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

Abstract

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.

1. Introduction

Carbometalation is an important synthetic method in organic synthesis because organometallic compounds are produced with an expansion of the carbon framework [1,2,3,4,5,6,7]. In particular, the allylmetalation of alkynes provides metalated skipped dienes (1,4-diene), which are effectively transformed to functionalized skipped dienes via sequential reactions [8,9,10,11,12,13,14,15,16,17,18]. Skipped diene units are present in many biologically important natural products, and are also versatile synthetic building blocks in organic synthesis [19,20,21,22]. Therefore, various types of allylmetalation of alkynes have been developed. However, most reported reactions involve a syn-addition to alkynes, and few reports have focused on anti-allylmetalation (Scheme 1). Allylmagnesations via direct anti-addition of allylic Grignard reagent were also reported (Scheme 1A,B), in which a directing group such as hydroxy and amino groups nearby the alkyne moiety are required [23,24,25,26,27,28,29]. Yamamoto reported an allylsilylation of simple alkynes with allylic silanes catalyzed by either HfCl₄ or EtAlCl₂-Me₃SiCl (Scheme 1C) [16,30,31,32]. However, the produced 1,4-dienyl trialkylsilanes cannot be applied to sequential transformations such as Hiyama coupling without activation by a strong base because of their low reactivity. In this context, we achieved regioselective anti-allylindation of simple alkynes using InBr₃ and allylic silanes (Scheme 1D). To the best of our knowledge, anti-allylindation of alkynes has never been established, while several syn-allylindations using allylic indiums have [13,33,34,35,36,37,38,39]. The 1,4-dienylindium compounds can be excellent precursors for functionalized skipped dienes due to their moderate reactivity and high compatibility with many functional groups. In fact, the 1,4-dienylindiums synthesized by the present allylindation can be easily transformed to functionalized skipped dienes by iodination or Pd-catalyzed cross coupling without the addition of bases in contrast to 1,4-dienylsilanes produced via allylsilylation.

2. 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. Optimization of reaction conditions for carboindation of alkyne 1a with allylic silane 2a ^a.

Entry	InX3	Solvent	Yield/%
1	InBr3	CH2Cl2	89
2 b	InCl3	CH2Cl2	42
3	InF3	CH2Cl2	0
4	InI3	CH2Cl2	0
5	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 ¹H-NMR using 1,1,2,2-tetrachloroethane as an internal standard; ^b Et₂O was used instead of THF.

). 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 anti-allylindation 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).

The scope of the alkynes 1 is shown in

Table 2. Scope and limitation of alkyne 1 in allylindation ^a.

Entry	Alkyne 1	Product 4	Yield/%
1	1b	4ba	64
2	1c	4ca	41
3	1d	4da	40
4	1e	4ea	0
5	1f	4fa	59
6	1g	4ga	80
7	1h	4ha	65
8			78 b

^a Alkyne 1 (1 mmol), allylic silane 2a (2 mmol), InBr₃ (1 mmol), CH₂Cl₂ (1 mL). Yields were determined by ¹H-NMR using 1,1,2,2-tetrachloroethane as an internal standard; ^b Me₂Si(OMe)₂ (1 mmol) was added.

. 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.

Next, we evaluated the scope of allylic silanes 2 in the allylindation of alkyne 1h in the presence of Me₂Si(OMe)₂ (

Table 3. Scope of allylic silane 2 in allylindation ^a.

Entry	Allylic Silane 2	Product 3	Yield/%
1	2b	4hb	48
2	2c	4hc	76
3	2d	4hd	72
4	2e	4he	39

^a Alkyne 1a (1 mmol), allylic silane 2 (2 mmol), InBr₃ (1 mmol), Me₂Si(OMe)₂ (1 mmol), and CH₂Cl₂ (1 mL). Yields were determined by ¹H-NMR using 1,1,2,2-tetrachloroethane as an internal standard.

). 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).

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 (H¹) at the α-position of the InBr₂ group appeared at δ 5.99 ppm (Figure 1B). The ¹³C-NMR spectrum of 3ha showed a slightly broad signal for C¹ 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 H¹ and H³ 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-dienylindium 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.

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).

3. Materials and Methods

3.1. Analysis

NMR spectra were recorded on a JEOL JNM-400 (400 MHz for ¹H-NMR and 100 MHz for ¹³C-NMR) spectrometer (JEOL Ltd., Tokyo, Japan). Chemical shifts were reported in ppm on the δ scale relative to tetramethylsilane (δ = 0 for ¹H-NMR) with the residual CHCl₃ (δ = 77.0 for ¹³C-NMR) used as an internal reference. ¹H and ¹³C-NMR signals of all new compounds were assigned by using HMQC, HMBC, COSY, and ¹³C 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.

3.2. 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 mixture was quenched by saturated Na₂S₂O₃ aq (10 mL), and then extracted with dichloromethane (3 × 10 mL). The collected organic layers were dried over MgSO₄, and concentrated under reduced pressure. The yield was determined by ¹H-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.

(E)-4-(Iodomethylene)-2-methyldodec-1-ene (4aa)

The alkyne 1-decyne (0.980 mmol, 0.1354 g) was added to a solution of InBr₃ (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 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 (0.279 g, 89%).

IR: (neat) 1650, 1457 cm⁻¹; ¹H-NMR: (400 MHz, CDCl₃) 5.92 (s, 1H, 4-CHI), 4.83 (s, 1H, 1-H), 4.75 (s, 1H, 1-H), 2.87 (s, 2H, 3-H₂), 2.16 (t, J = 7.8 Hz, 2H, 5-H), 1.65 (s, 3H, 2-Me), 1.43–1.23 (m, 14H), 0.88 (t, J = 6.8 Hz, 3H); ¹³C-NMR: (100 MHz, CDCl₃) 149.4 (s, C-4), 142.5 (s, C-2), 113.0 (t, C-1), 76.2 (d, 4-CHI), 45.8 (t, C-3), 36.4 (t, C-5), 31.9 (t), 29.43 (t), 29.38 (t), 29.22 (t), 27.0 (t), 22.7 (t), 21.8 (q, 2-Me), 14.1 (q, C-12); HRMS: (EI, 70 eV) Calculated (C₁₄H₂₅I) 320.1001 (M⁺), Found: 320.1000.

(E)-4-(Iodomethylene)-2,7-dimethyloct-1-ene (4ba)

The alkyne 5-methylhex-1-yne (1.02 mmol, 0.0985 g) was added to a solution of InBr₃ (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 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 (0.0930 g, 33%).

IR: (neat) 1650, 1467, 1455 cm⁻¹; ¹H-NMR: (400 MHz, CDCl₃) 5.90 (s, 1H, 4-CHI), 4.83 (s, 1H, 1-H), 4.75 (s, 1H, 1-H), 2.88 (s, 2H, 3-H₂), 2.18–2.16 (m, 2H, 5-H₂), 1.65 (s, 3H, 2-Me), 1.62–1.52 (m, 1H, 7-H), 1.30–1.24 (m, 2H, 6-H₂), 0.93 (d, J = 6.3 Hz, 6H, 8-H₃ and 7-Me); ¹³C-NMR: (100 MHz, CDCl₃) 149.5 (s, C-4), 142.4 (s, C-2), 113.1 (t, C-1), 75.9 (d, 4-CHI), 45.8 (t, C-3), 36.0 (t, C-6), 34.5 (t, C-5), 28.2 (d, C-7), 22.5 (q, C-8 and 7-Me), 21.8 (q, 2-Me); HRMS: (EI, 70 eV) Calculated (C₁₁H₁₉I) 278.0531 (M⁺), Found: 278.0529.

(E)-4-(Iodomethylene)-2,6-dimethylhept-1-ene (4ca)

The alkyne 4-methylpent-1-yne (1.06 mmol, 0.0872 g) was added to a solution of InBr₃ (1.02 mmol, 0.3606 g) and methallyl trimethylsilane (2.03 mmol, 0.2620 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 (0.0560 g, 20%).

IR: (neat) 1650, 1463 cm⁻¹; ¹H-NMR: (400 MHz, CDCl₃) 6.01 (s, 1H, 8-H), 4.84 (s, 1H, 1-H), 4.74 (s, 1H, 1-H), 2.87 (s, 2H, 3-H₂), 2.09 (d, J = 8.0 Hz, 2H, 5-H₂), 1.90 (septet, J = 8.0 Hz, 1H, 6-H), 1.65 (s, 3H, 2-Me), 0.93 (d, J = 0.8 Hz, 6H, 7-H₃ and 6-Me); ¹³C-NMR: (100 MHz, CDCl₃) 148.4 (s, C-4), 142.4 (s, C-2), 113.2 (t, C-1), 77.5 (d, C-8), 46.1 (t, C-3), 44.7 (t, C-5), 26.8 (d, C-6), 22.4 (q, C-7 and 6-Me), 21.8 (q, 2-Me); HRMS: (EI, 70 eV) Calculated (C₁₀H₁₇I) 264.0375 (M⁺), Found: 264.0370.

(Z)-(1-Iodo-4-methylpenta-1,4-dien-2-yl)cyclohexane (4da)

Ethynylcyclohexane (1.01 mmol, 0.1094 g) was added to a solution of InBr₃ (0.968 mmol, 0.3432 g) and methallyl trimethylsilane (1.98 mmol, 0.2540 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 (0.0607 g, 21%).

IR: (neat) 1650, 1448 cm⁻¹; ¹H-NMR: (400 MHz, CDCl₃) 5.83 (s, 1H, 11-H), 4.87 (s, 1H, 10-H), 4.77 (s, 1H, 10-H), 2.81 (s, 2H, 8-H₂), 2.63–2.56 (m, 1H, 1-H), 1.79–1.55 (m, 8H), 1.4–1.23 (m, 4H), 1.20–1.09 (m, 1H); ¹³C-NMR: (100 MHz, CDCl₃) 151.8 (s, C-7), 142.8 (s, C-9), 113.7 (t, C-10), 76.0 (d, C-11), 47.3 (d, C-1), 42.1 (t, C-8), 29.9 (t), 26.3 (t), 26.0 (t), 22.0 (t, C-12); HRMS: (EI, 70 eV) Calculated (C₁₂H₁₉I) 290.0531 (M⁺), Found: 290.0530.

(E)-(3-(Iodomethylene)-5-methylhex-5-en-1-yl)benzene (4fa)

Pent-4-yn-1-ylbenzene (1.01 mmol, 0.1314 g) was added to a solution of InBr₃ (0.979 mmol, 0.3471 g) and methallyl trimethylsilane (2.00 mmol, 0.2560 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 (0.1357 g, 43%).

IR: (neat) 1649, 1604, 1494, 1454 cm⁻¹; ¹H-NMR: (400 MHz, CDCl₃) 7.31–7.17 (m, 5H, Ph), 6.00 (s, 1H, 3-CHI), 4.85 (s, 1H, 6-H), 4.76 (s, 1H, 6-H), 2.86 (s, 2H, 4-H₂), 2.72–2.68 (m, 2H, 1-H₂), 2.48–2.44 (m, 2H, 2-H₂), 1.64 (s, 3H, 5-Me); ¹³C-NMR: (100 MHz, CDCl₃) 148.4 (s, C-3), 142.2 (s, C-5), 141.4 (s, i), 128.39 (d), 128.35 (d), 126.0 (d, p), 113.3 (t, C-6), 77.2 (d, 3-CHI), 46.3 (t, C-4), 38.6 (t, C-2), 33.3 (t, C-1), 21.8 (q, 5-Me); HRMS: (EI, 70 eV) Calculated (C₁₄H₁₇I) 312.0375 (M⁺), Found: 312.0377.

(E)-7-Chloro-4-(iodomethylene)-2-methylhept-1-ene (4ga)

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%).

IR: (neat) 1649, 1443 cm⁻¹; ¹H-NMR: (400 MHz, CDCl₃) 6.01 (s, 1H, 4-CHI), 4.84 (s, 1H, 7-H), 4.76 (s, 1H, 7-H), 3.54 (t, J = 7.3 Hz, 2H, 1-H₂), 2.88 (s, 2H, 5-H₂), 2.31 (t, J = 7.3 Hz, 2H, 3-H₂), 1.88 (quintet, J = 7.3 Hz, 2H, 2-H₂), 1.64 (s, 3H, 6-Me); ¹³C-NMR: (100 MHz, CDCl₃) 147.6 (s, C-4), 141.9 (s, C-6), 113.4 (t, C-7), 77.6 (d, 4-CHI), 46.0 (t, C-5), 44.5 (t, C-1), 33.9 (t, C-3), 30.0 (t, C-2), 21.7 (q, 6-Me); HRMS: (EI, 70 eV) Calculated (C₉H₁₄ClI) 283.9829 (M⁺), Found: 283.9823.

(Z)-(1-Iodo-4-methylpenta-1,4-dien-2-yl)benzene (4ha)

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%).

IR: (neat) 1650, 1490, 1442 cm⁻¹; ¹H-NMR: (400 MHz, CDCl₃) 7.38–7.30 (m, 3H, Ar), 7.21 (d, J = 6.8 Hz, 2H, Ar), 6.35 (s, 1H, 1-H), 4.78 (s, 1H, 5-H), 4.66 (s, 1H, 5-H), 3.20 (s, 2H, 3-H), 1.70 (s, 3H, 4-Me); ¹³C-NMR: (100 MHz, CDCl₃) 150.1 (s), 141.9 (s), 141.5 (s), 128.1 (d), 127.9 (d), 127.6 (d), 113.7 (t, C-5), 77.6 (d, C-1), 48.6 (t, C-3), 21.9 (q, 4-Me); Calculated (C₁₂H₁₃I) 284.0062 (M⁺), Found: 284.0062.

(Z)-(1-Iodopenta-1,4-dien-2-yl)benzene (4hb)

Phenylacetylene (1.00 mmol, 0.102 g) was added to a solution of InBr₃ (1.11 mmol, 0.3921 g), allyl trimethylsilane (1.96 mmol, 0.2236 g), and Me₂Si(OMe)₂ (1.00 mmol, 0.1202 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 (0.102 g, 38%).

IR: (neat) 1638 cm⁻¹; ¹H-NMR: (400 MHz, CDCl₃) 7.42–7.7.31 (m, 3H, Ar), 7.24–7.22 (m, 2H, Ar), 6.35 (t, J = 1.5 Hz, 1H, 1-H), 5.78 (m, 1H, 4-H), 5.11–5.06 (m, 2H, 5-H), 3.25 (dq, J = 6.8, 1.5 Hz, 2H, 3-H₂); ¹³C-NMR: (100 MHz, CDCl₃) 150.8 (s, C-2), 142.1 (s), 134.3 (d, C-4), 128.2 (d), 127.8 (d), 127.6 (d), 117.5 (t, C-5), 77.1 (d, C-1), 44.3 (t, C-3); HRMS: (EI, 70 eV) Calculated (C₁₁H₁₁I) 269.9905 (M⁺), Found: 269.9903.

(Z)-1-Iodo-2,4-diphenylpenta-1,4-diene (4hc)

Phenylacetylene (1.03 mmol, 0.1053 g) was added to a solution of InBr₃ (0.98 mmol, 0.3497 g), 2-phenylallyl trimethylsilane (2.00 mmol, 0.3813 g), and Me₂Si(OMe)₂ (1.00 mmol, 0.1207 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 (0.153 g, 43%).

IR: (neat) 1626, 1492, 1442 cm⁻¹; ¹H-NMR: (400 MHz, CDCl₃) 7.36–7.23 (m, 8H, Ar), 7.17–7.15 (m, 2H, Ar), 6.33 (s, 1H, 1-H), 5.41 (s, 1H, 5-H), 5.07 (s, 1H, 5-H), 3.65 (s, 2H, 3-H₂); ¹³C-NMR: (100 MHz, CDCl₃) 149.9 (s), 143.9 (s), 142.2 (s), 140.1 (s), 128.3 (d), 128.1 (d), 127.8 (d), 127. 6 (d), 126.0 (d), 115.8 (t, C-5), 78.6 (d, C-1), 45.6 (t, C-3); HRMS: (EI, 70 eV) Calculated (C₁₇H₁₅I) 346.0218 (M⁺) Found: 346.0221.

(Z)-(1-Iodo-3,3-dimethylpenta-1,4-dien-2-yl)benzene (4hd)

Phenylacetylene (1.02 mmol, 0.104 g) was added to a solution of InBr₃ (1.01 mmol, 0.3597 g), prenyl trimethylsilane (1.96 mmol, 0.2788 g), and Me₂Si(OMe)₂ (0.962 mmol, 0.1157 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 (0.126 g, 41%).

IR: (neat) 1638, 1490, 1462, 1442 cm⁻¹; ¹H-NMR: (400 MHz, CDCl₃) 7.41–7.7.32 (m, 3H, Ar), 7.04–7.00 (m, 2H, Ar), 6.53 (s, 1H, 1-H), 5.94 (dd, J = 17.4, 10.6 Hz, 1H, 4-H), 5.09 (d, J = 10.6 Hz, 1H, 5-H), 5.03 (d, J = 17.4 Hz, 1H, 5-H), 1.21 (s, 6H, 3-Me₂); ¹³C-NMR: (100 MHz, CDCl₃) 159.7 (s, C-2), 145.2 (d, C-4), 142. 4 (s), 128.9 (d), 127.8 (d), 127.1 (d), 112.3 (t, C-5), 80.2 (d, C-1), 45.1 (s, C-3), 26.4 (q, 3-Me₂); HRMS: (EI, 70 eV) Calculated (C₁₃H₁₅I) 298.0218 (M⁺), Found: 298.0219.

(Z)-1-Iodo-2,3-diphenylpenta-1,4-diene (4he)

Phenylacetylene (1.02 mmol, 0.1044 g) was added to a solution of InBr₃ (1.04 mmol, 0.3701 g), cinnamyl trimethylsilane (2.10 mmol, 0.4007 g), and Me₂Si(OMe)₂ (1.06 mmol, 0.1280 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 (0.080 g, 23%).

IR: (neat) 1636 cm⁻¹; ¹H-NMR: (400 MHz, CDCl₃) 7.29–7.14 (m, 8H, Ar), 6.99 (dd, J = 7.8, 2.0 Hz, 2H, Ar), 6.42 (s, 1H, 1-H), 6.11 (ddd, J = 17.4, 10.1, 7.3 Hz, 1H, 4-H), 5.19 (d, J = 10.1 Hz, 1H, 5-H), 5.00 (d, J = 17.4 Hz, 1H, 5-H), 4.47 (d, J = 7.3 Hz, 1H, 3-H); ¹³C-NMR: (100 MHz, CDCl₃) 154.1 (s), 142.3 (s), 139.8 (s), 138.2 (d, C-4), 128.48 (d), 128.40 (d), 128.2 (d), 127.9 (d), 127.4 (d), 126.8 (d), 117.3 (t, C-5), 80.4 (d, C-1), 58.8 (d, C-3); HRMS: (EI, 70 eV) Calculated (C₁₇H₁₅I) 346.0218 (M⁺), Found: 346.0214.

(Z)-(4-Methyl-2-phenylpenta-1,4-dien-1-yl)indium(III) bromide (3ha)

All manipulations were carried out in a globe box filled with nitrogen gas. Phenylacetylene (0.886 mmol, 0.0905 g) was added to a solution of InBr₃ (1.00 mmol, 0.3550 g), methallyl trimethylsilane (1.98 mmol, 0.2541 g), and Me₂Si(OMe)₂ (1.05 mmol, 0.1267 g) in dichloromethane (1 mL). The mixture was stirred at room temperature for 24 h. The volatiles were evaporated and the residual oil was washed with hexane to obtain the desired alkenylindium compound as a white solid (0.106 g, 26%).

¹H-NMR: (400 MHz, CDCl₃) 7.43–7.22 (m, 5H, Ar), 5.99 (s, 1H, 1-H), 4.83 (s, 1H, 5-H), 4.73 (s, 1H, 5-H), 3.30 (s, 2H, 3-H₂), 1.72 (s, 3H, 4-Me); ¹³C-NMR: (100 MHz, CDCl₃) 160.6 (s), 145.7 (s), 141.9 (s), 134.1 (d, C-1), 129.5 (d), 128.8 (d), 126.5 (d), 113.9 (t, C-5), 48.1 (t, C-3), 22.1 (q, 4-Me).

(Z)-4-Methy-1,2-diphenylpenta-1,4-diene (5)

Phenylacetylene (0.540 mmol, 0.0551 g) was added to a solutin of InBr₃ (0.532 mmol, 0.1885 g), methallyl trimethylsilane (1.01 mmol, 0.1290 g), and Me₂Si(OMe)₂ (0.499 mmol, 0.060 g) in dichloromethane (0.5 mL). The mixture was stirred at room temperature for 3 h. DMF (1 mL) was added to the reaction mixture at −78 °C. Then, the »reaction mixture was warmed to room temperature. PhI (0.749 mmol, 0.1528 g) and Pd(PPh₃)₄ (0.028 mmol, 0.0325g) were added to the reaction mixture, and the mixture was heated at 100 °C for 3 h. The mixture was quenched by H₂O (10 mL) and Et₂O (20 mL) at room temperature. The organic layer was washed by H₂O (3 × 10 mL), and 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 (0.0686 g, 54%).

IR: (neat) 1650, 1599, 1494, 1444 cm⁻¹; ¹H-NMR: (400 MHz, CDCl₃) 7.29–7.20 (m, 3H, Ar), 7.15 (d, J = 6.8 Hz, 2H, Ar), 7.12–7.04 (m, 3H, Ar), 6.95 (d, J = 6.8 Hz, Ar), 4.79 (s, 1H, 5-H), 4.72 (s, 1H, 5-H), 3.18 (s, 2H, 3-H₂), 1.76 (s, 3H, 4-Me); ¹³C-NMR: (100 MHz, CDCl₃) 142.9 (s, C-4), 141.1 (s), 140.4 (s), 137.3 (s), 129.0 (d), 128.6 (d), 128.3 (d), 128.1 (d), 127.8 (d), 126.9 (d), 126.3 (d), 113.1 (t, C-5), 49.1 (t, C-3), 22.1 (q, 4-Me); HRMS: (EI, 70 eV) Calculated (C₁₈H₁₈) 234.1409 (M⁺), Found: 234.1408.

4. Conclusions

We established a regioselective anti-allylindation of alkynes using InBr₃ and allylic silanes. Many types of aliphatic and aromatic alkynes were applicable. The present allylindation has a wide scope of allylic silanes, and the reactions using allyl, methallyl, prenyl, cinnamyl silanes gave the desired products. A 1,4-dienyl indium compound generated by the present allylindation was successfully isolated and characterized by NMR spectroscopy. The synthesized 1,4-dienyl indiums were applicable to iodination and Pd-catalyzed cross-coupling with an aryl iodide in a one-pot manner to give the corresponding functionalized skipped dienes.