Syntheses of 3,4- and 1,4-dihydroquinazolines from 2-aminobenzylamine

• Jimena E. Díaz,
• Silvia Ranieri,
• Nadia Gruber and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2017, 13, 1470–1477, doi:10.3762/bjoc.13.145

• propionamides 4a,b,h–k reacted readily under mild reaction conditions (Table 3, entries 1, 2, and 8–11), while for isobutyramide 4c a higher temperature was necessary (Table 3, entry 3). Finally, the more sterically hindered pivalamide 4d and the less reactive benzamides 4e–g required harsher reaction

A speedy route to sterically encumbered, benzene-fused derivatives of privileged, naturally occurring hexahydropyrrolo[1,2-b]isoquinoline

• Olga Bakulina,
• Alexander Ivanov,
• Vitalii Suslonov,
• Dmitry Dar’in and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2017, 13, 1413–1424, doi:10.3762/bjoc.13.138

• formation of HPA dimer 11 and product of its decarboxylation 12 (Scheme 1). The formation of these two products (observed by 1H NMR) was recently reported by Knapp et al. [35] as a result from the treatment of HPA with a strong base (which was absent in our case). The failure to activate sterically hindered

Detection of therapeutic radiation in three-dimensions

• John A. Adamovics

Beilstein J. Org. Chem. 2017, 13, 1325–1331, doi:10.3762/bjoc.13.129

• of the eight DTMs which varied from 4.5 times greater than LMG for the most sterically hindered bromide derivative 2 to the least for the ortho-fluoride 4 with 0.6 less dose sensitivity than LMG (Table 1). This is also consistent for the ortho-methyl derivative 5 being more dose sensitive than it’s

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• stereoselective elimination and decarboxylation in situ. The corresponding aldehyde 22 was then homologated by an Abiko–Masamune anti-aldol addition [74] with ephedrine-derived ester 23, which proceeded with excellent yield and stereoselectivity. However, the subsequent removal of the sterically hindered chiral

Regioselective (thio)carbamoylation of 2,7-di-tert-butylpyrene at the 1-position with iso(thio)cyanates

• Anna Wrona-Piotrowicz,
• Marzena Witalewska,
• Janusz Zakrzewski and
• Anna Makal

Beilstein J. Org. Chem. 2017, 13, 1032–1038, doi:10.3762/bjoc.13.102

• , 6 and 8 of 1. However, Friedel–Crafts alkylation of 1 with an excess of sterically hindered tert-butyl chloride leads to 2,7-di-tert-butylpyrene (2) [8]. This compound, owing to the presence of two bulky and electron-donating tert-butyl groups, displays different reactivity towards electrophiles. It

• sterically hindered pyrene 1-position, whereas the bulkier protonated acetyl trifluoroacetate (the postulated electrophile in the examined Friedel–Crafts acylation) attacks sterically the less hindered 4-position. Conclusion We found that triflic acid-promoted (thio)carbamoylation of 2 with aliphatic iso

• sterically hindered pyrene framework. Experimental General All reagents were purchased from Sigma-Aldrich and used without further purification. Solvents were purified before use by reported methods. Column chromatography was carried out on silica gel 60 (0.040–0.063 mm, 230–400 mesh, Fluka). 1H and 13C NMR

Synthesis of tetrasubstituted pyrazoles containing pyridinyl substituents

• Josef Jansa,
• Ramona Schmidt,
• Ashenafi Damtew Mamuye,
• Laura Castoldi,
• Alexander Roller,
• Vittorio Pace and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2017, 13, 895–902, doi:10.3762/bjoc.13.90

• homocoupling products 7a,b emerged as the predominant reaction products (Scheme 5, middle trace), probably due to preferable halogen–zinc exchange and subsequent homocoupling. Interestingly, such sterically hindered halides provided homocoupling products 7a,b in good yields (66% and 48%, respectively). The

DMAP-assisted sulfonylation as an efficient step for the methylation of primary amine motifs on solid support

• Johnny N. Naoum,
• Koushik Chandra,
• Dorit Shemesh,
• R. Benny Gerber,
• Chaim Gilon and
• Mattan Hurevich

Beilstein J. Org. Chem. 2017, 13, 806–816, doi:10.3762/bjoc.13.81

• several amine motifs. 4-Dimethylaminopyridine (DMAP) has been reported to assist in the sulfonylation and acylation of weak nucleophiles such as secondary amines, alcohols, amides, and sterically hindered amines when used as catalyst in addition to a base additive [28][29][30][31]. It has been suggested

• additive for sulfonylation of primary amines with o-NBS-Cl for the purpose of N-methylation on solid support. We herein report a DMAP-mediated strategy for the efficient regioselective N-methylation of sterically hindered primary amines as well as less hindered amines on solid support (Figure 1B). Our DFT

• electron-donating groups on the ring. Collidine has electron-donating groups that make it nucleophilic but it is sterically hindered, while DMAP is stabilized by resonance and much less hindered. Our results emphasized the effect of DMAP for the introduction of the o-NBS group as it proved the most

Transition-metal-catalyzed synthesis of phenols and aryl thiols

• Yajun Liu,
• Shasha Liu and
• Yan Xiao

Beilstein J. Org. Chem. 2017, 13, 589–611, doi:10.3762/bjoc.13.58

• , and 1,4-dioxane/H2O as solvent (Scheme 1). Under these conditions, a wide range of aryl bromides and chlorides could be readily converted to the corresponding phenols in high yields at 100 °C within 1–18 h. Moreover, sterically hindered ortho-functionalized aryl halides and heteroaryl halides were

Structure–efficiency relationships of cyclodextrin scavengers in the hydrolytic degradation of organophosphorus compounds

• Sophie Letort,
• Michaël Bosco,
• Benedetta Cornelio,
• Frédérique Brégier,
• Sébastien Daulon,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2017, 13, 417–427, doi:10.3762/bjoc.13.45

• the first group was introduced in position 2, the substitution reaction at O-3 on the adjacent unit A was performed. Due to the lower reactivity of this alcohol group, an excess of base and electrophile was required for this step. In addition, the presence of the sterically hindered trityl-protected

(Z)-Selective Takai olefination of salicylaldehydes

• Stephen M. Geddis,
• Caroline E. Hagerman,
• Warren R. J. D. Galloway,
• Hannah F. Sore,
• Jonathan M. Goodman and
• David R. Spring

Beilstein J. Org. Chem. 2017, 13, 323–328, doi:10.3762/bjoc.13.35

• state 5 containing two chromium ions bridged by a halogen. The less sterically hindered equatorial positions are occupied by the aldehyde substituent (R1 in Scheme 2) of 1 and halide group (X) of 3 and the aldehyde oxygen is thought to be coordinated to one of the Cr centres (the “coordinating” Cr

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• ) are applicable to this decyanation reaction. The use of hydrosilane as a mild reducing agent allows a high functional group tolerance (34b–e, 35, 39b, 43) and sterically hindered cyano groups are successfully removed (36, 41, 43). Reactions of benzyl cyanides proceed smoothly even in the absence of

Highly bulky and stable geometry-constrained iminopyridines: Synthesis, structure and application in Pd-catalyzed Suzuki coupling of aryl chlorides

• Yi Lai,
• Zhijian Zong,
• Yujie Tang,
• Weimin Mo,
• Nan Sun,
• Baoxiang Hu,
• Zhenlu Shen,
• Liqun Jin,
• Wen-hua Sun and
• Xinquan Hu

Beilstein J. Org. Chem. 2017, 13, 213–221, doi:10.3762/bjoc.13.24

• up to 325 °C. With these sterically hindered iminopyridine–palladium complexes Pd1 to Pd5 in hand, we firstly investigated their catalytic activity directly in Suzuki cross-coupling reactions with chlorobenzene as the electrophile. The reactions were performed under the previously reported conditions

• , entries 13). Different arylboronic acids were also examined to react with 4-chloroacetophenone in this system. No matter what kind of boronic acids were used: electron-deficient (Table 4, entry 14), electron-rich (Table 4, entries 15 and 16) or sterically hindered (Table 4, entry 17) arylboronic acids

Total synthesis of a Streptococcus pneumoniae serotype 12F CPS repeating unit hexasaccharide

• Peter H. Seeberger,
• Claney L. Pereira and
• Subramanian Govindan

Beilstein J. Org. Chem. 2017, 13, 164–173, doi:10.3762/bjoc.13.19

• azido group following β-glucoside formation [23]. Alternatively, a linear synthetic strategy in which the sterically hindered C4 hydroxy group would be glycosylated first, followed by the C3 hydroxy group of β-mannosazide building block 4, was designed in case the convergent approach proved unsuccessful

Facile synthesis of indolo[3,2-a]carbazoles via Pd-catalyzed twofold oxidative cyclization

• Chao Yang,
• Kai Lin,
• Lan Huang,
• Wei-dong Pan and
• Sheng Liu

Beilstein J. Org. Chem. 2016, 12, 2490–2494, doi:10.3762/bjoc.12.243

• -position, only one regioisomer 1i was observed. However, the selectivity was reversed when acetyl was present at the meta-position (5:1 for 2j). The main cyclized product of 2j was the corresponding ortho-acetyl product 1j. Unexpectedly, the reaction preferentially occurred at a more sterically hindered

An effective one-pot access to polynuclear dispiroheterocyclic structures comprising pyrrolidinyloxindole and imidazothiazolotriazine moieties via a 1,3-dipolar cycloaddition strategy

• Alexei N. Izmest’ev,
• Galina A. Gazieva,
• Natalya V. Sigay,
• Sergei A. Serkov,
• Valentina A. Karnoukhova,
• Vadim V. Kachala,
• Alexander S. Shashkov,
• Igor E. Zanin,
• Angelina N. Kravchenko and
• Nina N. Makhova

Beilstein J. Org. Chem. 2016, 12, 2240–2249, doi:10.3762/bjoc.12.216

• generated from isatins and sarcosine to benzylidene derivatives of the same imidazothiazolotriazine will proceed from the less sterically hindered side [41] (anti attack). Herein, we report a regio- and diastereoselective one-pot method for the synthesis of a novel class of polynuclear dispiroheterocyclic

Potent triazine-based dehydrocondensing reagents substituted by an amido group

• Munetaka Kunishima,
• Daiki Kato,
• Nobu Kimura,
• Masanori Kitamura,
• Kohei Yamada and
• Kazuhito Hioki

Beilstein J. Org. Chem. 2016, 12, 1897–1903, doi:10.3762/bjoc.12.179

• nucleophilic aniline 2b (Table 2, entry 2). To elucidate the reactivities of X and DMT-MM, time courses of amide-forming reactions using sterically hindered pivalic acid (1b) and 2-phenylethylamine (2a) in MeOH and THF were investigated by 1H NMR spectroscopy (Figure 2a,b, respectively). The steric hindrance

• the stability and non-hygroscopic property of the reagent (Table 2). In most cases, X exhibited similar reactivity in MeOH compared with DMT-MM, and the amides 3 were obtained with negligible formation of the corresponding methyl ester 8 (Table 2, entries 1, 5, 7, and 9). In the case of the sterically

• hindered secondary amine 2c, methyl ester 8 was obtained as a byproduct in 31% and 24% yields for X and DMT-MM (Table 2, entry 3), respectively. In contrast, the yields obtained in THF using X were superior to those obtained using DMT-MM (Table 2, entries 4, 6, 8, and 10), especially for the poorly

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

• as the result of imine oxidation and aryl migration. On the other hand, electron-withdrawing substituents on the aryl group (Ar) promote the formation of amides 119d–f as result of hydride migration. The sterically hindered and fully substituted pyrrole 120 underwent a Baeyer–Villiger reaction to

Flow carbonylation of sterically hindered ortho-substituted iodoarenes

• Carl J. Mallia,
• Gary C. Walter and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2016, 12, 1503–1511, doi:10.3762/bjoc.12.147

Development of chiral metal amides as highly reactive catalysts for asymmetric [3 + 2] cycloadditions

• Yasuhiro Yamashita,
• Susumu Yoshimoto,
• Mark J. Dutton and
• Shū Kobayashi

Beilstein J. Org. Chem. 2016, 12, 1447–1452, doi:10.3762/bjoc.12.140

•  2, entries 5–9). Sterically hindered substrates were also viable, and high enantioselectivities were obtained with 0.01 mol % catalyst loading (Table 2, entries 10–13). Other electrophiles were also successfully employed with 0.1 mol % catalyst loading (Scheme 1). N-Methylmaleimide reacted with 1a

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• furnished 96 in high yield and enantioselectivity (Scheme 23a) [24]. Thiols also added efficiently to itaconimide 95 using the same guanidine catalyst system. In general, sterically hindered tertiary thiols added with higher enantioselectivity (85.5:14.5 to 88:22 er) than aromatic thiols (72:28 to 79.5:20.5

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• function in a sterically hindered and electronically unreactive Cbz-protected amine substrate, which is in agreement with our observations above. Therefore, we decided to continue our route with the free amine 36 instead, which was directly coupled with TSNCO to give 39 in high yield. The reaction took

Cationic Pd(II)-catalyzed C–H activation/cross-coupling reactions at room temperature: synthetic and mechanistic studies

• Takashi Nishikata,
• Alexander R. Abela,
• Shenlin Huang and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2016, 12, 1040–1064, doi:10.3762/bjoc.12.99

• groups, as well as sterically hindered aromatic rings, all taking place at room temperature. Suzuki–Miyaura-type C–H coupling reactions are typically more tolerant of electron-withdrawing groups (3d, 3f, 3k) and ortho-substitution (3g) on the aryl ring. On the other hand, the reaction with 4

The synthesis of functionalized bridged polycycles via C–H bond insertion

• Jiun-Le Shih,
• Po-An Chen and
• Jeremy A. May

Beilstein J. Org. Chem. 2016, 12, 985–999, doi:10.3762/bjoc.12.97

• sterically hindered catalyst such as Rh2(esp)2 or Rh2(OPiv)4 is needed to prevent dimerization of the diazoacetate. These catalysts are presumed to protect the carbene intermediates from intermolecular reactions long enough to adopt the correct conformation for bridged-ring formation. An exploration of the

A convenient route to symmetrically and unsymmetrically substituted 3,5-diaryl-2,4,6-trimethylpyridines via Suzuki–Miyaura cross-coupling reaction

• Dariusz Błachut,
• Joanna Szawkało and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2016, 12, 835–845, doi:10.3762/bjoc.12.82

• derivatives 46–56, in a yield range of 82–91%, in less than 1 h, with exception of 48 (68%) and 52 (62%). In these cases the use of sterically hindered and less reactive 2-trifluorophenylboronic acid needed a longer reaction time of 3 hours and an increased arylboronic acid/substrate ratio. In order to obtain

Stereoselective amine-thiourea-catalysed sulfa-Michael/nitroaldol cascade approach to 3,4,5-substituted tetrahydrothiophenes bearing a quaternary stereocenter

• Sara Meninno,
• Chiara Volpe,
• Giorgio Della Sala,
• Amedeo Capobianco and
• Alessandra Lattanzi

Beilstein J. Org. Chem. 2016, 12, 643–647, doi:10.3762/bjoc.12.63

• catalysts (I–VII). Among the catalysts tested, compound VII proved to be the most active and enantioselective, giving the major diastereoisomer 7a with 44% ee (Table 1, entry 13). Taking into account that amine thiourea VII, bearing a sterically hindered secondary amine moiety, was significantly more