Scheme 20. Phosphonation of pyridinones.Scheme 21. CuI-catalyzed phosphoramidate formation.Scheme22. Phosphonation of coumarin and quinolinone.Scheme23. Silver(I)-catalyzed phosphonation of coumarins. Scheme 33. Electrochemical C(sp 2 )ÀHphosphonation of quinoxaline-2(1H)-ones. Scheme 39. Phosphorylation of quinoxaline-2(1 H)-ones. Scheme40. Autoxidative phosphorylation of quinoxalines. Scheme 41. DTBP-mediated formation of phosphonated benzothiazoles. Scheme42. Phosphonation of imidazole[2,1-b]thiazoles.Scheme 47. Copper(I)-catalyzedp hosphonationo fN-iminoisoquinolinium ylides. Scheme48. Aerobic phosphonationofC ( sp 3 ) À Hbonds. Scheme 49. Copper(II)/PBQ-catalyzed phosphorylation of 3,4-dihydro-1,4-benzoxazin-2-ones. Scheme 87. Asymmetric exo-selective [3+ +2] cycloaddition to afford phosphorus-substituted pyrrolidines. Scheme 95. Cascade condensation/cyclization to phosphonylated thienopyridines. Scheme 96. S N Ar'-involved cascade reactions to phosphonylated oxygenorn itrogen heterocycles.Scheme 97. Manganese(III)-mediated synthesis of 3-phosphonyldihydrofuransfrom b-ketophosphonates.Scheme98. Cyclization to phosphonated isochromenes.Scheme 121. Asymmetric [4+ +2] cycloaddition of b,g-unsaturated a-ketophosphonates.

Phosphorus-containing indole derivatives represent a special class of phosphorus-containing nitrogen heterocycles. This review summarizes the recent progress in the synthesis of such compounds, briefly discusses the reaction mechanisms and challenges, and outlines the synthetic opportunities still open.

A Brønsted acid catalysed regiodivergent phosphorylation of 2-indolylmethanols with diarylphosphine oxides has been established, which provides a brand-new strategy for accessing highly functionalized phosphorus-containing indoles with structural diversity. Under the catalysis of HOTs·H2O, 2-indolylmethanols undergo regioselective benzylic phosphorylation at room temperature to afford benzylic site phosphorylated indoles in good to high yields (29 examples, up to 98% yield), while C3-phosphorylated indoles are obtained in the presence of HOTf under heating conditions (16 examples, up to 83% yield). Preliminary mechanistic studies suggest that C3-phosphorylated indoles are possibly obtained partially from direct C3-phosphorylation and dominantly from a tandem benzylic phosphorylation/[1,3]-P migration/isomerization sequence from 2-indolylmethanols. Furthermore, the acidity of the Brønsted acid and the reaction temperature play a vital role in the [1,3]-P migration of benzylic phosphorylated indoles to form C3-phosphorylated indoles. This protocol serves as a good example for regioselective benzylic functionalization of 2-indolylmethanols.

A novel method to synthesize C2-phosphorylmethylindoles via the carbocation formation initiated tandem phosphorylative allenylation/cyclization of 1-(o-aminophenyl)prop-2-ynols with the P(O)–H species has been developed.

A highly efficient and general nucleophilic substitution reaction between dialkyl H-phosphonates or diarylphosphine oxides and triarylmethanols catalyzed by HOTf (trifluoromethanesulfonic acid) has been developed. It provides an atom-economical protocol for the synthesis of various symmetrical and unsymmetrical phosphorus-substituted triarylmethanes that constitute an emerging family of potent anticancer agents in rich diversity with 40 to 96% yields. The synthetic applicability of this protocol is demonstrated by gram-scale preparations.

An efficient and practical method for synthesis of C2‐phosphorylated indoles has been disclosed via a metal‐free 1,2‐phosphorylation of 3‐indolylmethanols with H‐phosphine oxides or H‐phosphonates. This alternative protocol features a broad substrate scope with respect to both 3‐indolylmethanols derived from isatins, acyclic α‐keto amide, α‐keto ester, 1,2‐diketone and simple ketones and H‐phosphine oxides or H‐phosphonates, moderate to high yields and mild reaction conditions. Mechanistic studies indicate that this reaction proceeds via an unusual direct 1,2‐addition pathway, in which the existence of an electron‐withdrawing group adjacent to the hydroxyl group of 3‐indolylmethanols plays a decisive role.magnified image

The construction of tetrasubstituted carbon centers (especially chiral ones) represents one of the most challenging and demanding topics in the synthesis of natural products and related drugs. The development of isoindolinones with this feature appears to be of great importance, because 3,3disubstituted isoindolinones, which feature all kinds of tetrasubstituted carbon centers, also including spirocyclic and all-carbon or heteroatom-containing centers, show a wide spectrum of biological and pharmaceutical activities. Therefore, the synthetic methodologies for preparing these skeletons have received significant attention during the past decade. In general, these strategies can be classified into two major categories, namely the direct functionalization of parent isoindolinones and lactam-ring-formationinvolved reactions, depending on whether there is a lactam-ring-formation process or not during the production of the final 3,3-disubstituted isoindolinone. Since the second strategy has been well reviewed, this review mainly summarizes the recent progress in the direct functionalization of parent isoindolinones to construct 3,3-disubstituted isoindolinones via three subdivided strategies.

In recent decades, reactions of inexpensive and abundantly available alcohols (C−OH) with nucleophilic P(O)−H compounds, leading to the construction of C−P bonds, have emerged as one of the most efficient strategies as it is an atom‐economical and environmental benign approach with water as the only by‐product. Various organophosphorus compounds bearing C(sp3)−P, C(aryl)−P and C(alkenyl)−P bonds have been achieved via this direct dehydrative cross‐couplings under Brønsted or Lewis acid catalysis. This review article aims to summarize the recent advances in such dehydrative and related C−P bond forming strategies, to briefly discuss the reaction mechanisms and challenges, and to outline synthetic opportunities that are still open.