Palladium‐Catalyzed Regioselective and Stereospecific Ring‐Opening Suzuki‐Miyaura Arylative Cross‐Coupling of 2‐Arylazetidines with Arylboronic Acids

Abstract

We have developed a palladium‐catalyzed regioselective and enantiospecific ring‐opening Suzuki–Miyaura arylative cross‐coupling of N‐tosyl‐2‐arylazetidines to give enantioenriched 3,3‐diarylpropylamines. This reaction represents an example of transition‐metal‐catalyzed ring‐opening cross‐coupling using azetidines as a non‐classical alkyl electrophile. Density functional theory rationalized the mechanism of the full catalytic cycle, which consists of the selectivity‐determining ring opening of the azetidine, reaction with water, rate‐determining transmetalation, and reductive elimination. Transition states of the selectivity‐determining ring‐opening step were systematically determined by the multi‐component artificial force induced reaction (MC‐AFIR) method to explain the regioselectivity of the reaction.

DFT Study on the Mechanisms of Iron-Catalyzed Ortho C–H Homoallylation of Aromatic Ketones with Methylenecyclopropanes

“…So that the ring-opening reaction is completed [the bond of C(5)–C(6) is broken] and a new double bond between C(4) and C(5) is formed. Similar ring-opening reaction mechanisms have been reported in the previous catalytic reactions …”

“…So that the ring-opening reaction is completed [the bond of C(5)–C(6) is broken] and a new double bond between C(4) and C(5) is formed. Similar ring-opening reaction mechanisms have been reported in the previous catalytic reactions Reductive elimination: from the intermediate 6 , reductive elimination reaction occurs where two carbon atoms originally connected with the iron center in 6 attack together to form the carbon–carbon single-bond in 7 after going through transition state TS 4 .…”

A Synthetic Route to Tetrahydro-1H-azepino[4,3,2-cd]indoles via Ring-Opening Cyclization of Activated Azetidines with 4-Bromoindole: Toward a Vasopressin V2 Receptor Antagonist

“…3,4,3,indole (3a). The general method A described above was followed when 1a (28.7 mg, 0.1 mmol, 1.0 equiv) was reacted with 4-bromo-1-methyl-1H-indole 2a (23.1 mg, 0.11 mmol, 1.1 equiv) in the presence of Yb(OTf) 3 (6.2 mg, 0.01 mmol, 10 mol %) at 50 °C for 1.0 h. After completion of the reaction, the solvent was evaporated; in the same pot, Pd(OAc) 2 (1.1 mg, 0.005 mmol, 5 mol %), K 2 CO 3 (28 mg, 0.2 mmol, 2.0 equiv), and PPh 3 (5.0 mg, 0.02 mmol, 20 mol %) were added, and the reaction was stirred at 120 °C in toluene (1.0 mL) for 10 h to obtain 3a as a white solid, in 80% (33.3 mg, 0.08 mmol) yield; R f = 0.5 (20% ethyl acetate in petroleum ether), mp = 178−180 °C; IR ṽm ax (KBr, cm −1 ): 3060,3027,2958,2924,2854,1890,1738,1664,1599,1564,1539,1493,1454,1419,1367,1343,1289,1260,1182,1160,1091,1019,978,912,878,801; 1 H NMR (400 MHz, CDCl 3 ): δ 7.57 (d, J = 8.7 Hz, 2H), 7.37 (d,J = 7.3 Hz,1H),3H),3H), 7.10−7.14 (m, 1H), 6.96−6.98 (m, 2H), 6.14 (d, J = 1.2 Hz, 1H), 4.25−4.32 (m, 1H), 3.96−4.03 (m, 1H), 3.76 (dd, J = 11.0, 5.5 Hz, 1H), 3.60 (s, 3H), 2.40 (s, 3H), 2.28−2.36 (m, 1H), 2.09−2.18 (m, 1H); 13 C{ 1 H} NMR (100 MHz, CDCl 3 ): δ 145. 2, 143.1, 139.0, 138.2, 134.6, 129.6, 128.5, 128.3, 127.7, 127.2, 126.6, 122.8, 121.7, 117.9, 115.7, 107.2, 50.9, 42.9, 37.0, 32.9, 21.6; HRMS (ESI-TOF) m/z: calculated for C 25 H 25 N 2 O 2 S (M + H) + , 417.1631; found, 417.1630.…”

Ligand-controlled regioselective and chemodivergent defluorinative functionalization of gem-difluorocyclopropanes with simple ketones

“…Notably, the highly regioselective ring-opening cross-couplings of relevant aziridines have been elegantly realized by Doyle 12 and Takeda. 13 …”