Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

• (9) and diphenyl-1,3,4-oxadiazole (10); and thioflavin-T analogues such as benzothiazole (11), benzoxazole (12), benzofuran (13), imidazopyridine (14), and benzimidazole (15); as well as quinoline (16) and naphthalene (17) derivatives (Figure 1B). In this review, we provide an overview of these AD

• ]. Benzofurans Replacement of the nitrogen of the benzoxazole backbone with carbon affords the benzofuran backbone of compounds 121–126 (Figure 4), which has also been successfully employed for radioimaging of Aβ plaques. The [11C]-labeled benzofuran 121 was prepared via Wittig reaction between the

• binding in vivo. Several [18F]-labeled benzofurans have been employed with success for Aβ imaging. [18F]FPYBF-1 (123a), which has a N,N-dimethyl-2-aminopyridine group attached to the benzofuran core, was synthesized via Suzuki coupling between 5-methoxybenzofuran-2-boronic acid (130) and 2-amino-5

Intramolecular carbonickelation of alkenes

• Rudy Lhermet,
• Muriel Durandetti and
• Jacques Maddaluno

Beilstein J. Org. Chem. 2013, 9, 710–716, doi:10.3762/bjoc.9.81

• a benzofuran or an indole core. Our first study involved the cyclization of allyl moieties such as allyl ether 1a or N-allyl protected anilines 1b–c, easily prepared by quantitative allylation of o-iodophenol and o-iodoanilines using allyl bromide in DMF (Scheme 1). Following the protocol optimized

• cyclohexenyl series, we were pleased to observe that ether 6a affords only the benzofuran 10a, but the conversion is limited (30% of the starting material 6a is recovered) and the yield modest (36% isolated, 51% based on recovered material, Scheme 5). Interestingly, the intracyclic character of the double bond

Palladium-catalyzed dual C–H or N–H functionalization of unfunctionalized indole derivatives with alkenes and arenes

• Gianluigi Broggini,
• Egle M. Beccalli,
• Andrea Fasana and
• Silvia Gazzola

Beilstein J. Org. Chem. 2012, 8, 1730–1746, doi:10.3762/bjoc.8.198

• indole, furan, and benzofuran rings (Scheme 2) [48]. Working with indole and methyl acrylates in the presence of Pd(OAc)2 and 1,4-benzoquinone in catalytic quantity with tert-butyl hydroperoxide as oxidant, 3-alkenyl-substituted products were obtained. The synthetic value of the direct catalytic C–H

• 6-membered ring, once again producing vinyl-substituted products. An analogous process for the direct intramolecular C–H functionalization of inactive alkenyl aryl ethers, giving benzofuran and dihydrobenzofuran derivatives, was successfully developed [67]. Both possible mechanistic pathways based

Asymmetric total synthesis of smyrindiol employing an organocatalytic aldol key step

• Dieter Enders,
• Jeanne Fronert,
• Tom Bisschops and
• Florian Boeck

Beilstein J. Org. Chem. 2012, 8, 1112–1117, doi:10.3762/bjoc.8.123

• benzofuran system; thus, for further modifications it was protected as acetonide 16 in a moderate yield (66%) using 2,2-dimethoxypropane under PPTA catalysis. As we turned towards the Sonogashira reaction of the iodide 16 with a propiolic acid derivative, we found that the allyl protecting group was cleaved

• protected ketoaldehyde 8 (PG = TBS) in the proline catalyzed aldol reaction led to complete condensation to the corresponding benzofuran. Propiolic acid esters are known to be problematic substrates for Sonogashira reactions, due to side reactions [15]. For this reason, we used an orthoester, which coupled

Synthesis, solid-state fluorescence properties, and computational analysis of novel 2-aminobenzo[4,5]thieno[3,2-d]pyrimidine 5,5-dioxides

• Kenichirou Yokota,
• Masayori Hagimori,
• Naoko Mizuyama,
• Yasuhisa Nishimura,
• Hiroshi Fujito,
• Yasuhiro Shigemitsu and
• Yoshinori Tominaga

Beilstein J. Org. Chem. 2012, 8, 266–274, doi:10.3762/bjoc.8.28

• derivative 3g was obtained from 1a with (S)-methylisothiourea sulfate (2b) in 87% yield (Scheme 2). Fused pyrimidine derivatives 6 and 7 containing the electron-rich heterocycles benzothiophene or benzofuran were prepared by the reaction of ketene dithioacetal 1b or 1c with guanidine carbonate (2a) in 74

A novel and facile synthesis of 3-(2-benzofuroyl)- and 3,6-bis(2-benzofuroyl)carbazole derivatives

• Wentao Gao,
• Meiru Zheng and
• Yang Li

Beilstein J. Org. Chem. 2011, 7, 1533–1540, doi:10.3762/bjoc.7.180

• substituted with a carbazole unit. Hence the synthesis of such compounds is desirable [29][30]. On the other hand, the benzofuran derivatives are an important class of heterocyclic compounds that are known to possess important biological properties [31][32][33]. Especially, recent studies have shown that some

• an attractive idea to construct new prototypes combining both the carbazole ring system and benzofuran framework in the same molecule. Such compounds are not only synthetically challenging but may also be vitally important for pharmacological studies or in the realization of new medicinal properties

• of 3-chloroacetyl-9-ethyl-9H-carbazole (1) with a variety of salicylaldehydes 2a–k is summarized in Scheme 1. The Rap–Stoermer reaction was normally performed in alcoholic medium but often produced poor to moderate yields of benzofuran products [47][48]. Considering this fact, we conducted our own

Directed ortho,ortho'-dimetalation of hydrobenzoin: Rapid access to hydrobenzoin derivatives useful for asymmetric synthesis

• Inhee Cho,
• Labros Meimetis,
• Lee Belding,
• Michael J. Katz,
• Travis Dudding and
• Robert Britton

Beilstein J. Org. Chem. 2011, 7, 1315–1322, doi:10.3762/bjoc.7.154

• diiodohydrobenzoin 12 in Cu-catalyzed C–N cross-coupling reactions [33] led only to the formation of cis-4b,9b-dihydrobenzofuro[3,2-b]benzofuran (24) [34]. Consequently, the diol 12 was converted to the corresponding acetonide 25 or methyl ether 26 prior to cross-coupling. In this manner, the diphenylhydrobenzoin

Functionalization of heterocyclic compounds using polyfunctional magnesium and zinc reagents

• Paul Knochel,
• Matthias A. Schade,
• Sebastian Bernhardt,
• Georg Manolikakes,
• Albrecht Metzger,
• Fabian M. Piller,
• Christoph J. Rohbogner and
• Marc Mosrin

Beilstein J. Org. Chem. 2011, 7, 1261–1277, doi:10.3762/bjoc.7.147

• ) is zincated without reacting with the nitro group, leading to the nitro-substituted zinc reagent 53. After allylation, the benzofuran 54 is obtained in 80% yield. The polyfunctional pyridine 55 is zincated with TMP2Zn·2MgCl2·2LiCl (42) leading to the zinc reagent 56. Subsequent allylation furnishes

• the trisubstituted pyridine 57 in 80% yield (Scheme 9) [28]. In some cases, the zincation using TMP2Zn·2MgCl2·2LiCl (42) is slow and requires long reaction times. This is the case for benzofuran (58), which requires 9 days at 25 °C for a complete zincation in position 2 leading to 59. The reaction

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

• compound [22][23]. In particular, several benzo[b]furan derivatives with oxygen-bearing substituents, such as hydroxy, or alkoxy, at the benzene moiety are known to be biologically active compounds [24][25][26][27][28] (Figure 1). Among the various approaches developed for the synthesis of the benzofuran

• B gave rise to better selectivities and yields of the desired alkynes 5–7 (Table 2, entries 4,6,10,12,16 and 18). According to our retrosynthetic analysis (Scheme 1), the final step to achieve the benzofuran derivatives should be the incorporation of the hydroxy group followed by in situ

• aryl bromides instead of aryl chlorides. In addition, we also observed better yields for the corresponding benzofuran derivatives 9 (Table 3, entries 5–9) derived from the starting o-alkynylhalobenzene derivatives 6, bearing the two methoxy groups in a 3,5-relationship relative to the halide. Moreover

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• -arylhydroxylamines with 1,3-dicarbonyl compounds in situ) to give 3-carbonylated benzofuran derivatives 300 [153]. Trisubstituted isoxazoles 303 were obtained from alkynyl oxime ether 301 through a gold-catalyzed domino reaction involving cyclization and subsequent Claisen-type rearrangement [154]. The presence of

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

First synthesis of 2-(benzofuran-2-yl)-6,7-methylene dioxyquinoline-3-carboxylic acid derivatives

• Wentao Gao,
• Jia Liu,
• Yun Jiang and
• Yang Li

Beilstein J. Org. Chem. 2011, 7, 210–217, doi:10.3762/bjoc.7.28

• Wentao Gao Jia Liu Yun Jiang Yang Li Institute of Superfine Chemicals, Bohai University, Jinzhou 121000, China 10.3762/bjoc.7.28 Abstract A facile and inexpensive synthesis of a series of novel methylenedioxy-bearing 2-(benzofuran-2-yl)-quinoline-3-carboxylic acid derivatives 3a–h via the one-pot

• ethyl 4-chloro-3-oxobutanoate using KHSO4 as catalyst under ultrasound irradiation conditions. The targeted compounds 3a–h were obtained in good yields of 52–82% and their structures were established based on spectral data and elemental analyses. Keywords: benzofuran; Friedländer condensation

• -(benzofuran-2-yl)-6,7-methylenedioxyquinoline-3-carboxylic acid derivatives (3, Figure 1) under mild conditions. Results and Discussion The targeted 2-(benzofuran-2-yl)-6,7-methylenedioxyquinoline-3-carboxylic acid derivatives 3a–g were synthesized via a two-step procedure, starting from ethyl 2-chloromethyl

Intramolecular hydroxycarbene C–H-insertion: The curious case of (o-methoxyphenyl)hydroxycarbene

• Dennis Gerbig,
• David Ley,
• Hans Peter Reisenauer and
• Peter R. Schreiner

Beilstein J. Org. Chem. 2010, 6, 1061–1069, doi:10.3762/bjoc.6.121

• intermediate leading to the tautomeric formyl group. Thermochemical computations at M06-2X/cc-pVDZ in conjunction with a self-consistent solvent reaction field model support this suggested reaction pathway. Keywords: benzofuran; C–H-insertion; hydroxycarbene; singlet carbene; tunneling; Introduction

Synthesis of novel photochromic pyrans via palladium- mediated reactions

• Christoph Böttcher,
• Gehad Zeyat,
• Saleh A. Ahmed,
• Elisabeth Irran,
• Thorben Cordes,
• Cord Elsner,
• Wolfgang Zinth and
• Karola Rueck-Braun

Beilstein J. Org. Chem. 2009, 5, No. 25, doi:10.3762/bjoc.5.25

• ]. However, only the rearranged and hydrodehalogenated benzofuran 14 was isolated in 65% yield after flash chromatography. Formation of the benzofuran can be rationalized by cleavage of the benzopyran ring and a subsequent rearrangement reaction [29][30]. However, by using standard Sonogashira conditions in

2-Arylhydrazononitriles as building blocks in heterocyclic synthesis: A novel route to 2-substituted- 1,2,3-triazoles and 1,2,3-triazolo[4,5-b]pyridines

• Saleh M. Al-Mousawi and
• Moustafa Sh. Moustafa

Beilstein J. Org. Chem. 2007, 3, No. 12, doi:10.1186/1860-5397-3-12

• as in 5 and therefore excluding 7 (Scheme 2). Typical of enaminones, compound 9 reacts with naphthoquinone to yield the benzofuran 12 and with hydrazine hydrate to yield pyrazolyl-1,2,3-triazole 13 in good yields. Attempts to convert 4 into oxadiazolylhydrazone 6 by heating in DMF afforded 14 whose