Molecular diversity of the reactions of MBH carbonates of isatins and various nucleophiles

• Zi-Ying Xiao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2025, 21, 286–295, doi:10.3762/bjoc.21.21

• Zi-Ying Xiao Jing Sun Chao-Guo Yan College of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou 225002, China 10.3762/bjoc.21.21 Abstract In this paper, the nucleophilic substitution reactions of various N- and P-containing nucleophiles to MBH carbonates of isatins were investigated

• . Diverse functionalized 3-substituted oxindole derivatives were successfully prepared in satisfactory yields and with high diastereoselectivity. In addition, the base-promoted dimerization of MBH carbonates of isatin afforded the ethylene-bridged bis(3-methylene)oxindole derivatives with nearly 4:1

• , the readily available Morita–Baylis–Hillman (MBH) carbonates of isatins have been recognized as one of the most powerful synthons for the construction of various spirooxindole skeletons [16][17][18][19][20][21][22][23][24][25]. MBH carbonates of isatins can be easily obtained via base-promoted MBH

Construction of diazepine-containing spiroindolines via annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates

• Xing Liu,
• Wenjing Shi,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1923–1932, doi:10.3762/bjoc.19.143

• and proceeds through a by base-promoted annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates. The reaction mechanism of this formal [4 + 3] annulation includes the in situ generated allylic ylide, nucleophilic substitution, Michael additon, and elimination processes

• the synthesis of spirooxindole derivatives continues to be a highly active subject in organic synthesis [31][32][33][34][35]. In recent years, the readily available isatin-derived Morita–Baylis–Hillman (MBH) carbonates have become one of the most powerful reagents for the construction of diverse

• spirooxindoles [36][37][38][39][40][41][42][43]. In the presence of Lewis bases, isatin-derived MBH carbonates usually undergo [3 + 2] and [3 + 3] cycloaddition reactions with a broad range of active C–C and C–N double bonds and 1,3-dipolarpohiles to give various five- or six-membered cyclic spirooxindoles [44

Selective construction of dispiro[indoline-3,2'-quinoline-3',3''-indoline] and dispiro[indoline-3,2'-pyrrole-3',3''-indoline] via three-component reaction

• Ziying Xiao,
• Fengshun Xu,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1234–1242, doi:10.3762/bjoc.19.91

• [12][13][14][15]. On the other hand, Morita–Baylis–Hillman (MBH) carbonates of isatins, which could be easily prepared by the MBH reactions of isatins with acrylonitrile or alkyl acrylates also became valuable synthons [16][17][18][19][20][21][22][23][24][25]. The active 3-methyleneoxindoles could act

Direct C(sp³)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

• Siyu Wang,
• Lianyou Zheng,
• Shutao Wang,
• Shulin Ning,
• Zhuoqi Zhang and
• Jinbao Xiang

Beilstein J. Org. Chem. 2021, 17, 2505–2510, doi:10.3762/bjoc.17.167

• (sp3)–H allylic alkylation of 2-alkylpyridines with Morita–Baylis–Hillman (MBH) carbonates is described. A plausible mechanism of the reaction might involve a tandem SN2’ type nucleophilic substitution followed by an aza-Cope rearrangement. Various alkyl substituents on 2-alkylpyridines were tolerated

• synergistic catalyzed allylic alkylation between electron-deficient 2-ethyl benzoxazoles and MBH carbonates by the combination of a Lewis base and a metal salt [24]. In their studies, although pyridine derivatives were also applicable in the reaction, the presence of a strong electron-withdrawing NO2 group

• was necessary to promote the reaction but only with low yield (30%) (Scheme 1c). Recently, electron-deficient 3,5-dimethyl-4-nitroisoxazole and 2-methyl-3-nitroindoles were also served as vinylogous pronucleophiles to proceed the asymmetric allylic alkylation with MBH carbonates [25][26]. Overall, the

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• described an allylic alkylation reaction between 3-cyano-4-methylcoumarins 39 and Morita–Baylis–Hillman (MBH) carbonates 40 [45]. In this case, the catalyst (DHQ)2PYR 42 activates the MBH substrate and generates the dienolate in the vinylogous coumarin moiety, acting as a base. After the nucleophilic

• reaction between 3-cyano-4-methylcoumarins 39 and MBH carbonates 40. Enantioselective synthesis of cyclopropa[c]coumarins 45. NHC-catalyzed lactonization of 2-bromoenals 46 with 4-hydroxycoumarin (1). NHC-catalyzed enantioselective synthesis of dihydrocoumarins 51. Domino reaction of enals 2 with

DABCO- and DBU-promoted one-pot reaction of N-sulfonyl ketimines with Morita–Baylis–Hillman carbonates: a sequential approach to (2-hydroxyaryl)nicotinate derivatives

• Soumitra Guin,
• Raman Gupta,
• Debashis Majee and
• Sampak Samanta

Beilstein J. Org. Chem. 2018, 14, 2771–2778, doi:10.3762/bjoc.14.254

• -Michael reaction between MBH carbonates derived from an acrylate/acrylonitrile and N-sulfonyl ketimines as C,N-binucleophiles catalyzed by DABCO, followed by elimination of SO2 under the influence of base and subsequent aromatization in an open atmosphere. Keywords: MBH carbonates; metal-free; N-sulfonyl

• on the above experimental results as well as our previous report on DABCO-catalyzed reactions of cyclic sulfamidate imines with MBH carbonates of isatins [75], a plausible mechanism is presented and depicted in Scheme 2. For the first step, the nucleophilic Lewis base DABCO reacts with 2a in an SN2

• generality and scope of the reaction by reacting several aryl/heteroaryl-substituted MBH carbonates derived from acrylates 2a–j and 4-methyl-N-sulfonyl ketimines 1a–e under present sequential reaction conditions. The results are incorporated in Scheme 3. The regioselective allylic alkylation/aromatization

First DMAP-mediated direct conversion of Morita–Baylis–Hillman alcohols into γ-ketoallylphosphonates: Synthesis of γ-aminoallylphosphonates

• Marwa Ayadi,
• Haitham Elleuch,
• Emmanuel Vrancken and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2906–2915, doi:10.3762/bjoc.12.290

• , without any additive, provided, after thermal Arbuzov rearrangement, a variety of diethyl allylphosphonates (Scheme 1, reaction 3) [18]. Moreover, the asymmetric allylic substitution of MBH carbonates with diphenyl phosphonate using chiral thiourea phosphite as catalyst, afforded the related

Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

• Laura A. Bryant,
• Rossana Fanelli and
• Alexander J. A. Cobb

Beilstein J. Org. Chem. 2016, 12, 429–443, doi:10.3762/bjoc.12.46

• ; elimination of the catalyst then generates the exo-methylene adduct. For example, Lu and co-workers have used β-ICPD to react isatin-derived MBH carbonates 18 with nitroalkanes 19 [29]. The resulting adducts 20 could be converted to the corresponding spiroxindole 21 via a Zn/HOAc mediated reduction of the

• nitro functionality (Scheme 5). Similarly, Kesavan and co-workers reacted 3-O-Boc-oxindoles 23 with MBH carbonates 22 to generate a range of spirocyclic scaffolds containing α-exo-methylene-γ-butyrolactone 24 – again using β-ICPD (Scheme 6) [30]. Nazarov cyclization An asymmetric Nazarov cyclization has

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• developments in nucleophilic chiral phosphine-catalyzed asymmetric reactions, including annulations of allenes, ketenes, alkynes, and Morita–Baylis–Hillman (MBH) carbonates with activated alkenes and imines, allylic substitution of MBH acetates and carbonates, Michael additions, γ-umpolung additions, and

• catalyst F2 was required, even though it was responsible for promoting the two proposed steps. 2.5 [3 + 2] Annulations of MBH carbonates with activated alkenes MBH carbonates, which are readily accessible from the adducts of MBH reactions, have been used extensively in organocatalysis for the formation of

• C–C and C–heteroatom bonds [71][72]. In addition to activated allenes and alkynes, MBH carbonates are often employed as versatile substrates for the phosphine-catalyzed annulations. In 2010, using the cyclic phosphine (S)-DMM-SITCP D3, Tang and Zhou developed an intramolecular asymmetric [3 + 2

Asymmetric allylic alkylation of Morita–Baylis–Hillman carbonates with α-fluoro-β-keto esters

• Lin Yan,
• Zhiqiang Han,
• Bo Zhu,
• Caiyun Yang,
• Choon-Hong Tan and
• Zhiyong Jiang

Beilstein J. Org. Chem. 2013, 9, 1853–1857, doi:10.3762/bjoc.9.216

• ], Shibata and co-workers [16] and Rios and co-workers [17] reported the addition of fluoromethyl(bisphenylsulfones) to MBH carbonates to access chiral monofluoromethyl derivatives. Furthermore, Rios and co-workers presented an asymmetric substitution of MBH carbonates with 2-fluoromalonates in good

• enantioselectivities [38]. Notably, the reaction between an achiral fluorocarbon nucleophile with MBH carbonates, to afford compounds with chiral quaternary carbon centres bearing a fluorine atom, remains a formidable task. Since 2009, we developed a highly enantioselective and diastereoselective guanidine-catalyzed

• conjugate addition and Mannich reaction of α-fluoro-β-ketoesters with excellent results [38][39][40]. Herein, we wish to report the first allylic alkylation of MBH carbonates with α-fluoro-β-ketoesters in excellent enantioselectivities and moderate diastereoselectivities, furnishing enantiopure fluorinated

Organocatalytic asymmetric allylic amination of Morita–Baylis–Hillman carbonates of isatins

• Hang Zhang,
• Shan-Jun Zhang,
• Qing-Qing Zhou,
• Lin Dong and
• Ying-Chun Chen

Beilstein J. Org. Chem. 2012, 8, 1241–1245, doi:10.3762/bjoc.8.139

• the other hand, the asymmetric addition to electrophilic imines of isatins is also an attractive pathway, and a variety of examples have been presented [16][17][18][19][20][21]. Recently, we have developed the asymmetric allylic alkylation reactions [22] with Morita–Baylis–Hillman (MBH) carbonates of

• isatins to obtain 2-oxindoles bearing a C3-quaternary chiral center, by the catalysis of chiral tertiary amines, β-isocupreidine (β-ICD) or its derivatives [23][24]. We envisaged that such a catalytic strategy should be applicable to the allylic amination of the corresponding MBH carbonates [25][26][27

• catalysis of DABCO. No desired reaction occurred for phthalimide [25] or N-allyl p-toluenesulfonamide [27], which has been successfully applied in the asymmetric amination of MBH carbonates derived from aryl aldehydes. Pleasingly, the reaction took place smoothly to afford product 4a when hydroxylamine 3a

Chiral multifunctional thiourea-phosphine catalyzed asymmetric [3 + 2] annulation of Morita–Baylis–Hillman carbonates with maleimides

• Hong-Ping Deng,
• De Wang,
• Yin Wei and
• Min Shi

Beilstein J. Org. Chem. 2012, 8, 1098–1104, doi:10.3762/bjoc.8.121

• (MBH) carbonates with maleimides, which can efficiently construct functionalized cyclopentenes bearing three contiguous stereocenters in moderate to excellent yields and excellent diastereo- and enantioselectivities. A plausible mechanism has been also proposed on the basis of control experiments and

• ] have also developed asymmetric [3 + 2] annulations of allenoates to give the corresponding cyclopentene derivatives in good yields with excellent enantioselectivities [37]. On the other hand, some examples of phosphine-catalyzed [3 + 2] annulation of MBH carbonates with electron-deficient alkenes have

• been reported in the literature recently. Lu and co-workers first disclosed the formation of 1,3-dipoles through phosphine-catalyzed MBH carbonates under mild conditions, which can efficiently react with various electron-deficient olefins to afford the desired cyclic products in good yields along with