Enantioconvergent catalysis

• Justin T. Mohr,
• Jared T. Moore and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2016, 12, 2038–2045, doi:10.3762/bjoc.12.192

• . Enantioconvergent synthesis of phosphines governed by Curtin–Hammett/Winstein–Holness kinetics (TMS = trimethylsilyl, Is = 2,4,6-triisopropylphenyl). Stoltz’ stereoablative oxindole functionalization. Fu’s type II enantioconvergent Cu-catalyzed photoredox reaction. Stereoablative enantioconvergent allylation and

Bridgehead vicinal diallylation of norbornene derivatives and extension to propellane derivatives via ring-closing metathesis

• Sambasivarao Kotha and
• Rama Gunta

Beilstein J. Org. Chem. 2016, 12, 1877–1883, doi:10.3762/bjoc.12.177

• ring-closing metathesis (RCM) [24][25][26][27][28][29][30][31][32]. Whereas, the diallyl derivative 2 can be derived from a readily available Diels–Alder (DA) adduct 3 through an allylation sequence. Results and Discussion Installation of two C–C bonds to generate quaternary centers in a

• in Figure 2. At this point, we turned our attention to understand the configurational origin of the allyl groups in 2a. To understand whether compound 2a was formed by Claisen rearrangement (CR) of the corresponding O-allyl compound or by carbanion mediated C-allylation of the DA adduct 3a, we

• X-ray diffraction analysis. A control experiment with propyl bromide provided an insight into the reaction mechanism that the bridgehead allylation proceeds through enolization, O-allylation followed by CR and not via carbanion chemistry. This alternative strategy is useful to introduce vicinal

Synthesis of 2-oxindoles via 'transition-metal-free' intramolecular dehydrogenative coupling (IDC) of sp² C–H and sp³ C–H bonds

• Nivesh Kumar,
• Santanu Ghosh,
• Subhajit Bhunia and
• Alakesh Bisai

Beilstein J. Org. Chem. 2016, 12, 1153–1169, doi:10.3762/bjoc.12.111

• elaboration and functionalization. A few substrates were treated under decarboxylative allylation (DcA) conditions in the presence of 10 mol % of Pd(PPh3)4 in refluxing tetrahydrofuran (7–8 h), which afforded products 26a–d in up to 99% yield (Scheme 11). Interestingly, oxidative coupling products with

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

• already been reported in preliminary form [31]. Homoallylic amines of type 12 may be efficiently obtained through multicomponent reactions. These involve the nucleophilic allylation of imines which may be generated in situ by the condensation of an amine and a carbonyl compound. As shown in Scheme 2, two

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• metal-catalyzed synthesis The chiral ligand/metal complexes have been widely employed in catalytic asymmetric synthesis of enantioenriched 3-hydroxyoxindoles, achieving good to excellent enantioselectivities and high yields. Pd-catalyzed allylation of isatins The palladium catalyst is widely used in

• organic synthesis and has showed its usefulness in the allylation of isatins. In 2014, Song and co-workers designed the chiral CNN (three atoms attched to the palladium) pincer Pd complexes, which were proved to be efficient in catalyzing the enantioselective allylation of isatins with allyltributytin

• allylated product in 93% yield and 72% ee value when cat. 2 was used (Scheme 2). Kesavan and co-workers described that the Pd/bis(oxazoline) (L1) complex can catalyze the asymmetric allylation of 3-O-Boc-oxindole, yielding the 3-allyl-3-hydroxyoxindoles in good yields (up to 93% yield) and with high

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

• -catalyzed allylation substitution reaction of oxazol-4(5H)-ones and thiazol-4(5H)-ones to afford enantioenriched tertiary alcohols and thioethers (Scheme 19) [42]. In this case the diastereoselectivity is controlled by cations, in contrast to most of the described protocols wherein it is modulated by anions

• . The authors found that whilst the best results for allylation of oxazol-4-(5H)-ones were achieved from zinc enolates, thiazol-4-(5H)-ones produced the best outcome when the magnesium enolate was used. After optimization it was shown that the reaction was efficient with different cinnamyl tert-butyl

New metathesis catalyst bearing chromanyl moieties at the N-heterocyclic carbene ligand

• Agnieszka Hryniewicka,
• Szymon Suchodolski,
• Agnieszka Wojtkielewicz,
• Jacek W. Morzycki and
• Stanisław Witkowski

Beilstein J. Org. Chem. 2015, 11, 2795–2804, doi:10.3762/bjoc.11.300

• -trimethylphenol analogously to the procedure described for 2,2,5,8-tetramethyl-6-chromanol by Dean [27]. 2,3-Dihydroxy-1,4-dioxane was obtain according to Venuti [37]. Substrates for testing catalysts in RCM reactions were prepared by allylation of commercial diethyl malonate with allyl bromide and/or 3-chloro-2

Catalytic asymmetric formal synthesis of beraprost

• Yusuke Kobayashi,
• Ryuta Kuramoto and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2015, 11, 2654–2660, doi:10.3762/bjoc.11.285

• could be readily prepared from ortho-bromophenol (9, Scheme 2). O-Allylation of 9 followed by Lewis acid-mediated Claisen rearrangement afforded ortho-allylphenol 11, whose olefin moiety was ozonolyzed and subsequently treated with Wittig reagent 13 to provide amide 7 in 55% yield over four steps from 9

Recent developments in copper-catalyzed radical alkylations of electron-rich π-systems

• Kirk W. Shimkin and
• Donald A. Watson

Beilstein J. Org. Chem. 2015, 11, 2278–2288, doi:10.3762/bjoc.11.248

• nitronate anions are known to undergo alkylation with alkyl radicals, these radicals are often accessed using highly undesirable methods such as stoichiometric alkylmetal reagents or highly complex alkylating agents [17]. Although allylation [18][19][20][21][22][23] and arylation [24][25][26] of

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

• compound 38 as the key starting synthone, easily prepared from 36 via an N-allylation sequence. Next, diallyl compound 38 was treated with catalyst 2 to deliver the expected bipiperidine derivative 39 in 60% yield. Further, this protocol has been extended to various oxygenated systems (Scheme 5). Snapper

• required building block 85 has been prepared from compound 84 by allylation with allyl bromide (37). Later, the pyran derivative 85 was treated with catalyst 2 to generate the bicyclic system 86 (73%) (Scheme 17). They also demonstrated a RCM–ROM–RCM cascade using a strain-free allyl heterocycle as useful

• derived from cyclopentadiene (111) and 1,4-benzoquinone. The diol 132 was produced by reduction of 131 in an efficient manner. To this end, the bis-O-allylated compound 133 was prepared by an allylation sequence using allyl bromide (37) in the presence of NaH starting with the diol 132, whereas compound

Design and synthesis of propellane derivatives and oxa-bowls via ring-rearrangement metathesis as a key step

• Sambasivarao Kotha and
• Rama Gunta

Beilstein J. Org. Chem. 2015, 11, 1727–1731, doi:10.3762/bjoc.11.188

• from readily accessible starting materials such as p-benzoquinone, 1,4-naphthoquinone and 1,4-anthraquinone. Keywords: allylation; propellane derivatives; quinones; ring-rearrangement metathesis; Introduction The synthesis of complex target structures requires bond-disconnection analysis of the

• propellane derivatives and oxa-bowls is shown in Figure 1. Oxa-bowl 1 can be synthesized from the tetracyclic compound 2 using RRM, which could be obtained from the known DA adduct 3 by O-allylation. On the other hand, the propellane derivative 7 may be synthesized from the tetraallyl compound 6 by a RRM

• sequence. Further, the tetraallyl compound 6 can be assembled from the C-allyl derivative 4 via reduction followed by O-allylation. The C-allyl derivative 4 may be obtained from the known DA adduct 3 by a C-allylation sequence which in turn could be prepared by the DA reaction of the corresponding 1,4

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

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