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

Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

• Bernd Schmidt and
• Sylvia Hauke

Beilstein J. Org. Chem. 2014, 10, 1023–1031, doi:10.3762/bjoc.10.102

• or its epimer rhodinose, respectively [33]. An approach to amicetose (and a few other 6-desoxy sugars) involves the formation of an enantiopure β,γ-unsaturated δ-valerolactone via ring closing metathesis (RCM). The RCM product is subsequently converted into L-amicetose in four steps [34

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

• phosphinic acid using different alcohols in large excess (Scheme 1) [11][12]. Six phospholes 2a–f were prepared in yields up to 94%. Montchamp and coworkers have synthesized phospholes 4a,b by ring closing metathesis using 2 or 5 mol % of 2nd generation Grubbs’ catalyst (Scheme 2) [13][14]. Two compounds 4a

• corresponding analog of cyclic AMP, but no biological activity was reported. 1,2-Oxaphosphorines Gouverneur and coworkers have realized the synthesis of several 1,2-oxaphosphorine derivatives 53a–k using diastereoselective ring closing metathesis with 2 to 4 mol % of various catalysts (Scheme 22) [34]. During

• and broader structural diversity. While, like with any other P-heterocycles the phosphinates can be employed for the synthesis of novel phosphine ligands, their potential for the discovery of novel biologically active motifs is tantalizing. McCormack synthesis. Ring-closing metathesis. Phospha

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

• -components that bear an additional alkene, alkyne or azide moiety and can be cyclized via either a deprotection–cyclization strategy, a ring-closing metathesis, a 1,3-dipolar cycloaddition or even via a sequence of multiple multicomponent reactions. The sequential IMCR-cyclization reactions can afford small

• subsequent transformations [19][22][26]. Examples of IMCR orthogonal species or functionalities are alkenes, alkynes and azides which may give the cyclic analogues via subsequent ring closing metathesis (RCM) or 1,3-dipolar cycloadditions. In contrast, protected functional groups first require a deprotection

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

• closing metathesis (RCM) [69] with Grubbs-II-catalyst smoothly leading to the structurally interesting macrocyclic compound 34 in 73% yield. Compounds of this type – incorporating a 17-membered ring – have the potential to serve as structurally quite unique ligands for a variety of applications, e.g. in

• 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

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

• directing effect of the β-hydroxy group. Bicyclic system 65 could be obtained by ring-closing metathesis using Grubbs 1st generation catalyst and subsequent selective deprotection of the primary silyl ether. After esterification with 4-oxocyclohexanecarboxylic acid (25) and protection of the remaining two

• order to allow the synthetic access to further B-seco limonoid analogues, the C14-epi B-seco limonoid scaffold 78 and C14-epi/C9-epi scaffold 79 were accessed (Scheme 11). Starting from diol 74, the C14-epi rearrangement precursor 77 was synthesized employing a sequence of ring-closing metathesis, TBS

• quaternary centers at the ring junction. We decided to start the sequence with known enone 15 [39] and intended to construct the all-carbon quaternary center at C13 by substrate controlled α-functionalization. The second quaternary center at C14 might be established by 1,2-addition and finally, ring-closing

The difluoromethylene (CF₂) group in aliphatic chains: Synthesis and conformational preference of palmitic acids and nonadecane containing CF₂ groups

• Yi Wang,
• Ricardo Callejo,
• Alexandra M. Z. Slawin and
• David O’Hagan

Beilstein J. Org. Chem. 2014, 10, 18–25, doi:10.3762/bjoc.10.4

• that it can accommodate angle strain. For example CF2 compounds display an apparent Thorpe–Ingold effect relative to CH2 in ring closing metathesis reactions (RCM) to cycloheptene [8]. Comparison of the rates of reaction with different substituents at the C-5 position of the diene precursors 1a–d

A unified approach to the important protein kinase inhibitor balanol and a proposed analogue

• Tapan Saha,
• Ratnava Maitra and
• Shital K. Chattopadhyay

Beilstein J. Org. Chem. 2013, 9, 2910–2915, doi:10.3762/bjoc.9.327

• developed using an efficient fragment coupling protocol which proceeded in good overall yield. Keywords: azepane; balanol; Garner’s aldehyde; PKC inhibitor; ring-closing metathesis; Introduction Protein kinase C (PKC) is a family of phospholipid-dependent kinases that phosphorylate serine and threonine

• yield of 64% over two steps. The undesired anti-isomer 23 could be effectively converted to the desired syn-isomer 22 by a Mitsunobu-type inversion [64]. The major syn-isomer 22 was then acetylated and the resulting diene 24 was subjected to ring-closing metathesis [65] in the presence of Grubbs’ second

Synthesis of indole-based propellane derivatives via Weiss–Cook condensation, Fischer indole cyclization, and ring-closing metathesis as key steps

• Sambasivarao Kotha,
• Ajay Kumar Chinnam and
• Arti Tiwari

Beilstein J. Org. Chem. 2013, 9, 2709–2714, doi:10.3762/bjoc.9.307

• propellane derivatives involves a Weiss–Cook condensation, a Fischer indole cyclization, and a ring-closing metathesis as key steps. Keywords: allylation; indole derivatives; propellanes; ring-closing metathesis; Weiss–Cook condensation; Introduction Propellanes are tricyclic systems conjoined with carbon

• diindole based propellane derivatives involving the Weiss–Cook condensation [36], Fischer indole cyclization [37][38], and ring-closing metathesis as key steps [39][40][41][42] (Figure 3). Here, we report a new synthetic strategy to indole-based propellane derivatives and our approach has several points of

Bidirectional cross metathesis and ring-closing metathesis/ring opening of a C₂-symmetric building block: a strategy for the synthesis of decanolide natural products

• Bernd Schmidt and
• Oliver Kunz

Beilstein J. Org. Chem. 2013, 9, 2544–2555, doi:10.3762/bjoc.9.289

• -diene-3,4-diol. Key elements of the stagonolide E synthesis are the two-directional functionalization of the enantiopure, C2-symmetrical starting material through cross metathesis and a one-flask ring-closing metathesis/base-induced ring-opening sequence, a Ru–lipase-catalyzed dynamic kinetic resolution

Enantioselective synthesis of planar chiral ferrocenes via palladium-catalyzed annulation with diarylethynes

• Yan-Chao Shi,
• Rong-Fei Yang,
• De-Wei Gao and
• Shu-Li You

Beilstein J. Org. Chem. 2013, 9, 1891–1896, doi:10.3762/bjoc.9.222

• and co-workers reported the synthesis of planar chiral ferrocenes by utilizing an external chiral base such as (−)-sparteine [22][23]. Ogasawara and co-workers used the ring closing metathesis reaction to provide a novel and efficient route to synthesize the planar chiral ferrocenes [24][25][26][27

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• Prusov extended their synthetic method to syntheses of 15-deoxyripostatin A, and later ripostatin A itself [9]. All of these approaches to the ripostatins share several key features: use of ring-closing metathesis to form the 14-membered macrocycle, preceded by one or more Stille couplings to generate

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

Cyclization of ortho-hydroxycinnamates to coumarins under mild conditions: A nucleophilic organocatalysis approach

• Florian Boeck,
• Max Blazejak,
• Markus R. Anneser and
• Lukas Hintermann

Beilstein J. Org. Chem. 2012, 8, 1630–1636, doi:10.3762/bjoc.8.186

• , a lack of regioselectivity [7][8][9][10]. Such problems may be circumvented by using ring-closing metathesis [11][12] or other approaches [13][14][15]. In selective synthetic schemes, the generation of coumarins is typically realized by the cyclization of ortho-hydroxycinnamates (Scheme 1). This

Synthesis of a library of tricyclic azepinoisoindolinones

• Bettina Miller,
• Shuli Mao,
• Kara M. George Rosenker,
• Joshua G. Pierce and
• Peter Wipf

Beilstein J. Org. Chem. 2012, 8, 1091–1097, doi:10.3762/bjoc.8.120

• , the addition to in situ prepared N-acyliminium species, and ring-closing metathesis (RCM) were key steps in the preparation of a tricyclic isoindolinone scaffold. An unusual alkene isomerization process during the RCM was identified and studied in some detail. Chemical diversification for library

• commercially available or easily prepared starting materials and creates many opportunities for further functionalization and chemical library synthesis. For example, a ring-closing metathesis of the alkene addition product affords structurally novel tricyclic isoindolinones with a newly formed seven-membered

• afford diene 2 [19][24]. Ring-closing metathesis of 2 using Grubbs 2nd generation catalyst [25] in the presence of 1 equiv of Ti(OiPr)4 [26][27] at room temperature provided, surprisingly, a modest 45% yield of the alkene-isomerized homoallylic amide 3 instead of the expected allylic amide 4 (Scheme 1

Algicidal lactones from the marine Roseobacter clade bacterium Ruegeria pomeroyi

• Ramona Riclea,
• Julia Gleitzmann,
• Hilke Bruns,
• Corina Junker,
• Barbara Schulz and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2012, 8, 941–950, doi:10.3762/bjoc.8.106

• , syntheses of reference compounds were carried out (Scheme 1). Methacryloyl chloride (12) was esterified with but-3-en-2-ol (13) in the presence of triethylamine to yield but-3-en-2-yl methacrylate (15). Ring-closing metathesis with Grubbs catalyst of the second generation gave 2-methylpent-2-en-4-olide (11

• methacrylate (16), ring-closing metathesis to 2-methylhex-2-en-4-olide (17), and catalytic hydrogenation. The isomerisation of 9 with KOt-Bu in t-BuOH again provided a mixture of 9 and its diastereomer trans-2-methylhexan-4-olide (10). Comparison of GC retention times and mass spectra of the synthetic material

• ), 990 (w), 930 (m), 810 (w), 657 (w) cm−1; UV–vis: λmax (log ε): 228 (2.83) nm. General procedure for the ring-closing metathesis to butenolides: Grubbs catalyst of the second generation (0.05 equiv) was added to a solution of the ester 15 or 16 (1.0 equiv) in dry dichloromethane (0.05 M). The mixture

Stereoselective, nitro-Mannich/lactamisation cascades for the direct synthesis of heavily decorated 5-nitropiperidin-2-ones and related heterocycles

• Pavol Jakubec,
• Dane M. Cockfield,
• Madeleine Helliwell,
• James Raftery and
• Darren J. Dixon

Beilstein J. Org. Chem. 2012, 8, 567–578, doi:10.3762/bjoc.8.64

• ][28][29], reduction of unsaturated heterocycles [30][31][32], ring closure via intramolecular nucleophilic substitution [33][34][35][36][37], cascade reactions of enamines/imines and aldehydes [38][39][40][41], and ring-closing metathesis followed by hydrogenation [42][43][44][45][46][47][48

Branching out at C-2 of septanosides. Synthesis of 2-deoxy-2-C-alkyl/aryl septanosides from a bromo-oxepine

• Supriya Dey and
• Narayanaswamy Jayaraman

Beilstein J. Org. Chem. 2012, 8, 522–527, doi:10.3762/bjoc.8.59

• been explored in many instances, for example, (i) hemiacetal or acetal formation from a linear precursor containing aldehyde and an appropriately positioned hydroxyl group [4][5][6][7][8]; (ii) Knoevenagel-type condensation of sugar aldehyde with active methylene compounds [9][10]; (iii) ring-closing

• metathesis reactions of appropriately installed diene derivatives [11][12][13]; (iv) ring expansion of 1,2-cyclopropanated sugars [14][15][16][17]; (v) Baeyer–Villiger oxidation of inositol derivatives [18][19] and (vi) electrophile-induced cyclization [20]. We recently developed a new methodology to prepare

Binding of group 15 and group 16 oxides by a concave host containing an isophthalamide unit

• Jens Eckelmann,
• Vittorio Saggiomo,
• Svenja Fischmann and
• Ulrich Lüning

Beilstein J. Org. Chem. 2012, 8, 11–17, doi:10.3762/bjoc.8.2

• double amide formation between an isophthaloyl dichloride and two equivalents of a bis(alkenyloxy)aniline, followed by ring-closing metathesis and hydrogenation. In contrast to many related isophthalamides, the concave host exhibits a better binding for oxides, such as DMSO or pyridine-N-oxide, than for

• 3 gave the open diamide 5. This tetraalkene 5 was then converted to bi-macrocycle 1 by ring-closing metathesis followed by catalytic hydrogenation. Model compound 2 was obtained by reacting isophthaloyl dichloride 3 with 2,6-dimethoxyaniline (6). The two products 1 and 2 were isolated and

Selectivity in C-alkylation of dianions of protected 6-methyluridine

• Ngoc Hoa Nguyen,
• Christophe Len,
• Anne-Sophie Castanet and
• Jacques Mortier

Beilstein J. Org. Chem. 2011, 7, 1228–1233, doi:10.3762/bjoc.7.143

• development of new cyclonucleosides 5 [5][6], we envisioned that the general transformation outlined in Scheme 1 might afford a facile entry to 5 from dialkenyl precursors 4 by ring-closing metathesis [10][11][12]. The strategy relies on the preparation of unknown 6-ω-alkenyluridine key intermediates 3. We

Metathesis access to monocyclic iminocyclitol-based therapeutic agents

• Ileana Dragutan,
• Valerian Dragutan,
• Carmen Mitan,
• Hermanus C.M. Vosloo,
• Lionel Delaude and
• Albert Demonceau

Beilstein J. Org. Chem. 2011, 7, 699–716, doi:10.3762/bjoc.7.81

• et al. [72] based again on the Garner aldehyde 69 derived from D-serine. To construct the chiral 1,2,5,6-tetrahydropyridine core 125, the authors resorted to catalytic ring-closing metathesis induced by the 1st-generation Grubbs catalyst 2, with subsequent stereoselective dihydroxylation (under

Ene–yne cross-metathesis with ruthenium carbene catalysts

• Cédric Fischmeister and
• Christian Bruneau

Beilstein J. Org. Chem. 2011, 7, 156–166, doi:10.3762/bjoc.7.22

• type of reaction in a selective manner it is required that the two double bonds have different reactivities with respect to EYCM and that the intramolecular olefin ring closing metathesis is not efficient. Such a reaction has been performed from dienes containing a non-activated double bond and an

• The positive influence of ethylene in metathesis in the presence of ruthenium catalysts was first evidenced by Mori during the intramolecular ring closing metathesis of enynes [83]. The excess of ethylene would favor the formation of ruthenium methylidene intermediates, and thus prevent catalyst

Olefin metathesis in nano-sized systems

• Didier Astruc,
• Abdou K. Diallo,
• Sylvain Gatard,
• Liyuan Liang,
• Cátia Ornelas,
• Victor Martinez,
• Denise Méry and
• Jaime Ruiz

Beilstein J. Org. Chem. 2011, 7, 94–103, doi:10.3762/bjoc.7.13

• ) or, more usefully, dendrimer encapsulation – ring closing metathesis (RCM), cross metathesis (CM), enyne metathesis reactions (EYM) – for reactions in water without a co-solvent and (ii) construction and functionalization of dendrimers by CM reactions. Keywords: dendrimer; green chemistry

• the metathesis of polyolefin dendrimers or star compounds from which ring-closing metathesis products were formed. For instance, a third generation Fréchet-type dendrimer containing 24 allyl ether end groups was synthesized by the Zimmerman group, cross-linked using the RCM reaction, and the core

Recent advances in the development of alkyne metathesis catalysts

• Xian Wu and
• Matthias Tamm

Beilstein J. Org. Chem. 2011, 7, 82–93, doi:10.3762/bjoc.7.12

• ring-closing metathesis (RORCM) leads to an equilibrium between monomeric and dimeric products and their ratios are determined by their relative stabilities [77]. The catalytic performance of 6a and 6b in RCAM was demonstrated for the substrates m-bis(3-pentynyloxymethyl)benzene (17b) and bis(3

Hoveyda–Grubbs type metathesis catalyst immobilized on mesoporous molecular sieves MCM-41 and SBA-15

• Hynek Balcar,
• Tushar Shinde,
• Naděžda Žilková and
• Zdeněk Bastl

Beilstein J. Org. Chem. 2011, 7, 22–28, doi:10.3762/bjoc.7.4

• found for ring-closing metathesis of 1,7-octadiene in cyclohexane – 0.04% of catalyst Ru content). Results of XPS, UV–vis and NMR spectroscopy showed that at least 76% of the Ru content was bound to the support surface non-covalently and could be removed from the catalyst by washing with THF. Keywords

• metathesis polymerization (ROMP) of cyclooctene, ring-closing metathesis (RCM) of diallylsilanes and several types of cross-metathesis reactions. High stability of catalysts, reusability and low Ru leaching were also reported. However, the mode of attachment of the Ru species on the silica surface was