Synthesis of Polycyclic Amides via Tandem Rh^III‐Catalyzed C−H Activation and Annulation from Dioxazolones and Alkynes

Abstract

Ah ighly efficient synthesis of polycyclic amides by aR h III -catalyzed cascade cyclization of 3-phenyl-1,4,2dioxazol-5-one and diphenylacetylene has been developed. This one-pot strategy expandedt he application scope of directing groups to dioxazolones. Scheme3.The scopeo fs ubstituted alkynes. General reaction conditions unless otherwise specified:0.05mmol of 1a,2.5 equiv of 2,2 .5 mol %o f [Cp*RhCl 2 ] 2 ,0 .5 mL of DCE, 2.2 equiv of AgOAc,2equiv of 1-AdCOOH, 120 8C, Ar atmosphere, 22 h. Isolated yield. [a] Reactionp erformedon 0.2 mmol scale of 1a.Scheme4.Reactionof1a with 5-decyne. Scheme5.Intermolecular competition experiments.Scheme6.Deuterium-labeling experiments.

Construction of Pyranoisoquinolines via Ru(II)-Catalyzed Unsymmetrical Double Annulation of N-Methoxybenzamides with Unactivated Alkynes

“…Motivated by the successful double annulation of arenes with aliphatic alkynes (Scheme ), we next performed an identical transformation to explore two distinct alkynes. We anticipate that each alkyne would be able to undergo annulations with the respective N -methoxybenzamide derivative to provide a mixture of products [symmetrical double annulation with 1,2-dialkyl alkyne to provide A , double annulation with 1,2-diaryl alkyne to linearly fused π-extended heterocycle B , unsymmetrical double annulation at first with 1,2-diaryl alkyne and then with 1,2-dialkyl alkyne to linearly fused π-extended heterocycle C , and finally, the desired product D formed through unsymmetrical double annulation at first with 1,2-dialkyl alkyne and then with 1,2-diaryl alkyne; Scheme ], as each step of the annulation does not necessarily run to completion. ,, To avoid the competitive annulations associated from each alkyne and the formation of several byproducts from incomplete/nonselective annulation, a two-step synthetic strategy has therefore been planned. Thus, the first step involves a NHOMe-promoted o -C–H monoannulation with 1,2-dialkyl alkyne, and the second step comprises the C(8)–H activation and the annulation of isoquinolone, obtained from the first step, with structurally diverse alkynes.…”

“… , In this context, the synthetically viable transition metal-catalyzed directing group (DG) that promoted annulation of inert C–H bonds has principally been found to be beneficial for the fabrication of complex heterocycles. , Thus, the domain of monoannulation strategies has widely been investigated by roping the heteroatom of the DG along with inert C–H bonds (close proximity to the DG) of the molecular scaffold and/or a connecting unit (olefin/alkyne/carbene/etc. ). ,− In addition, multiple C–H bonds have been used in the development of stepwise (under different catalytic conditions; Scheme A) and sequential (one catalytic system with successive addition of reactive agents; Scheme A) annulation methods for the construction of π-extended fused heterocycles. , However, in most cases, a single o -C–H bond of the parent hetero­(arene) motif has exclusively been involved in the double annulations with alkynes accessing linearly fused π-extended heterocycles (path I, Scheme B). , On the other hand, both o -C–H bonds of hetero­(arenes) for the identical double annulation with alkynes to the synthesis of an angularly fused π-extended heterocycle has been less explored (path II, Scheme B); mainly, the molecular rigidity and conformation strain obstruct this challenging transformation. , Moreover, the undisputed concerns, i.e., uncontrolled reactivity and the lack of selectivity attenuated in each annulation and the catalyst dependable DG-assisted functionalization of a particular o -C–H bond, make the angular double annulations ineffective (path II, Scheme B) . In spite of these challenges, both o -C–H bonds of benzoylacetonitrile, enaminoester, or polyaromatic aldehyde have successfully been employed for the one-pot double annulation with alkynes in the presence of rhodium (Rh) catalyst.…”

Transition Metal‐Catalyzed Intermolecular Cascade C−H Activation/Annulation Processes for the Synthesis of Polycycles

“…Control experiments indicated that this transformation is a stepwise process and that isoquinolone is the key intermediate. Inspired by their works, Zhao, [23] Shi [24] and Dong [25] independently investigated Rh III ‐catalyzed cascade double C−H activation/annulation for the synthesis of the same type of tetracyclic products using different directing groups (Scheme 4).…”

Ir(III)/MPAA-Catalyzed Mild and Selective C–H Amidation of N-Sulfonyl Ketimines: Access To Benzosultam-Fused Quinazolines/Quinazolinones

“…Unfortunately, their use has been limited to Rh, − Co, − and Ru catalysts with rather strong coordinating groups. Apart from direct C–H amidation, they have also been employed in several amidation–cyclization cascades and, lately, also as a directing group . However, a versatile and mild amidation reaction employing them under iridium catalysis has hardly been explored. , In continuation of our transition-metal-catalyzed C–H bond activation program, we now wish to report an oxidant-free MPAA accelerated Ir­(III)-catalyzed ortho- selective C–H amidation at a near ambient temperature for weak directing N -sulfonyl ketimines, using 1,4,2-dioxazol-5-ones as the amidating reagents.…”