1.4- Disubstituted 2-butynes

Reaction of 1 with excess methyllithium at - 50° results in a dianion of 2-butyne that reacts with electrophiles to give 1,4-disubstituted 2-butynes. 

Pyrazoles are formed when the diazo compounds react with alkynes or with functionalized alkenes, viz. the enols of /3-diketones. Pyrazolenines (353 Section 4.04.2.2.1) are isolated from disubstituted diazomethanes. Many pyrazoles, difficult to obtain by other methods, have been prepared by this procedure, for example 3-cyanopyrazole (616) is obtained from cyanoacetylene and diazomethane (7iJCS(C)2i47), 3,4,5-tris(trifiuoromethyl)pyrazole (617) from trifluorodiazoethane and hexafluoro-2-butyne (8lAHC(28)l), and 4-phenyl-3-triflylpyrazole (618 R =H) from phenyltriflylacetylene and diazomethane (82MI40402). An excess of diazomethane causes iV-methylation of the pyrazole (618 R = H) and the two isomers (618 R = Me) and (619) are formed in a ratio of 1 1. 

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]. 

In contrast, synthesis of 3,4-diphosphorylthiophenes requires more elaboration because of low reactivity of 3,4-positions of thiophene and unavailability of 3,4-dihalo or dimetallated thiophenes. Minami et al. synthesized 3,4-diphosphoryl thiophenes 16 as shown in Scheme 24 [46], Bis(phosphoryl)butadiene 17 was synthesized from 2-butyne-l,4-diol. Double addition of sodium sulfide to 17 gave tetrahydrothiophene 18. Oxidation of 18 to the corresponding sulfoxide 19 followed by dehydration gave dihydrothiophene 20. Final oxidation of 20 afforded 3,4-diphosphorylthiophene 16. 3,4-Diphosphorylthiophene derivative 21 was also synthesized by Pd catalyzed phosphorylation of 2,5-disubstituted-3,4-dihalothiophene and converted to diphosphine ligand for Rh catalysts for asymmetric hydrogenation (Scheme 25) [47],... 

A / -disubstituted acid amides are often prepared by reaction of acyl halides with secondary amines. This method is attractive when the acyl halide is readily available. This is not the case with pentynoyl chloride, which has to be synthesised by a two-step procedure from butyne (see exp. 8). In analogy with the carboxyalkylarion with alkyl chloroformates (exp. 2), an... 

Zirconocene diiodide can promote the addition of diallylzinc to a,/1-disubstituted unactivated alkynes. Thus, in the case of 5-decyne, a 94/6 mixture of the two isomeric alkenyl iodides (derived respectively from syn and anti additions to the triple bond) was obtained after iodinolysis (equation 74)108. However, the stereoselectivity was lower for 2-butyne (80/20) and the case of unsymmetrical alkynes was not mentioned. 

Higher-order zinc cyanocuprates react in a similar manner with propargyl chlorides and bromides46. Allenes are the result (S 2 substitution), except in the case of l,4-dihalo-2-butynes, which undergo two successive S 2 substitutions to afford 2,3-disubstituted butadienes (equations 33 and 34)47. 

DisubstUuted butadienes. 2,3-Bis(trimethylstannyl)-l, 3-butadiene (1) can be prepared by reaction of 2,3-dicblorobutadiene or 1,4-dicbloro-2-butyne with 2 equiv. of trimetbylstannyllitbium (equation 1). 2,3-Disubstituted butadienes can be prepared from I in one step by reaction of tbe dianion formed with metbyllitbium at - 78° with 2 equiv. 

The application of these effects in the determination of the isotopic purity of disubstituted alkynes is obvious and we have used it to follow the H -> D exchange when we prepared 2-butyne(De) . The method is very convenient since it does not... 

Trialkyl and triaryl Cr(III) compounds are effective in promoting the cyclic trimerization of disubstituted acetylenes to aromatic hydrocarbons 222, 457). In the reaction of Ph3Cr -3THF with 2-butyne, the bisarene complexes of hexamethylbenzene and 1,2,3,4-tetramethylnaphthalene are obtained, as well as the free aromatic hydrocarbons 222). It is clear that a phenyl substituent has been incorporated in the formation of the coordinated and uncoordinated 1,2,3,4-tetramethylnaphthalene. Al-... 

Cyclodimerization of disubstituted alkynes R C=CR" mediated by this type of precatalyst (Ln = La, Ce Y is unreactive) seems to be limited to alkynes bearing at least one a-methyl group (R ) and a small second alkyl group (eq. (6)) [97]. Already use of R" = Et, n-Pr results in formation of two isomers. For example, formation of l,2-dimethyl-3-ethylidenecyclobutene from excess 1- butyne is complete in ca. 10 h at 80 °C, giving a TOF of 2 h. Unprecedented propargylic metalation/alkyne insertion are the key steps of the proposed mechanistic cycle. 

Acetylene and disubstituted acetylene (such as 2-butyne) do not form copolymers with SO2. However, -alkyl acetylenes and phenylacetylene reaction to give a copolymer. 

A series of A,A -disubstituted diazacyclodecadiynes (35) was synthesized by a one-pot reaction between the amine component (R = CH3, C2H5, C 3H7, cyclohexyl) and l,4-dibromo-2-butyne in the presence of K2CO3 in THE giving low (5%) yields (Equation (8)) <91TL2887>. 

Co-trimerization of the unreactive disubstituted acetylenes with acetylene proved possible in some cases. For instance, acetylene with 2-butyne produced benzene, o-xylene (72), tetramethylbenzene (67), and styrene (72, 67). Acetylene and divinylacetylene yielded mainly o-divinylbenzene (13, 74). The co-trimerization of acetylene with vinylacetylene yielded styrene (75). This reaction probably also accounts for formation of styrene during cyclotrimerization of acetylene, because small amounts of vinyl-acetylene are usually present or are formed from acetylene under the reaction conditions. 

Finally,but-3-en-l-yne (vinylacetylene, HC C-CH=CH2) can be prepared (Table 6.8, example 5) by the catalyzed dimerization of ethyne (acetylene, HC CH) itself. Interestingly, this is only one of the possiblities of reaction of this alkyne (and substituted alkynes) with itself (or themselves). For example, as shown in Scheme 6.75, treatment of a disubstituted alkyne, such as 2-butyne (dimethylacetylene, CHsC CCHs) with zirconcene hydridochloride ([Cp]2ZrHCl, where Cp = cyclopen-tadienyl [see. Table 6.6]) apparently causes the formation of a vinylic zirconium intermediate. When the intermediate is treated with methyllithium (CHsLi) and then a second alkyne (or a second equivalent of the original) added, and this is followed by aqueous acid, a conjugated diene results. 

We also found it possible to make 2,3-disubstituted-1,3-butadienes using CuCN LiBr and cross-coupling with l,4-dichloro-2-butyne. This reaction was... 

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