Synthesis of a tricyclic lactam via Beckmann rearrangement and ring-rearrangement metathesis as key steps

• Sambasivarao Kotha,
• Ongolu Ravikumar and
• Jadab Majhi

Beilstein J. Org. Chem. 2015, 11, 1503–1508, doi:10.3762/bjoc.11.163

• -rearrangement metathesis as key steps. Here, we used a simple starting material such as dicyclopentadiene. Keywords: allylation; Beckmann rearrangement; lactams; oximes; ring-rearrangement metathesis; Introduction The Beckmann rearrangement (BR), a well-known protocol for the conversion of ketoxime to an

• , reflux, 15 h, CH3CN (c) PPA, reflux for 20 min. Surprisingly, in all these instances no rearrangement product was observed. Interestingly, when the mixture of oximes 8a and 8b was treated with TsCl in the presence of NaOH at rt lactams 9a and 9b were obtained in 66% combined yield for two steps (9a:9b

• lactams 9a and 9b were obtained in 48% yield (9a:9b = 2:1) the ratio of oximes 9a and 9b was calculated based on 1H NMR spectral data (Scheme 3). Having prepared the lactams 9a and 9b, the allylation reaction was attempted with the lactam mixture in the presence of NaH/allyl bromide in dry DMF to generate

Tandem cross enyne metathesis (CEYM)–intramolecular Diels–Alder reaction (IMDAR). An easy entry to linear bicyclic scaffolds

• Javier Miró,
• María Sánchez-Roselló,
• Álvaro Sanz,
• Fernando Rabasa,
• Carlos del Pozo and
• Santos Fustero

Beilstein J. Org. Chem. 2015, 11, 1486–1493, doi:10.3762/bjoc.11.161

• 1–3). Comparable yields were obtained with either electron-donating or electron-withdrawing substituents in the starting alkyne 1 (Table 2, entries 4 and 5). In addition, 5- and 7-membered bicyclic lactams 3f and 3g were also synthesized in moderate yields (Table 2, entries 6 and 7). Again, all

Synthesis of novel N-cyclopentenyl-lactams using the Aubé reaction

• Madhuri V. Shinde,
• Rohini S. Ople,
• Ekta Sangtani,
• Rajesh Gonnade and
• D. Srinivasa Reddy

Beilstein J. Org. Chem. 2015, 11, 1060–1067, doi:10.3762/bjoc.11.119

• cyclopentenyl-substituted lactams. Upon dihydroxylation, this affords the N-cyclopentenyl-lactam compounds in racemic form. Given the numerous uses of nucleosides and related compounds, we were interested in the synthesis of carbocylic nucleoside mimics. The attempts and results are described herein. Keywords

• : Aubé reaction; biological activity; carbocyclic nucleosides; cyclopentenylated lactams; cyclopentylated lactams; Introduction One popular method for the synthesis of N-substituted lactams is the Aubé reaction [1][2][3][4]. Over the last few decades, this reaction has gained popularity and resulted in

• between an azido alcohol and a ketone to provide lactams through an in situ-generated hemiacetal as a temporary tether. This helps the azide addition in an intramolecular fashion, followed by ring expansion (Scheme 1) [1][2][3][4]. Recently, we applied this reaction for the synthesis of sugar–lactam

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• demonstrated in the synthesis of many natural products, materials, and pharmacological agents. In the last three decades, there has been a significant increase in the development of asymmetric variants of this reaction. Unfortunately, conjugate addition reactions using α,β-unsaturated amides and lactams remain

• underdeveloped due to their inherently low reactivity. This review highlights the work that has been done on both diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams. Keywords: α,β-unsaturated amides; α,β-unsaturated lactams; conjugate addition

• expanded to include α,β-unsaturated ketones, aldehydes, lactones, esters, nitroolefins, and to a lesser extent α,β-unsaturated amides and lactams. Review The lack of development in the CA of α,β-unsaturated amides and lactams is not surprising because these substrates are significantly less reactive than

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• ]. The scope of the anodic methoxylation has so far been limited to either acyclic or 4–6-membered ring sizes, the use of electrosynthetic approaches can also be applied to larger 7-membered ring systems, albeit less frequently [65][66]. β-Lactams (4-membered rings) undergo anodic oxidation of the carbon

• proved difficult to determine the cis/trans relationship in many examples due to the presence of rotameric forms, however the products of phenyl magnesiumbromide were identified to be trans presumably due to opposite face attack of intermediate 52b. Bicyclic lactams [73] and tricyclic systems [74] have

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• N-acyliminium species have been developed, resulting in the synthesis of a number of lactams and lactam-derived heterocycles [52]. One representative example is depicted in Scheme 10, where dipeptide 25 cyclizes via intramolecular nucleophilic attack of the hydroxy group on the anodically generated

Stereoselective synthesis of perillaldehyde-based chiral β-amino acid derivatives through conjugate addition of lithium amides

• Zsolt Szakonyi,
• Reijo Sillanpää and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2014, 10, 2738–2742, doi:10.3762/bjoc.10.289

• obtained. These include the selective reduction of β-enamino ester enantiomers [14], enzyme-catalyzed kinetic resolution [15], and a variety of asymmetric syntheses, for example, the enantioselective syntheses of β-lactams followed by ring opening [16][17], or the enantioselective desymmetrization of

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• dichloromethane or tetrahydrofuran, the reaction of disubstituted ketenes and N-tosyl arylimines provided corresponding trans-β-lactams in moderate to excellent ee (up to 98%), diastereoselectivities (up to 99:1 dr), and yields (up to >99%). Of particular interest, this methodology facilitates the formation of

• diverse trans-β-lactams that are complimentary to the related cis-lactams. 2.10 [4 + 1] Annulations of MBH carbonates with dienes Phosphine-catalyzed asymmetric [4 + 1] annulations between MBH carbonates and activated dienes could be achieved when using the bifunctional phosphine G6 as the catalyst

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• high level of stereocontrol (Scheme 4) [37][38][39][40]. Thus, vicinal and quartenary carbon centers can be obtained in high diasteromeric purity by conjugate additions of allyl, crotyl, and cinnamyl-derived anions to Michael acceptors such as enones, lactones, lactams, and α,β-unsaturated esters

• cyclopropane 50a. Starting with (cis,R,R)-47b, the isomeric exo,endo product 50b is obtained as major isomer. The cyclopropanation reaction tolerates a wide range of Michael acceptor subtrates such as enones, lactones, lactams, and acyclic α,β-unsaturated esters. The obtained products can easily be cleaved to

• eight benzyl protecting groups was accomplished using Pearlman’s catalyst under mild acidic conditions to give fumonisin B2 (20) [45][46][47][84]. Tricylic β-lactams (1997) β-Lactam antibiotics are the most prescribed and successful class of antibiotics developed and used in clinical practice. This

Visible-light-induced, Ir-catalyzed reactions of N-methyl-N-((trimethylsilyl)methyl)aniline with cyclic α,β-unsaturated carbonyl compounds

• Dominik Lenhart and
• Thorsten Bach

Beilstein J. Org. Chem. 2014, 10, 890–896, doi:10.3762/bjoc.10.86

• lactone and lactam substrates, the latter products were the only products isolated. For the six-membered lactones and lactams and for cyclopentenone the simple addition products prevailed. Keywords: cyclization; electron transfer; iridium; photochemistry; photoredox catalysis; radical reactions

• reactions to other cyclic α,β-unsaturated carbonyl compounds. In particular, we were interested to see whether cyclization reactions as for product 4 would be observed when using α,β-unsaturated lactones and lactams in combination with a silylated amine and an iridium catalyst. In this article, we provide

• formation of a tricyclic product. Addition to cyclic α,β-unsaturated lactams Lactams offer the possibility of reactivity tuning by choosing an appropriate protecting group at the nitrogen atom. Since initial experiments with unprotected pyrrolin-2-one were not promising the respective tert-butyloxycarbonyl

Aza-Diels–Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome

• Amitabh Jha,
• Ting-Yi Chou,
• Zainab ALJaroudi,
• Bobby D. Ellis and
• T. Stanley Cameron

Beilstein J. Org. Chem. 2014, 10, 848–857, doi:10.3762/bjoc.10.81

• ]quinolin-11(5H)-ones via [4 + 2] imino-Diels–Alder cyclization from N-aryl-3-hydroxyisoindolinones and N-vinyl lactams under Lewis acid-catalysed anhydrous conditions is reported. Reactions of N-(2-substituted-aryl)-3-hydroxyisoindolinones with N-vinylpyrrolidone under identical conditions resulted in the

• fashion or otherwise) with N-(2-substituted phenyl)-1-oxo-1H-isoindolium ions. Conclusion 6,6a-Dihydroisoindolo[2,1-a]quinolin-11(5H)-one derivatives were synthesized from N-aryl-3-hydroxyisoindolinones and N-vinyl lactams under Lewis acid-catalysed anhydrous conditions in fair to good yields. As expected

• , the reaction appeared to proceed via the formation of an N-acyliminium ion which underwent an inverse-electron demand imino-Diels–Alder reaction. While reactions of this type are known to occur, this is the first report of the use of N-vinyl lactams as a dienophile for the inverse-electron demand

Synthesis of (2S,3R)-3-amino-2-hydroxydecanoic acid and its enantiomer: a non-proteinogenic amino acid segment of the linear pentapeptide microginin

• Rajendra S. Rohokale and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2014, 10, 667–671, doi:10.3762/bjoc.10.59

• -groups to olefinic acid by either asymmetric epoxidation, dihydroxylation or aminohydroxylation [10][11][12][13][14][15], (ii) the asymmetric synthesis of β-lactams by a Staudinger reaction between ketene and imine to give the corresponding amino acids [16], and (iii) the Lewis acid catalyzed

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• ease of preparation via IMCRs [27][28][29]. First, the β-lactams will be described followed by five-membered rings varying from pyrrolidines to tetrazoles based amide bond isosteres. Examples of the six-membered rings showing peptide like-properties are the piperazines, homoprolines, dihydropyrimidones

• and triazines, whereas azepines form an important class of seven-membered cyclic peptidomimetics. Four membered ring constraints β-Lactams The smallest class of cyclic peptidomimetics is that of the β-lactams. β-lactams are effective antibiotics [30] but also show inhibitory activities against serine

• - [31], elastase- [32][33][34][35], and HIV-1 protease [36] and papain [37]. For the design of β-lactams, the Staudinger reaction involving a [2 + 2] cycloaddition of ketenes and imines is the most common method used [38]. However, Ugi reactions starting form β-amino acids are also described. In 2002

Stereoselectively fluorinated N-heterocycles: a brief survey

• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2013, 9, 2696–2708, doi:10.3762/bjoc.9.306

• Enzyme catalysis was presented earlier (Scheme 1) as a strategy for synthesising fluorinated β-lactams (4) [18]. At that time, we were interested in the effect that the fluorine substituents had on the reactivity of the β-lactam derivatives. However this work now merits further attention, because it also

Diastereoselectivity in the Staudinger reaction of pentafluorosulfanylaldimines and ketimines

• Alexander Penger,
• Cortney N. von Hahmann,
• Alexander S. Filatov and
• John T. Welch

Beilstein J. Org. Chem. 2013, 9, 2675–2680, doi:10.3762/bjoc.9.303

• Alexander Penger Cortney N. von Hahmann Alexander S. Filatov John T. Welch Department of Chemistry, University at Albany, SUNY, 1400 Washington Ave., Albany, NY 12222, USA 10.3762/bjoc.9.303 Abstract β-Lactams were diastereoselectively formed by the reaction of SF5-containing aldimines, or an SF5

• minimization of unfavourable hydrophobic interactions. Results and Discussion The use of fluoroalkylimines to form β-lactams has proven especially useful in synthesis [24][25][26] especially in the Ojima β-lactam synthon method [27][28][29] used to prepare docetaxel analogs [26]. The general utility of the

• familiar Staudinger reaction of imines to transform readily accessible aldehydes to β-lactams has been well reviewed [30][31][32][33], yet in spite of this familiarity, the mechanism of this process remains a topic of interest [34][35][36]. Previously, it has been shown that fluorinated imines can undergo

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• inactivated alkenes was also exploited for the synthesis of highly substituted lactams 59, also in a preparative scale [53]. When alkenyl β-keto amides 60 were reacted with a 1:1 mixture of phosphine-gold complex 20a and AgOTf (toluene, 50–90 °C), exo-trig hydroalkylation of the C–C double bond took place

• , affording 5-, 6-membered lactams and spiro-lactams 61 in excellent yields and high trans diastereoselectivity (Scheme 16). 4.2 The hydroarylation reaction In addition to methylene active compounds, electron-rich benzenes and heteroaromatics can be added to gold activated alkenes under suitable conditions

Towards stereochemical control: A short formal enantioselective total synthesis of pumiliotoxins 251D and 237A

• Jie Zhang,
• Hong-Kui Zhang and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2013, 9, 2358–2366, doi:10.3762/bjoc.9.271

• mixture of lactams. Without separation, the mixture was treated with TBAF in dichloromethane to produce alcohols 18 and 20 (combined yield: 62% over 3 steps) in a ratio of 95:5 (determined by 1H NMR), along with the keto-amide 21 in 13% yield (Scheme 7). Separation of the mixture by column chromatography

Diastereoselective radical addition to γ-alkyl-α-methylene-γ-butyrolactams and the synthesis of a chiral pyroglutamic acid derivative

• Tomoko Yajima,
• Eriko Yoshida and
• Masako Hamano

Beilstein J. Org. Chem. 2013, 9, 1432–1436, doi:10.3762/bjoc.9.161

• Tomoko Yajima Eriko Yoshida Masako Hamano Department of Chemistry, Ochanomizu University, Otsuka, Bunkyo-ku, Tokyo, 112-8610, Japan 10.3762/bjoc.9.161 Abstract The cis- and trans-stereoselective radical additions to α-methylene-γ-alkyl- γ-lactams were investigated and the scope and limitation of

• the reaction were also revealed. This stereoselective radical reaction was used for synthesis of chiral pyroglutamic acid derivatives starting from a commercially available chiral amino acid. Keywords: chelation controlled reaction; diastereoselective reaction; free radical; lactams; pyroglutamic

• acid derivative; radical alkylation; Introduction γ-Lactams exist in many natural products and biologically active compounds and are one of the most important classes of compounds for drug discovery [1][2][3]. Substituted γ-lactams, in particular, have potential application in drug synthesis, but the

α-Bromodiazoacetamides – a new class of diazo compounds for catalyst-free, ambient temperature intramolecular C–H insertion reactions

• Åsmund Kaupang and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2013, 9, 1407–1413, doi:10.3762/bjoc.9.157

• thermolysis perform intramolecular C–H insertions to produce α-halo-β-lactams. When carried out with α-bromodiazoacetamides bearing cyclic side chains, the thermolysis reaction affords bicyclic α-halo-β-lactams, in some cases in excellent yields, depending on the ring size and substitution pattern of the

• -bromodiazoacetamides to form α-bromo-β-lactams. Results The diazoacetamides 3a–f were synthesised from α-bromoacetamides 2a–f using a protocol published by Toma et al. [40], modified by exchanging the base employed in the original procedure (DBU) for 1,1,3,3-tetramethylguanidine (TMG). The use of TMG allowed for a

• -bromodiazoacetamides will rapidly lose their bright red colour at temperatures above 0 °C. As can be seen in Table 1, the obtained yields of the α-bromo-β-lactams 5a–f vary significantly throughout the series. Among the derivatives with aliphatic amide side chains, the yields increase dramatically with ring size

A construction of 4,4-spirocyclic γ-lactams by tandem radical cyclization with carbon monoxide

• Mitsuhiro Ueda,
• Yoshitaka Uenoyama,
• Nozomi Terasoma,
• Shoko Doi,
• Shoji Kobayashi,
• Ilhyong Ryu and
• John A. Murphy

Beilstein J. Org. Chem. 2013, 9, 1340–1345, doi:10.3762/bjoc.9.151

• Technology, 5-16-1 Ohmiya, Asahi-ku, Osaka 535-8585, Japan Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, UK 10.3762/bjoc.9.151 Abstract A straightforward synthesis of 4,4-spirocyclic indol γ-lactams by tandem radical cyclization of iodoaryl allyl

• azides with CO was achieved. The reaction of iodoaryl allyl azides, TTMSS and AIBN under CO pressure (80 atm) in THF at 80 °C gave the desired 4,4-spirocyclic indoline, benzofuran, and oxindole γ-lactams in moderate to good yields. Keywords: 4,4-spirocyclic indol γ-lactams; carbon monoxide; free radical

• ; iodoaryl allyl azides; tandem radical cyclization; Introduction 4,4-Spirocyclic oxindole γ-lactams containing a quaternary carbon center are key structures for the synthesis of biologically active natural products and the related analogues [1][2][3][4]. Therefore, the development of an efficient synthesis

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• by the rich array of lactams 159a–f [67]. In the case of ketoester 159c, the reaction was carried out at room temperature [68]. The formation of unsaturated lactam 159f is particularly interesting, since it involves the use of a mild oxidant (cupric acetate) in a reducing medium [69]. Another

• formally produced in these transformations, the addition of sodium acetate to buffer the medium is often beneficial. The easy access to unsaturated lactams such as 165 and 166 may be exploited to construct complex structures by subsequent application of radical, ionic, or organometallic transformations

• agents. Radical allylations using allylic alcohol derivatives. Synthesis of variously substituted lactams. Nickel-mediated synthesis of unsaturated lactams. Total synthesis of (±)-3-demethoxy-erythratidinone. Generation and capture of an iminyl radical from an oxime ester. Acknowledgements We are

Development of peptidomimetic ligands of Pro-Leu-Gly-NH₂ as allosteric modulators of the dopamine D₂ receptor

• Swapna Bhagwanth,
• Ram K. Mishra and
• Rodney L. Johnson

Beilstein J. Org. Chem. 2013, 9, 204–214, doi:10.3762/bjoc.9.24

• β-turn that is mimicked is dictated by the chirality of C-3. Lactams 1, 2, 4–6, and 9 (Figure 2) were active in enhancing the binding of the dopamine receptor agonist 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN) to dopamine receptors, while 3, 7, and 8 were inactive [19][20]. The

• Freidinger lactams that employs the piperidin-2-one scaffold yielded the active PLG peptidomimetic 14 [32]. Another example is the pyridine-based PLG peptidomimetics developed by Saitton et al. [33][34] and illustrated by 15. Peptidomimetic 15 cannot adopt a type II β-turn, but rather exists in an extended

Polar reactions of acyclic conjugated bisallenes

• Reiner Stamm and
• Henning Hopf

Beilstein J. Org. Chem. 2013, 9, 36–48, doi:10.3762/bjoc.9.5

• transformations. Keywords: β-lactams; conjugated bisallenes; cyclopentenones; epoxidation; halogen addition; hydrohalogenation; ionic additions; metalation; Introduction Whereas the use of hexa-1,2,4,5-tetraene (1) and its derivatives in pericyclic reactions is well documented [2][3][4][5][6], relatively little

Flow photochemistry: Old light through new windows

• Jonathan P. Knowles,
• Luke D. Elliott and
• Kevin I. Booker-Milburn

Beilstein J. Org. Chem. 2012, 8, 2025–2052, doi:10.3762/bjoc.8.229