Two Titanium-Catalyzed Reaction Sequences for Syntheses of Pyrroles from (E/Z)-Chloroenynes or α-Haloalkynols

Abstract

Titanium-catalyzed intermolecular hydroaminations of (E/Z)-chloroenynes enabled an efficient pyrrole synthesis, which set the stage for the development of a user-friendly one-pot reaction for the regioselective preparation of fully substituted pyrroles from easily accessible alpha-haloalkynols.

One-pot synthesis of 1,3-enynes with a CF3 group on the terminal sp2 carbon by an oxidative Sonogashira cross-coupling reaction

“…In organic synthesis, the 1,3-enyne motif plays a pivotal role as a versatile building block for constructing numerous compounds such as substituted naphthalenes 3 and heterocycles [4][5][6][7] . Additionally, they are present in a wide range of bioactive compounds with promising biological properties, including terbinafine 8 , which is used to treat fungal infections, and NNC 61-4655 9 , which is a peroxisome proliferator-activated receptor agonist and is used to reduce blood lipids.…”

“…(E)-1-Methoxy-4-(5,5,5-trifluoropent-3-en-1-ynyl)benzene 3dThe title product (3d) was obtained as a colorless oil (32.9 mg, 91%) after column chromatography (hexane 100%). δ H (CDCl 3 , 400 MHz) 3.82 (3H, s), 6.10 (1H, qd, J 6.8, 16.0 Hz),6.48 (1H, qd, J 2.3, 15.9 Hz), 6.87 (2H, d, J 8.7 Hz), 7.41 (2H, d, J 8.8 Hz); δ C (CDCl 3 , 400 MHz) 55.5, 83.2, 96.7, 113.9, 114.1, 119.1 (q, J 7.8 Hz), 122.7 (q, J 268.8 Hz), 126.2 (q, J 32.6 Hz), 133.4, 160.4; δ F (CDCl 3 , 90 MHz) -65.23 (3F, d, J 6.4 Hz); m/z (EI) 226.0607 (M + . C 12 H 9 F 3 O requires 226.0605).…”

Transition Metal-Mediated Synthesis of Monocyclic Aromatic Heterocycles

“…In contrast to the Buchwald protocol (Scheme 238), this transformation proceeds via an amination of the triple bond ( 3-242 ), followed by an intermolecular nucleophilic substitution in 3-243 (Scheme 239). 393 …”

Titanium Reagents in Heterocyclic Synthesis

“…In another report, Ackermann et al have described the synthesis of pyrro le through titaniu m cataly zed inter-mo lec ular hydroamination reaction through diasteromeric mixtu re of chloroenyes. [29] Synthesis of pyrrole ut ilizes α-haloalky Application of TiCl 4 as catalyst extends to the synthesis of aromat ic thiazoles. 2-Arylbenzothiazole has been prepared fro m bis-(2-benzalaminophenyl)disulfide using titaniu m tetrachloride and samariu m powder in anhydrous tetrahydrofuran (Scheme 8).…”