Gold‐Catalyzed Dual Annulation of Homopropargyl Alcohols with Nitrones: Synthesis of Tetrahydropyrano[4,3‐b]indole Scaffolds

Abstract

An unprecedented gold-catalyzed dual annulation of homopropargyl alcohols with nitrones has been developed, which provides an effective access to the 1,3,4,5-tetrahydropyrano[4,3-b]indole derivatives in good to high yields. Mechanistically, this one-pot three-step cascade reaction is initiated by a gold-catalyzed alkyne oxoarylation, followed by an intramolecular cyclodehydration and terminated with an intermolecular cyclization with aldehyde which is a leaving species in the early stage of this cascade process.

Gold‐Catalyzed Iminations of Terminal Propargyl Alcohols with Anthranils with Atypical Chemoselectivity for C(1)‐Additions and 1,2‐Carbon Migration

“…Running this mixture at 70 8Cl ed to ac omplete consumption of species 1a,g enerating the desired compound 3a in 72 %y ield (entry 2). We applied thesec onditions to other gold catalysts, L'AuCl/AgNTf 2 (L' = IPr,P Ph 3 ,a nd P(OPh) 3 ); the desired 3a were obtained in 52-42 %y ield with IPr being the most productive (entries [3][4][5]. With variations of the silver salts as in P(tBu) 2 (obiphenyl)AuCl/AgX 2 (X = SbF 6 and OTf), the yields of compound 3a were 10 %a nd 21 %, respectively (entries6-7).…”

“…[1] In the context of regioselectivity,i ntermolecular nucleophilica dditions occur typically with the more positive C(2)-carbonso ft erminal alkynes bearing an alkyl, aryl, heteroaryl, sulfonamide, or alkoxy group. [1][2][3] Despitei ntensive interest, we are aware of very few instances [4][5] focusingo nt he alteration of the reactionc hemoselectivity with alkyne substituents.W er ecently reported gold-catalyzed oxidative Mannich reactions of 1-butyn-4-ols with nitro-nes, leading to formation of a-oxo goldc arbenes (In-2); [4] the regioselectivity followed at ypicalC (2)-addition [Scheme 1 (2)]. In contrast, their siloxy derivatives preferably undergo distinct oxoarylations through a3 ,3-sigmatropic shift of key intermediate ln-3,affording indole products [Scheme 1 (3)].…”

“…In contrast, their siloxy derivatives preferably undergo distinct oxoarylations through a3 ,3-sigmatropic shift of key intermediate ln-3,affording indole products [Scheme 1 (3)]. [5] These two distinct C(2)-regioselectiver eactions indicate that af ree alcohol, as in species ln-1 and ln-2,t ends to stabilize aoxo gold carbenes (I)t hrough aw eak Au-OH bonding. Recently,Hashmi,Y e, and colleagues reported gold-catalyzed intermolecular [3+ +2]-annulationso ft erminal alkynes with anthranils or isoxazoles throughat raditional C(2)-addition[ Scheme 1 (4)].…”

“…[6,7] In this work, we disclose the feasibility of novel C(1)-iminations between substituted prop-1-yn-3-ols and isozaxoles or anthranil nucleophiles. Notably,t he unsubstituted (R = H) and siloxy derivatives of thesep rop-1-yn-3-ols follow at ypical C(2)-addition route to afford indole products [Scheme 1 (5)]. A ccordingly,t his work first realizes the C(1)-regioselectivity,w hich is controlled by neighboringb ulky alcohols.…”

“…Apart from this C(1)-regioselectivity,t his gold catalysis generates a-imino gold carbenes that preferably have phenyl, vinyl, and cyclo-propyl substituents as 1,2-migratingg roups whereas the hydrogeni sn ot movable [Scheme 1 (5)]. T his 1,2migration pattern is novel for gold carbenes.…”