ChemInform Abstract: The Dual Role of Ruthenium and Alkali Base Catalysts in Enabling a Conceptually New Shortcut to N‐Unsubstituted Pyrroles Through Unmasked α‐Amino Aldehydes.

Abstract

Unmasked α-Amino Aldehydes. -A virtually salt-free and straightforward bimolecular assembly giving N-unsubstituted pyrroles through fully unmasked intermediately formed α-amino aldehydes, which is enabled by the dual effects of a catalytic ruthenium complex and an alkali metal base, is reported. The versatile nature of this approach is further demonstrated by a short and simple access to the core pyrrole (VII) of atorvastatin. The applied catalyst is readily available in two steps from commercial resources (not shown). -(IIDA, K.; MIURA, T.; ANDO, J.; SAITO*, S.; Org. Lett. 15 (2013) 7, 1436-1439, http://dx.doi.org/10.1021/ol4001262 ; Grad. Sch. Sci., Nagoya Univ., Chikusa, Nagoya 464, Japan; Eng.) -H. Haber 33-110

General Transition Metal-Free Synthesis of NH-Pyrroles from Secondary Alcohols and 2-Aminoalcohols

“…1 H NMR (400 MHz, CDCl 3 , δ): 7.91 (s, br, 1H), 7.45−7.13 (m, 7H), 6.86 (d, J = 8.7 Hz, 2H), 6.30 (m, 1H), 6.01 (m, 1H), 4.00 (s, 2H), 3.79 (s, 3H). 13 2-Benzyl-5-pentyl-1H-pyrrole (3f). 2-Heptanol (300 mg, 1.0 equiv, 2.58 mmol), phenylalaninol (429 mg, 1.1 equiv, 2.84 mmol), NaO t Bu (273 mg, 1.1 equiv, 2.84 mmol), benzophenone (2.82 g, 6.0 equiv, 15.49 mmol), dry toluene 9 mL, 110 °C, reaction time is overnight (∼18 h).…”

“…1 H NMR (400 MHz, CDCl 3 , δ): 7.52 (s, br, 1H), 7.30 (t, 2H), 7.22 (t, 3H), 5.84 (m, 1H), 5.81 (m, 1H), 3.94 (s, 2H), 2.83 (sept, 1H), 1.20 (d, J = 6.9 Hz, 6H). 13 2-Benzyl-4,5,6,7,8,9-hexahydro-1H-cycloocta [b]pyrrole (3h). Cyclooctanol (300 mg, 1.0 equiv, 2.340 mmol), phenylalaninol (389 mg, 1.1 equiv, 2.57 mmol), NaO t Bu (247 mg, 1.1 equiv, 2.57 mmol), benzophenone (2.56 g, 6.0 equiv, 14.04 mmol), dry toluene 9 mL, 110 °C, reaction time is overnight (∼18 h).…”

“…1 H NMR (400 MHz, CDCl 3 , δ): 7.88 (s, 1H), 7.28 (m, 5H), 7.13 (m, 2H), 6.99 (m, 2H), 5.87 (s, 1H), 4.00 (s, 2H), 2.90 (t, J = 7.6 Hz, 2H), 2.69 (t, J = 7.6 Hz, 2H). 13 2-Isopropyl-5-phenyl-1H-pyrrole (3k). 1-Phenylethanol (300 mg, 1.0 equiv, 2.456 mmol), 2-amino-3-methyl-1-butanol (279 mg, 1.1 equiv, 2.70 mmol), NaO t Bu (260 mg, 1.1 equiv, 2.70 mmol), benzophenone (2.68 g, 6.0 equiv, 14.73 mmol), dry toluene 9 mL, 110 °C, reaction time is overnight (∼18 h).…”

“…11b These methods use iridium complex PN 5 P−Ir and Ir@SiCN nanoparticles as a catalyst system to obtain 2,5-and 2,3,5-substituted pyrroles in very high yield. 12 Moreover, in the same line methodology, Saito and co-workers 13 and the Beller research group 14 were able to synthesize various pyrroles starting from enolizable ketones, diols, and primary amines or ammonia. Despite these advances in pyrrole synthesis using very advanced transition metal catalyst systems, the following challenging issues still remain: the development of environmentally benign synthetic strategies, and access to various substituted pyrroles without using expensive transition metals and ligands, which in many cases are not commercially available and need to be synthesized in multistep procedures.…”

NNN-Ruthenium Catalysts for the Synthesis of Pyridines, Quinolines, and Pyrroles by Acceptorless Dehydrogenative Condensation

“…1d,2 Acceptorless dehydrogenation condensation (ADC), which is mechanistically related to the HA/BH reaction, enables the synthesis of aromatic N-heterocycles from secondary alcohols with amino alcohols. 3−15 For instance, the groups of Kempe, 4 Milstein, 5 Saito, 6 Beller, 7 Sun, 8 Yu, 9 and others 10 reported efficient Ru-and Ir-catalyzed coupling cyclization, and a series of pyridines, pyrroles, and quinolones were synthesized. However, most of their catalysts were synthesized on the basis of air-sensitive phosphine ligands.…”