Chiral Brønsted acid-catalyzed asymmetric intermolecular [4 + 2] annulation of ynamides with para-quinone methides

Primary activation ofpara-quinone methides by chiral phosphoric acid for enantioselective construction of tetraarylmethanes

“…3 Their strong tendency for aromatization permits the catalytic asymmetric 1,6-conjugate nucleophilic addition to the remote methide position, enabling rapid construction of a range of a benzylic stereogenic centers. 4,5 While a range of catalytic asymmetric systems have been reported for these reactions, many of them required the presynthesis of those generally unstable QMs and thus limited the utility of such reactions. 4 In 2015, we reported the first example of using chiral phosphoric acids (CPAs) as catalysts for the asymmetric nucleophilic addition to p -QMs (Scheme 1a).…”

“…4,5 While a range of catalytic asymmetric systems have been reported for these reactions, many of them required the presynthesis of those generally unstable QMs and thus limited the utility of such reactions. 4 In 2015, we reported the first example of using chiral phosphoric acids (CPAs) as catalysts for the asymmetric nucleophilic addition to p -QMs (Scheme 1a). 5 a Notably, this catalytic system does not require the presynthesis of p -QMs, as it allows the in situ generation of QMs from the corresponding stable, racemic benzylic alcohols and subsequent asymmetric addition to take place in a one-pot fashion.…”

“…However, despite the broad utility of CPA catalysts 7 in p -QM chemistry, 4–6 it is worth noting that, due to the typically long distance between the carbonyl activation site and the nucleophilic addition site, so far all the CPA-catalyzed p -QM addition reactions took advantage of the bifunctional activation mode, i.e. , the CPA catalyst not only activates the QM carbonyl, but also has an effective hydrogen bonding interaction with the nucleophile partner (Scheme 1a).…”

Three-component approach to modular synthesis of tetra-substituted furans and pyrroles

“…12 Initiated by 1,6-addition with a nucleophile or a radical donor, a series of functionalized phenols and derivatives were constructed in high efficiency. 13 With our continuous interest in excavating the potential chemical reactivity of TMSCF 2 Br and p -QMs, 14 we herein report a three-component one-pot reaction of p -QMs, TMSCF 2 Br and 1,3-dicarbonyl compounds for the modular synthesis of tetra-substituted furans and pyrroles (Scheme 1c). Initiated by 1,6-addition between p -QMs and TMSCF 2 Br, adducts 2 were obtained in excellent yields.…”

3-Nitroindoles Serving as N-Centered Nucleophiles for Aza-1,6-Michael Addition to para-Quinone Methides

“…Among these reactions, 3-nitroindoles are characterized by their readiness to be attacked by nucleophiles at the C2-position and sequentially trapped by electrophiles with the C3-position for the synthesis of indoline-containing polycyclic compounds ( Scheme 2 a). On the other hand, we have noticed that in the field of para -quinone methides ( p -QMs) chemistry [ 34 , 35 , 36 , 37 ], ortho -hydrophenyl p -QMs have been used as donors to trigger some cycloaddition reactions with electron-deficient 2π-components, providing an access to chromans with structural diversity [ 38 , 39 , 40 , 41 , 42 , 43 , 44 ]. Along this line, as well as our continuing efforts on the dearomatization of nitroheteroarenes [ 45 , 46 , 47 , 48 ], we conceived that the dearomative [4 + 2] cycloaddition of electron-deficient 3-nitroindoles and ortho -hydrophenyl p -QMs might occur via the tandem oxy -Michael addition/1,6-addition under alkaline conditions ( Scheme 2 b) [ 49 ].…”