Base‐Promoted Formation of an Annelated Pyrrolo‐1,4‐oxazine Ensemble from 1H‐pyrrol‐2‐ylmethanol and Propargyl Chloride: A Theoretical and Experimental Study

Abstract

Base-Promoted Formationofa nA nnelated Pyrrolo-1,4-oxazine Ensemblefrom 1H-pyrrol-2-ylmethanol and Propargyl Chloride:ATheoretical and Experimental Study What prompted you to investigate this topic/problem?The Irkutsk School of Organic Chemistry has rich and broad experience in building and functionalizing pyrrole systems in ac onvenient and universal fashion. The work presented is ac ontinuation of as eries of investigations to activate several reactive centers of pyrrole with the aim to synthesize previously unknown compounds with promising properties, such as drugs and precursors of materials with specific characteristics.Invited for this month'sc over is the group of Prof. Dr.N adezhda M. Vitkovskaya at Irkutsk State University and the group of Dr.A ndrey V. Ivanova tt he A. E. Favorsky Irkutsk Institute of Chemistry,R ussian Federation.The image shows that three different pyrrole derivatives can be obtained from the same starting reagents. The reaction is easily controlled by the ratio of the reagents, the amount of alkali, and the degree of dilution.T he three strings of the balalaika (a Russianf olk instrument) that represent these parametersc an produce melodies from the same notes symbolizing the reagents. The sheets with quantum-chemical calculations under the musical notebooks ymbolize thatt he experimental work is based on the theoretical investigations. Read the full text of the article at

A Practical Synthesis of Densely Functionalized Pyrroles via a Three-Component Cascade Reaction between Carbohydrates, Oxoacetonitriles, and Ammonium Acetate

“…As a demonstration and since formyl pyrroles and hydroxymethyl pyrroles are important building blocks for many natural products, pyrrole 6a was converted to 5-formyl pyrrole 20 in 95% yield, which in turn was converted to 5-hydroxymethyl pyrrole 21 in almost quantitative yield (Scheme a) . Further, we demonstrated efficient synthesis of pyrroloozazine 25 in 53% overall yield from pyrrole 6b through a series of reactions, as shown in Scheme b. , There are very limited routes to synthesize pyrroloozazine despite their many reported bioactivities. , Our approach represents a sustainable synthesis with high substitution at the pyrrole ring and gives excellent overall yield. Additionally, C -glycoside 26 was synthesized smoothly in 76% yield by simple treatment of pyrrole 4a with FeCl 3 (Scheme c) .…”

“…51 Further, we demonstrated efficient synthesis of pyrroloozazine 25 in 53% overall yield from pyrrole 6b through a series of reactions, as shown in Scheme 2b. 52,53 There are very limited routes to synthesize pyrroloozazine despite their many reported bioactivities. 54,55 Our approach represents a sustainable synthesis with high substitution at the pyrrole ring and gives excellent overall yield.…”

“…NaOH (119 mg, 3.15 mmol) was added in compound 24 (585 mg, 2.33 mmol) in ethanol/H 2 O solution (1:1, 10 mL) reflux for 8 h. After completion of the reaction (30% EtOAc/hexane, TLC), the solvent was evaporated under a vacuum and the crude product flushed through a silica gel chromatography column and eluted with 10% EtOAc/hexane to give 25 (486 mg, 83% yield) as a pale yellow solid. , IR (KBr film) ν max = 2917, 2215, 1683, 1487, 1438, 1379, 1144 cm –1 . 1 H NMR (300 MHz, CDCl 3 ) δ 7.32–7.27 (m, 2H), 7.22 (d, J = 8.1 Hz, 2H), 6.22 (dd, J = 1.1, 0.7 Hz, 1H), 6.17 (d, J = 0.6 Hz, 1H), 4.95 (d, J = 0.7 Hz, 2H), 2.33 (s, 3H), 1.76 (d, J = 1.2 Hz, 3H).…”

“…NaOH (119 mg, 3.15 mmol) was added in compound 24 (585 mg, 2.33 mmol) in ethanol/H 2 O solution (1:1, 10 mL) reflux for 8 h. After completion of the reaction (30% EtOAc/hexane, TLC), the solvent was evaporated under a vacuum and the crude product flushed through a silica gel chromatography column and eluted with 10% EtOAc/hexane to give 25 (486 mg, 83% yield) as a pale yellow solid. 52,53 5-((2R,3R,4R)-3,4-Dihydroxytetrahydrofuran-2-yl)-2-phenyl-1Hpyrrole-3-carbonitrile (26). FeCl 3 (17 mg, 0.11 mmol) was added to a stirred solution of pyrrole 4a (100 mg, 0.35 mmol) in H 2 O/EtOH mixture (1:4, 10 mL) heated at 90 °C.…”

Synthesis of densely functionalize pyrroles from unprotected carbohydrates

“…165 Further, we demonstrated efficient synthesis of pyrroloozazine 25 in 53% overall yield from pyrrole 6b through a series of reactions as shown in Scheme 2-2b. 166,167 There are very limited routes to synthesize pyrroloozazine despite their many reported bioactivities. 168,169 Our approach represents a sustainable synthesis with high substitution at the pyrrole ring and gives excellent overall yield.…”