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

• prepared by cyclization of azidonitriles [15]. These methods usually require drastic reaction conditions and are generally limited to 2-iminopyrrolidines and/or to N-unsubstituted or N-alkyl derivatives. Other methods involve cyclic precursors such as lactams [4][6][7][16], thiolactams [3][6] or 2

Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes

• Lucie Brulíková,
• Aidan Harrison,
• Marvin J. Miller and
• Jan Hlaváč

Beilstein J. Org. Chem. 2016, 12, 1949–1980, doi:10.3762/bjoc.12.184

• -lactams 63 (Scheme 16) [95], which is in accordance with the general prediction. The exclusive regioselectivity of this reaction is due to steric effects. Similar conclusions result from the reaction of 1,3-butadienes 65 with various nitroso heterodienophiles 66, giving proximal isomer 67 (Scheme 17) [85

• acids and therefore they were applied to the synthesis of transient acylnitroso intermediates. Moderate to high yields (45–98%) with good diastereoselectivities (de 42–72%) were obtained through the hetero-Diels–Alder reaction of chiral lactams with acylnitroso intermediates. Approach based on the

Rh-Catalyzed reductive Mannich-type reaction and its application towards the synthesis of (±)-ezetimibe

• Motoyuki Isoda,
• Kazuyuki Sato,
• Yurika Kunugi,
• Satsuki Tokonishi,
• Atsushi Tarui,
• Masaaki Omote,
• Hideki Minami and
• Akira Ando

Beilstein J. Org. Chem. 2016, 12, 1608–1615, doi:10.3762/bjoc.12.157

• -1 Hirokoshingai, Kure, Hiroshima 737-0112, Japan 10.3762/bjoc.12.157 Abstract An effective synthesis for syn-β-lactams was achieved using a Rh-catalyzed reductive Mannich-type reaction. A rhodium–hydride complex (Rh–H) derived from diethylzinc (Et2Zn) and a Rh catalyst was used for the 1,4

• Mannich-type reactions have been reported to give β-amino esters and/or β-lactams by using metal enolates [10][11][12][13][14][15][16][17]. In contrast, most of reductive Mannich-type reactions using imines and α,β-unsaturated carbonyl compounds gave β-amino esters, but there are only a few reports for a

• direct synthesis of β-lactams by reductive Mannich-type reactions [14][18][19][20][21]. We recently reported a reductive Mannich-type reaction using a combination of RhCl(PPh3)3 and Et2Zn to give the corresponding syn-β-lactams from α,β-unsaturated esters and imines in good to excellent yields together

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• their standard catalytic repertoire (Scheme 1). They transacylate the thioester of a PKS-bound polyketide onto a nucleophile. If the nucleophile is water, this leads to carboxylic acids. The reactions of backbone hydroxy groups or amines consequently give lactones and lactams. TE domains mostly form

• the respective heterocycles. We will not cover medium-sized and macrocyclic lactones and lactams, but concentrate on small heterocycles with ring sizes between 3 and 6 atoms (for a review about macrolactones see reference [12]). Review 1 Oxygen-containing heterocycles Oxygen-containing heterocycles

From N-vinylpyrrolidone anions to modified paraffin-like oligomers via double alkylation with 1,8-dibromooctane: access to covalent networks and oligomeric amines for dye attachment

• Daniela Obels,
• Melanie Lievenbrück and
• Helmut Ritter

Beilstein J. Org. Chem. 2016, 12, 1395–1400, doi:10.3762/bjoc.12.133

• can easily be monitored with UV–vis spectroscopy as well as with the naked eye. This work contributes to the increasing area of α-alkylation reactions of N-vinyl lactams and the subsequent application of the so obtained compounds to the synthesis of functionalized oligomers. Chemical structure of

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• irradiation. Thus, the development of novel MCR based on phosphorous reagents would allow the synthesis of macrocyclic and medium or large-sized heterocyclic systems, substances which are currently underrepresented in the literature. Further, the design of new biocompatible scaffolds such as β-lactams and

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

• % yield, 95.5:4.5 to 97:3 er). The resulting nitroalkane adduct 159 could be reduced and cyclized to access α,γ-disubstituted γ-lactams. Ellman and co-workers, in the second example of conjugate addition–enantioselective protonation with nitroalkenes, showed that thioacids 160 could be added in high

One-pot synthesis of enantiomerically pure N-protected allylic amines from N-protected α-amino esters

• Gastón Silveira-Dorta,
• Sergio J. Álvarez-Méndez,
• Víctor S. Martín and
• José M. Padrón

Beilstein J. Org. Chem. 2016, 12, 957–962, doi:10.3762/bjoc.12.94

• -membered ring lactams [20]. Finally, a one-pot reduction-olefination involving an α-amino β-hydroxy ester and a phosphonium salt, both bearing free hydroxy groups, has been used in the synthesis of (−)-α-conhydrine [21]. In this work, our aim was to study in more detail this one-pot strategy. Similarly to

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• corresponding halide in the presence of sodium hydride, giving thus access to thioether derivatives of type 68, which can also be converted into γ-lactams such as 69. On the other hand, experiments carried out with pyridyl and quinoylthiazolone substrates reveal that in these cases selectivity is higher than

New synthetic strategies for xanthene-dye-appended cyclodextrins

• Milo Malanga,
• Andras Darcsi,
• Mihaly Balint,
• Gabor Benkovics,
• Tamas Sohajda and
• Szabolcs Beni

Beilstein J. Org. Chem. 2016, 12, 537–548, doi:10.3762/bjoc.12.53

• University, Hlavova 8, 12843 Prague 2, Czech Republic 10.3762/bjoc.12.53 Abstract Xanthene dyes can be appended to cyclodextrins via an ester or amide bridge in order to switch the fluorescence on or off. This is made possible through the formation of nonfluorescent lactones or lactams as the fluorophore

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• state, the substituents are oriented with minimal steric hindrance to give the E,E-configured nine-membered ring. Ring contraction reactions of 13-membered lactams afford cyclononenes via intramolecular acyl transfer reactions. The configuration of the double bond derives from precursor D and thus

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• synthesis of a lactam via chelating-group-assisted copper catalysis. As outlined in Scheme 8, the N-quinolin-8-yl substituted amides 27 could be smoothly transformed into lactams 28 and/or 28' via C–H amidation by using Cu(OAc)2 as catalyst and Ag2CO3 as a base. In a specific case, the C(sp2)–H bond could

• (Scheme 8). Almost at the same time, Ge et al. [53] reported a similar intramolecular C–H amidation for the synthesis of lactams using CuCl as copper catalyst. When substrates possessing more than one γ-alkyl C–H bond were used, as the case occurred in Kuninobu and Kanai’s work, the primary C–H was

• underwent C–H amidation with lactams 52 to yield 2-aminoquinoline N-oxides 54 with generally excellent yield. Notably, the catalytic system also allowed a C–H bond amination by using secondary amines 53 for the synthesis of 2-aminoquinoline N-oxides 55. What’s more, the N-oxides could be efficiently reduced

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• step starting with 2-methoxyphenol. Later, compound 316 was subjected to a RRM under the influence of catalyst 2 in the presence of ethylene (24) to deliver the expected rearranged product 317 (Scheme 68). Vanderwal and co-workers [66] described the synthesis of polycyclic lactams obtained by arene

• /allene cycloaddition, discovered by Himbert and Henn were found to undergo a RRM in a facile manner in the presence of catalyst 6 to produce complex polycyclic lactams. In this regard, the required building block 319 was obtained from compound 318 by cycloaddition reaction. A variety of complex molecular

• frames were accessed via the RRM sequence under the influence of catalyst 6 in toluene at 50–100 °C in the presence of 24. The procedure is suitable for the preparation of diverse polycyclic lactams with a variety of substitution patterns (Scheme 69). Kotha and Ravikumar [44] have successfully executed

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