This work describes gold‐catalyzed annulations of electron‐deficient alkynes with benzisoxazoles to yield quinoline oxides chemoselectively. Chemical functionalizations of these resulting azacyclic ...compounds afforded various oxygenated tetrahydroquinolines which are present as the cores of many bioactive molecules. With the same reactants, a new relay catalysis using gold and zinc(II) catalysts affords highly oxygenated tetrahydroquinoline derivatives stereoselectively.
Tag team: This work describes gold‐catalyzed 4+2 annulation/cyclization cascades of electron‐deficient alkynes with benzisoxazoles to yield quinoline oxides chemoselectively. With the same reactants, a new relay catalysis using gold and zinc(II) catalysts afford highly oxygenated tetrahydroquinoline derivatives stereoselectively. Tf=trifluoromethanesulfonyl.
Nitrone and nitroso species are versatile compounds to react with alkenes or butadienes to access five‐ and six‐membered nitroxy (NO) containing heterocycles, to offer further access to acyclic 1,3‐ ...and 1,4‐amino alcohols after facile cleavage of the NO bonds. The N‐ and O‐functionalizations of alkynes with nitrones or nitroso species have been explored less well than the corresponding alkene reactions. In recent decades, gold catalysts have enabled the electrophilic activation of alkynes with weak nucleophiles. This review summarizes recent progress to implement N‐ and O‐functionalizations of alkynes with common NO containing species including nitrone, nitroso, nitro and other nitroxy derivatives. Reported reactions include the following three topics: (i) 1,2‐difunctionalizations, (ii) cyclizations and (iii) cycloaddition or annulation reactions. The review is organized according to the types of nucleophiles, followed by reactions of the mentioned types. Enantioselective functionalizations of alkynes with these nitroxy nucleophiles are also included.
Gold‐catalyzed cycloadditions of ynamides with azidoalkenes or 2H‐azirines give 3+2 or 4+3 formal cycloadducts of three classes. Cycloadditions of ynamides with 2H‐azirine species afford pyrrole ...products with two regioselectivities when the Cβ‐substituted 2H‐azirine is replaced from an alkyl (or hydrogen) with an ester group. For ynamides substituted with an electron‐rich phenyl group, their reactions with azidoalkenes proceed through novel 4+3 cycloadditions to deliver 1H‐benzodazepine products instead.
Completing the ring: Gold‐catalyzed cycloadditions of ynamides with azidoalkenes or 2H‐azirines give three distinct classes of 3+2 or 4+3 cycloadducts, depending on the types of the initial ynamides and 2H‐azirines (see scheme; EWG=electron‐withdrawing group).
The catalytic formation of gold enolates from alkynes, nitrones, and nucleophiles is described, and their Mannich reactions result in nucleophile‐directed chemoselectivity through cooperative ...catalysis. For 1‐alkyn‐4‐ols and 2‐ethynylphenols, their gold‐catalyzed nitrone oxidations afforded N‐containing dihydrofuran‐3(2H)‐ones with syn selectivity. The mechanism involves the Mannich reactions of gold enolates with imines through an O‐H‐N hydrogen‐bonding motif. For aryloxyethynes, their gold enolates react selectively with nitrones to deliver 3‐alkylidenebenzofuran‐2‐ones, as controlled by a C‐H‐O hydrogen‐bonding motif.
’Syn'tax: Reported is the catalytic formation of gold enolates from alkynes, nitrones, and nucleophiles. The resulting Mannich reactions result in nucleophile‐directed chemoselectivity derived from cooperative catalysis. For 1‐alkyn‐4‐ols and 2‐ethynylphenols, their gold‐catalyzed nitrone oxidations afforded N‐containing dihydrofuran‐3(2H)‐ones with syn selectivity, and for aryloxyethynes, 3‐alkylidenebenzofuran‐2‐ones are delivered.
Reported herein is the novel gold‐catalyzed intermolecular 2+2+2 cycloaddition of ynamides with two discrete nitriles to form monomeric 4‐aminopyrimidines, which are pharmaceutically important ...structural motifs. The utility of this new cycloaddition is demonstrated by the excellent regioselectivity obtained using a variety of ynamides and nitriles.
In addition: A novel gold‐catalyzed intermolecular 2+2+2 cycloaddition of ynamides with two discrete nitriles leads to monomeric 4‐aminopyrimidines. The utility of this cycloaddition is demonstrated by the excellent regioselectivity obtained by using a variety of ynamides and nitriles. DCE=1,2‐dichloroethane, EWG=electron‐withdrawing group.
Gold‐catalyzed cascade reactions between 1,5‐diyn‐3‐ols and nitrones to deliver carbazole derivatives are described. Such cascade reactions are applicable to facile synthesis of polyaromatic ...compounds containing carbazole subunits. Notably, the reaction mechanism involves unexpected oxoarylations, rather than oxidative Mannich reactions as known for but‐1‐yn‐4‐ols. Our control experiments indicate that the presence of a second alkyne as in 1,5‐diyn‐3‐ols enables such oxoarylations due to a weak bonding between gold and this alkyne, rending the tethered alcohol less conformationally flexible.
This work reports gold‐catalyzed 4+3‐annulations of 2‐(1‐alkynyl)‐2‐alken‐1‐ones with anthranils to yield epoxybenzoazepine products with excellent exo‐diastereoselectivity (dr>25:1). The utility of ...this new gold catalysis is manifested by applicable substrates over a broad scope. More importantly, the enantioselective versions of these 4+3‐cycloadditions have been developed satisfactorily with chiral gold catalysts under ambient conditions (DCM, 0 °C); the ee levels range from 88.0–99.9 %. With DFT calculations, we postulate a stepwise pathway to rationalize the preferable exo‐stereoselection.
Gold‐catalyzed 4+3‐annulations of 2‐(1‐alkynyl)‐2‐alken‐1‐ones with anthranils to yield epoxybezoazepine products with excellent exo‐diastereoselectivity (dr>25:1) are reported. More importantly, enantioselective versions of these 4+3‐cycloadditions have been developed with chiral gold catalysts under ambient conditions (DCM, 0 °C), with ee levels of 88.0–99.9 %, further highlighting their synthetic values.
Gold‐catalyzed cycloadditions of ethyl diazoacetate, nitrosoarenes, and vinyldiazo carbonyl species to yield isoxazolidine derivatives stereoselectively are described. Treatment of these ...isoxazolidine products with the same catalyst results in a novel 1,2‐H shift/3,3 rearrangement to give benzobazepine compounds. The mechanism of this skeletal rearrangement is elucidated with deuterium‐labeling experiments.
A little shifty: The title reaction yields isoxazolidine derivatives stereoselectively. Treatment of these isoxazolidine products with the same catalyst results in a novel 1,2‐H shift/3,3 rearrangement to give benzobazepine compounds. The mechanism of this skeletal rearrangement is elucidated with deuterium‐labeling experiments. FG=functional group.
Gold‐catalyzed 5+1‐annulations between allenylacetals with diazo esters to form 1,3‐disubstituted naphthoate derivatives are described. Notably, this reaction chemoselectivity is switched to ...2,3‐naphthoate products when using the HOTf catalyst. Mechanistic studies of these reactions support an acetal activation, in which oxoniums are formed initially, followed by attack of the allene, generating allyl cations to trap α‐diazo esters. In gold catalysis, such diazo addition intermediates undergo Roskamp rearrangement, whereas in HOTf catalysis the same intermediates undergo a Conia‐ene reaction instead.
This work reports gold‐catalyzed bicyclic annulations of 2‐alkynyl‐1‐carbonylbenzenes with vinyldiazo ketones that serve as five‐atom building units. The importance of these reactions is to access ...4,5‐dihydro‐benzogindazoles, which form the structural cores of various bioactive molecules. According to our mechanistic analysis, we postulate initial 5+4‐cycloadditions between benzopyrilium intermediates and vinyldiazo ketones, followed by 6‐π‐electrocyclizations to achieve the excellent stereoselectivity.
Golden rings: Gold‐catalyzed annulations of 2‐alkynyl‐1‐carbonylbenzenes with vinyldiazo ketones that serve as five‐atom building units were developed. These reactions provide stereoselective access to 4,5‐dihydro‐benzogindazoles, which form the structural cores of various bioactive molecules.
![Gold‐Catalyzed [4+2] Annula...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1433-7851/small "Gold‐Catalyzed [4+2] Annulation/Cyclization Cascades of Benzisoxazoles with Propiolate Derivatives to Access Highly Oxygenated Tetrahydroquinolines")
