GaCl3-Promoted Addition Reactions of Carbon Nucleophiles to Alkyne YoshiyukiKido, Mieko Arisawa, and Masahiko Yamaguchi* Departmentof OrganicChemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Received June 6, 2000 Abstract : GaCl3 promotes addition reactions of carbon nucleophiles to a C-C triple bond. Interaction of alkyne with GaCl3 generates a highly reactive electrophile, which aromatic hydrocarbon attacks to give an alkenylated arene. Silylethyne reacts predominantly at the p-position of toluene, while disilylated 1, 3-butadiyne exhibits ƒÍ-selectivity. The behavior of a silylated 1, 2-propadiene is intermediate between that of the silylethyne and the disilylated 1, 3-butadiyne. In the presence of GaCl3, electrophilic trimerization of silylethyne takes place to give a conjugated hexatriene. In this reaction, silylethyne attacks the GaCl3-acti- vated C-C triple bond. Carbometalation is another interesting addition reaction of an organogallium com- pound to alkyne. Alkynyldichlorogallium dimerizes in hydrocarbon solvents to give 1,1-dimetallo-1-buten- 3-yne. In the presence of GaCl3, silyl enol ether is ethenylated at the ƒ¿-carbon atom with trimethylsi- lylethyne. Treatment of lithium phenoxide with silylethyne in the presence of GaCl3 gives ƒÍ-(ƒÀ-silylethenyl) phenol. These reactions involve carbogallation of alkynylgallium, gallium enolate, or gallium phenoxide. 1. Introduction 2. Nucleophilic Addition Reactions to Alkyne Activated by GaCl3 Gallium is a group 13 element, and sits just below alu- minum in the periodic table. Its derivatives have rarely been 2.1 Aromatic Alkenylation Reactions used in organic synthesis,1,2 although aluminum derivatives GaCl3 activates a C-C triple bond electrophilically and are quite popular. Attempts to utilize organogallium com- promotes nucleophilic attack of ƒÎ-compounds such as pounds generally revealed that they are less reactive than arene4,5 or alkyne.6 GaCl3-activated silylethyne reacts with organoaluminum compounds. The reduced reactivity has an aromatic hydrocarbon or 1,2,3-trimethoxybenzene.4,5 been attributed to the less polarized nature of the Ga-C Other unsaturated compounds, 1, 4-disilyl-1, 3-butadiyne7 bond compared to the Al-C bond, based on the relative elec- and 1,2-propadiene,8 when treated with GaCl3, are also tronegativity of Ga (1.8) and Al (1.5).3 We found that GaCl3 attacked by an aromatic hydrocarbon. promotes addition reactions of carbon nucleophiles to C-C The structure of the complex derived from the unsaturated triple bond, and that the reactions proceed much more effec- compound and GaCl3 can be studied in some cases by tively than with AlCl3. The reactions take place either via i) low-temperature NMR (Figure 2). Complexation of GaCl3 cicctrophilic activation of alkyne by formation of a ƒÎ-com- and silylethyne at -78 •Ž results in a low-field chemical plex with GaCl3, or ii) carbogallation. Described here are shifts of the acetylenic proton and carbons.5 Calculations several such examples. GaCl3 of high purity is commercially indicate a ƒÎ-complex structure rather than an open cationic available at modest price. GaCl3 is soluble in various organic structure. Treatment of 1-triethylsily1-1,2-propadiene with solvents even in hydrocarbons, and can conveniently be han- GaCl3 at -85 •Ž results in a low-field shift of 1-H by 1H-NMR dled as stock solutions. We prefer to use methylcyclohexane , while the shift was subtle at 3-H. 2-C shifts to as the solvent, since its melting point is much lower than that low field by 13C-NMR, and 3-C slightly to high field.8 It is of cyclohexane. likely that GaCl3 interacts with the double bond of the allene adjacent to the silyl group. 1. Electrophilic activation of it-electron system Figure 2 2. Carbogallation GaCl3 promotes aromatic ƒÀ-silylethenylation (Scheme 1).4,5 Treatment of trimethylsilylethyne (1) and aromatic hydrocar- bon with GaCl3 at -78 •Ž followed by methyllithium or THE gives (E)-(ƒÀ-trimethylsilylethenyl)arene. Since the silyl Figure 1 group can be removed, this is a formal aromatic ethenylation.9 1030 ( 6 ) J. Synth . Org . Chem . , Jpn . Use of GaC13 or GaBr3 is critical; other Lewis acids (A1C13, introduced from the organometallic reagent at the 5-position. A1Br3, InCl3, SnC14, SbC15, SbF5), protic acids (CF3S03H Two carbon-carbon bonds, one electrophilically and the and HC1), or heterogeneous acids (Na-Montmorillonite, other nucleophilically, are formed on a benzene ring. The Sn-Montmorillonite, Montmorillonite K 10) are not effective. first step of the ipso-substitution is the reaction of the elec- It should be emphasized that the ,8-silylethenylation is pro- trophilic gallium complex with 1, 2, 3-trimethoxybenzene at moted by GaC13 but not by A1C13. 2-position by a similar mechanism described in Scheme 2. Scheme 1 Scheme 3 The reaction proceeds via several organogallium intermedi- ates (Scheme 2). The conventional aromatic alkenylation 1,4-Ditrimethylsily1-1,3-butadiyne 5 can also be used for reactions were generally conducted at 0 •Ž to room tempera- the alkenylation (Scheme 4).7 Arene and 5 are reacted with ture using aromatic compounds in large excess.10 In contrast, GaC13 at -90 to -100 •Ž for 1-2 h. Addition of THE and this ƒÀ-silylethenylation proceeds at -78 •Ž within several an aqueous workup give (Z)-1,4-di (trimethylsilyl)-2- hours employing close to an equimolar amount of arene and aryl- 1-buten-3-yne 6 and 4-trimethylsily1-2-ary1-1- silylethyne. Apparently, a much more reactive electrophilic buten-3-yne 7.5 The olefinic trimethylsilyl group of 6 can be reagent is generated here. We ascribe it to the formation of a removed, producing 7, by careful treatment with CF3COOH. π-complex derived from silylethyne and GaCl3. The next Scheme 4 step in the ƒÀ-silylethenylation is the nucleophilic attack of an aromatic hydrocarbon to the complex at the ƒÀ-carbon atom. The regioselectivity may be explained by the ƒÀ-cation stabi- 5 lizing effect of the trialkylsilyl group.11 Addition of methyl- lithium or THF to the resulted arenium cation 2 provides vinylgallium intermediate 3 or 4, respectively. Methyllithium or THF is essential for the aromatization of the arenium cation 2 by deprotonation. Usually, polyalkenylation does not take place in this reaction, which may be due to the for- mation of such stable arenium cation in the reaction mixture. These vinylgalliums 3 and 4 can be detected spectroscopical- 6 7 ly, and workup with D20 gives the corresponding deuterated product. Scheme 2 2 GaC13 activates not only the C-C triple bond but also the doublc bond of allene.8 When arene and 1-tilethylsily1-1,2- propadiene (8) are reacted with GaC13, (E)-1-sily1-1- 3 propen-2-ylated arene is obtained (Scheme 5). The C-C bond formation takes place exclusively at the 2-position of 8. β-Cation stabilization by the silicon substituent probably plays an important role.11 This alkenylation is likely to pro- 4 ceed via an organogallium electrophile generated from 8 and GaC13 (Figure 2). Scheme 5 Unusual ipso-substitution reaction takes place with 1,2, 3-trimethoxybenzene (Scheme 3).5 When an equimolar amount of 1,2,3-trimethoxybenzene is treated with dimethylphenylsilylethyne in the presence of GaC13 at -90 8 ℃, which is fbllowed by methyllithium or alkylmagnesium bromide and acetic acid, a silylethenylated product was Alkylallene shows different behavior from that of 8. 1,2- obtained. The substitution of the 2-methoxy group with the Undecadiene (9) is reacted with p-xylene at -78 •Ž in the silylethenyl group occurs. In addition, an alkyl group is presence of GaC13, which is followed by methylmagnesium Vo1.58 No.11 2000 ( 7 ) 1031 bromide and D20. An isomeric mixture of allylated product at the p-position predominantly. In contrast, the reaction 10 (X=D) and alkenylated product (E)-11 is obtained with with 5 occurs exclusively at the o-position. The electrophile the former predominating (Scheme 6). The alkyl substituent derived from 5 shows unusually high tendency to alkenylate of 9 appears to stabilize the allyl cation rather than the vinyl the o-position of alkyl substituents : Ethylbenzene and iso- cation. While 10 is deuterated, (E)-11 is not. The com- propylbenzene also predominantly react at the o-position pound 10 (X-=D), therefore, should be formed from the cor- (Scheme 4). t-Butylbenzene gives a m-isomer as the major responding vinylgallium 10 (X= GaMe2) by a similar mecha- product. Development of the o-selective reaction in the elec- nism to the reaction of 1 (Scheme 2). trophilic aromatic substitution is an issue still not solved.12 Several benzene derivatives possessing heteroatom functional- Scheme 6 ities are known to exhibit such o-selectivity, which are ascribed to the interaction between the electrophile and the substituent.13 The o-selectivity in the GaC13-promoted reac- tion of alkylbenzenes, which lack such functionality, there- fore, is interesting.14 The structure of the electrophile precur- 9 sor is also very important for the o-selectivity (Figure 3). Disilylated octatetrayne 12 exhibits p-selectivity. The behav- ior of silyl-1, 2-propadiene 8 is intermediate between 1 and 5. This series probably reflects some property of the complexes derived from GaC13 and the unsaturated compounds. Polysubstituted benzenes also show tendency to react with 10 (E)-11 1 at the less hindered sites and with 5 at the adjacent posi- tions of the alkyl substituents (Figure 4). The orientation of the reaction using 8 is again intermediate. o-Xylene is exclu- sively alkenylated at the 4-position with 1 and the 3-position The organogallium electrophile generated by the interac- with 5; 1,2,3,4-tetrahydronaphthalene predominantly reacts tion of an unsaturated compound and GaC13 shows several interesting properties in the aromatic alkenylation.