Natural phenolic metabolites with anti-angiogenic properties – a review from the chemical point of view

• Qiu Sun,
• Jörg Heilmann and
• Burkhard König

Beilstein J. Org. Chem. 2015, 11, 249–264, doi:10.3762/bjoc.11.28

• , DCM, −5 °C to rt, overnight; (c) BBr3, DCM, −78 °C to rt, overnight. Synthesis of xanthohumol 58. Reagents and conditions: (a) MOMCl, diisopropylethylamine, CH2Cl2; (b) 3-methyl-2-butene-1-ol, diethyl azodicarboxylate, PPh3, toluene/THF; (c) N,N-dimethylaniline, reflux; (d) (CH3O)SO2, K2CO3, acetone

4-Hydroxy-6-alkyl-2-pyrones as nucleophilic coupling partners in Mitsunobu reactions and oxa-Michael additions

• Michael J. Burns,
• Thomas O. Ronson,
• Richard J. K. Taylor and
• Ian J. S. Fairlamb

Beilstein J. Org. Chem. 2014, 10, 1159–1165, doi:10.3762/bjoc.10.116

• propiolate esters. Both procedures are mild, tolerate a wide range of functionality, and afford good to excellent yields of products in the majority of cases. Results and Discussion Mitsunobu reactions Using the standard conditions of stirring diisopropyl azodicarboxylate (DIAD) and triphenylphosphine in

Regioselective S_N2' Mitsunobu reaction of Morita–Baylis–Hillman alcohols: A facile and stereoselective synthesis of α-alkylidene-β-hydrazino acid derivatives

• Silong Xu,
• Jian Shang,
• Junjie Zhang and
• Yuhai Tang

Beilstein J. Org. Chem. 2014, 10, 990–995, doi:10.3762/bjoc.10.98

• triphenylphosphine is developed, which provides an easy access to α-alkylidene-β-hydrazino acid derivatives in high yields and good stereoselectivity. This reaction represents the first direct transformation of MBH alcohols into hydrazines. Keywords: azodicarboxylate; hydrazine; Mitsunobu reaction; Morita–Baylis

• reaction exhibited poor chemoselectivity which gave comparable yields of tri- and tetrasubstituted hydrazines. For example, the reaction of MBH acetate 1a' with diisopropyl azodicarboxylate (2a) and PPh3 afforded hydrazines 3a and 4a in 51% and 46% yields, respectively. Inspired by this report, and a

• approach (Scheme 1, bottom). As part of our interest in exploring new reactivities of MBH adducts [33][34], herein we wish to report the preliminary results from such an investigation. Results and Discussion In our initial study, MBH alcohol 1a was treated with 2.0 equivalents of diethyl azodicarboxylate

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

• , reflux, 16 h; e) TBAF (1 M THF), THF, 0 °C → rt, 1 h; f) TPP, DIAD, DPPA, THF, −20 °C → rt, 2 d; g) TBSOTf, Et3N, CH2Cl2, 0 °C → rt, 3.5 h; h) TPP, THF/H2O, rt, 16 h. [Ms = methanesulfonate, TPP = triphenylphosphane, DIAD = diisopropyl azodicarboxylate, DPPA = diphenylphosphoryl azide] Hydrogenolyses of

Diversity-oriented synthesis of dihydrobenzoxazepinones by coupling the Ugi multicomponent reaction with a Mitsunobu cyclization

• Lisa Moni,
• Luca Banfi,
• Andrea Basso,
• Alice Brambilla and
• Renata Riva

Beilstein J. Org. Chem. 2014, 10, 209–212, doi:10.3762/bjoc.10.16

• have been varied and the overall yields are generally good (>45% overall yield from azides 2 to dihydrobenzoxazepinones 10). In general diethyl azodicarboxylate (DEAD) or di-t-butyl azodicarboxylate gave similar results and the choice of the reagent was made only on the basis of the easiness of

The total synthesis of D-chalcose and its C-3 epimer

• Jun Sun,
• Song Fan,
• Zhan Wang,
• Guoning Zhang,
• Kai Bao and
• Weige Zhang

Beilstein J. Org. Chem. 2013, 9, 2620–2624, doi:10.3762/bjoc.9.296

• two steps; (e) DEAD, PPh3, PhCOOH, THF, 40 °C; 2) 10% NaOH, THF, rt, 91% in two steps. TBDPS = t-butyldiphenylsilyl, DMAP = N,N-4-dimethylaminopyridine, DIBAL-H = diisobutylaluminum hydride, DIAD = diisopropyl azodicarboxylate, DEAD = diethyl azodicarboxylate. Reagents and conditions: (a) MeI, t-BuOK

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

• triphenylphosphine (1.1 equiv, 5.5 mmol) are added successively. The solution was cooled to 0 °C and diethyl azodicarboxylate (1.2 equiv, 6 mmol) was added dropwise. The ice bath was removed and the reaction was stirred overnight. The solvents were removed under reduced pressure and the resulting crude was subjected

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

• to the cyclization product 108 irreversibly by giving one electron and one proton to the superoxide. The Nishibayashi group also successfully trapped α-amino radicals derived from N-aryltetrahydroquinolines and N-arylindolines using di-tert-butyl azodicarboxylate 110 to form N,N-acetal products 111

• provides an indirect approach for α-C–H functionalization of N-aryltetrahydroquinolines and N-arylindolines. Based on the feasibility of oxidation of aromatic amines as well as reduction of di-tert-butyl azodicarboxylate (110) by the photoexcited Ir(III) complex [98][99], the authors favored a mechanism

• that does not involve the direct addition of α-amino radical 112 to di-tert-butyl azodicarboxylate (110). Oxidation of N-phenyltetrahydroquinoline by the photoexcited Ir(III) complex followed by deprotonation provides α-amino radical 112 with the concomitant formation of the Ir(II) complex. Di-tert

[3 + 2]-Cycloadditions of nitrile ylides after photoactivation of vinyl azides under flow conditions

• Stephan Cludius-Brandt,
• Lukas Kupracz and
• Andreas Kirschning

Beilstein J. Org. Chem. 2013, 9, 1745–1750, doi:10.3762/bjoc.9.201

• with thermal formation of 2H-azirines. Photochemically, the ring of the 2H-azirines was opened to yield the nitrile ylides, which underwent a [3 + 2]-cycloaddition with 1,3-dipolarophiles. When diisopropyl azodicarboxylate serves as the dipolarophile, 1,3,4-triazoles become directly accessible starting

• azodicarboxylate (DIAD, 4e) as the dipolarophile (Scheme 5). Additionally, we found that even electron-deficient alkynes such as 4f can serve as dipolarophiles in these reactions (Scheme 6). However, the resulting pyrrole 5k could only be isolated in 26% yield. Alternatively, the in-situ generated nitrile ylide

• experiments were conducted at room temperature in a photochemical flow-reactor (see above) using Teflon (FEP) tubing (volume: 5.5 mL, inner diameter = 0.75 mm) at a concentration of 0.05 M in CH3CN; isolated yields are given. Photoinduced cycloaddtion of vinyl azide 1c and diisopropyl azodicarboxylate (4e

Metal-free aerobic oxidations mediated by N-hydroxyphthalimide. A concise review

• Lucio Melone and
• Carlo Punta

Beilstein J. Org. Chem. 2013, 9, 1296–1310, doi:10.3762/bjoc.9.146

• azodicarboxylate reagent [73]. The proposed mechanism (Scheme 27) suggests a double function of the dialkyl azodicarboxylate, which acts both as an oxidant, promoting the oxidation of NHPI to PINO by ET process, and as acceptor of carbon radicals generated via HAT by PINO, leading to the formation of hydrazine

Asymmetric synthesis of host-directed inhibitors of myxoviruses

• Terry W. Moore,
• Kasinath Sana,
• Dan Yan,
• Pahk Thepchatri,
• John M. Ndungu,
• Manohar T. Saindane,
• Mark A. Lockwood,
• Michael G. Natchus,
• Dennis C. Liotta,
• Richard K. Plemper,
• James P. Snyder and
• Aiming Sun

Beilstein J. Org. Chem. 2013, 9, 197–203, doi:10.3762/bjoc.9.23

• -methylaniline (16) [17] (Scheme 4b)) in the presence of a slight excess of triphenylphosphine and diethyl azodicarboxylate, we acquired the desired products 14 in good yield and ee. This methodology is attractive because of the high ee that can be obtained from the inexpensive and readily available (L)-lactic

A quantitative approach to nucleophilic organocatalysis

• Herbert Mayr,
• Sami Lakhdar,
• Biplab Maji and
• Armin R. Ofial

Beilstein J. Org. Chem. 2012, 8, 1458–1478, doi:10.3762/bjoc.8.166

• -nitrostyrene (E = –13.9) [85] or di-tert-butyl azodicarboxylate (E = –12.2) [86]. The less basic imidazolidinones, which yield the less nucleophilic enamines 32d and 32e, are suitable catalysts for reactions with stronger electrophiles, such as the chlorinating agent 2,3,4,5,6,6-hexachlorocyclohexan-2,4-dien-1

• of the C–C bond. The observation that β-nitrostyrene, a neutral electrophile, also reacts 102 times faster with 33– than with 36 also excludes Coulomb attraction to be the major factor for the high reactivity of 33−. On the other hand, di-tert-butyl azodicarboxylate reacts only six times faster with

Organocatalytic asymmetric Michael addition of unprotected 3-substituted oxindoles to 1,4-naphthoquinone

• Jin-Sheng Yu,
• Feng Zhou,
• Yun-Lin Liu and
• Jian Zhou

Beilstein J. Org. Chem. 2012, 8, 1360–1365, doi:10.3762/bjoc.8.157

• enantioenriched 3-hydroxyoxindoles [22][23][24]. For the synthesis of chiral 3-aminooxindoles, we developed the first example of catalytic asymmetric addition of nucleophiles to isatin-derived ketoimines using TMSCN [25] and the amination of unprotected 3-prochiral oxindoles using di-tert-butyl azodicarboxylate

Synthesis of oleophilic electron-rich phenylhydrazines

• Aleksandra Jankowiak and
• Piotr Kaszyński

Beilstein J. Org. Chem. 2012, 8, 275–282, doi:10.3762/bjoc.8.29

• increases its stability in the reaction medium. The hydrazines were isolated in 60–86% yields and purities >90%. The hydrazides 2 were obtained in 43–71% yields from aryl bromides 5, which were lithiated with t-BuLi and subsequently reacted with di-tert-butyl azodicarboxylate (DTBAD). Keywords

• deprotection of hydrazides II have been developed (Figure 1). Hydrazides II are efficiently obtained by the addition of organometallic reagents III, prepared from aryl halide IV, to azodicarboxylate diesters (AD) [16][17]. Alternatively, II can be obtained in the Pd(0)- or Cu2+-catalyzed reaction of

• amination of arenes VI with bis(2,2,2-trichloroethyl) azodicarboxylate (BTCEAD) under Lewis [21][22] or Brønsted [23] acid conditions. By judicious choice of the substituent R, the removal of the protecting group in II and formation of arylhydrazines I can be accomplished under acidic (R = t-Bu) [16

Photoinduced homolytic C–H activation in N-(4-homoadamantyl)phthalimide

• Nikola Cindro,
• Margareta Horvat,
• Kata Mlinarić-Majerski,
• Axel G. Griesbeck and
• Nikola Basarić

Beilstein J. Org. Chem. 2011, 7, 270–277, doi:10.3762/bjoc.7.36

• the laboratory according to a known procedure [56]. Phthalimide, triphenylphosphine, lithium aluminum hydride (LAH) and diethyl azodicarboxylate (DEAD) were obtained from commercial sources. All photochemical experiments were performed in a Rayonet photochemical reactor equipped with 300 nm lamps. 4

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

ADDP and PS-PPh₃: an efficient Mitsunobu protocol for the preparation of pyridine ether PPAR agonists

• Paul S. Humphries,
• Quyen-Quyen T. Do and
• David M. Wilhite

Beilstein J. Org. Chem. 2006, 2, No. 21, doi:10.1186/1860-5397-2-21

• was the limiting reagent. Upon closer examination, compound 5 was observed as a major by-product (46% based on 3). By-products analogous to 5 have been observed in the literature when diethyl azodicarboxylate (DEAD) is used in certain Mitsunobu reactions.[18][19] This by-product formation is believed

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

• diethyl azodicarboxylate or Ph3P-CCl4 were low yielding (entries 1, 2).[22] Interestingly, small amounts of the 2,6-cis-disubstituted dihydropyran 6a were detected under these conditions, suggesting the intervention of a competitive double inversion process or a carbocation-mediated cyclization process