Using the Type II Cycloisomerization Reaction of 1,6‐Enynes as a Mechanistic Probe to Identify the Real Catalytic Species of GaX₃ and InX₃

Abstract

Previously, we found that InCl 2 + is the real catalytic species in InCl 3 -catalyzed type II cycloisomerization of 1,6-enynes for generating nonconjugated dienes. We further used this cycloisomerization reaction as a mechanistic probe to study whether GaCl 3 , GaBr 3 , InBr 3 , InI 3 also have GaCl 2 + , GaBr 2 + , InBr 2 + , and InI 2 + as the real catalytic species. Experimental and computational results from the mechanistic probe reaction here support that the real catalytic species are positively charged GaCl 2 + , GaBr 2 + , InBr 2 + , and InI 2 + .The Lewis acids of group IIIA metals, [1,2] [2][3][4] and InA C H T U N G T R E N N U N G (III), [2,5] have been widely used as catalysts in synthesis. However, knowledge of the real catalytic species of these precatalysts is limited but is important for understanding and designing reactions. To date, several significant advances in the in-depth understanding of these group IIIA metals have been made. For example, it was found that Me 2 AlCl has Me 2 Al + as the catalytic species in the Diels-Alder reaction and Petasis-Ferrier rearrangements.[6] Transition-metal-catalyzed type I, II, and III cycloisomerizations of 1,6-enynes have been developed for the synthesis of dienes (Scheme 1).[7] InCl 3 and GaCl 3 can also be used as catalysts for these cycloisomerizations. Recently, we found that InCl 2 + is the real catalytic species in InCl 3 -catalyzed type II cycloisomerization of 1,6-enynes (Scheme 2 a). [8,9] Our DFT calculations found that, using InCl 3 or its dimer as catalyst, the reaction would give conjugated type II dienes instead of the experimentally obtained nonconjugated diene (Scheme 2 c).[8] Based on experimental results that shown InCl 3 can dissociate into InCl 2 + and InCl 4 À , we hypothesized that InCl 2 + was the real catalyst in the InCl 3 -catalyzed cycloisomerization (Scheme 2 b). This hypothesis was further supported by DFT calculations.The main reason for generating the nonconjugated diene is the coordination of InCl 2 + to the alkene moiety in the transition states, which induces positive charge in the C1=C3 bond and makes the [1,2]-H shifts from the allylic position to generate conjugated diene disfavored. In contrast, the nonconjugated [1,2]-H shifts from the ordinary hydrogen atoms at the C8 position is further stabilized by the methyl group when InCl 2 + is the catalyst. If InCl 3 was the real catalyst, the C1=C3 bond would not coordinate to In, which is already saturated in terms of coordination. Consequently, [1,2]

Indium-catalyzed intramolecular hydroarylation of aryl propargyl ethers

“…24 According to the general procedure, the reaction of 1a (120 mg, 0.742 mmol) with InI 3 afforded, after purification by column chromatography (R f = 0.24, 5% EtOAc-hexanes, 1% Et 3 N), 2a as a colorless oil (94 mg, 0.631 mmol, 85%): 1 H NMR (300 MHz, CDCl 3 ) δ 6.74-6.66 (m, 2H), 6.56 6-Methyl-2H-chromene (2b). 24 According to the general procedure, the reaction of 1b (108 mg, 0.742 mmol) with InI 3 afforded, after purification by column chromatography (R f = 0.25, 2% EtOAc-hexanes, 1% Et 3 N), 2b as a colorless oil (68 mg, 0.467 mmol, 63%): 1 According to the general procedure, the reaction of 1d (128 mg, 0.742 mmol) with InI 3 afforded, after purification by column chromatography (R f = 0.28, 10% EtOAc-hexanes, 1% Et 3 N), 2e as a light yellow solid (129 mg, 0.727 mmol, 98%): mp 134-135 °C; 1 H NMR (300 MHz, CDCl 3 ) δ 8.02 (dd, J = 8.9, 2.7 Hz, 1H), 7.85 (d, J = 2.7 Hz, 1H), 6.80 (d,J = 8.9 Hz,1H),6.45 (dt,J = 9.8,1.7 Hz,1H),5.88 (dt,J = 10.0,3.4 Hz,1H) 2H-Chromene-6-carbonitrile (2e). 6d According to the general procedure, the reaction of 1e (117 mg, 0.742 mmol) with InI 3 afforded, after purification by column chromatography (R f = 0.30, 10% EtOAc-hexanes, 1% Et 3 N), compound 2e as a white solid (74 mg, 0.467 mmol, 63%): mp 65-67 °C; 1 6-Bromo-2H-chromene (2f ).…”

“…According to the general procedure, the reaction of 3d (129 mg, 0.462 mmol) with InI 3 afforded, after purification by column chromatography (R f = 0.22, 2% EtOAc-hexanes), compound 4d as a light yellow solid (58 mg, 0.208 mmol, 45%): mp 84-86 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 7.87 (dd, J = 8.5, 2. 1 Hz,1H),7.74 (d,J = 2.1 Hz,1H),7.27 (br s,4H),6.91 (d,J = 8.5 Hz,1H), 5.80 (t, J = 3.9 Hz, 1H), 4.95 (d,J = 3.9 Hz,2H) 2951,2923,2850,2225,1713,1605,1507,1436 6-Methoxy-4-methyl-2H-chromene (4f ). 25 According to the general procedure, the reaction of 3f (81 mg, 0.462 mmol) with InI 3 afforded, after purification by column chromatography (R f = 0.41, 5% EtOAc-hexanes), compound 4f as a light yellow oil (79 mg, 0.448 mmol, 97%): 1 H NMR (300 MHz, CDCl 3 ) δ 6.77-6.66 (m, 3H), 5.62 (dd, J = 3.…”

“…According to the general procedure, the reaction of 3j (124 mg, 0.462 mmol) with InI 3 afforded, after purification by column chromatography (R f = 0.28, 10% EtOAc-hexanes), compound 4j as a white solid (112 mg, 0.416 mmol, 90%): mp 104-106 °C; . According to the general procedure, the reaction of 3k (133 mg, 0.462 mmol) with InCl 3 (5.1 mg, 0.023 mmol) afforded, after purification by column chromatography (R f = 0.32, 10% EtOAc-hexanes), compound 4k as a yellow oil (126 mg, 0.439 mmol, 95%): 1 H NMR (300 MHz, CDCl 3 ) δ 6.85 (d,J = 2.6 Hz,1H),2H)…”

Cyclobutene vs 1,3-Diene Formation in the Gold-Catalyzed Reaction of Alkynes with Alkenes: The Complete Mechanistic Picture

“…On the basis of studies on the mechanism of gold(I)-catalyzed cyclization of 1, n -enynes 21 − 24 and other electrophiles, 25 , 26 we hypothesized that the reaction of alkynes with alkenes could take place by the electrophilic addition of (η 2 -alkyne)gold(I) complexes 7 to the alkene to form intermediate cyclopropyl gold(I) carbenes 8 , which undergo ring expansion to give (η 2 -cyclobutene)gold(I) complexes 9 ( Scheme 2 ). An intermediate (η 2 -cyclobutene)gold(I) complex has been spectroscopically detected at low temperature from a 1,6-enyne.…”

Indium-Catalyzed Cycloisomerization of 1,6-Cyclohexenylalkynes

“…Indium was considered as InCl3 or InCl2 as previously advocated [9,[35][36][37]. Following the seminal work from Gandon [9] and Yu [38][39][40] with indium and gallium salts, In and Au intermediates C and D were optimized with the dispersion corrected B3LYP-D3 exchange-correlation functional [41][42][43][44][45] and the results are collected in Table 2. The effective-core potential of Hay and Wadt with a double-ξ valence basis set (LANL2DZ) was used to describe In and Au [46] and the other atoms were described by the 6-31g(d,p) basis set.…”