Transition-metal-catalyzed synthesis of quinazolines: A review

Abstract

Quinazolines are a class of nitrogen-containing heterocyclic compounds with broad-spectrum of pharmacological activities. Transition-metal-catalyzed reactions have emerged as reliable and indispensable tools for the synthesis of pharmaceuticals. These reactions provide new entries into pharmaceutical ingredients of continuously increasing complexity, and catalysis with these metals has streamlined the synthesis of several marketed drugs. The last few decades have witnessed a tremendous outburst of transition-metal-catalyzed reactions for the construction of quinazoline scaffolds. In this review, the progress achieved in the synthesis of quinazolines under transition metal-catalyzed conditions are summarized and reports from 2010 to date are covered. This is presented along with the mechanistic insights of each representative methodology. The advantages, limitations, and future perspectives of synthesis of quinazolines through such reactions are also discussed.

Keywords: catalysis; mechanism; quinazoline; synthesis; transition-metal.

FIGURE 1

Quinazoline-containing drugs and natural products.

FIGURE 2

First-, second-, and third-row transition-metal-catalyzed synthesis of quinazolines and first reported examples involved in the synthesis of quinazolines (2012–2022).

SCHEME 1

(A) Titanium tetraiodide and TMSI synergistically induced synthesis of 2-aryl-4-iodoquinazolines (B) Synthesis of quinazolines and spiro-quinazolines using Ti catalyst (C) Proposed Mechanism for the construction of quinazolines.

SCHEME 2

(A) Synthesis of quinazolines using MnO₂ as catalyst (B) Synthesis of quinazolines using Manganese oxide OMS-2 catalyst (C) Synthesis of quinazolines using Manganese-Pincer complex.

SCHEME 3

(A) Synthesis of quinazolines under Manganese catalysis (B) Synthesis of quinazolines using Manganese based nanocomposites OMS-2.

SCHEME 4

(A) Synthesis of quinazolines catalyzed by magnetic ionic liquid bmim [FeCl₄] (B) Fe/Cu relay-catalyzed synthesis of quinazolines (C) FeBr₂ catalyzed synthesis of quinazolines (D) Synthesis of quinazolines via iron-catalyzed C(sp³)-H oxidation.

SCHEME 5

(A) Synthesis of quinazolines by Fe-catalyzed acceptorless dehydrogenative coupling (B) Synthesis of quinazolines using Fe₃O₄@Sap/Cu(II) nanocatalyst.

SCHEME 6

(A) Cobalt imidazolate framework ZIF-67 catalyzed synthesis of quinazolines (B) Cp*Co(CO)I₂ catalyzed synthesis of quinazolines (C) Synthesis of quinazolines via Co catalyzed [4 + 2] cycloaddition (D) Co-catalyzed ADC coupling for the synthesis of quinazolines.

SCHEME 7

(A) Synthesis of quinazolines via Ni-catalyzed acceptorless dehydrogenative coupling (B) Plausible mechanism for the construction of quinazolines through ADC reaction (C) Synthesis of quinazolines via Ni catalyzed dehydrogenative coupling (D) Synthesis of quinazolines via Ni-catalyzed C-N cross coupling (E) Proposed mechanism for Ni-catalyzed synthesis of quinazolines.

SCHEME 8

(A) Proposed mechanism for Ni-catalyzed synthesis of quinazolines (B) Proposed mechanism for Ni-catalyzed synthesis of quinazolines (C) CuBr catalyzed synthesis of quinazolines via C-H alkynylation (D) CuO NPs catalyzed synthesis of quinazolines (E) CuCl catalyzed synthesis of quinazolines.

SCHEME 9

(A) CuCl/DABCO/TEMPO- catalyzed synthesis of quinazolines (B) Cu(OTf)₂ catalyzed synthesis of quinazolines via [2 + 2+2] annulation (C) CuBr catalyzed synthesis of quinazolines (D) Cu-catalyzed annulation of amidines for the synthesis of quinazolines (E) CuCl catalyzed cascade synthesis of quinazolines.

SCHEME 10

(A) Cu(OAc)₂ catalyzed synthesis of quinazolines (B) Cu-benzotriazole catalyzed synthesis of quinazolines (C) Cu-catalyzed cascade coupling and aerobic oxidation for the synthesis of quinazolines (D) CuFe₂O₄ NPs catalyzed synthesis of quinazolines.

SCHEME 11

(A) Synthesis of quinazolines via CuO NPs catalyzed oxidative coupling (B) Cu(I)-catalyzed N-arylation for the synthesis of quinazolines (C) Cu-catalyzed amination/one-pot method for the synthesis of quinazolines.

SCHEME 12

(A) Cu-catalyzed dual oxidative benzylic C-H amination for the synthesis of quinazolines (B) Cu2O nanocubes-catalyzed synthesis of quinazolines (C) Synthesis of quinazolines via Cu-catalyzed transimination.

SCHEME 13

(A) Cu(OAc)₂ catalyzed C-C bond cleavage for the synthesis of quinazolines (B) Cu-catalyzed oxidative amination of methanol for the synthesis of quinazolines (C) Cu-catalyzed aerobic oxidative cyclization for the synthesis of quinazolines.

SCHEME 14

(A) Cu/Ag-catalyzed synthesis of quinazolines (B) Cu-catalyzed photoredox synthesis of quinazolines (C) Cu-catalyzed [3 + 2 + 1] annulation for the synthesis of quinazolines (D) I₂/CuCl₂-copromted [4 + 1 + 1] cyclization for the synthesis of quinazolines (E) Fe₃O₄@SiO₂-SMTU-Cu nanocomposite catalyzed synthesis of quinazolines.

SCHEME 15

(A) Ru₃(CO)₁₂ catalyzed ADC coupling for the synthesis of quinazolines (B) Ru-catalyzed C-H activation and annulation for the synthesis of quinazolines (C) Ligand-promoted Ru-catalyzed synthesis of quinazolines.

SCHEME 16

(A) Ru(II) NNN pincer catalyzed synthesis of quinazolines (B) Ru(III)-catalyzed ADC synthesis of quinazolines (C) Ru NNN pincer catalyzed acceptorless dehydrogenative synthesis of quinazolines.

SCHEME 17

(A) Rh(III)-catalyzed synthesis of quinazolines (B) Rh- and Cu-co-catalyzed C-H activation for the synthesis of quinazolines (C) Rh(II)- catalyzed transannulation for the synthesis of quinazolines.

SCHEME 18

(A) Rh(III)-catalyzed [5 + 1] annulation for the synthesis of quinazolines (B) Rh(III)-catalyzed synthesis of quinazolines (C) Rh(III)-catalyzed one-pot cascade synthesis of quinazolines (D) Rh(III)-catalyzed tandem access to quinazolines.

SCHEME 19

(A) Pd-catalyzed carbonylative synthesis of quinazolines (B) Pd-catalyzed carbonylative synthesis of quinazolines (C) Pd-catalyzed synthesis of quinazolines via hydrogen transfer strategy (D) Pd-catalyzed synthesis of quinazolines under microwave irradiation (E) Heterogenous Pd-catalyzed synthesis of quinazolines via HT approach.

SCHEME 20

(A) Pd-catalyzed synthesis of quinazolines via reductive carbonylation (B) Pd-N,N,O-pincer type complex for the synthesis of quinazolines via double dehydrogenative coupling.

SCHEME 21

Ag/Pd NPs catalyzed synthesis of quinazolines.

SCHEME 22

(A) Iridium catalyzed synthesis of quinazolines via hydrogen transfer strategy (B) Ir-catalyzed synthesis of quinazolines via acceptorless dehydrogenative cyclization (C) Ir-catalyzed synthesis of quinazolines via ligand promoted dehydrogenation (D) Naphthyridine-based Ir-catalyst for the synthesis of quinazolines (E) Ir-catalyzed synthesis of quinazolines via ADC reaction.

SCHEME 23

(A) Pt NPs catalyzed synthesis of quinazolines via acceptorless dehydrogenation (B) TiO₂-supported Au-NPs for the synthesis of quinazolines via hydrogen transfer strategy.