% in total) gave product 95 in 97% yield. When less catalyst was used, significantly lower yields of 95 were obtained. syn-Dihydroxylation of the 3-pyrroHne 95 and an additional five more steps were required to obtain (+)-l-epi-australine (93) as a colorless oil. 

Property Hexynol Ethyl-octynol Methyl-butynol Methyl-pentyn... 

Optimization of the Pd-catalyzed coupling reaction between iodoaniline 28 and bis-trialkylsily 1 butynol ether 29. 

Optimization of the Pd-Catalyzed Coupling Reaction Between Iodoaniline 28 and Bis-TES Butynol Ether... 

Scheme 4.9 Mechanism for the formation of impurities derived from coupling of iodoaniline 28 and TMS-butynol 36.

As shown in Figure 4.2, protection of the hydroxy group also played an important role in the yield of the coupling. For instance, coupling of iodoaniline 28 with 40d (Rj = TBDMS) gave 41d (R, = TBDMS, 77%) as compared to 56% yield with 36 (Rj = H). The C, O-bis-TBDMS-protected butynol 40c provided an 18% higher yield than the C-mono-TBDMS butynol 40e, 78% and 60%, respectively. 

An additional example of an oxonium ion generated via the acid catalyzed rearrangement has been used to prepare a dihydropyran <06TL6149>. The oxonium ion 54 generated by the reaction of an epoxide with ZrCl4 can be trapped by a nucleophile such as butynol to prepare dihydropyran 55. A variety of mono- and disubstituted epoxides have been used in this reaction. 

Dialkoxycarbonylation has been reported using a Pd-catalyst/oxidant system on propynols or butynols furnishing respectively /3- or y-lactone derivatives with a-(alkoxycarbonyl)ethylene chains (Scheme 24) [83,137, 138]. This reaction occurs in a stereospecific way leading exclusively to cis-dicarbonylated products in fair to excellent yields (25-97%). Noteworthy, a butynol bearing an alkyl or an aryl substituent instead of a TMS one undergoes a different course of reaction under the same conditions here frans-alkoxycarbonylation takes place selectively (Scheme 25). 

Scheme 24 Double carbonylation of various butynols or propynols...

Calcium hypochlorite, Acetylene, 3924 Chloroacetylene, 0652 4-Chloro-2-butynol, 1455 Chlorocyanoacetylene, 1036 Chloroiodoacetylene, 0598 3-Chloro-l-iodopropyne, 1073... 

Ethynyl Terminated Monomer/Oligomer Mixtures from VI (VII). A mixture of the bis-butynol adduct, VI (3.9 mmol), toluene (40mL) and 10% methanolic K0H (40mL) was heated to reflux under nitrogen. The methanol and toluene were removed by distillation, adding more toluene as needed to maintain the reaction volume at 40mL. After... 

Bromoacetylene, 0651 Bromochloroacetylene, 0578 l-Bromo-l,2-cyclotridecadien-4,8,10-triyne, 3599 t 3-Bromopropyne, 1090 Calcium hypochlorite, Acetylene, 3924 Chloroacetylene, 0652 4-Chloro-2-butynol, 1455 Chlorocyanoacetylene, 1036 Chloroiodoacetylene, 0598 3-Chloro-l-iodopropyne, 1073 1 -Chloro-3 -phenyIpent-1 -en-4-yn-3 -ol, 4680 t 3-Chloropropyne, 1092... 

The Merck process group in Rahway has developed two syntheses of rizatriptan (4) utilizing palladium catalyzed indolization reactions (Schemes 19 and 20). Both routes start from the iodoaniline 51, which was prepared by reaction of 47 with iodine monochloride in the presence of CaCOa. " Palladium catalyzed coupling of iodoaniline 51 with bis-triethylsilyl protected butynol in the presence of NaaCOa provided a mixture of indoles 52a and 52b. This mixture was desilylated with aqueous HCl in MeOH to furnish the tryptophol 53 in 75% yield from 51. Protection of the alkyne prevented coupling at the terminal carbon of the alkyne and tnethylsilyl (TES) was found to be optimal because it offered the correct balance between reactivity (rate of coupling) and... 

The enantiomerieally pure protected butynol 40 ahead) reflects the stereochemistry of the lactone Moreover, the chain can be ex tended by the missing CVunit in the reaction ol 40 with 11, and the alcohol at 0-4 arises simultaneously in a stereoselective way Finally, the propargylic alcohol is converted in only three steps into an a,(i-unsaturated lactone. 

Chloro-l-buten-3-one, 1450 4-Chloro-2-butynol, 1451 (Chlorocarbonyl)imidosulfur difluoride, 0317 A -(Chlorocarbonyloxy)trimethylurea, 1918... 

When the reaction between tellurium and acetylene was carried out in the presence of 3-hydroxy-l-butyne, the 3-hydroxyvinyl vinyl telluriums, observed as by-products in reactions without the butynol, were formed in yields between 30 and 40%1. 

Enantiomerically enriched 2,5-dihydrofuran derivatives can be obtained from easily available enantiomerically enriched trisubstituted (acyloxy)butynols of type 30. These compounds were transformed into (acyloxy)dihydrofur-ans with complete stereospecificity by Ag(l)-mediated rearrangement to allenic intermediates 31, followed by Ag(l)-assisted cyclization (Scheme 36). This sequence was successfully applied to the formal synthesis of a differentiation-inducing antibiotic, (i)-(—)-ascofuranone <1999BCJ279>. 

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