Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• -catalyzed [3 + 2] annulation/ring-opening/dehydration domino reaction of oxabicyclic alkenes 30 with 2-(1-methylhydrazinyl)pyridine (MHP) directed arenes 87 for the synthesis of benzo[b]fluorenones 88 (Scheme 16) [52]. C–H bond functionalization with heterobicyclic alkenes as annulation partners has

Molecular diversity of the base-promoted reaction of phenacylmalononitriles with dialkyl but-2-ynedioates

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 991–998, doi:10.3762/bjoc.18.99

• furnished a chiral thiosquaramide-catalyzed tandem Michael–Henry reaction of phenacylmalononitriles and nitroolefins for the enantioselective synthesis of cyclopent-3-ene-1-carboxamides [32] (reaction 2 in Scheme 1). Mohanan and co-workers reported a PBu3-catalyzed [3 + 2] annulation of

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• 1,2-azaphospholidine 2-oxides and their fused derivative, [4 + 1] annulations and more occasionally a [3 + 2] annulation. [4 + 1] Annulation via formations of both C–N and N–P bonds Miles and Street prepared 2-aryl/dimethylamino-1-ethoxy-2-hydrobenzo[c][1,2]azaphosphol-3-one 1-oxides 201 from 2

• )acetates 247 in moderate yields of 53–71% with diastereomeric ratios of 1:1.7 to 1:3. The synthetic strategy is more versatile (Scheme 39) [60]. [3 + 2] Annulation via formations of both C–C and P–N bonds After oxidation with K3Fe(CN)6, diphenyl 3,5-di(tert-butyl)-4-hydroxybenzylphosphonate (248) was

• + 1] Annulations have been mainly utilized in the construction of the 1,2-azaphospholidine ring, while the [3 + 2] annulation has been seldomly used in the synthesis of pyridine-fused 1,2-azaphospholidine 2-oxide only. Few asymmetric synthetic methods have been developed to date. Thus, highly

New advances in asymmetric organocatalysis

• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 240–242, doi:10.3762/bjoc.18.28

• nitromethane to β-silyl α,β-unsaturated carbonyl compounds catalyzed by bifunctional squaramide catalysts are effective under solvent-free conditions [26]. Zhai and Du demonstrated that asymmetric [3 + 2] annulation reactions of 2-isothiocyanato-1-indanones with barbiturate-based olefins are efficiently

Bifunctional thiourea-catalyzed asymmetric [3 + 2] annulation reactions of 2-isothiocyanato-1-indanones with barbiturate-based olefins

• Jiang-Song Zhai and
• Da-Ming Du

Beilstein J. Org. Chem. 2022, 18, 25–36, doi:10.3762/bjoc.18.3

• Jiang-Song Zhai Da-Ming Du School of Chemistry and Chemical Engineering, Beijing Institute of Technology, No.5 Zhongguancun South Street, Beijing 100081, People’s Republic of China 10.3762/bjoc.18.3 Abstract Bifunctional thiourea-catalyzed asymmetric [3 + 2] annulation reactions of 2

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• ]. Zhou and co-workers published an excellent paper in 2019 on the conversion of central to axial chirality in an enantioselective [3 + 2] annulation of 1-styrylnaphthols 32 with azonaphthalenes 33. Under defined conditions, the cycloaddition product 34 was prepared in high yield (99%) with exclusive

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• converted to fused sultams (Scheme 30) [56]. Anand et al. reported a Cu-catalyzed one-pot method for the preparation of 1,2,3-triazole-fused tricyclic heterocycles 106 via an intramolecular [3 + 2]-annulation. This strategy includes the 1,6-conjugate addition of Me3SiN3 to o-alkynylated p-quinone methides

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• -pyrrolines 82 were formed as single diastereomers [101]. The whole process could be considered a [3 + 2] annulation, and aziridines were not observed as competing reaction products (see above Scheme 11). In addition, hindered imines, ethers, sulfonates, heteroaryl substituents, and conjugated imines were all

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• natural product syntheses featuring all-carbon [3 + 2] annulation are elaborated. Lastly, we discuss future directions and opportunities for the all-carbon [3 + 2] cycloaddition. Review In 1981, Little and co-workers utilized a trimethylenemethane (TMM) cycloaddition as the key reaction to synthesize the

• rearrangement product 99 in 85% yield. The synthesis of daphenylline (11) was completed by a seven-step synthesis from benzofuran 99. Phosphine-catalyzed enantioselective [3 + 2] annulation In 2019, Lu and co-workers disclosed a novel chiral-phosphine-catalyzed enantioselective [3 + 2] annulation of allenes and

• isoindigos to give an enantioenriched annulation adduct bearing vicinal quaternary stereocenters [46] (Scheme 7A). Both symmetric and unsymmetric isoindigos can undergo enantioselective [3 + 2] annulation with an allene and produced a chiral adduct with high yield and high ee value. When unsymmetric

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• opening of nitrogen-containing small rings was also exploited by our group in 2019 (Scheme 36) [154]. Starting from the aminocyclopropanes 36.1 and the cyclopropenes 36.2, a [3 + 2] annulation led to the bicyclo[3.1.0]hexanes 36.3. Under visible-light irradiation, the excited-state photocatalyst OD7

• performs an SET oxidation of an cyclopropylaniline 36.1, leading to an N-centred radical cation after ring opening. The latter undergoes a [3 + 2] annulation with cyclopropenes 36.2, affording a bicyclic product 36.3. The key to the broad substrate tolerance relied on using 4DPAIPN (OD7), which is a mild

Switchable selectivity in Pd-catalyzed [3 + 2] annulations of γ-oxy-2-cycloalkenones with 3-oxoglutarates: C–C/C–C vs C–C/O–C bond formation

• Yang Liu,
• Julie Oble and
• Giovanni Poli

Beilstein J. Org. Chem. 2019, 15, 1107–1115, doi:10.3762/bjoc.15.107

• Yang Liu Julie Oble Giovanni Poli Sorbonne Université, Faculté des Sciences et Ingénierie, CNRS, Institut Parisien de Chimie Moléculaire, IPCM, 4 place Jussieu, 75005 Paris, France 10.3762/bjoc.15.107 Abstract Two complementary [3 + 2] annulation protocols between 3-oxoglutarates and cyclic γ-oxy

• success of this bis-nucleophile/bis-electrophile [3 + 2] annulation is its well-defined step chronology in combination with the total chemoselectivity of the former step. This [3 + 2] C–C/O–C bond forming annulation protocol could be also extended to 1,3,5-triketones as well as 1,3-bis-sulfonylpropan-2

• nucleophile is chemoselectivity control. Herein we disclose two chemodivergent [3 + 2] annulation reactions taking place between dialkyl-3-oxoglutarates I and α,β-unsaturated-γ-oxycarbonyl derivatives II that differ simply by the reaction temperature adopted. These methods allow the exclusive [3 + 2] C–C/C–C

Dirhodium(II)-catalyzed [3 + 2] cycloaddition of N-arylaminocyclopropane with alkyne derivatives

• Wentong Liu,
• Yi Kuang,
• Zhifan Wang,
• Jin Zhu and
• Yuanhua Wang

Beilstein J. Org. Chem. 2019, 15, 542–550, doi:10.3762/bjoc.15.48

• . Experimental General procedure for the [3 + 2] annulation of cyclopropylanilines: An oven-dried Schlenk tube equipped with a stirring bar was charged with Rh2(5S,R-MenPY)4 (0.1 mol %), alkyne (5.0 mmol), and dry DCE (5 mL). The tube was degassed through three freeze–pump–thaw cycles. After evacuating and

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• another molecule Mn(OAc)3 [48]. Later, Shi et al. demonstrated an oxidative annulation of MCPs 1 with 1,3-dicarbonyl compounds 7 using manganese(III) catalysis under room temperature conditions, which afforded 4,5-dihydrofuran derivatives 8 as [3 + 2] annulation products (cyclopropyl retained adducts) in

• moderate to good yields [49]. This transformation also gave another six-membered cyclic compounds 9 (cyclopropyl opened adducts) via ring-opening and cyclization process (Scheme 3). However, the [3 + 2] annulation reaction did not occur under the standard conditions when the MCPs 1 was without an aromatic

• . Finally, the intermediate 136 underwent oxidation and deprotonation to give the desired product 132. In this year, Melchiorre’s group reported the ring-opening and [3 + 2]-annulation of cyclopropanols 91 with α,β-unsaturated aldehydes 138 for the synthesis of stereochemically dense cyclopentanols 139 with

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• asymmetric formal [3 + 2] annulation reaction between N-Boc-isatin imines 3 and 1,4-dithiane-2,5-diol (53) as equal equivalent of 2-mercaptoacetaldehyde [78]. The domino reaction catalyzed by chiral tertiary amine-squaramide catalyst 54 began with the addition of 2-mercaptoacetaldehyde to isatin imine 3

Synergistic chiral iminium and palladium catalysis: Highly regio- and enantioselective [3 + 2] annulation reaction of 2-vinylcyclopropanes with enals

• Haipan Zhu,
• Peile Du,
• Jianjun Li,
• Ziyang Liao,
• Guohua Liu,
• Hao Li and
• Wei Wang

Beilstein J. Org. Chem. 2016, 12, 1340–1347, doi:10.3762/bjoc.12.127

• enals and a transition metal promoting to open the 2-vinylcyclopropanes for highly regio- and enantioselective [3 + 2] cycloaddition reaction of 2-vinylcyclopropanes with α,β-unsaturated aldehydes has been developed. Keywords: [3 + 2] annulation; enals; synergistic catalysis; vinylcyclopropanes

• acid [56]. Herein we wish to disclose the first synergistic catalytic enantioselective [3 + 2] annulation reaction between 2-vinylcyclopropanes and enals via 1,4-addition (Scheme 1, reaction 2). The process proceeds highly regio- and enantioselectively with C=C bonds in enals. Notably, a synergistic

• catalytic system is implemented and makes this previously inaccessible [3 + 2] annulation transformation possible. Results and Discussion To render the [3 + 2] annulation reaction to selectively act on the C=C double bond rather than on the aldehyde in enals 1, we proposed a new cooperative iminium and

Enantioselective [3 + 2] annulation of α-substituted allenoates with β,γ-unsaturated N-sulfonylimines catalyzed by a bifunctional dipeptide phosphine

• Huanzhen Ni,
• Weijun Yao and
• Yixin Lu

Beilstein J. Org. Chem. 2016, 12, 343–348, doi:10.3762/bjoc.12.37

• Huanzhen Ni Weijun Yao Yixin Lu Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore, 117543 10.3762/bjoc.12.37 Abstract The first enantioselective [3 + 2] annulation of α-substituted allenoates with β,γ-unsaturated N-sulfonylimines is described. In the presence

• of a dipeptide phosphine catalyst, a wide range of highly functionalized cyclopentenes bearing an all-carbon quaternary center were obtained in moderate to good yields and with good to excellent enantioselectivities. Keywords: [3 + 2] annulation; α-substituted allenoate; dipeptide phosphine

• ; enantioselective; Introduction Over the past decade, chiral phosphine catalysts have been utilized extensively for the construction of a broad range of synthetically useful molecular structures [1][2][3][4][5][6][7][8][9][10][11][12][13]. Since the initial discovery of phosphine-catalyzed [3 + 2] annulation of

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

• variety of methods for enantioselective syntheses of structurally diverse acyclic, carbocyclic, and heterocyclic compounds. 2.1 [3 + 2] Annulation of allenes with activated alkenes Nucleophilic phosphine-catalyzed annulations have been established as very useful tools for the syntheses of carbo- and

• binaphthyl skeleton, Fu and co-workers developed the first asymmetric [3 + 2] annulation of ethyl allenoate with various α,β-unsaturated enones to provide functionalized cyclopentenes (Scheme 2) [35]. The key structural feature of the chiral catalyst B1 is its rigid binaphthyl skeleton. This approach allowed

• spirocyclic compounds containing two neighboring quaternary and tertiary stereocenters in modest to excellent yields (up to 97%) and high enantioselectivities (up to 95% ee). Subsequently, the Fu group applied this approach to the [3 + 2] annulation of allenes with 1,1-disubstituted olefins to synthesize

Visible light mediated intermolecular [3 + 2] annulation of cyclopropylanilines with alkynes

• Theresa H. Nguyen,
• Soumitra Maity and
• Nan Zheng

Beilstein J. Org. Chem. 2014, 10, 975–980, doi:10.3762/bjoc.10.96

• Theresa H. Nguyen Soumitra Maity Nan Zheng Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas, 72701, USA 10.3762/bjoc.10.96 Abstract Intermolecular [3 + 2] annulation of cyclopropylanilines with alkynes is realized using visible light photoredox catalysis

• synthetic potential of amine radical cations [21][27][28]. One of the reported methods from our group involves [3 + 2] annulation of cyclopropylanilines with alkenes [29]. We were intrigued by the possibility of extending this annulation method to include alkynes. The immediate benefits of using alkynes

• intermolecular [3 + 2] annulation of monocyclic cyclopropylanilines with alkynes under visible light photoredox conditions. Results and Discussion Biphenylcyclopropylamine 1 and phenylacetylene (2) were chosen as the standard substrates to optimize the catalyst system for the [3 + 2] annulation with alkynes

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• ) followed by oxidative coupling of the formed alkylgold moiety with the ortho C–H bond of the tethered phenyl group. Compound 137 was finally obtained via reductive elimination of intermediate 141 (Scheme 34). The formal [3 + 2] annulation between the aniline moiety and the C–C double bond constitutes the

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• (distonic ion) [106]. We have applied Ru(bpz)3(PF6)2-catalyzed photooxidation of N-cyclopropylanilines to induce this rearrangement reaction. The resulting distonic ion was then intercepted by alkenes to produce [3 + 2] annulation products (Scheme 32) [107]. An aryl group on the amine was required for the

• azodicarboxylates. α-Arylation of amines. Plausible mechanism for α-arylation of amines. Photoinduced C–C bond cleavage of tertiary amines. Photoredox cleavage of C–C bonds of 1,2-diamines. Proposed mechanism photoredox cleavage of C–C bonds. Intermolecular [3 + 2] annulation of cyclopropylamines with olefins

• . Proposed mechanism for intermolecular [3 + 2] annulation. Photoinduced clevage of N–N bonds of aromatic hydrazines and hydrazides.

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

• of Chemistry & Molecular Engineering, East China University of Science and Technology, and 130 MeiLong Road, Shanghai 200237, People’s Republic of China 10.3762/bjoc.8.121 Abstract We have developed a multifunctional thiourea-phosphine catalyzed asymmetric [3 + 2] annulation of Morita–Baylis–Hillman

• previous literature. Keywords: asymmetric [3 + 2] annulation; maleimides; Morita–Baylis–Hillman carbonates; multifunctional thiourea-phosphine; organocatalysis; Introduction Highly functionalized cyclopentene derivatives are important subunits in a variety of biologically active molecules and have

• attracted the broad attention of synthetic and pharmaceutical chemists [1][2]. Among numerous synthetic approaches, phosphine-mediated [3 + 2] annulation of electron-deficient olefins is an efficient method to construct this interesting structural motif [3][4][5][6][7][8][9][10]. According to the pioneering

Recent developments in gold-catalyzed cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2011, 7, 1075–1094, doi:10.3762/bjoc.7.124

• ) catalyst is able to activate these allenic intermediates in situ, triggering a stepwise intramolecular (3 + 2) annulation reaction with the pendant alkene. This cycloaddition provides a cyclic gold carbene species XXV, which is eventually transformed into the final bicyclic adduct by a 1,2-hydrogen shift

• ethers and alkenes (MOM = methoxymethyl, Scheme 25) [90]. The activation of these allenes by the dichloro(pyridine-2-carboxylato)Au(III) complex Au7 generates an oxocarbenium intermediate XXVII, which undergoes the (3 + 2) annulation with the alkene. The resulting bicyclo[3.1.0] species XXVIII, related

Recent progress on the total synthesis of acetogenins from Annonaceae

• Nianguang Li,
• Zhihao Shi,
• Yuping Tang,
• Jianwei Chen and
• Xiang Li

Beilstein J. Org. Chem. 2008, 4, No. 48, doi:10.3762/bjoc.4.48

• data (1H and 13C NMR) of synthetic asimicin was identical to those of naturally occurring compounds. In 2005, Roush’s group synthesized the bis-THF core of asimicin [98] from two sequential chelate-controlled [3+2] annulation reactions of allylsilanes and appropriately substituted aldehydes (Scheme 38

• ). Subjecting the protected allylsilane 281 to the [3+2] annulation reaction with α-benzyloxyacetaldehyde (282) afforded the 2,5-trans-THF 283. Conversion of 283 to aldehyde 284 was achieved by reductive removal of the benzyl group and subsequent oxidation of the alcohol. Treatment of aldehyde 284 with

• group reported the total synthesis of (+)-bullatacin (311) via a diastereoselective [3+2] annulation reaction (Scheme 43) [104]. Racemic aldehyde 314, which was prepared from allylsilane (±)-312 and α-benzyloxy acetaldehyde (313), was treated with the highly enantiomerically enriched allylsilane 315 in

Synthesis of highly substituted allenylsilanes by alkylidenation of silylketenes

• Stephen P. Marsden and
• Pascal C. Ducept

Beilstein J. Org. Chem. 2005, 1, No. 5, doi:10.1186/1860-5397-1-5

• -carbon partners in [3+2] annulation reactions. Thus, reaction with aldehydes,[7] imines/iminiums,[7][8] enones [9][10][11] and nitrosyl cations [12] leads to dihydrofurans, dihydropyrroles, cyclopentenes and isoxazoles respectively.[13] In most cases the silicon is retained in the final product and can