Stereoselective synthesis of fused tetrahydroquinazolines through one-pot double [3 + 2] dipolar cycloadditions followed by [5 + 1] annulation

• Xiaofeng Zhang,
• Kenny Pham,
• Shuai Liu,
• Marc Legris,
• Alex Muthengi,
• Jerry P. Jasinski and
• Wei Zhang

Beilstein J. Org. Chem. 2016, 12, 2204–2210, doi:10.3762/bjoc.12.211

• formaldehyde through [5 + 1] annulation to afford a novel polycyclic scaffold bearing tetrahydroquinazoline, pyrrolidine, pyrrolidinedione, and N-substituted maleimide in stereoselective fashion. Keywords: [5 + 1] annulation; [3 + 2] cycloaddition; one-pot reactions; stereoselective synthesis

• second [3 + 2] cycloaddition of azide compounds 2 with maleimides and sequential denitrogenation to products 7 is proposed in Scheme 2. 1,5-Diamino compounds 7 generated by one-pot reactions are good substrates for [5 + 1] annulation with aldehydes to form tetrahydroquinazolines 1 [34][35]. After

• exploring the reaction conditions, it was found that the reaction of 7a with formaldehyde in 1,4-dioxane at 110 °C afforded product 1a in 93% isolated yield (Table 2, entry 3). Other reactants such as HC(OEt)3, HCO2H, and paraformaldehyde (PFA) were also employed for the [5 + 1] annulation reactions. But

Scope and limitations of a DMF bio-alternative within Sonogashira cross-coupling and Cacchi-type annulation

• Kirsty L. Wilson,
• Alan R. Kennedy,
• Jane Murray,
• Ben Greatrex,
• Craig Jamieson and
• Allan J. B. Watson

Beilstein J. Org. Chem. 2016, 12, 2005–2011, doi:10.3762/bjoc.12.187

• . Keywords: Cacchi annulation; cross-coupling; heterocycles; Sonogashira; sustainable solvent; Introduction The Sonogashira reaction [1][2] (Scheme 1) is a robust and broadly applicable Pd-catalysed bond-forming process that, alongside the Suzuki–Miyaura reaction [3], has steadily become an indispensible

• annulation (Scheme 3) [42][43]. Specifically, employing ortho-amino (5) or ortho-hydroxyaryl iodides (6) in the Sonogashira process generated an alkyne intermediate that, upon increasing the reaction temperature from 30 °C to 60 °C, could undergo 5-endo-dig cyclisation to forge functionalised and

• alternative to DMF, Cyrene. In addition, we have shown the capacity for extension of the utility of this new solvent towards enabling the cascade synthesis of functionalised indoles and benzofurans via a Cacchi-type annulation. Perhaps more importantly, we have documented some of the limitations of the use of

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

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

• 4:1 in the presence of 4 Å molecular sieves (Scheme 59) [97]. A sequential three-component enamine–azoene annulation reaction of primary aliphatic amines 292, activated methylene compounds 293, and 1,2-diaza-1,3-dienes (DDs, 294) has been reported to give polysubstituted pyrroles 295 (Scheme 60) [98

Stereoselective synthesis of tricyclic compounds by intramolecular palladium-catalyzed addition of aryl iodides to carbonyl groups

• Jakub Saadi,
• Christoph Bentz,
• Kai Redies,
• Dieter Lentz,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1236–1242, doi:10.3762/bjoc.12.118

• not allow an unambiguous determination. Considering the result obtained with the cycloheptanone derivative where two diastereomers could be assigned by X-ray crystal structure analyses make the proposed trans-annulation of the five- and six-membered rings fairly likely. The palladium-catalyzed

• suitable for X-ray crystal structure analyses could be obtained (Figure 3 and Figure 4) [16][17]. Again, the configurations of the precursors are reflected in the product structure. Compound 5b provided product 15b with trans-annulation of the two rings and we assume that compound 15a with cis-annulated

Iodine-mediated synthesis of 3-acylbenzothiadiazine 1,1-dioxides

• Long-Yi Xi,
• Ruo-Yi Zhang,
• Lei Shi,
• Shan-Yong Chen and
• Xiao-Qi Yu

Beilstein J. Org. Chem. 2016, 12, 1072–1078, doi:10.3762/bjoc.12.101

• of luotonin F and derivatives from aromatic ketones and 2-aminobenzamides via iodination/Kornblum oxidation/annulation [25]. We envisioned that 2-aminobenzenesulfonamides would undergo a similar reaction to afford 3-acylbenzothiadiazine 1,1-dioxides. Herein, we report the first synthesis of 3

A robust synthesis of 7,8-didemethyl-8-hydroxy-5-deazariboflavin

• Matthias Bender,
• Henrik Mouritsen and
• Jens Christoffers

Beilstein J. Org. Chem. 2016, 12, 912–917, doi:10.3762/bjoc.12.89

• chromatography. We first investigated the conversion of this material with aldehyde 13 to furnish the isopropylidene-protected annulation product. However, subsequent deprotection gave compound 1 containing significant impurities. If compound 11 is first deprotected (product 12 was obtained in 99% yield without

Synthesis of 2,1-benzisoxazole-3(1H)-ones by base-mediated photochemical N–O bond-forming cyclization of 2-azidobenzoic acids

• Daria Yu. Dzhons and
• Andrei V. Budruev

Beilstein J. Org. Chem. 2016, 12, 874–881, doi:10.3762/bjoc.12.86

• nitro compounds [17][18][19][20][21], two other routes are available: the annulation of nitroso compounds [22][23] and the thermal [24], catalytic [25][26][27] or photochemical cyclization of aryl azides [28][29][30][31]. However, the presence of electron-withdrawing substituents in the 3-, 5- and 7

Strecker degradation of amino acids promoted by a camphor-derived sulfonamide

• M. Fernanda N. N. Carvalho,
• M. João Ferreira,
• Ana S. O. Knittel,
• Maria da Conceição Oliveira,
• João Costa Pessoa,
• Rudolf Herrmann and
• Gabriele Wagner

Beilstein J. Org. Chem. 2016, 12, 732–744, doi:10.3762/bjoc.12.73

• types of reactions include the alkylation of the imine nitrogen atom followed by ring annulation [6], cleavage of the sulfonimine [7][8] or camphor [9] rings, reduction of the CO or CN double bonds [10], addition of acetylide anions to form dialkynes that can undergo complex skeletal rearrangements and

Regiodefined synthesis of brominated hydroxyanthraquinones related to proisocrinins

• Joyeeta Roy,
• Tanushree Mal,
• Supriti Jana and
• Dipakranjan Mal

Beilstein J. Org. Chem. 2016, 12, 531–536, doi:10.3762/bjoc.12.52

• condensation; Hauser annulation; proisocrinins; Introduction Anthraquinones constitute the largest group of naturally occurring quinones [1][2][3][4][5]. Isolated mainly from fungal sources, they display a wide range of biological activities which include anti-inflammatory, antifungal, antiparasidal, and

• biomimetic aldol condensations [17][18][19][20][21][22][23], and reports on the synthesis of brominated anthraquinones are scare [12][13][14][15]. Having inspired by the convergence and the regiochemical integrity of the Hauser annulation [24][25][26][27][28][29][30], we explored it for the construction of

• the bromoanthraquinone scaffolds of proisocrinins 6–11. Results and Discussion First synthetic route Anthraquinone 14 was proposed to be synthesized by the Hauser annulation of cyanophthalide 12 and cyclohexenone 13 (Scheme 1). A functional group manipulation of 14 was expected to give anthraquinone

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• indole derivatives 2. Indeed, as discussed below, other authors proposed the compound 6 as a plausible bifunctional catalyst. The Enders’ group used its enantiomer (ent-6) to develop a pioneering scalable one-pot multicatalytic method for the C2/C3-annulation of the indoles 2 (Scheme 4) [26]. In this

• catalyzed by thiourea ent-4 in the presence of D-mandelic acid as a Brønsted acid additive. Friedel–Crafts alkylation of indoles catalyzed by the chiral thioamide 6. Scalable tandem C2/C3-annulation of indoles, catalyzed by the thioamide ent-6. Plausible tandem process mechanism for the sequential, double

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• ]. Meanwhile, the Breslow intermediate is produced from the aldehyde by the thiazolium 31-derived NHC. The union of these two reactive intermediates furnished α-amidoketones 32 in excellent yields (Scheme 18). A diastereoselective [4 + 1] annulation of phthalaldehyde with imines leading to the formation of cis

• . Although the presence of an isoxazole moiety is not a prerequisite for the success of this annulation, its rigid nature presumably renders the reaction highly stereoselective [47]. This simple and mild method allowed the construction of orthogonally protected polycyclic quinones from readily available

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

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

• lengthy substrate synthesis, high cost of catalysts and tedious procedures. Therefore, general synthetic methods for accessing substituted chromene derivatives from readily available materials are still in demand. During the course of our recent investigations on annulation reactions of unsaturated

• -mentioned reactions (Scheme 1, path d) [24]. The facile cyclocondenzation of salicylaldehyde with 2a (Scheme 1, path c) prompted us to explore analogous annulation reactions for the synthesis of functionalized chromene derivatives. The biological activities exhibited by many 4H-chromene derivatives provided

• an added incentive for this investigation [1]. We envisaged that the presence of a Michael acceptor double bond at the ortho position of a phenol would offer avenues for carbon–carbon bond forming annulation in its reaction with 2a,b. In view of their well-known reactivity profiles, diversity options

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• plumisclerin A by Pauson–Khand annulation and SmI2-mediated radical cyclization [59]. The xenicane-related diterpenoid (isolated from the same marine organism as xenicin 116) possesses a complex ring system that is proposed to be biosynthetically derived from the xenicin diterpenoid 116 by an intramolecular [2

• + 2] cycloaddition (Scheme 12) [60]. The synthetic route commenced with known aldehyde 119 which was converted to triol 120 in five steps (Scheme 13). The introduction of the benzyl ether next to the alkyne moiety was necessary to control the stereochemical outcome of the key annulation, and further

• three steps enabled preparation of the annulation precursor 121. The following Pauson–Khand reaction [61] for the construction of the fused bicyclic structure 122 was performed by treatment of 121 with dicobaltoctacarbonyl in the presence of cyclohexylamine. Hydrolysis of the acetonide, chemoselective

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• donor to provide a methyl radical as the precursor of the methyl cation which was crucial for the subsequent annulation. The radical process of the reaction was also supported by the EPR experiment (Scheme 25). While most of the known C–H amidation-based cascade reactions afforded six-membered or

C–H bond halogenation catalyzed or mediated by copper: an overview

• Wenyan Hao and
• Yunyun Liu

Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230

• -component annulation intermediate 60 which led to the formation of indolizine 61 via oxidative decarboxylation. And the bromination of 61 took place in situ to give products 59 via an unprecedented dehydrogenative bromination (Scheme 19). By making use of the copper-mediated arene C–H bond halogenation

The facile construction of the phthalazin-1(2H)-one scaffold via copper-mediated C–H(sp²)/C–H(sp) coupling under mild conditions

• Wei Zhu,
• Bao Wang,
• Shengbin Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2015, 11, 1624–1631, doi:10.3762/bjoc.11.177

• organocopper(II) complex M2, which undergoes Cu(OAc)2-promoted oxidation and intramolecular C–H cupration to deliver chelated organocopper(III) intermediate M4. The corresponding product 3a is formed by the subsequent reductive elimination and intramolecular annulation. Conclusion In conclusion, we have

Spiro annulation of cage polycycles via Grignard reaction and ring-closing metathesis as key steps

• Sambasivarao Kotha,
• Mohammad Saifuddin,
• Rashid Ali and
• Gaddamedi Sreevani

Beilstein J. Org. Chem. 2015, 11, 1367–1372, doi:10.3762/bjoc.11.147

Pd(OAc)₂-catalyzed dehydrogenative C–H activation: An expedient synthesis of uracil-annulated β-carbolinones

• Biplab Mondal,
• Somjit Hazra,
• Tarun K. Panda and
• Brindaban Roy

Beilstein J. Org. Chem. 2015, 11, 1360–1366, doi:10.3762/bjoc.11.146

• dehydrogenative annulation of indole-carboxamides with alkynes etc [36]. The development of metal-catalyzed C–H activation reaction has revolutionized the way a synthetic chemist now approaches a traditional C–C bond disconnection [32][33][34][35][36][37][38][39][40][41][42][43][44]. Dehydrogenative C–H

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• (Scheme 48). Ohsima and co-workers [182] have reported a rhodium-catalyzed [2 + 2 + 2] cyclotrimerization of triynes 283 in a water-organic biphasic system. The biphasic system provides dilute reaction conditions suitable for macrocyclization. Selective cross-annulation between hydrophobic diynes and

Hybrid macrocycle formation and spiro annulation on cis-syn-cis-tricyclo[6.3.0.0^2,6]undeca-3,11-dione and its congeners via ring-closing metathesis

• Sambasivarao Kotha,
• Ajay Kumar Chinnam and
• Rashid Ali

Beilstein J. Org. Chem. 2015, 11, 1123–1128, doi:10.3762/bjoc.11.126

Anionic sigmatropic-electrocyclic-Chugaev cascades: accessing 12-aryl-5-(methylthiocarbonylthio)tetracenes and a related anthra[2,3-b]thiophene

• Laurence Burroughs,
• John Ritchie,
• Mkhethwa Ngwenya,
• Dilfaraz Khan,
• William Lewis and
• Simon Woodward

Beilstein J. Org. Chem. 2015, 11, 273–279, doi:10.3762/bjoc.11.31

• rearrangement of 1a [14] or by SN2’ carbonate displacement in 1b by Pd0(PPh3)2 in Liu’s case [16]. To circumvent reversibility of these pericyclic annulation strategies Lin relied on PhSOH elimination while Liu relied on ubiquitous palladium β-hydride steps leading to tetracenes 3 and 4. We are interested in

2-(1-Hydroxypropyn-2-yl)-1-vinylpyrroles: the first successful Favorsky ethynylation of pyrrolecarbaldehydes

• A. V. Ivanov,
• V. S. Shcherbakova,
• I. A. Ushakov,
• L. N. Sobenina,
• O. V. Petrova,
• A. I. Mikhaleva and
• B. A. Trofimov

Beilstein J. Org. Chem. 2015, 11, 228–232, doi:10.3762/bjoc.11.25

• spasm, brain ischemia, cerebral and myocardial infarction, nephritis, immune diseases, and Crohn’s disease [3]. 2-(1-Hydroxypropyn-2-yl)pyrroles have also been employed for the annulation of a cyclopentanone ring onto a pyrrole to form fused bicycles which then have abundant use as synthetic

Copper-promoted hydration and annulation of 2-fluorophenylacetylene derivatives: from alkynes to benzo[b]furans and benzo[b]thiophenes

• Yibiao Li,
• Liang Cheng,
• Xiaohang Liu,
• Bin Li and
• Ning Sun

Beilstein J. Org. Chem. 2014, 10, 2886–2891, doi:10.3762/bjoc.10.305

• reaction and its application in the synthesis of benzo[b]furan and benzo[b]thiophene derivatives is presented starting from readily available 2-fluorophenylacetylene derivatives. The key annulation step involves the hydration of the C–F bond of 2-fluorophenylacetylene derivatives followed by an

• intramolecular annulation to afford benzo[b]furan and benzo[b]thiophene derivatives. Moreover, structurally important 2,2'-bisbenzofuran scaffolds are provided in good yields. Keywords: annulation; benzo[b]furan; C–F activation; copper-promoted; heterocycle; Introduction The development of general and

• nucleophilic annulation process (Scheme 1b) [24]. But this method involves a two-step process and the usage of two different metal salts may complicate further processing. The direct design of a Pd or Cu-catalyzed one-pot synthesis of benzo[b]thiophenes from 2-bromoalkynylbenzenes and a thiol derivative has