Regio- and Stereoselective Allylindation of Alkynes Using InBr3 and Allylic Silanes: Synthesis, Characterization, and Application of 1,4-Dienylindiums toward Skipped Dienes

Regioselective anti-allylindation of alkynes was achieved using InBr3 and allylic silanes. Various types of alkynes and allylic silanes were applicable to the present allylindation. This sequential process used the generated 1,4-dienylindiums to establish novel synthetic methods for skipped dienes. The 1,4-dienylindiums were characterized by spectral analysis and treated with I2 to stereoselectively give 1-iodo-1,4-dienes. The Pd-catalyzed cross coupling of 1,4-dienylindium with iodobenzene successfully proceeded in a one-pot manner to afford the corresponding 1-aryl-1,4-diene.


Results
Recently, we reported regioselective anti-carbometalations of alkynes using organosilicon nucleophiles and metal halides such as InBr3 [40], GaBr3 [41], BiBr3 [42], ZnBr2 [43], and AlBr3 [44]. In our established carbometalations, a metal halide directly activates an alkyne, and then an organosilicon nucleophile adds to the alkyne from an opposite site of the metal halide. Therefore, we applied a combination of indium trihalides and allylic silanes to establish anti-allylindation of alkynes. First, various indium salts were investigated for the reaction using alkyne 1a and methallyl trimethylsilane 2a (Table 1). InBr3, 1a, and 2a were mixed in CH2Cl2, and then the reaction mixture was stirred at room temperature for 24 h. After an I2 solution in THF was added at −78 °C, alkenyl iodide 4aa was obtained as a single isomer in 89% yield (Entry 1). An iodine group was introduced exclusively cis to the allylic group. The production of 4aa by quenching with I2 suggested that antiallylindation regioselectively proceeded to give the corresponding 1,4-dienylindium 3aa. The use of InCl3 instead of InBr3 afforded 4aa in a 42% yield (Entry 2). On the other hand, examinations using InF3, InI3, and In(OTf)3 resulted in no reaction (Entries 3-5). The thermodynamic stability of a generated side product Me3SiX might influence the driving force of the reaction. An investigation of the solvent effect was carried out. The reaction performed in non-polar solvents such as toluene resulted in no product because InBr3 did not dissolve the solvent (Entry 6). Polar solvents such as Et2O, CH3CN, and THF were not suitable to the present allylindation because of the deactivation of InBr3 by the solvent coordination (Entries 7-9). Scheme 1. Anti-allylmetalation of alkynes.

Results
Recently, we reported regioselective anti-carbometalations of alkynes using organosilicon nucleophiles and metal halides such as InBr 3 [40], GaBr 3 [41], BiBr 3 [42], ZnBr 2 [43], and AlBr 3 [44]. In our established carbometalations, a metal halide directly activates an alkyne, and then an organosilicon nucleophile adds to the alkyne from an opposite site of the metal halide. Therefore, we applied a combination of indium trihalides and allylic silanes to establish anti-allylindation of alkynes. First, various indium salts were investigated for the reaction using alkyne 1a and methallyl trimethylsilane 2a (Table 1). InBr 3 , 1a, and 2a were mixed in CH 2 Cl 2 , and then the reaction mixture was stirred at room temperature for 24 h. After an I 2 solution in THF was added at −78 • C, alkenyl iodide 4aa was obtained as a single isomer in 89% yield (Entry 1). An iodine group was introduced exclusively cis to the allylic group. The production of 4aa by quenching with I 2 suggested that anti-allylindation regioselectively proceeded to give the corresponding 1,4-dienylindium 3aa. The use of InCl 3 instead of InBr 3 afforded 4aa in a 42% yield (Entry 2). On the other hand, examinations using InF 3 , InI 3 , and In(OTf) 3 resulted in no reaction (Entries 3-5). The thermodynamic stability of a generated side product Me 3 SiX might influence the driving force of the reaction. An investigation of the solvent effect was carried out. The reaction performed in non-polar solvents such as toluene resulted in no product because InBr 3 did not dissolve the solvent (Entry 6). Polar solvents such as Et 2 O, CH 3 CN, and THF were not suitable to the present allylindation because of the deactivation of InBr 3 by the solvent coordination (Entries 7-9).  In (OTf)3  CH2Cl2  0  6  InBr3  toluene  0  7  InBr3  Et2O  0  8  InBr3  CH3CN  0  9 InBr3 THF 0 a InX3 (1 mmol), alkyne 1a (1 mmol), allylic silane 2a (2 mmol), solvent (1 mL), room temperature, 24 h. I2 (1.5 mmol), THF (2 mL). Yields were determined via 1 H-NMR using 1,1,2,2-tetrachloroethane as an internal standard; b Et2O was used instead of THF.
The scope of the alkynes 1 is shown in Table 2. Sterically hindered aliphatic alkynes 1b and 1c (R = primary alkyl group) that were slightly larger than 1a resulted in lower yields of the corresponding alkenyl iodides 4ba and 4ca, respectively (Entries 1 and 2). Cyclohexylacetylene 1d (R = secondary alkyl group) gave a moderate yield (Entry 3), and the allylindation of tert-butylacetylene 1e did not proceed due to large steric hindrance (Entry 4). These results showed that the steric hindrance on an alkyne disturbs the allylindation. This allylindation system tolerated functionalities such as Ph and alkyl chloride moieties (Entries 5 and 6). Aromatic alkyne 1h was also applicable to the present allylindation. In this case, the addition of Me2Si(OMe)2 effectively increased the yield of the desired alkenyl iodide 4ha (Entries 7 and 8), probably because the MeO group of Me2Si(OMe)2 coordinated to an indium atom of the produced 1,4-dienylindium 3 to stabilize 3, and to avoid protonation of 3 by alkyne 1h. The scope of the alkynes 1 is shown in Table 2. Sterically hindered aliphatic alkynes 1b and 1c (R = primary alkyl group) that were slightly larger than 1a resulted in lower yields of the corresponding alkenyl iodides 4ba and 4ca, respectively (Entries 1 and 2). Cyclohexylacetylene 1d (R = secondary alkyl group) gave a moderate yield (Entry 3), and the allylindation of tert-butylacetylene 1e did not proceed due to large steric hindrance (Entry 4). These results showed that the steric hindrance on an alkyne disturbs the allylindation. This allylindation system tolerated functionalities such as Ph and alkyl chloride moieties (Entries 5 and 6). Aromatic alkyne 1h was also applicable to the present allylindation. In this case, the addition of Me 2 Si(OMe) 2 effectively increased the yield of the desired alkenyl iodide 4ha (Entries 7 and 8), probably because the MeO group of Me 2 Si(OMe) 2 coordinated to an indium atom of the produced 1,4-dienylindium 3 to stabilize 3, and to avoid protonation of 3 by alkyne 1h.  The scope of the alkynes 1 is shown in Table 2. Sterically hindered aliphatic alkynes 1b and 1c (R = primary alkyl group) that were slightly larger than 1a resulted in lower yields of the corresponding alkenyl iodides 4ba and 4ca, respectively (Entries 1 and 2). Cyclohexylacetylene 1d (R = secondary alkyl group) gave a moderate yield (Entry 3), and the allylindation of tert-butylacetylene 1e did not proceed due to large steric hindrance (Entry 4). These results showed that the steric hindrance on an alkyne disturbs the allylindation. This allylindation system tolerated functionalities such as Ph and alkyl chloride moieties (Entries 5 and 6). Aromatic alkyne 1h was also applicable to the present allylindation. In this case, the addition of Me2Si(OMe)2 effectively increased the yield of the desired alkenyl iodide 4ha (Entries 7 and 8), probably because the MeO group of Me2Si(OMe)2 coordinated to an indium atom of the produced 1,4-dienylindium 3 to stabilize 3, and to avoid protonation of 3 by alkyne 1h.  The scope of the alkynes 1 is shown in Table 2. Sterically hindered aliphatic alkynes 1b and 1c (R = primary alkyl group) that were slightly larger than 1a resulted in lower yields of the corresponding alkenyl iodides 4ba and 4ca, respectively (Entries 1 and 2). Cyclohexylacetylene 1d (R = secondary alkyl group) gave a moderate yield (Entry 3), and the allylindation of tert-butylacetylene 1e did not proceed due to large steric hindrance (Entry 4). These results showed that the steric hindrance on an alkyne disturbs the allylindation. This allylindation system tolerated functionalities such as Ph and alkyl chloride moieties (Entries 5 and 6). Aromatic alkyne 1h was also applicable to the present allylindation. In this case, the addition of Me2Si(OMe)2 effectively increased the yield of the desired alkenyl iodide 4ha (Entries 7 and 8), probably because the MeO group of Me2Si(OMe)2 coordinated to an indium atom of the produced 1,4-dienylindium 3 to stabilize 3, and to avoid protonation of 3 by alkyne 1h.  The scope of the alkynes 1 is shown in Table 2. Sterically hindered aliphatic alkynes 1b and 1c (R = primary alkyl group) that were slightly larger than 1a resulted in lower yields of the corresponding alkenyl iodides 4ba and 4ca, respectively (Entries 1 and 2). Cyclohexylacetylene 1d (R = secondary alkyl group) gave a moderate yield (Entry 3), and the allylindation of tert-butylacetylene 1e did not proceed due to large steric hindrance (Entry 4). These results showed that the steric hindrance on an alkyne disturbs the allylindation. This allylindation system tolerated functionalities such as Ph and alkyl chloride moieties (Entries 5 and 6). Aromatic alkyne 1h was also applicable to the present allylindation. In this case, the addition of Me2Si(OMe)2 effectively increased the yield of the desired alkenyl iodide 4ha (Entries 7 and 8), probably because the MeO group of Me2Si(OMe)2 coordinated to an indium atom of the produced 1,4-dienylindium 3 to stabilize 3, and to avoid protonation of 3 by alkyne 1h.  The scope of the alkynes 1 is shown in Table 2. Sterically hindered aliphatic alkynes 1b and 1c (R = primary alkyl group) that were slightly larger than 1a resulted in lower yields of the corresponding alkenyl iodides 4ba and 4ca, respectively (Entries 1 and 2). Cyclohexylacetylene 1d (R = secondary alkyl group) gave a moderate yield (Entry 3), and the allylindation of tert-butylacetylene 1e did not proceed due to large steric hindrance (Entry 4). These results showed that the steric hindrance on an alkyne disturbs the allylindation. This allylindation system tolerated functionalities such as Ph and alkyl chloride moieties (Entries 5 and 6). Aromatic alkyne 1h was also applicable to the present allylindation. In this case, the addition of Me2Si(OMe)2 effectively increased the yield of the desired alkenyl iodide 4ha (Entries 7 and 8), probably because the MeO group of Me2Si(OMe)2 coordinated to an indium atom of the produced 1,4-dienylindium 3 to stabilize 3, and to avoid protonation of 3 by alkyne 1h.  The scope of the alkynes 1 is shown in Table 2. Sterically hindered aliphatic alkynes 1b and 1c (R = primary alkyl group) that were slightly larger than 1a resulted in lower yields of the corresponding alkenyl iodides 4ba and 4ca, respectively (Entries 1 and 2). Cyclohexylacetylene 1d (R = secondary alkyl group) gave a moderate yield (Entry 3), and the allylindation of tert-butylacetylene 1e did not proceed due to large steric hindrance (Entry 4). These results showed that the steric hindrance on an alkyne disturbs the allylindation. This allylindation system tolerated functionalities such as Ph and alkyl chloride moieties (Entries 5 and 6). Aromatic alkyne 1h was also applicable to the present allylindation. In this case, the addition of Me2Si(OMe)2 effectively increased the yield of the desired alkenyl iodide 4ha (Entries 7 and 8), probably because the MeO group of Me2Si(OMe)2 coordinated to an indium atom of the produced 1,4-dienylindium 3 to stabilize 3, and to avoid protonation of 3 by alkyne 1h. such as Ph and alkyl chloride moieties (Entries 5 and 6). Aromatic alkyne 1h was also applicable to the present allylindation. In this case, the addition of Me2Si(OMe)2 effectively increased the yield of the desired alkenyl iodide 4ha (Entries 7 and 8), probably because the MeO group of Me2Si(OMe)2 coordinated to an indium atom of the produced 1,4-dienylindium 3 to stabilize 3, and to avoid protonation of 3 by alkyne 1h. Next, we evaluated the scope of allylic silanes 2 in the allylindation of alkyne 1h in the presence of Me2Si(OMe)2 (Table 3). Allylindation using the simplest allylic silane 2b effectively proceeded to give the desired product 4hb in 48% yield (Entry 1). Allylic silane 2c bearing a Ph group at the 2position also afforded a high yield (Entry 2). Allylindations using prenylsilane 2d and cinnamylsilane 2e, which have a substituent at the 3-position, effectively occurred to give the corresponding iodinated skipped dienes 4hd and 4he in 72% and 39% yields, respectively (Entries 3 and 4).  (1 mL). Yields were determined by 1 H-NMR using 1,1,2,2-tetrachloroethane as an internal standard; b Me2Si(OMe)2 (1 mmol) was added.
Next, we evaluated the scope of allylic silanes 2 in the allylindation of alkyne 1h in the presence of Me2Si(OMe)2 (Table 3). Allylindation using the simplest allylic silane 2b effectively proceeded to give the desired product 4hb in 48% yield (Entry 1). Allylic silane 2c bearing a Ph group at the 2position also afforded a high yield (Entry 2). Allylindations using prenylsilane 2d and cinnamylsilane 2e, which have a substituent at the 3-position, effectively occurred to give the corresponding iodinated skipped dienes 4hd and 4he in 72% and 39% yields, respectively (Entries 3 and 4). Table 3. Scope of allylic silane 2 in allylindation a .
Next, we evaluated the scope of allylic silanes 2 in the allylindation of alkyne 1h in the presence of Me2Si(OMe)2 (Table 3). Allylindation using the simplest allylic silane 2b effectively proceeded to give the desired product 4hb in 48% yield (Entry 1). Allylic silane 2c bearing a Ph group at the 2position also afforded a high yield (Entry 2). Allylindations using prenylsilane 2d and cinnamylsilane 2e, which have a substituent at the 3-position, effectively occurred to give the corresponding iodinated skipped dienes 4hd and 4he in 72% and 39% yields, respectively (Entries 3 and 4). Table 3. Scope of allylic silane 2 in allylindation a .
Next, we evaluated the scope of allylic silanes 2 in the allylindation of alkyne 1h in the presence of Me2Si(OMe)2 (Table 3). Allylindation using the simplest allylic silane 2b effectively proceeded to give the desired product 4hb in 48% yield (Entry 1). Allylic silane 2c bearing a Ph group at the 2position also afforded a high yield (Entry 2). Allylindations using prenylsilane 2d and cinnamylsilane 2e, which have a substituent at the 3-position, effectively occurred to give the corresponding iodinated skipped dienes 4hd and 4he in 72% and 39% yields, respectively (Entries 3 and 4). Table 3. Scope of allylic silane 2 in allylindation a .

Entry
Allylic Next, we evaluated the scope of allylic silanes 2 in the allylindation of alkyne 1h in the presence of Me2Si(OMe)2 (Table 3). Allylindation using the simplest allylic silane 2b effectively proceeded to give the desired product 4hb in 48% yield (Entry 1). Allylic silane 2c bearing a Ph group at the 2position also afforded a high yield (Entry 2). Allylindations using prenylsilane 2d and cinnamylsilane 2e, which have a substituent at the 3-position, effectively occurred to give the corresponding iodinated skipped dienes 4hd and 4he in 72% and 39% yields, respectively (Entries 3 and 4). Table 3. Scope of allylic silane 2 in allylindation a .

Entry
Allylic Next, we evaluated the scope of allylic silanes 2 in the allylindation of alkyne 1h in the presence of Me2Si(OMe)2 (Table 3). Allylindation using the simplest allylic silane 2b effectively proceeded to give the desired product 4hb in 48% yield (Entry 1). Allylic silane 2c bearing a Ph group at the 2position also afforded a high yield (Entry 2). Allylindations using prenylsilane 2d and cinnamylsilane 2e, which have a substituent at the 3-position, effectively occurred to give the corresponding iodinated skipped dienes 4hd and 4he in 72% and 39% yields, respectively (Entries 3 and 4). Next, we evaluated the scope of allylic silanes 2 in the allylindation of alkyne 1h in the presence of Me 2 Si(OMe) 2 (Table 3). Allylindation using the simplest allylic silane 2b effectively proceeded to give the desired product 4hb in 48% yield (Entry 1). Allylic silane 2c bearing a Ph group at the 2-position also afforded a high yield (Entry 2). Allylindations using prenylsilane 2d and cinnamylsilane 2e, which have a substituent at the 3-position, effectively occurred to give the corresponding iodinated skipped dienes 4hd and 4he in 72% and 39% yields, respectively (Entries 3 and 4). Table 3. Scope of allylic silane 2 in allylindation a . Next, we evaluated the scope of allylic silanes 2 in the allylindation of alkyne 1h in the presence of Me2Si(OMe)2 (Table 3). Allylindation using the simplest allylic silane 2b effectively proceeded to give the desired product 4hb in 48% yield (Entry 1). Allylic silane 2c bearing a Ph group at the 2position also afforded a high yield (Entry 2). Allylindations using prenylsilane 2d and cinnamylsilane 2e, which have a substituent at the 3-position, effectively occurred to give the corresponding iodinated skipped dienes 4hd and 4he in 72% and 39% yields, respectively (Entries 3 and 4). Next, we evaluated the scope of allylic silanes 2 in the allylindation of alkyne 1h in the presence of Me2Si(OMe)2 (Table 3). Allylindation using the simplest allylic silane 2b effectively proceeded to give the desired product 4hb in 48% yield (Entry 1). Allylic silane 2c bearing a Ph group at the 2position also afforded a high yield (Entry 2). Allylindations using prenylsilane 2d and cinnamylsilane 2e, which have a substituent at the 3-position, effectively occurred to give the corresponding iodinated skipped dienes 4hd and 4he in 72% and 39% yields, respectively (Entries 3 and 4). Next, we evaluated the scope of allylic silanes 2 in the allylindation of alkyne 1h in the presence of Me2Si(OMe)2 (Table 3). Allylindation using the simplest allylic silane 2b effectively proceeded to give the desired product 4hb in 48% yield (Entry 1). Allylic silane 2c bearing a Ph group at the 2position also afforded a high yield (Entry 2). Allylindations using prenylsilane 2d and cinnamylsilane 2e, which have a substituent at the 3-position, effectively occurred to give the corresponding iodinated skipped dienes 4hd and 4he in 72% and 39% yields, respectively (Entries 3 and 4).  of Me2Si(OMe)2 (Table 3). Allylindation using the simplest allylic silane 2b effectively proceeded to give the desired product 4hb in 48% yield (Entry 1). Allylic silane 2c bearing a Ph group at the 2position also afforded a high yield (Entry 2). Allylindations using prenylsilane 2d and cinnamylsilane 2e, which have a substituent at the 3-position, effectively occurred to give the corresponding iodinated skipped dienes 4hd and 4he in 72% and 39% yields, respectively (Entries 3 and 4).   The 1,4-dienylindium 3 synthesized by the present allylindation were isolated and characterized ( Figure 1). After the allylindation of alkyne 1h using InBr3 and methallylsilane 2a, the volatiles were evaporated and the residual oil was washed with hexane to obtain the desired 1,4-dienylindium 3ha as a white solid ( Figure 1A). The 1,4-dienylindium 3ha was characterized by NMR spectroscopy. The resonance of a vinylic proton (H 1 ) at the α-position of the InBr2 group appeared at δ 5.99 ppm ( Figure  1B). The 13 C-NMR spectrum of 3ha showed a slightly broad signal for C 1 at δ 134.1 ppm. These chemical shift values are similar to those of previously reported alkenylindium generated by the carboindation of alkyne 1h with InBr3 and a silyl ketene acetal [41]. A nuclear Overhauser effect between H 1 and H 3 was observed, which showed that anti-allylindation proceeded stereoselectively to give 1,4-dienylindium with a trans-configuration between the InBr2 and allylic groups. A plausible reaction mechanism is illustrated in Scheme 2. A carbon-carbon triple bond of alkyne 1 coordinates to InBr3, and then the positive charge on the internal carbon atom of alkyne 1 is The 1,4-dienylindium 3 synthesized by the present allylindation were isolated and characterized ( Figure 1). After the allylindation of alkyne 1h using InBr3 and methallylsilane 2a, the volatiles were evaporated and the residual oil was washed with hexane to obtain the desired 1,4-dienylindium 3ha as a white solid ( Figure 1A). The 1,4-dienylindium 3ha was characterized by NMR spectroscopy. The resonance of a vinylic proton (H 1 ) at the α-position of the InBr2 group appeared at δ 5.99 ppm ( Figure  1B). The 13 C-NMR spectrum of 3ha showed a slightly broad signal for C 1 at δ 134.1 ppm. These chemical shift values are similar to those of previously reported alkenylindium generated by the carboindation of alkyne 1h with InBr3 and a silyl ketene acetal [41]. A nuclear Overhauser effect between H 1 and H 3 was observed, which showed that anti-allylindation proceeded stereoselectively to give 1,4-dienylindium with a trans-configuration between the InBr2 and allylic groups. A plausible reaction mechanism is illustrated in Scheme 2. A carbon-carbon triple bond of alkyne 1 coordinates to InBr3, and then the positive charge on the internal carbon atom of alkyne 1 is The 1,4-dienylindium 3 synthesized by the present allylindation were isolated and characterized ( Figure 1). After the allylindation of alkyne 1h using InBr3 and methallylsilane 2a, the volatiles were evaporated and the residual oil was washed with hexane to obtain the desired 1,4-dienylindium 3ha as a white solid ( Figure 1A). The 1,4-dienylindium 3ha was characterized by NMR spectroscopy. The resonance of a vinylic proton (H 1 ) at the α-position of the InBr2 group appeared at δ 5.99 ppm ( Figure  1B). The 13 C-NMR spectrum of 3ha showed a slightly broad signal for C 1 at δ 134.1 ppm. These chemical shift values are similar to those of previously reported alkenylindium generated by the carboindation of alkyne 1h with InBr3 and a silyl ketene acetal [41]. A nuclear Overhauser effect between H 1 and H 3 was observed, which showed that anti-allylindation proceeded stereoselectively to give 1,4-dienylindium with a trans-configuration between the InBr2 and allylic groups. A plausible reaction mechanism is illustrated in Scheme 2. A carbon-carbon triple bond of alkyne 1 coordinates to InBr3, and then the positive charge on the internal carbon atom of alkyne 1 is increased. Allylic silane 2 adds to the internal carbon atom from the opposite side of InBr3 to give 1,4- The 1,4-dienylindium 3 synthesized by the present allylindation were isolated and characterized (Figure 1). After the allylindation of alkyne 1h using InBr3 and methallylsilane 2a, the volatiles were evaporated and the residual oil was washed with hexane to obtain the desired 1,4-dienylindium 3ha as a white solid ( Figure 1A). The 1,4-dienylindium 3ha was characterized by NMR spectroscopy. The resonance of a vinylic proton (H 1 ) at the α-position of the InBr2 group appeared at δ 5.99 ppm ( Figure  1B). The 13 C-NMR spectrum of 3ha showed a slightly broad signal for C 1 at δ 134.1 ppm. These chemical shift values are similar to those of previously reported alkenylindium generated by the carboindation of alkyne 1h with InBr3 and a silyl ketene acetal [41]. A nuclear Overhauser effect between H 1 and H 3 was observed, which showed that anti-allylindation proceeded stereoselectively to give 1,4-dienylindium with a trans-configuration between the InBr2 and allylic groups. A plausible reaction mechanism is illustrated in Scheme 2. A carbon-carbon triple bond of alkyne 1 coordinates to InBr3, and then the positive charge on the internal carbon atom of alkyne 1 is increased. Allylic silane 2 adds to the internal carbon atom from the opposite side of InBr3 to give 1,4-4he 39 a Alkyne 1a (1 mmol), allylic silane 2 (2 mmol), InBr 3 (1 mmol), Me 2 Si(OMe) 2 (1 mmol), and CH 2 Cl 2 (1 mL). Yields were determined by 1 H-NMR using 1,1,2,2-tetrachloroethane as an internal standard.
The 1,4-dienylindium 3 synthesized by the present allylindation were isolated and characterized (Figure 1). After the allylindation of alkyne 1h using InBr 3 and methallylsilane 2a, the volatiles were evaporated and the residual oil was washed with hexane to obtain the desired 1,4-dienylindium 3ha as a white solid ( Figure 1A). The 1,4-dienylindium 3ha was characterized by NMR spectroscopy. The resonance of a vinylic proton (H 1 ) at the α-position of the InBr 2 group appeared at δ 5.99 ppm ( Figure 1B). The 13 C-NMR spectrum of 3ha showed a slightly broad signal for C 1 at δ 134.1 ppm. These chemical shift values are similar to those of previously reported alkenylindium generated by the carboindation of alkyne 1h with InBr 3 and a silyl ketene acetal [41]. A nuclear Overhauser effect between H 1 and H 3 was observed, which showed that anti-allylindation proceeded stereoselectively to give 1,4-dienylindium with a trans-configuration between the InBr 2 and allylic groups. The 1,4-dienylindium 3 synthesized by the present allylindation were isolated and characterized (Figure 1). After the allylindation of alkyne 1h using InBr3 and methallylsilane 2a, the volatiles were evaporated and the residual oil was washed with hexane to obtain the desired 1,4-dienylindium 3ha as a white solid ( Figure 1A). The 1,4-dienylindium 3ha was characterized by NMR spectroscopy. The resonance of a vinylic proton (H 1 ) at the α-position of the InBr2 group appeared at δ 5.99 ppm ( Figure  1B). The 13 C-NMR spectrum of 3ha showed a slightly broad signal for C 1 at δ 134.1 ppm. These chemical shift values are similar to those of previously reported alkenylindium generated by the carboindation of alkyne 1h with InBr3 and a silyl ketene acetal [41]. A nuclear Overhauser effect between H 1 and H 3 was observed, which showed that anti-allylindation proceeded stereoselectively to give 1,4-dienylindium with a trans-configuration between the InBr2 and allylic groups. A plausible reaction mechanism is illustrated in Scheme 2. A carbon-carbon triple bond of alkyne 1 coordinates to InBr3, and then the positive charge on the internal carbon atom of alkyne 1 is increased. Allylic silane 2 adds to the internal carbon atom from the opposite side of InBr3 to give 1,4dienylindium 3. The iodination of 1,4-dienylindium 3 with I2 proceeds with retention of the double bond configuration of 3 to yield alkenyl iodide 4 as a single isomer. A plausible reaction mechanism is illustrated in Scheme 2. A carbon-carbon triple bond of alkyne 1 coordinates to InBr 3 , and then the positive charge on the internal carbon atom of alkyne 1 is increased. Allylic silane 2 adds to the internal carbon atom from the opposite side of InBr 3 to give 1,4-dienylindium 3. The iodination of 1,4-dienylindium 3 with I 2 proceeds with retention of the double bond configuration of 3 to yield alkenyl iodide 4 as a single isomer. Finally, we applied the synthesized 1,4-dienylindium to Pd-catalyzed cross coupling [40,45,46]. After 1,4-dienylindium 3ha was produced via the allylindation of alkyne 1h with allyl silane 2a and InBr3, iodobenzene, a catalytic amount of Pd(PPh3)4, and DMF were added to the reaction mixture in a one-pot manner. Then, the Pd-catalyzed coupling reaction of 3ha with iodobenzene smoothly proceeded at 100 °C to give the desired skipped diene 5 as a single isomer. It should be noted that the coupling product 5 was stereoselectively obtained with retention of the double bond configuration of the alkenylindium (Scheme 3).

Analysis
NMR spectra were recorded on a JEOL JNM-400 (400 MHz for 1 H-NMR and 100 MHz for 13 C-NMR) spectrometer (JEOL Ltd., Tokyo, Japan). Chemical shifts were reported in ppm on the δ scale relative to tetramethylsilane (δ = 0 for 1 H-NMR) with the residual CHCl3 (δ = 77.0 for 13 C-NMR) used as an internal reference. 1 H and 13 C-NMR signals of all new compounds were assigned by using HMQC, HMBC, COSY, and 13 C off-resonance techniques. Infrared (IR) spectra were recorded on a JASCO FT/IR-6200 Fourier transform infrared spectrophotometer (JASCO Co., Tokyo, Japan). Silica gel column chromatography was performed using an automated flash chromatography system from the Yamazen Co. (W-Prep 2XY) (Yamazen Co., Osaka, Japan). Gel permeation chromatography (GPC) was performed using a NEXT recycling preparative HPLC from the Japan Analytical Industry Co. (Tokyo, Japan) (solvent: CHCl3; column: JAIGEL-1HH and JAIGEL-2HH). Reactions were carried out in dry solvents under a nitrogen atmosphere, unless otherwise stated. All allylic silanes were prepared by reported methods. Other reagents were purchased from Sigma-Aldrich Co. (St. Louis, MO, USA), the Tokyo Chemical Industry Co., Ltd. (TCI) (Tokyo, Japan) or Wako Pure Chemical Industries, Ltd. (Osaka, Japan), and used after purification by distillation or used without purification for solid substrates.

Typical Procedure
Alkyne 1 (1 mmol) was added to a solution of InBr3 (1 mmol) and allylic silane 2 (2 mmol) in dichloromethane (1 mL). The mixture was stirred at room temperature for 24 h, and then 0.75 M I2 in THF solution (2 mL) was added at −78 °C. The resultant mixture was stirred at −78 °C for 30 min. The Finally, we applied the synthesized 1,4-dienylindium to Pd-catalyzed cross coupling [40,45,46]. After 1,4-dienylindium 3ha was produced via the allylindation of alkyne 1h with allyl silane 2a and InBr 3 , iodobenzene, a catalytic amount of Pd(PPh 3 ) 4 , and DMF were added to the reaction mixture in a one-pot manner. Then, the Pd-catalyzed coupling reaction of 3ha with iodobenzene smoothly proceeded at 100 • C to give the desired skipped diene 5 as a single isomer. It should be noted that the coupling product 5 was stereoselectively obtained with retention of the double bond configuration of the alkenylindium (Scheme 3). Finally, we applied the synthesized 1,4-dienylindium to Pd-catalyzed cross coupling [40,45,46]. After 1,4-dienylindium 3ha was produced via the allylindation of alkyne 1h with allyl silane 2a and InBr3, iodobenzene, a catalytic amount of Pd(PPh3)4, and DMF were added to the reaction mixture in a one-pot manner. Then, the Pd-catalyzed coupling reaction of 3ha with iodobenzene smoothly proceeded at 100 °C to give the desired skipped diene 5 as a single isomer. It should be noted that the coupling product 5 was stereoselectively obtained with retention of the double bond configuration of the alkenylindium (Scheme 3).

Analysis
NMR spectra were recorded on a JEOL JNM-400 (400 MHz for 1 H-NMR and 100 MHz for 13 C-NMR) spectrometer (JEOL Ltd., Tokyo, Japan). Chemical shifts were reported in ppm on the δ scale relative to tetramethylsilane (δ = 0 for 1 H-NMR) with the residual CHCl3 (δ = 77.0 for 13 C-NMR) used as an internal reference. 1 H and 13 C-NMR signals of all new compounds were assigned by using HMQC, HMBC, COSY, and 13 C off-resonance techniques. Infrared (IR) spectra were recorded on a JASCO FT/IR-6200 Fourier transform infrared spectrophotometer (JASCO Co., Tokyo, Japan). Silica gel column chromatography was performed using an automated flash chromatography system from the Yamazen Co. (W-Prep 2XY) (Yamazen Co., Osaka, Japan). Gel permeation chromatography (GPC) was performed using a NEXT recycling preparative HPLC from the Japan Analytical Industry Co. (Tokyo, Japan) (solvent: CHCl3; column: JAIGEL-1HH and JAIGEL-2HH). Reactions were carried out in dry solvents under a nitrogen atmosphere, unless otherwise stated. All allylic silanes were prepared by reported methods. Other reagents were purchased from Sigma-Aldrich Co. (St. Louis, MO, USA), the Tokyo Chemical Industry Co., Ltd. (TCI) (Tokyo, Japan) or Wako Pure Chemical Industries, Ltd. (Osaka, Japan), and used after purification by distillation or used without purification for solid substrates.

Typical Procedure
Alkyne 1 (1 mmol) was added to a solution of InBr3 (1 mmol) and allylic silane 2 (2 mmol) in dichloromethane (1 mL). The mixture was stirred at room temperature for 24 h, and then 0.75 M I2 in Scheme 3. Pd-catalyzed cross-coupling of alkenylindium with iodobenzene.

Analysis
NMR spectra were recorded on a JEOL JNM-400 (400 MHz for 1 H-NMR and 100 MHz for 13 C-NMR) spectrometer (JEOL Ltd., Tokyo, Japan). Chemical shifts were reported in ppm on the δ scale relative to tetramethylsilane (δ = 0 for 1 H-NMR) with the residual CHCl 3 (δ = 77.0 for 13 C-NMR) used as an internal reference. 1 H and 13 C-NMR signals of all new compounds were assigned by using HMQC, HMBC, COSY, and 13 C off-resonance techniques. Infrared (IR) spectra were recorded on a JASCO FT/IR-6200 Fourier transform infrared spectrophotometer (JASCO Co., Tokyo, Japan). Silica gel column chromatography was performed using an automated flash chromatography system from the Yamazen Co. (W-Prep 2XY) (Yamazen Co., Osaka, Japan). Gel permeation chromatography (GPC) was performed using a NEXT recycling preparative HPLC from the Japan Analytical Industry Co. (Tokyo, Japan) (solvent: CHCl 3 ; column: JAIGEL-1HH and JAIGEL-2HH). Reactions were carried out in dry solvents under a nitrogen atmosphere, unless otherwise stated. All allylic silanes were prepared by reported methods. Other reagents were purchased from Sigma-Aldrich Co. (St. Louis, MO, USA), the Tokyo Chemical Industry Co., Ltd. (TCI) (Tokyo, Japan) or Wako Pure Chemical Industries, Ltd. (Osaka, Japan), and used after purification by distillation or used without purification for solid substrates.

Typical Procedure
Alkyne 1 (1 mmol) was added to a solution of InBr 3 (1 mmol) and allylic silane 2 (2 mmol) in dichloromethane (1 mL). The mixture was stirred at room temperature for 24 h, and then 0.75 M I 2 in THF solution (2 mL) was added at −78 • C. The resultant mixture was stirred at −78 • C for 30 min. The mixture was quenched by saturated Na 2 S 2 O 3 aq (10 mL), and then extracted with dichloromethane (3 × 10 mL). The collected organic layers were dried over MgSO 4 , and concentrated under reduced pressure. The yield was determined by 1 H-NMR using 1,1,2,2-tetrachloroethane as an internal standard. The crude product was purified by flash chromatography (spherical silica gel 60 µm, 30 g, diameter 2.7 cm) and GPC to give the product. standard. The crude product was purified by flash chromatography (spherical silica gel 60 μm, 30 g, diameter 2.7 cm) and GPC to give the product.
The alkyne 1-decyne (0.980 mmol, 0.1354 g) was added to a solution of InBr 3 (0.996 mmol, 0.3530 g) and methallyl trimethylsilane (2.07 mmol, 0.2654 g) in dichloromethane (1 mL). The mixture was stirred at room temperature for 24 h. The reaction mixture was cooled to −78 • C, and 0.75 M I 2 in THF solution (2 mL) was added. The resultant mixture was stirred at −78 • C for 30 min. The mixture was quenched by saturated Na 2 S 2 O 3 aq (10 mL). The mixture was extracted with dichloromethane (3 × 10 mL). The collected organic layer was dried over MgSO 4 . The solvent was evaporated, and the residue was purified by column chromatography (hexane, column length 10 cm, diameter 26 mm silica gel) and GPC (CHCl 3 ) to give the product (0.279 g, 89%). standard. The crude product was purified by flash chromatography (spherical silica gel 60 μm, 30 g, diameter 2.7 cm) and GPC to give the product.
The alkyne 5-methylhex-1-yne (1.02 mmol, 0.0985 g) was added to a solution of InBr 3 (0.983 mmol, 0.3485 g) and methallyl trimethylsilane (1.94 mmol, 0.2487 g) in dichloromethane (1 mL). The mixture was stirred at room temperature for 24 h. The reaction mixture was cooled to −78 • C, and 0.75 M I 2 in THF solution (2 mL) was added. The resultant mixture was stirred at −78 • C for 30 min. The mixture was quenched by saturated Na 2 S 2 O 3 aq (10 mL). The mixture was extracted with dichloromethane (3 × 10 mL). The collected organic layer was dried over MgSO 4 . The solvent was evaporated and the residue was purified by column chromatography (hexane, column length 10 cm, diameter 26 mm silica gel) and GPC (CHCl 3 ) to give the product (0.0930 g, 33%). The mixture was quenched by saturated Na2S2O3 aq (10 mL). The mixture was extracted with dichloromethane (3 × 10 mL). The collected organic layer was dried over MgSO4. The solvent was evaporated and the residue was purified by column chromatography (hexane, column length 10 cm, diameter 26 mm silica gel) and GPC (CHCl3) to give the product (0.0930 g, 33%).
The alkyne 5-chloropent-1-yne (1.01 mmol, 0.1031 g) was added to a solution of InBr 3 (0.983 mmol, 0.3486 g) and methallyl trimethylsilane (1.99 mmol, 0.2557 g) in dichloromethane (1 mL). The mixture was stirred at room temperature for 24 h. The reaction mixture was cooled to −78 • C, and 0.75 M I 2 in THF solution (2 mL) was added. The resultant mixture was stirred at −78 • C for 30 min. The mixture was quenched by saturated Na 2 S 2 O 3 aq (10 mL). The mixture was extracted with dichloromethane (3 × 10 mL). The collected organic layer was dried over MgSO 4 . The solvent was evaporated and the residue was purified by column chromatography (hexane, column length 10 cm, diameter 26 mm silica gel) to give the product (0.1676 g, 59%). The alkyne 5-chloropent-1-yne (1.01 mmol, 0.1031 g) was added to a solution of InBr3 (0.983 mmol, 0.3486 g) and methallyl trimethylsilane (1.99 mmol, 0.2557 g) in dichloromethane (1 mL). The mixture was stirred at room temperature for 24 h. The reaction mixture was cooled to −78 °C, and 0.75 M I2 in THF solution (2 mL) was added. The resultant mixture was stirred at −78 °C for 30 min. The mixture was quenched by saturated Na2S2O3 aq (10 mL). The mixture was extracted with dichloromethane (3 × 10 mL). The collected organic layer was dried over MgSO4. The solvent was evaporated and the residue was purified by column chromatography (hexane, column length 10 cm, diameter 26 mm silica gel) to give the product (0.1676 g, 59%). Phenylacetylene (1.08 mmol, 0.110 g) was added to a solution of InBr3 (1.00 mmol, 0.3541 g), methallyl trimethylsilane (1.99 mmol, 0.2552 g), and Me2Si(OMe)2 (1.02 mmol, 0.1230 g) in dichloromethane (1 mL). The mixture was stirred at room temperature for 24 h. The reaction mixture was cooled to −78 °C, and 0.75 M I2 in THF solution (2 mL) was added. The resultant mixture was stirred at −78 °C for 30 min. The mixture was quenched by saturated Na2S2O3 aq (10 mL). The mixture was extracted with dichloromethane (3 × 10 mL). The collected organic layer was dried over MgSO4. The solvent was evaporated and the residue was purified by column chromatography (hexane, column length 10 cm, diameter 26 mm silica gel) and GPC (CHCl3) to give the product (0.169 g, 55%).