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

• target molecule 1 is shown in Figure 1. RRM of the tricyclic allylated compound 2 can deliver the target lactam 1. The key synthon 2 can be derived by allylation of lactam 3, which in turn can be prepared via BR starting with the known enone 4 [25][26][27], derived from dicyclopentadiene (5) [28][29][30

• 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

Design and synthesis of polycyclic sulfones via Diels–Alder reaction and ring-rearrangement metathesis as key steps

• Sambasivarao Kotha and
• Rama Gunta

Beilstein J. Org. Chem. 2015, 11, 1373–1378, doi:10.3762/bjoc.11.148

• alkenylated sulfone derivatives. In this regard, Bloch and co-workers reported a useful preparation of monoallylated sulfone 8a [34]. To this end, we carried out the allylation of sulfone 6 with allyl bromide (1.2 equiv) and n-BuLi (2.7 equiv) at −75 °C to rt. The monoallylated sulfone 8a was obtained in 22

• supported by HRMS data. In addition, the structure and stereochemistry of the allyl groups present in compound 2a have been confirmed by single-crystal X-ray diffraction studies and this data clearly indicated that the allylation had occurred at α-position of the sulfone moiety and the two allyl groups are

Spiro annulation of cage polycycles via Grignard reaction and ring-closing metathesis as key steps

• Sambasivarao Kotha,
• Mohammad Saifuddin,
• Rashid Ali and
• Gaddamedi Sreevani

Beilstein J. Org. Chem. 2015, 11, 1367–1372, doi:10.3762/bjoc.11.147

• -closing metathesis (RCM) are considered as viable options. The retrosynthetic analysis to the target bis-spiro-cage compound 7 is shown in Figure 2. The target compound 7 could be obtained from O-allylation of the Grignard addition product 11 followed by the two-fold RCM sequence. The required cage dione

• Grignard reagent attacks the other carbonyl group in a transannular fashion to generate hemiketal derivatives 12 and 13. Later, the diallyldiol 11 was subjected to an O-allylation sequence under NaH/allyl bromide conditions in DMF to deliver the desired tetraallyl compound 15 (53%) along with the triallyl

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• , reduction with LiAlH4, reductive amination and allylation that afforded the indole derivatives 63 (18%) and N-Boc protected compound 68 (23%). The reaction of 63 with Pd(OAc)2 (25 mol %) and tri(o-tolyl)phosphine (55 mol %) at reflux gave 9-endo-64a (24%) and 8-exo-65b (21%). However, the compound 68 under

• –Miyaura coupling: Bodwell and Li [127] have reported the synthesis of the cyclophane 130 involving hydroboration and the Suzuki–Miyaura (SM) coupling [128][129][130][131][132][133][134][135] as key steps. 1,3-Diallylindole (127) was first synthesized in two steps from indole (123) by successive allylation

• at the 3 position to give 126 (66%) and later, N-allylation was carried out to afford the diallylindole 127 (69%, Scheme 18). A three-step (123→124→125→127) sequence was found to give a higher yield of the 1,3-diallylindole (127). Iodination of 123 gave the 3-iodoindole (124) quantitatively, which on

Design and synthesis of fused polycycles via Diels–Alder reaction and ring-rearrangement metathesis as key steps

• Sambasivarao Kotha and
• Ongolu Ravikumar

Beilstein J. Org. Chem. 2015, 11, 1259–1264, doi:10.3762/bjoc.11.140

• this strategy, next we focussed on the preparation of an analogous bicyclo[2.2.2] system and to this end, the DA reaction of 1,3-cyclohexadiene (7) with 1,4-benzoquinone (2) furnished the known bis-adduct 8 [27][28], which on treatment with allylmagnesium bromide delivered diol 9. Later, O-allylation

• of diol 9 with four equivalents of allyl bromide in the presence of NaH in DMF gave the mono O-allyl compound 10. Attempts to achieve complete allylation of 10 were not successful. Finally, the RRM of compound 10 in the presence of G-I catalyst (Figure 1) under ethylene atmosphere gave the hexacyclic

Hybrid macrocycle formation and spiro annulation on cis-syn-cis-tricyclo[6.3.0.0^2,6]undeca-3,11-dione and its congeners via ring-closing metathesis

• Sambasivarao Kotha,
• Ajay Kumar Chinnam and
• Rashid Ali

Beilstein J. Org. Chem. 2015, 11, 1123–1128, doi:10.3762/bjoc.11.126

• its subsequent utility in assembling the macrocyclic system 6 via RCM. During this venture, we also found that the tricyclic dione 2 is a useful substrate for the synthesis of spiro-polyquinane derivative 7 via a six fold allylation followed by a three-fold RCM and a hydrogenation sequence. Results

• -phenylhydrazine under conditions using the described low melting mixture. Next, the N-allylation of the diindole derivative 8 with allyl bromide in the presence of NaH/DMF gave diallyl derivative 10, which was subjected to the RCM sequence in the presence of Grubbs’ 2nd generation catalyst to produce the cyclized

• [63]. The present example involving the generation of triple spirocyclic compound 7 is unique and demonstrates the power and scope of the RCM approach. It is worth mentioning that previous attempts to functionalize 2 were unsuccessful [47]. To generalize the spiroannulation sequence, allylation of

Highly selective palladium–benzothiazole carbene-catalyzed allylation of active methylene compounds under neutral conditions

• Antonio Monopoli,
• Pietro Cotugno,
• Carlo G. Zambonin,
• Francesco Ciminale and
• Angelo Nacci

Beilstein J. Org. Chem. 2015, 11, 994–999, doi:10.3762/bjoc.11.111

• -2-ylidene complex I was found to be a chemoselective catalyst for the Tsuji–Trost allylation of active methylene compounds carried out under neutral conditions and using carbonates as allylating agents. The proposed protocol consists in a simplified procedure adopting an in situ prepared catalyst

• allylation; Introduction The α-allylation of carbonyl compounds is one of the most important reactions in organic chemistry, since it opens the way to the synthesis of a plethora of interesting molecules such as pheromones, perfumes, or bio-active compounds such as prostaglandin E2 or F2α. After the

• pioneering works by Tsuji [1][2] and Trost [3][4], the Pd-catalyzed allylation of various nucleophiles is a largely used strategy and a variety of efficient and robust homogeneous [5][6][7][8][9] and heterogeneous [10][11][12][13] Pd catalysts have been reported, until now. Recently, synergistic or

Further exploration of the heterocyclic diversity accessible from the allylation chemistry of indigo

• Alireza Shakoori,
• John B. Bremner,
• Mohammed K. Abdel-Hamid,
• Anthony C. Willis,
• Rachada Haritakun and
• Paul A. Keller

Beilstein J. Org. Chem. 2015, 11, 481–492, doi:10.3762/bjoc.11.54

• Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), 113 Phaholyothin Road, Klong1, Klong Luang, Pathumanthani 12120, Thailand 10.3762/bjoc.11.54 Abstract Diversity-directed synthesis based on the cascade allylation chemistry of indigo, with its

• -closing metathesis of the N,O-diallylic spiro structure and subsequent Claisen rearrangement gave rise to the new (1R,8aS,17aS)-rel-1,2-dihydro-1-vinyl-8H,17H,9H-benz[2',3']pyrrolizino[1',7a':2,3]pyrido[1,2-a]indole-8,17-(2H,9H)-dione heterocyclic system. Keywords: allylation; cascade reactions; indigo

• structural complexity through post-allylation ring-closing metathesis, plus new biological activity investigations, which are now reported herein. Results and Discussion A range of strategies are available to potentially control reaction-path selectivity in cascade pathways [5][6] but in these indigo

Synthesis of the furo[2,3-b]chromene ring system of hyperaspindols A and B

• Danielle L. Paterson and
• David Barker

Beilstein J. Org. Chem. 2015, 11, 265–270, doi:10.3762/bjoc.11.29

• reaction with triethylphosphonoacetate to give ester 11 [19] in 94% yield (Scheme 1). Hydrogenation of the alkene followed by protection of the phenol gave benzyl ether 12 in 88% yield over two steps. Initially the preparation of alkene 13 through the allylation of ester 12 was attempted, however keto

• -methylenedioxybenzene and t-butyllithium) to give ketone 17 in 84% yield (Scheme 2). Allylation of ketone 17 proved problematic with the use of strong bases such as LDA and LiHMDS, giving none of the desired product. However, the use of allyl bromide and NaH in the presence of TBAI, in THF at reflux, gave the desired

One-pot functionalisation of N-substituted tetrahydroisoquinolines by photooxidation and tunable organometallic trapping of iminium intermediates

• Joshua P. Barham,
• Matthew P. John and
• John A. Murphy

Beilstein J. Org. Chem. 2014, 10, 2981–2988, doi:10.3762/bjoc.10.316

• albeit in lower yield (68%). Murthy and Blechert and their respective co-workers reported allylation of THIQs under aerobic conditions using allyltrialkylstannanes [12][16] (Blechert’s studies also included success with allylboron reagents). Whilst our reactions are carried out under N2, the indium metal

Inherently chiral calix[4]arenes via oxazoline directed ortholithiation: synthesis and probe of chiral space

• Simon A. Herbert,
• Laura J. van Laeren,
• Dominic C. Castell and
• Gareth E. Arnott

Beilstein J. Org. Chem. 2014, 10, 2751–2755, doi:10.3762/bjoc.10.291

• examined as ligands in the palladium-catalyzed Tsuji–Trost allylation reaction, returning results comparable to their planar chiral ferrocene counterparts pointing towards future application of these types of compounds. Keywords: calix[4]arene; inherently chiral; ortholithiation; oxazoline; Tsuji–Trost

• to synthesize inherently chiral calixarenes and the surprising reversal of diastereoselectivity obtained when a different alkyllithium was employed. We also wish to report a preliminary study on the application of inherently chiral calix[4]arenes in the classic asymmetric Tsuji–Trost allylation

• calixarenes 5–8, we noted their similarity to planar chiral thioether oxazoline ferrocene ligands (9 in Figure 1) already reported by Dai and co-workers [35]. We therefore initiated a pilot study with our inherently chiral calix[4]arenes, using the palladium-catalyzed Tsuji–Trost allylation reaction (Scheme 3

Formal total syntheses of classic natural product target molecules via palladium-catalyzed enantioselective alkylation

• Yiyang Liu,
• Marc Liniger,
• Ryan M. McFadden,
• Jenny L. Roizen,
• Jacquie Malette,
• Corey M. Reeves,
• Douglas C. Behenna,
• Masaki Seto,
• Jimin Kim,
• Justin T. Mohr,
• Scott C. Virgil and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2014, 10, 2501–2512, doi:10.3762/bjoc.10.261

• install the initial stereocenters (Scheme 3). Treatment of 16 with LiHMDS in THF, followed by allyl chloroformate, furnished the known carbonate 17 in high yield [34]. This substrate smoothly undergoes palladium-catalyzed enantioselective decarboxylative allylation in the presence of (S)-t-Bu-PHOX (5

Indium-mediated allylation in carbohydrate synthesis: A short and efficient approach towards higher 2-acetamido-2-deoxy sugars

• Christopher Albler,
• Ralph Hollaus,
• Hanspeter Kählig and
• Walther Schmid

Beilstein J. Org. Chem. 2014, 10, 2230–2234, doi:10.3762/bjoc.10.231

• azide reduction followed by final deacetylation using methanolic sodium methoxide furnishes the title compounds. Keywords: allylation; carbohydrates; epoxidation; indium; multivalent glycosystems; organocatalysis; Introduction The indium-mediated allylation of carbonyl compounds has proven to be a

• allowing for an evaluation of structure–activity relationships. Results and Discussion We started our reaction sequence with an indium-mediated allylation of unprotected carbohydrates using D-arabinose (1a), D-galactose (1b) and D-glucose (1c) as starting materials. The Barbier-type chain elongation

• synthesis of rare, 2-amino-functionalized heptoses and octoses. The indium-mediated allylation strategy again revealed to be a useful tool for the preparation of two-carbon chain elongated carbohydrates. Two new stereocenters were formed with high diastereoselectivity in the course of the synthesis owing to

Relay cross metathesis reactions of vinylphosphonates

• Raj K. Malla,
• Jeremy N. Ridenour and
• Christopher D. Spilling

Beilstein J. Org. Chem. 2014, 10, 1933–1941, doi:10.3762/bjoc.10.201

• phosphonates. The proposed mechanism of the TBAI catalyzed allylation (Scheme 12) involves cleavage of the Me–O bond to form a phosphonate anion 35. The anion is re-alkylated with allyl bromide to produce the mono-allyl phosphonate 14a. The major weakness of this approach is that the mono-allyl phosphonate can

• 14b. Analysis of the TBAI allylation mechanism suggested that a good approach to mono-allyl phosphonate 14a would be a stoichiometric demethylation followed by a rapid allylation under ambient conditions. During the synthesis of phosphonate based ionic liquids, Sachnov et al. showed that

Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications

• Mahesh K. Lakshman,
• Manish K. Singh,
• Mukesh Kumar,
• Raghu Ram Chamala,
• Vijayender R. Yedulla,
• Domenick Wagner,
• Evan Leung,
• Lijia Yang,
• Asha Matin and
• Sadia Ahmad

Beilstein J. Org. Chem. 2014, 10, 1919–1932, doi:10.3762/bjoc.10.200

• BtO− is a nucleofuge, several Bt-OCH2Ar substrates have been evaluated in nucleophilic substitution reactions. Finally, the possible formation of Pd π–allyl complexes by departure of BtO− has been queried. Thus, alpha-allylation of three cyclic ketones was evaluated with 1-(cinnamyloxy)-1H-benzo[d

• , the enamine was formed in situ in this study, with catalytic pyrrolidine. These results appear to indicate that the easily synthesized allylic benzotriazolyl derivatives described herein may be promising reagents for the α-allylation of carbonyl compounds. As a final note, while this work was in

• slightly incomplete. Finally, we have evaluated the departure of BtO− from an allylic position leading to a putative Pd π–allyl complex. In unoptimized preliminary results, Pd-catalyzed α-allylation of three cyclic ketones was accomplished with a cinnamyloxy benzotriazolyl derivative, through in situ

Postsynthetic functionalization of glycodendrons at the focal point

• Thisbe K. Lindhorst and
• Katharina Elsner

Beilstein J. Org. Chem. 2014, 10, 1482–1487, doi:10.3762/bjoc.10.152

• divalent glycodendron 3 (Scheme 1). Then, ozonolysis yields the alcohol 4 in a quantitative reaction, which can be further modified at the focal hydroxy group, leading to 5 after allylation and to the primary alcohol 6 in the following ozonolysis step. However, the alcohol 4 can also be employed in another

Stereoselective synthesis of carbocyclic analogues of the nucleoside Q precursor (PreQ₀)

• Sabin Llona-Minguez and
• Simon P. Mackay

Beilstein J. Org. Chem. 2014, 10, 1333–1338, doi:10.3762/bjoc.10.135

• developed by Springthorpe et al. [32], we then investigated a route to prepare the enantiopure (1S,2R,3S,4R)-4-aminocyclopentane-1,2,3-triol analogue of PreQ0 16 (Figure 5). The first step is a Tsuji–Trost allylation of sodium di-tert-butyliminodicarboxylate. The reaction proceeded with an overall retention

Phosphinate-containing heterocycles: A mini-review

• Olivier Berger and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2014, 10, 732–740, doi:10.3762/bjoc.10.67

• slight excess of diphenyldiazomethane. The two diastereoisomers obtained were readily separable by column chromatography. Another example has been synthesized in 45% yield by Montchamp and coworkers (Scheme 18) [14]. To prepare the required phosphinate 45 a double allylation of H3PO2 was performed using

Synthesis of complex intermediates for the study of a dehydratase from borrelidin biosynthesis

• Frank Hahn,
• Nadine Kandziora,
• Steffen Friedrich and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 634–640, doi:10.3762/bjoc.10.55

• allylation as well as an anti-selective aldol reaction. Reference compounds representing the E- and Z-configured double bond isomers as potential products of the dehydratase reaction were obtained from a common precursor aldehyde by Wittig olefination and Still–Gennari olefination. The final deprotection of

Direct and indirect single electron transfer (SET)-photochemical approaches for the preparation of novel phthalimide and naphthalimide-based lariat-type crown ethers

• Dae Won Cho,
• Patrick S. Mariano and
• Ung Chan Yoon

Beilstein J. Org. Chem. 2014, 10, 514–527, doi:10.3762/bjoc.10.47

• . For example, Kubo and coworkers [47] showed that photoreactions of N-methyl-1,2- and 2,3-naphthalimides 8 and 12 with allylsilane 9 in MeCN can produce allylation products [48][49][50][51][52] that arise by a well-known sequence involving intermolecular SET, radical cation desilylation and radical

• into the amidols 69 can be easily achieved by employing Lewis acid-catalyzed reactions with allyltrimethylsilane, which produce the allylation products 71. Hydroboration–oxidation of the terminal olefin moieties in 71 then forms the corresponding alcohols 70 that contain key hydroxypropyl side chains

The Flögel-three-component reaction with dicarboxylic acids – an approach to bis(β-alkoxy-β-ketoenamides) for the synthesis of complex pyridine and pyrimidine derivatives

• Mrinal K. Bera,
• Moisés Domínguez,
• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 394–404, doi:10.3762/bjoc.10.37

• sodium borohydride the obtained products could be separated by column chromatography providing the dialcohol 32a in 51% yield over two steps and the monoalcohol 32b in 25% yield, respectively. The subsequent O-allylation of 32a furnished bisallyl ether 33 with 77% yield that was subjected to a ring

Boron-substituted 1,3-dienes and heterodienes as key elements in multicomponent processes

• Ludovic Eberlin,
• Fabien Tripoteau,
• François Carreaux,
• Andrew Whiting and
• Bertrand Carboni

Beilstein J. Org. Chem. 2014, 10, 237–250, doi:10.3762/bjoc.10.19

• /allylboration reactions [41]. In the case of the 4-methoxy-substituted diene, if the first step occurred at 80 °C in toluene, it was impossible to obtain the allylation products, even by heating at higher temperature or by activation with EtAlCl2. By contrast, with the 3-OTES derivative, bicyclic, three

• -hydroxyalkyldihydropyrans were reported; a substructure frequently encountered in the core of a wide range of natural products [59][60][61]. As in the carbocylic variant, the intermediate cyclic allylboronate (+)-19, prepared from 3-boronoacrolein, was the key element of a sequential Diels–Alder/allylation. In this case

• ]-cycloadditons, can further be engaged in an allylation reaction that significantly increased the structural diversity of the final products (Scheme 24). As 3-boronoacrolein esters which have been used in metal-catalyzed inverse electron demand [4 + 2]-cycloadditions, 32 reacted with ethyl vinyl ether in the

Synthesis of the B-seco limonoid core scaffold

• Hanna Bruss,
• Hannah Schuster,
• Rémi Martinez,
• Markus Kaiser,
• Andrey P. Antonchick and
• Herbert Waldmann

Beilstein J. Org. Chem. 2014, 10, 194–208, doi:10.3762/bjoc.10.15

• alkylation of the lithium enolate of 15 with alkyl halides under several conditions. They incorporated an α-allyl side chain via an α-bromo-enone, which can be obtained from an initially formed silyl enol ether, and subsequent reaction with NBS. Keck allylation of the α-bromo-enone using allyltributyltin and

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• , reduction of the remaining double bond and subsequent Krapcho decarboxylation [132] resulted in less functionalized ketone 150. Aldol condensation with furfural followed by O-allylation and Claisen rearrangement furnished enone 151. Standard functional group interconversiones were used to access TIPS

• underwent DVCPR to give cyclohexane 216. Tsuji–Trost allylation [176][177] furnished the quartenary carbon center. A two-step Fischer-indole strategy [178][179] finished tetracycle 217 under forcing conditions. Takeda and coworkers [180] set out to investigate the use of an anionic oxy-cis

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

• used for the generation of the hydroperoxide group. The intramolecular cyclization afforded 3-methyl-5-pentyl-1,2-dioxolan-3-ol (134), which could be easily reacted with monomethylethylene glycol to form 3-(2-methoxyethoxy)-3-methyl-5-pentyl-1,2-dioxolane (135). Allylation of the latter produced 3