Microwave-assisted cyclizations promoted by polyphosphoric acid esters: a general method for 1-aryl-2-iminoazacycloalkanes

• Jimena E. Díaz,
• María C. Mollo and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2016, 12, 2026–2031, doi:10.3762/bjoc.12.190

• of conventional heating [17]. In previous work, we reported the microwave-assisted synthesis of 5 to 8 membered cyclic amidines by cyclodehydration of N-aryl-N´-acyl-1,n-alkanediamines (n = 2–5) promoted by polyphosphoric acid (PPA) esters PPE and PPSE (Scheme 1, reaction 1) [41][42][43]. In this

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• catalytic role for this metal [33]. However, this role was later demonstrated to be structural rather than catalytic [34]. The Mitchell group showed [35] that the D-protein is actually directly involved in catalysis and uses ATP to activate the backbone amide bond for cyclodehydration, thus explaining the

Synthesis and fluorosolvatochromism of 3-arylnaphtho[1,2-b]quinolizinium derivatives

• Phil M. Pithan,
• David Decker,
• Manlio Sutero Sardo,
• Giampietro Viola and
• Heiko Ihmels

Beilstein J. Org. Chem. 2016, 12, 854–862, doi:10.3762/bjoc.12.84

• -benzylpyridinium derivative 3 and the subsequent cyclodehydration [27] in refluxing HBr (w = 48%) gave the bromonaphtho[1,2-b]quinolizinium 4 in 57% overall yield (Scheme 1). The Suzuki–Miyaura coupling reactions of 3-bromonaphthoquinolizinium derivative 4 with the arylboronic acids 5a–e were performed under

An oxidative amidation and heterocyclization approach for the synthesis of β-carbolines and dihydroeudistomin Y

• Suresh Babu Meruva,
• Akula Raghunadh,
• Raghavendra Rao Kamaraju,
• U. K. Syam Kumar and
• P. K. Dubey

Beilstein J. Org. Chem. 2014, 10, 471–480, doi:10.3762/bjoc.10.45

• was subjected to a Bischler–Napieralski cyclodehydration reaction in presence of POCl3 [27], however under these conditions 2,9-dihydro-β-carboline derivative 7 was obtained as the major product (less than 10% yield) instead of 4-9-dihydro-β-carboline derivative 12 (Scheme 4). Our attempts to improve

• the yield of 7 under Bischler–Napieralski cyclodehydration reaction conditions using POCl3 as the Lewis acid were proved to be futile. This prompted us to test the efficiency of other Lewis acids in this cyclodehydration reaction. The Bischler–Napieralski cyclodehydration reaction was then carried out

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• of the NK-1 inhibitor L-733,060 in 8 steps. Additionally, a cyclodehydration-realizing simple triethylphosphite as a substitute for triphenylphosphine is developed. Here the stoichiometric oxidized P(V)-byproduct (triethylphosphate) is easily removed during the work up through saponification

• overcoming separation difficulties usually associated to triphenylphosphine oxide. Keywords: amino acids; asymmetric synthesis; cyclodehydration; hydroxypiperidines; natural products; one-pot; Introduction 1,2-Amino alcohols of the type A (Figure 1) represent a frequent core motif of many pharmacologically

• , in an additional step, was reported to effect cyclodehydration of diols to furans and pyrans [47][48] (for recent examples for cyclodehydration protocols see [49][50]). Thereby, the volatile products were separated from O=P(OEt)3 through distillation. After our initial short communication [51] about

Synthesis of new enantiopure poly(hydroxy)aminooxepanes as building blocks for multivalent carbohydrate mimetics

• Léa Bouché,
• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 213–223, doi:10.3762/bjoc.10.17

• of the seven-membered polyhydroxylated oxacycle, are for instance cycloaddition [9][10][11] or cyclodehydration of commercially available alcohols [12][13][14]. The disadvantages of these methods are the lack of selectivity as well as of stereocontrol and hence other routes are needed. One

Synthesis and characterization of novel bioactive 1,2,4-oxadiazole natural product analogs bearing the N-phenylmaleimide and N-phenylsuccinimide moieties

• Catalin V. Maftei,
• Elena Fodor,
• Peter G. Jones,
• M. Heiko Franz,
• Gerhard Kelter,
• Heiner Fiebig and
• Ion Neda

Beilstein J. Org. Chem. 2013, 9, 2202–2215, doi:10.3762/bjoc.9.259

• ′-carbonyldiimidazole (CDI). In the first step the amidoxime is O-acylated with the activated derivative in a condensation reaction. The O-acylated amidoxime can be isolated or it can immediately undergo the cyclisation to the heterocyclic oxadiazole ring. This cyclodehydration reaction takes place by heating to

• underwent a cyclodehydration reaction, delivering aniline 1 with 59% yield after purification. The structure of compound 1 was confirmed by X-ray structure determination (Figure 3 and Figure 4). It crystallizes with two molecules in the asymmetric unit, which differ in the relative orientation of the rings

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

•  12) using a dimethylformamide acetal-mediated cyclodehydration of 105. The isoindole unit of 105 was prepared from the condensation of 103 and 104. Oxygen–sulfur exchange provided the thiophthalimide 105, which could be converted to magallanesine (97) via an intramolecular aldol condensation in one

One-step synthesis of pyridines and dihydropyridines in a continuous flow microwave reactor

• Mark C. Bagley,
• Vincenzo Fusillo,
• Robert L. Jenkins,
• M. Caterina Lubinu and
• Christopher Mason

Beilstein J. Org. Chem. 2013, 9, 1957–1968, doi:10.3762/bjoc.9.232

• material. In the Bohlmann–Rahtz reaction, the use of a Brønsted acid catalyst allows Michael addition and cyclodehydration to be carried out in a single step without isolation of intermediates to give the corresponding trisubstituted pyridine as a single regioisomer in good yield. Furthermore, 3

• synthetic transformations (Scheme 1), including Bohlmann–Rahtz cyclodehydration of aminodienones 1 to the corresponding pyridines 2 [44][45], Fischer indole synthesis of tetrahydrocarbazole 5 from phenylhydrazine (3) and cyclohexanone (4) [44], and hydrolysis of 4-chloromethylthiazole (6) to give the

• continuous flow reactor examined the cyclodehydration of Bohlmann–Rahtz aminodienone intermediates in the presence of a Brønsted acid catalyst [44][45]. This relatively simple cyclization reaction was utilized previously as we had already established its facility under microwave irradiation and so it

Combined directed ortho-zincation and palladium-catalyzed strategies: Synthesis of 4,n-dimethoxy-substituted benzo[b]furans

• Verónica Guilarte,
• M. Pilar Castroviejo,
• Estela Álvarez and
• Roberto Sanz

Beilstein J. Org. Chem. 2011, 7, 1255–1260, doi:10.3762/bjoc.7.146

• ring system, the cyclodehydration of α-aryloxy ketones [29], the Claisen rearrangement of an allyl aryl ether followed by Pd-catalyzed intramolecular oxidative cyclization [30], and the tandem Sonogashira coupling/heterocyclization of 2-halophenols with terminal alkynes [31], are some of the most used

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• 283 was then subjected to cyclodehydration using phosphoryl chloride to give a chloromethyl oxadiazole derivative 284. In a cleverly staged transformation, this compound was treated with diaminoethane to yield the piperazine ring 285, which, on heating under reflux in methanol, undergoes a further

Approaches towards the synthesis of 5-aminopyrazoles

• Ranjana Aggarwal,
• Vinod Kumar,
• Rajiv Kumar and
• Shiv P. Singh

Beilstein J. Org. Chem. 2011, 7, 179–197, doi:10.3762/bjoc.7.25

• methylene chloride followed by condensation with β-ketonitriles 1 (Scheme 11) [42]. 1-ethyl-3-[3-(dimethylamino)propyl] carbodiimide hydrochloride (EDCI) mediated intramolecular cyclodehydration resulted in the formation of the 5,5-ring system, imidazo[1,2-b]pyrazol-2-one 46. 3-Oxopropanenitriles 16 on

Silica- bound benzoyl chloride mediated the solid- phase synthesis of 4H-3,1-benzoxazin- 4-ones

• Kurosh Rad-Moghadam and
• Somayeh Rouhi

Beilstein J. Org. Chem. 2009, 5, No. 13, doi:10.3762/bjoc.5.13

• features, a number of approaches have been developed for the synthesis of 4H-3,1-benzoxazin-4-ones. A literature survey regarding the synthesis of 2-substituted 4H-3,1-benzoxazin-4-one derivatives disclosed a variety of methods, including cyclodehydration of N-acylanthranilic acids by acetic anhydride [20

• ], photoisomerization of 2-arylisatogen [25], and cyclocondensation of anthranilic acid with orthoesters [26]. Meanwhile, the cyclodehydration of N-acylanthranilic acids in refluxing acetic anhydride has been the prevalent method used for production of 4H-3,1-benzoxazin-4-ones. However, use of traditional dehydrating

Synthesis of 2-substituted 9-oxa-guanines {5-aminooxazolo[5,4-d]pyrimidin- 7(6H)-ones} and 9-oxa-2-thio- xanthines {5-mercaptooxazolo[5,4-d]pyrimidin- 7(6H)-ones}

• Subrata Mandal,
• Wen Tai Li,
• Yan Bai,
• Jon D. Robertus and
• Sean M. Kerwin

Beilstein J. Org. Chem. 2008, 4, No. 26, doi:10.3762/bjoc.4.26

• to naturally occurring nucleic acid bases, this heterocyclic ring system continues to generate interest. Approaches to the oxazolo[5,4-d]pyrimidine ring system generally involve either cyclodehydration of an 5-(acylamino)-4-hydroxypyrimidine [6][7][8][9][10] or elaboration of a 4-cyano- or 4

• preparation of analogs suitable for further elaboration, for example by “click” chemistry employing copper-catalyzed Huisgen 1,3-dipolar cycloadditions [18]. Results and Discussion Our previous route [5] to 8-methyl-9-oxa-guanine (2a) involved the thermal cyclodehydration of 5-(acetylamino)-2-amino-4,6

• -dihydroxypyrimidine (1a) [19] (Figure 2). Unfortunately, for other 5-acylamino analogs of 1a, this route failed to afford the required oxazolo[5,4-d]pyrimidines, presumably due to decomposition of the product at the temperatures required for cyclodehydration. Other cyclodehydration conditions (POCl3, PPA) were also

Synthesis of (–)-Indolizidine 167B based on domino hydroformylation/cyclization reactions

• Giuditta Guazzelli,
• Raffaello Lazzaroni and
• Roberta Settambolo

Beilstein J. Org. Chem. 2008, 4, No. 2, doi:10.1186/1860-5397-4-2

• remains a target compound for many research groups [4][5][6]. We recently reported the synthesis of Indolizidine 167B both in racemic and optically active form [7][8]; the crucial key was the cyclodehydration of 4-carboxyethyl-4-(pyrrol-1-yl)butanal, obtained via selective reduction of pyrrole masked

• -alkyl intermediates and carries on with the intramolecular cyclodehydration of the formed linear aldehyde followed by hydrogenation. All steps occur with almost complete configurational stability and the final indolizine has the same optical purity as the starting material. The hydroformylation

Diastereoselective synthesis of some novel benzopyranopyridine derivatives

• Pradeep K. Mohakhud,
• Sujeet M. R. Kumar,
• Vasanth M. R. Kumar,
• Ravi M. R. Kumar,
• Moses D. R. Babu,
• Vyas D. R. K and
• Om D. R. Reddy

Beilstein J. Org. Chem. 2006, 2, No. 25, doi:10.1186/1860-5397-2-25

• phenols and mesylate derivatives, unexpectedly resulted in cyclodehydration leading to new benzopyrano derivatives, N-substituted-1,2,3,4-tetrahydro[1,3]-dioxolo-[6,7]-5H-[1]benzopyrano [3,4-c]pyridines. The process involves the deprotection of the carbonyl protecting group, and then the cyclization

• to 5a and 5b, instead of the desired ketone 4c. A proposed mechanism for the cyclodehydration leading to the cyclized product is discussed below. The cyclized product 5b, was dealkylated using chloroformates by two different methods to yield 6 as a free base. Also compound 6 was obtained by

• reports the formation of 7 via key intermediates 5a and 5b. It is hypothesized that the presence of the activated aromatic ring facilitates the cyclodehydration in acidic medium leading to the benzopyranopyridine derivative. The saturated cis derivative 7 is successfully resolved to get the individual

One-pot synthesis of novel 1H-pyrimido[4,5-c][1,2]diazepines and pyrazolo[3,4-d]pyrimidines

• Dipak Prajapati,
• Partha P. Baruah,
• Baikuntha J. Gogoi and
• Jagir S. Sandhu

Beilstein J. Org. Chem. 2006, 2, No. 5, doi:10.1186/1860-5397-2-5

• starting material occurred. Although we could not isolate any intermediate from the reaction mixture a plausible mechanism for the formation of the products entails an initial Michael reaction of 1 to 2 followed by cyclodehydration possibly by a Bohlmann-Ratz type[32] reaction leading to a seven-membered

Synthesis of 2,6-trans- disubstituted 5,6-dihydropyrans from (Z)-1,5-syn-endiols

• Eric M. Flamme and
• William R. Roush

Beilstein J. Org. Chem. 2005, 1, No. 7, doi:10.1186/1860-5397-1-7

• enantioselectivity.[1] In connection with an ongoing natural product synthesis project, we were interested in developing methods to transform diols 2 into dihydropyrans 3 or the enantiomeric dihydropyrans ent-3 through complementary, regioselective cyclodehydration processes (Scheme 1). 2,6-Disubstituted

• -dihydropyrans. Furthermore, there are only limited reports describing the stereoselective synthesis of related tetrahydropyrans through cyclodehydration of enantiopure 1,5-diols substrates.[17] The challenge of synthesizing dihydropyrans 3 or ent-3 from 1,5-diols such as 2 lies in the differentiation of the two

• dihydropyan ent-3. Cyclic ethers of various ring size have been synthesized by the cyclodehydration of diols through the use of oxyphosphonium salts and phosphorane reagents.[18][19][20][21][22][23] We reasoned that because the rate determining step of these cyclizations is believed to be the nucleophilic