Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• protic solvents such as H2O or EtOH at 100 °C, the desired products were formed in short reactions (1–20 min) and chromene-2-carbonitriles 12–15 were isolated in 61–88% yields. Saito et al. generated o-QMs starting from Mannich bases by low-energy UV irradiation in aqueous acetonitrile [68]. In the

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• . Reactions with oxygen nucleophiles: In 1964 Schweizer reported the synthesis of 2H-chromene (39) by reaction of vinyltriphenylphosphonium bromide (8) with salicylaldehyde sodium salt in a yield of 62–71%, depending on the reaction conditions (Scheme 27) [1]. In a similar reaction with the use of 3-hydroxy-2

• -butanone, 2,5-dihydro-2,3-dimethylfuran (40) was obtained in a yield of 89% (Scheme 28) [1]. Several years later, Schweizer et al. applied analogous reaction conditions to the synthesis of 3-substituted derivative of 2H-chromene 41 and 2,5-dihydrofuran derivative 42 in yields in the range of 30–58% and 36

• vinylphosphonium halides and nucleophiles containing carbonyl function in the molecule. Synthesis of 2H-chromene by reaction of vinyltriphenylphosphonium bromide with sodium 2-formylphenolate. Synthesis of 2,5-dihydro-2,3-dimethylfuran by reaction of vinylphosphonium bromide with 3-hydroxy-2-butanone in the

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• dicyanofumarates E-1 via competitive nucleophilic attack of C4 or NH2. Heterocyclization reaction of thiosemicarbazone 86 with E-1a. Formation of diethyl 4-cyano-5-oxotetrahydro-4H-chromene-3,4-dicarboxylate (90) from E-1a via heterocyclization reaction. Reaction of dialkyl dicyanofumarates E-1 with cysteamine (92

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• , benzaldehydes and electron-rich phenols in presence of 5 mol % of POPI, afforded near quantitative yield of chromene derivatives within 20 min (Scheme 40). Similarly, various benzaldehydes with electron-withdrawing groups at the o/p-position accelerated the reaction and electron-donating groups slowed that down

• particles [146]. Mechanochemical synthesis of 1,2-di-substituted benzimidazoles [149]. Mechanochemical click reaction using an alumina-supported Cu-catalyst [152]. Mechanochemical click reaction using copper vial [155]. Mechanochemical indole synthesis [157]. Mechanochemical synthesis of chromene [158

A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring

• John Andraos

Beilstein J. Org. Chem. 2016, 12, 2420–2442, doi:10.3762/bjoc.12.236

• showed that benzimidazoles, Biginelli adducts, dihydropyridines, furans, pyrans, pyridinones, and thiophenes had a high representation of intrinsic greenness; whereas, a high proportion of MCRs producing chromene-4-ones, coumarins, indoles, and pyrazoles had low probabilities of achieving intrinsic

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• phosphonylpyrans 152, 154 and 156, respectively (Scheme 33). 3.2 Three-component synthesis of (2-amino-3-cyano-4H-chromen-4-yl)phosphonates Because of the widespread biological activities related to 2-amino-4H-chromene derivatives, the synthesis of (2-amino-3-cyano-4H-chromen-4-yl)phosphonates has attracted much

A practical way to synthesize chiral fluoro-containing polyhydro-2H-chromenes from monoterpenoids

• Oksana S. Mikhalchenko,
• Dina V. Korchagina,
• Konstantin P. Volcho and
• Nariman F. Salakhutdinov

Beilstein J. Org. Chem. 2016, 12, 648–653, doi:10.3762/bjoc.12.64

• the presence of K10 montmorillonite clay forms chiral heterocyclic compounds with the hexahydro-2H-chromene scaffold 2 (Scheme 1) [1][2][3][4]. Products of these reactions are of interest as many of them exhibit a significant analgesic activity in vivo [2][3][4]. In terms of structure–activity

• groups are trans-located in compound 4 (while cis-located in monoterpenoid 1). When a reaction of isopulegol (4) with 3,4,5-trimethoxybenzaldehyde (6a) was conducted under the conditions previously optimised for diol 1, fluorinated product 11 with the chromene scaffold and its analogue 12 with a hydroxy

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• resulting enolate is directed to the upper face of the 3-nitro-2H-chromene due to hydrogen bonding of the enolate with the ammonium cation. The thiourea moiety, firstly activates the 3-nitro-2H-chromene through two hydrogen bonds, making it more electrophilic (LUMO lowering effect) and secondly it orients

• (Scheme 42) [62]. The resulting (R)-3-nitro-2H-chromene was isolated in rather moderate optical purity. In 2010, a domino Michael hemiacetalization reaction was reported between cyclic 1,3-dicarbonyl compounds 134 and β-unsaturated α-ketoesters 87 utilizing a novel tyrosine-derived thiourea 135 (Scheme 43

Facile synthesis of 4H-chromene derivatives via base-mediated annulation of ortho-hydroxychalcones and 2-bromoallyl sulfones

• Srinivas Thadkapally,
• Athira C. Kunjachan and
• Rajeev S. Menon

Beilstein J. Org. Chem. 2016, 12, 16–21, doi:10.3762/bjoc.12.3

• furnished 3-arylsulfonyl-4H-chromene derivatives in 58–67% yield (18 examples). 2-Bromoallyl sulfones functioned as synthetic surrogates for allenyl sulfones in the reaction. Keywords: allenes; chromenes; cyclocondenzation; sulfones; vinylic substitution; Findings Benzo[b]dihydropyran, commonly known as

• 4H-chromene (1), is a privileged heterocyclic scaffold that is found in a variety of biologically active natural and synthetic products (Figure 1) [1][2][3]. For example, the synthetic chromene derivative HA14-1 (Figure 1) has been shown to bind to the cellular protein Bcl-2 and to induce apoptotic

• cell death [4]. The natural chromene rhodomyrtone (Figure 1) is known to exhibit potent antibacterial activity [5]. As a consequence, a number of methods have been developed for the synthesis of substituted 4H-chromenes [6]. This includes, inter alia, transition metal-mediated cyclizations [7

New metathesis catalyst bearing chromanyl moieties at the N-heterocyclic carbene ligand

• Agnieszka Hryniewicka,
• Szymon Suchodolski,
• Agnieszka Wojtkielewicz,
• Jacek W. Morzycki and
• Stanisław Witkowski

Beilstein J. Org. Chem. 2015, 11, 2795–2804, doi:10.3762/bjoc.11.300

• catalysts 1 and 2 [23]. The introduction of a nitro group into the 6-position of the chromene moiety in catalyst 8 led to a decrease in the stability of the complex [22]. The aforementioned modifications concerned the benzylidene moiety of the catalysts and affected the initiation rate of the metathesis

Enantioselective additions of copper acetylides to cyclic iminium and oxocarbenium ions

• Jixin Liu,
• Srimoyee Dasgupta and
• Mary P. Watson

Beilstein J. Org. Chem. 2015, 11, 2696–2706, doi:10.3762/bjoc.11.290

• /BnBox catalyst, moderate to high yields and enantioselectivities were achieved in the addition of arylalkynes. Both yields and ee’s drop with vinyl- or alkylalkynes. Recently, we have demonstrated that enantioselective, copper-catalyzed alkynylations of oxocarbenium ions derived from chromene acetals 43

• can also be achieved in high yields and ee’s (Scheme 16) [56]. In this case, the reaction concentration has a significant impact on the enantioselectivity. We also observed that the alkynylation of chromene acetals with electron-donating substituents proceeds in higher ee’s than less electron-rich

• of N-carbomoylquinolinium ions using StackPhos as ligand. Carreira’s enantioselective, catalytic alkynylation of aldehydes. Watson’s alkynylation of isochroman oxocarbenium ions. Watson’s alkynylation of chromene oxocarbenium ions. Watson’s alkynylation to set diaryl tetrasubstituted stereocenters

Synthesis of the furo[2,3-b]chromene ring system of hyperaspindols A and B

• Danielle L. Paterson and
• David Barker

Beilstein J. Org. Chem. 2015, 11, 265–270, doi:10.3762/bjoc.11.29

• Danielle L. Paterson David Barker School of Chemical Sciences, University of Auckland, 23 Symonds St, Auckland, New Zealand 10.3762/bjoc.11.29 Abstract The synthesis of the unique furo[2,3-b]chromene ring system found in hyperaspidinols A and B, acylphloroglucinols from Hypericum chinense has

• been achieved in twelve steps. By comparison of the NMR spectra of the synthesized compounds with those of the natural products, a relative stereochemistry is suggested, especially that of the ketal carbon. Keywords: acylphloroglucinols; bicyclisation; furo[2,3-b]chromene; fused ketal; Introduction

• both possess a highly functionalised furo[2,3-b]chromene ring system (Figure 2, highlighted in blue) and differ only with the nature of the ketone side-chain. Furo[2,3-b]chromenes have not been reported in any other natural products to date with the closest related system being the chromeno[2,3-b

Organobase-catalyzed three-component reactions for the synthesis of 4H-2-aminopyrans, condensed pyrans and polysubstituted benzenes

• Moustafa Sherief Moustafa,
• Saleh Mohammed Al-Mousawi,
• Maghraby Ali Selim,
• Ahmed Mohamed Mosallam and
• Mohamed Hilmy Elnagdi

Beilstein J. Org. Chem. 2014, 10, 141–149, doi:10.3762/bjoc.10.11

• , P.O. Box 83523, Qena, Egypt 10.3762/bjoc.10.11 Abstract Novel routes for the preparation of 2-amino-4H-pyran-3-carbonitrile 9, amino-arylbenzoic acid ester derivatives 13a,b, 2-aminotetrahydro-4H-chromene-3-carbonitrile 18, 3-amino-4-cyanotetrahydronaphthalene-2-carboxylic acid ester 26 and 4-amino

Gold(I)-catalyzed hydroarylation reaction of aryl (3-iodoprop-2-yn-1-yl) ethers: synthesis of 3-iodo-2H-chromene derivatives

• Pablo Morán-Poladura,
• Eduardo Rubio and
• José M. González

Beilstein J. Org. Chem. 2013, 9, 2120–2128, doi:10.3762/bjoc.9.249

• hydroarylation steps. Keywords: alkyne; chromene; gold; gold catalysis; hydroarylation; iodine; Introduction The structure of 2H-chromene embodies a relevant heterocyclic motif, which is present in naturally occurring compounds [1][2][3][4][5][6] and encodes interesting properties that renders it attractive

• -chromenes (see Scheme 1, entries a and b, respectively). However, they fail to produce simple 3-halo-4-unsubstituted derivatives. This synthetic context suggests a timely opportunity for devising new protocols to access the latter class of 3-halo-2H-chromene scaffolds from readily available precursors

• ground, we were curious about the attractive possibility of combining known reaction profiles in an attempt to execute an efficient entry into the elusive 4-unsubstituted-3-iodo-2H-chromene derivatives. We hypothesize that this specific heterocyclic motif can be conveniently prepared from cyclization of

Reactions of salicylaldehyde and enolates or their equivalents: versatile synthetic routes to chromane derivatives

• Ishmael B. Masesane and
• Zelalem Yibralign Desta

Beilstein J. Org. Chem. 2012, 8, 2166–2175, doi:10.3762/bjoc.8.244

• -amine-mediated tandem reactions of salicylaldehyde and α,β-unsaturated compounds to give chromane derivatives have been reported. Stukan and co-workers, for example, used an Et3N-mediated reaction of salicylaldehyde (5) and nitropropene 46 in the synthesis of 2,3-disubstituted chromene 47 in a low yield

• ) with tert-butyl acrylate (56) to give the Baylis–Hillman product 57, which was subsequently cyclized in the presence of acetic acid to give chromene 58 in a low yield of 24%, together with coumarin 59 in 40% yield (Scheme 20). An asymmetric amine-catalyzed reaction of salicylaldehyde (5) and α,β

• (5), followed by an intramolecular aldol reaction and final dehydration to give the desired chromene derivative. Related work involving asymmetric reaction of salicylaldehyde derivatives and α,β-unsaturated carbonyl compounds in the synthesis of 2-phenylchromenes was reported by Li and co-workers

Organocatalytic tandem Michael addition reactions: A powerful access to the enantioselective synthesis of functionalized chromenes, thiochromenes and 1,2-dihydroquinolines

• Chittaranjan Bhanja,
• Satyaban Jena,
• Sabita Nayak and
• Seetaram Mohapatra

Beilstein J. Org. Chem. 2012, 8, 1668–1694, doi:10.3762/bjoc.8.191

• acyclic/cyclic α,β-unsaturated compounds The racemic synthesis of 2H-chromene was reported by Bräse et al. in 2005 [39][40]. A strategy based on the organocatalytic enantioselective synthesis of chiral 2H-chromenes through tandem-oxa-Michael–aldol sequence was first reported by Arvidsson et al. [41] in

• elimination to afford the chromene 3 (Scheme 1). The same reaction was also repeated with various catalysts, which are presented in Scheme 1. Several base and acid additives were found to affect both the enantioselectivities and the yields of the product. The overall reaction sequence provided chromenes with

• tertiary amine-modified diarylpyrrolinol-TMS ether III as a water-soluble and recyclable organocatalyst with 4-chlorobenzoic acid as cocatalyst (Scheme 5) for the synthesis of 2H-chromene derivatives 3. The electronic effect of the tertiary amine group in the modified catalyst was believed to enhance the

Highly enantioselective access to cannabinoid-type tricyles by organocatalytic Diels–Alder reactions

• Stefan Bräse,
• Nicole Volz,
• Franziska Gläser and
• Martin Nieger

Beilstein J. Org. Chem. 2012, 8, 1385–1392, doi:10.3762/bjoc.8.160

• % ee) with its (2S,5S)-derivate (Table 5, entry 3). Conclusion In conclusion, we have demonstrated that the Diels–Alder reaction of 3-vinyl-2H-chromene with acrolein can be accelerated with different thioureas, obtained in a one-step synthesis (in some cases with quantitative conversion). Application

Asymmetric reactions in continuous flow

• Xiao Yin Mak,
• Paola Laurino and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2009, 5, No. 19, doi:10.3762/bjoc.5.19

• of asymmetric transfer hydrogenation in flow have also been reported [51][52]. Supported catalysis has been extended to reactions involving the use of continuous flow membrane reactors [19][20][21][22]. For example, the asymmetric epoxidation of a chromene derivative 49, catalyzed by homogeneous