Selective Preparation of Pyridines, Pyridones, and Iminopyridines from Two Different Alkynes via Azazirconacycles

Abstract

Selective preparation of pyridine derivatives from two different alkynes and a nitrile was achieved by a novel procedure in which an alkyne and a nitrile couple first to give an azazirconacyclopentadiene followed by reaction with the second alkyne in the presence of 1 equiv of NiCl(2)(PPh(3))(2). This procedure gives only single products of pyridine derivatives from two different symmetrical alkynes and a nitrile. Our novel procedure can be used even with two similar alkyl-substituted alkynes such as 3-hexyne and 4-octyne. Two possible pyridine isomers from 3-hexyne, 4-octyne, and acetonitrile could be completely and independently prepared as single products by this method. The origin of the selectivity comes from the addition order of two different alkynes. This method was applied for the formation of pyridones and iminopyridines using isocyanate and carbodiimide derivatives instead of nitriles, respectively. Reaction of an alkyne with Cp(2)ZrEt(2) and an isocyanate or a carbodiimide gives an azazirconacycle. Treatment of the azazirconacycle with the second alkyne in the presence of 1 equiv of NiCl(2)(PPh(3))(2) gave a pyridone or an iminopyridine derivative. The use of two different unsymmetrical alkynes afforded the pyridine with five different substituents when the first alkyne has a trialkylsilyl group and the second alkyne has a phenyl group as functional groups. On the other hand, azazirconacyclopentadienes reacted with propargyl bromide in the presence of CuCl with excellent regioselectivity to give tetrasubstituted pyridine derivatives as single products. With the assistance of the trialkylsilyl groups, pyridines with all different substituents including H were also prepared.

Synthesis, Coordination Chemistry and Bonding of Strong N‐Donor Ligands Incorporating the 1H‐Pyridin‐(2E)‐Ylidene (PYE) Motif

“…Ligand synthesis and characterisation: There are a limited number of methods for the preparation of hydrocarbyl-substituted PYEs, which have mainly relied on a cyclotrimerisation methodology, [4,[6][7][8][9]12] because the alkylation of 2-aminopyridine [2,3] is typically unselective and condensation reactions between 2-pyridinone and primary amines generally do not occur. Consequently, none of these methods are compatible with the synthesis of compounds containing multiple PYE motifs.…”

Synthesis of Multi‐Substituted 2‐Iminopyridine by Conjugate Addition of Ethyl Cyanoacetate Derivatives to Alkynyl Imines

“…5 M e P h T f O H [g] (1.0) [e] in TFA [b] 24.0 12a 70 reflux temp. 6 M e nBu TfOH [g] (1.3) [e] in TFA [b] 24.0 12b 47 (48) [c] reflux temp. 7 M e nBu TfOH [g] (3.0) [e] in TFA [b] 24.0 12b 59 reflux temp.…”

“…[6] However, the former methods are not satisfactory from the point of view of synthesizing 2-iminopyridines possessing the desired substituents. Therefore, the development of alternative methods for the synthesis of multi-substituted 2-iminopyridines from readily available starting materials is highly desirable.…”

Recent Strategies for the Synthesis of Pyridine Derivatives

“…[47] This process involves nitrile displacement of Scheme 27. The original [3 + 3] Bohlmann-Rahtz pyridine synthesis.…”