Phosphine‐Catalyzed (3+2) Annulation of Isoindigos with Allenes: Enantioselective Formation of Two Vicinal Quaternary Stereogenic Centers

Abstract

Construction of contiguous all‐carbon quaternary stereogenic centers is a long‐standing challenge in synthetic organic chemistry. In this report, a phosphine‐catalyzed enantioselective (3+2) annulation reaction between allenes and isoindigos, containing either two identical or different oxindole moieties, is introduced as a powerful strategy for the construction of spirocyclic bisindoline alkaloid core structures. The reported reactions feature high chemical yields, excellent enantioselectivities, and very good regioselectivities, and are highly useful for creating structurally challenging bisindoline natural products.

Stereoselective synthesis and applications of spirocyclic oxindoles

“…28 was found to give the highest yield and enantioselectivity in Et 2 O for the [3 + 2] annulation of isoindigos and allenes (Scheme 27). 126 Lu and Mei additionally showed unsymmetrical isoindigos in this process with high regiocontrol, as well as the formal syntheses of a number of complex natural products. Lu, with Ullah, then reported the annulation of pyrazoloneyldiene oxindoles with MBH carbonates using asymmetric phosphorus catalyst, SITCP 29 (Scheme 27).…”

Catalytic Asymmetric Formal [3+2] Cycloaddition of Azoalkenes with 3-Vinylindoles: Synthesis of 2,3-Dihydropyrroles

“…It is intriguing to note that such subtle difference in substrate structure could result in totally different chemoselectivity. The presence of a 2-methyl group may render indole higher nucleophilicity at the C3-position, thus favoring the dearomative process (Mei et al, 2020). Furthermore, no reaction was observed when N-methyl vinylindole 2d was employed (Scheme 1 Equation 3), indicating the indispensability of hydrogen bonding interactions between CPA and the substrates, not only in asymmetric induction but also in reaction activation.…”

“…In the currently available mode of cycloaddition, Wang and others employed azoalkenes as 4-atom (A 4 ) synthons (Int-I), making use of C4 electrophilicity and N1 nucleophilicity of azoalkenes for various asymmetric formal [4 + n] cycloaddition processes (Chen et al, 2012;Gao et al, 2013;Huang et al, 2016;Tong et al, 2014;Wei et al, 2017Wei et al, , 2018Wei and Wang, 2015;Zhang et al, 2018;Zhang and Song, 2018). Very recently, our group discovered an azoalkene-enabled enantioselective dearomatization of indoles (Mei et al, 2020). Given the ubiquitous existence of nitrogen-containing cyclic structural motifs, we questioned whether it might be possible to utilize azoalkenes as a carbon-carbon-nitrogen (CCN) 1,3-diplole surrogate, a 3-atom (A 3 ) synthon (Int-II) in asymmetric formal [3 + 2] cycloaddition reactions, and thereby to access a broad range of nitrogen-containing ring systems (Attanasi et al, 2002a(Attanasi et al, , 2002b(Attanasi et al, , 2005(Attanasi et al, , 2013a(Attanasi et al, , 2013bClarke et al, 1983;Karapetyan et al, 2008;Mari et al, 2017;Ran et al, 2017;Sommer, 1979).…”

“…More recently, Miura and Murakami, as well as the Fokin group, reported enantioselective preparation of 2,3-dihydropyrroles via RhII-catalyzed asymmetric annulations of triazoles with alkenes (Kwok et al, 2014;Miura et al, 2013). As part of our continuous interests in developing enantioselective cycloaddition reactions for the preparation various heterocyclic ring systems (Chan et al, 2019;Han et al, 2014Han et al, , 2016Li et al, 2019;Ni et al, 2017;Yao et al, 2016;Wu et al, 2019), we questioned the feasibility of establishing an effective asymmetric synthesis of 2,3-dihydropyrroles via a formal [3 + 2] cycloaddition reaction, by utilizing azoalkenes as an electrophilic CCN 1,3-dipole surrogate and employing simple 3-vinylindoles (Gioia et al, 2008;Li et al, 2018;Sun et al, 2016;Tan et al, 2011;Yang et al, 2019;Zhang et al, 2018;Zheng et al, 2015) as a C2 reaction partner ( Figure 3). In this report, we document a formal [3 + 2] cycloaddition reaction for enantioselective creation of 2,3-dihydropyrroles under the catalysis of chiral phosphoric acid (CPA) (Akiyama, 2007;Terada, 2008Terada, , 2010Wu et al, 2015;Yu et al, 2011).…”

Enantioselective synthesis of mixed 3,3′-bisindoles via a phosphine-catalyzed umpolung γ-addition of 3′-indolyl-3-oxindoles to allenoates

“…We envisaged that the employment of prochiral pronucleophilic 3 0 -indolyl-3-oxindoles in a phosphine-mediated catalytic umpolung c-addition reaction may offer brand new synthetic perspectives -inversion of reactivities of substrates is especially noteworthy. The past decade has seen marvelous advancement of asymmetric phosphine catalysis [39][40][41][42][43][44][45], and in these endeavors, our group introduced a new family of amino acid-based bifunctional phosphines and applied them to a wide range of asymmetric transformations [46][47][48][49][50][51][52][53].…”