Gold(i)-catalyzed diastereoselective synthesis of 1-α-oxybenzyl-1H-indenes

Abstract

The gold(i)-catalyzed oxycyclization of β-aryl monosubstituted o-(alkynyl)styrenes gives rise to 1-α-methoxy or 1-α-hydroxybenzyl-1H-indenes in a diastereospecific way. In contrast to β,β-disubstituted o-(alkynyl)styrenes, the stereochemical outcome of this process, diastereospecific reaction supports the higher contribution of a gold intermediate with a cyclopropylcarbene-like character.

Unlocking the 5‐exo Pathway with the AuI‐Catalyzed Alkoxycyclization of 1,3‐Dien‐5‐ynes

“…We selected dienyne 1a, bearing an internal alkyne moiety, as model substrate for which the expected endo-cyclization would give rise to a cyclopropylgold carbene intermediate A that could lead to different products derived from formal 6-endo or 5-endo cyclization modes. Considering our previous results (see Scheme 1b,c), [15][16][17] -methoxybenzyl cyclopentadiene 2´a should be the preferred product (Scheme 2). An alternative exocyclization would lead to a highly strained cyclopropylgold carbene intermediate B and was unprecedented in the literature (Scheme 2).…”

“…[16] Additionally, we have recently reported the regio and diastereospecific 5-endo nucleophilic cyclization of monosubstituted o-(alkynyl)styrenes (Scheme 1c). [17] In our experience, the involved gold intermediates are well described as homoallylically stabilized carbocations with different degrees of gold carbene-type contribution mainly due to the substrate structure but not to the ancillary ligand electronic properties. Herein, we report the first general example of a gold(I)-catalyzed 5-exo cyclization of 1,5-enynes consisting on the alkoxycyclization of 1-monosubstituted 1,3-dien-5-ynes [18] that takes place in a regio-and diastereospecific manner thus initially supporting the intermediacy of an elusive cyclopropyl gold carbene on a strained bicyclo[2.1.0]pentane skeleton (Scheme 1d).…”

Recent Advances in the Synthesis of Indenes

“…The nucleophilic addition of external oxygen nucleophiles (methanol or water) to β‐arylmonosubstituted o ‐(alkynyl)styrenes 68 under gold(I) catalysis leads selectively to a family of functionalized indene derivatives 69 , through 5‐ endo‐dig cyclizations and in a diastereospecific manner (Scheme ). This could be explained by the likely reaction mechanism in which the contribution of cyclopropyl gold carbene II is greater, if not exclusive, than the one of alkenylgold carbocation I .…”

Gold(i)-catalyzed nucleophilic cyclization of β-monosubstituted o-(alkynyl)styrenes: a combined experimental and computational study

“…As reported in our prior publication, 15 we had described the regiospecific 5-endo methoxycyclization of selected -aryl o-(alkynyl)styrenes 1 that diastereospecifically led to 1methoxybenzyl-1H-indenes 2 in high yields and typically short reaction times ( Then, we turned our attention to -alkyl monosubstituted o-(alkynyl)styrenes 3. (E)-3a, bearing a methyl group as substituent at the -position, was selected as model substrate and submitted to the same reaction conditions prior described for -aryl o-(alkynyl)styrenes 1.…”

“…14 With this goal in mind, we have recently reported the methoxycyclization of -aryl o-(alkynyl)styrenes that takes place in a regiospecific 5-endo mode (Scheme 1b). 15 However, for these substrates the regiochemistry of the potential cyclization is not obviously predicted. 16 Considering the carbocationic-like intermediates that would account for the competitive 5-endo and 6-endo cyclizations, both types of ring closures must locate the positive charge at secondary carbon atoms (Scheme 1c).…”