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

• combing organic fragments in natural product synthesis, the value of vinylphosphonates as synthetic intermediates would increase if their reactivity could be enhanced to a level where they would participate in cross metathesis reactions. As an example, we recently described a method for the formal

• synthesis of centrolobine (8) [9], an antileishmananial compound isolated from the heartwood of various Centrolobium species [12][13][14][15][16] (Scheme 2). The cis-THP substituted vinylphosphonate 5, formed by a stereospecific palladium-catalyzed cyclization of phosphono allylic carbonate 4, was cleaved

Structure elucidation of female-specific volatiles released by the parasitoid wasp Trichogramma turkestanica (Hymenoptera: Trichogrammatidae)

• Armin Tröger,
• Teris A. van Beek,
• Martinus E. Huigens,
• Isabel M. M. S. Silva,
• Maarten A. Posthumus and
• Wittko Francke

Beilstein J. Org. Chem. 2014, 10, 767–773, doi:10.3762/bjoc.10.72

• approach includes a formal synthesis of optically active A and B. Until now, we did not find suitable conditions to separate the enantiomers of the tetramethyldiene 22 and the respective allyl alcohol 23 (or corresponding derivatives thereof) in order to assign the absolute configuration of the natural

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

• (51) could be accessed after 10 or 7 steps respectively. Piers and co-workers were the first to examine the DVCPR as a key step in the formal synthesis of (±)-quadrone (55, see Scheme 9) [49], and the total syntheses of sinularene (59) [50], prezizanol (63) and prezizaene (64) [51]. The synthesis of

• ). Davies and co-worker [91][92] investigated the formal synthesis of the sequiterpene-hydroquinone derivative frondosin B (99, see Scheme 12) [93] via an enantioselective cyclopropanation of trans-piperylene and subsequent divinylcyclopropane rearrangement, to further demonstrate the versatility of their

• over several steps (77% over three steps and 98% over two steps, respectively). Overman’s total synthesis of scopadulcic acid B. Davies’ total syntheses of tremulenolide A and tremulenediol A. Davies formal [4 + 3] cycloaddition approach towards the formal synthesis of frondosin B. Davies and Sarpongs

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

Gold(I)-catalyzed enantioselective cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2013, 9, 2250–2264, doi:10.3762/bjoc.9.264

• intramolecular cyclopropanation. Gold-catalyzed cyclohepta-annulation cascade. Application to the formal synthesis of frondosin A. Gold(I)-catalyzed enantioselective cyclopropenation of alkynes. Enantioselective cyclopropanation of diazooxindoles. Gold-catalyzed enantioselective [2 + 2] cycloadditions of

A concise enantioselective synthesis of the guaiane sesquiterpene (−)-oxyphyllol

• Martin Zahel and
• Peter Metz

Beilstein J. Org. Chem. 2013, 9, 2028–2032, doi:10.3762/bjoc.9.239

• (−)-oxyphyllol (1) and 5, we decided to use a modification of our route to 5 for the synthesis of 1 that would also constitute a formal synthesis of the related guaiane (+)-orientalol E (2) [4][7]. As illustrated in Scheme 1, we selected tertiary alcohol 3 as a retrosynthetic precursor for 1. The acetyl group of

• , a formal synthesis of (+)-orientalol E (2) as well by a modification of our previously developed route for setting up the oxygen-bridged framework present in (−)-englerin A (5). The reaction sequence presented herein allows the preparation of the guaiane 1 in only 10 steps with an overall yield of

Formal synthesis of (−)-agelastatin A: an iron(II)-mediated cyclization strategy

• Daisuke Shigeoka,
• Takuma Kamon and
• Takehiko Yoshimitsu

Beilstein J. Org. Chem. 2013, 9, 860–865, doi:10.3762/bjoc.9.99

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

• starting xanthate. For instance, a regioselective Sonogashira coupling leading to compound 57 may be performed without affecting the less reactive chlorine substituent. The annelation commencing with xanthate 58 and furnishing indole derivative 59, an advanced intermediate in the formal synthesis of

• , this strategy was applied to a formal synthesis of (±)-hirsutic acid [39]. Access to polycyclic structures can be accomplished by cyclisation of propargyl radicals. Alkynes or allenes can be obtained, depending on the disposition of the internal alkene with respect to the delocalised radical [40][41

Alternaric acid: formal synthesis and related studies

• Michael C. Slade and
• Jeffrey S. Johnson

Beilstein J. Org. Chem. 2013, 9, 166–172, doi:10.3762/bjoc.9.19

• Michael C. Slade Jeffrey S. Johnson Caudill Laboratories, Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, USA 10.3762/bjoc.9.19 Abstract A silyl glyoxylate three-component-coupling methodology has been exploited to achieve a formal synthesis, an

• complex molecule synthesis. Keywords: formal synthesis; multicomponent coupling; natural products; silyl glyoxylates; Introduction The rapid development of molecular complexity from simple starting materials is an important goal in modern synthetic organic chemistry. In this context, streamlined one-pot

• attractive starting point for synthetic planning (Scheme 1B). This paper summarizes our synthetic work in this arena, which culminated in a formal synthesis, an analogue of another formal synthesis, and a unique approach to the target; each of the routes was enabled by distinct coupling partners. Alternaric

Intramolecular carbolithiation of N-allyl-ynamides: an efficient entry to 1,4-dihydropyridines and pyridines – application to a formal synthesis of sarizotan

• Wafa Gati,
• Mohamed M. Rammah,
• Mohamed B. Rammah and
• Gwilherm Evano

Beilstein J. Org. Chem. 2012, 8, 2214–2222, doi:10.3762/bjoc.8.250

• formal synthesis of the anti-dyskinesia agent sarizotan, further extends the use of ynamides in organic synthesis and further demonstrates the synthetic efficiency of carbometallation reactions. Keywords: carbolithiation; carbometallation; dihydropyridines; organolithium reagents; pyridines; sarizotan

• formal synthesis of the anti-dyskinesia agent sarizotan. Results and Discussion Feasibility of the deprotonation/intramolecular carbolithiation To first evaluate the compatibility of the ynamide moiety with the lithiation step and address potential problems associated with competitive carbolithiation of

• , which does confirm that our deprotonation/carbometallation sequence is not suitable for the preparation of C-2-substituted (1,4-dihydro)pyridines. Application to a formal synthesis of sarizotan To further probe the synthetic utility of our pyridine synthesis, we next envisioned its use for the synthesis

Stereoselective synthesis of trans-fused iridoid lactones and their identification in the parasitoid wasp Alloxysta victrix, Part I: Dihydronepetalactones

• Nicole Zimmermann,
• Robert Hilgraf,
• Lutz Lehmann,
• Daniel Ibarra and
• Wittko Francke

Beilstein J. Org. Chem. 2012, 8, 1246–1255, doi:10.3762/bjoc.8.140

• could be separated by column chromatography over silica. Starting from the enantiomer of 26, a mixture of dihydronepetalactones c' and d' was synthesized by following the same reaction sequence. Formal synthesis of a mixture of trans-fused dihydronepetalactones a and b from (R)-limonene As outlined

• formal synthesis of a and a'. A mixture of a and b will be easily obtained from the protected hydroxy aldehyde 24 by the straight forward procedure outlined in Scheme 6. Reduction of the aldehyde function of 24 and acetylation of the resulting primary alcohol followed by cleavage of the silyl group will

• (71%); b) p-TsOH, benzene, reflux (96%); c) NaBH4, MeOH, −20 °C; d) TBDMSCl, imidazole, DMF, 0 °C (78%) (over two steps); e) KOH, MeOH, rt (94%); f) RuCl3·3H2O (2 mol %), NaIO4, CCl4, CH3CN, phosphate buffer (pH 7), rt (69%); g) HF, CH3CN, rt (98%); h) DCC, DMAP, CH2Cl2 (62%). Formal synthesis of a

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

• an enantioenriched form by using an organocatalytic Michael addition methodology, which was developed by our group and others [54][55][56][57][58][59]. In pursuit of this we have successfully harnessed the power of the nitro-Mannich/lactamisation cascade in a formal synthesis of (3S,4R)-paroxetine

Directed aromatic functionalization in natural-product synthesis: Fredericamycin A, nothapodytine B, and topopyrones B and D

• Charles Dylan Turner and
• Marco A. Ciufolini

Beilstein J. Org. Chem. 2011, 7, 1475–1485, doi:10.3762/bjoc.7.171

• -mediated cyclization reaction. This led to the formation of compound 35 in about 60% yield (based on 1H NMR; Scheme 6). A late intermediate in the Kelly synthesis of 1 [6][7] is structurally very similar to 35. Consequently, the preparation of 35 corresponds to a formal synthesis of fredericamycin A [31

• oxidation thereof. Formal synthesis of fredericamycin A. A useful pyridone synthesis. Retrosynthetic logic for nothapodytine B. Preparation of a key nothapodytine fragment. Total synthesis of nothapodytine B. Retrosynthetic logic for the linear series of topopyrones. Construction of the molecular subunit

Directed ortho,ortho'-dimetalation of hydrobenzoin: Rapid access to hydrobenzoin derivatives useful for asymmetric synthesis

• Inhee Cho,
• Labros Meimetis,
• Lee Belding,
• Michael J. Katz,
• Travis Dudding and
• Robert Britton

Beilstein J. Org. Chem. 2011, 7, 1315–1322, doi:10.3762/bjoc.7.154

• prepared in an overall yield of 32% from (R,R)-hydrobenzoin (3) without purification of 20, compared to 21% when the intermediate bis(benzoxaborol) 20 was purified by column chromatography [23]. Finally, the efficiency of this process was demonstrated in a short formal synthesis of (R,R)-Vivol (4). Thus, a

• various electrophiles. Reactions of the diiodohydrobenzoin 12 and X-ray crystal structure of the dihydrosilepin 31. Cross coupling reactions of the bis(benzoxaborol) 20 and a short formal synthesis of (R,R)-Vivol (4). Optimization of the synthesis of the diiodohydrobenzoin 12. Supporting Information

A racemic formal total synthesis of clavukerin A using gold(I)-catalyzed cycloisomerization of 3-methoxy-1,6-enynes as the key strategy

• Jae Youp Cheong and
• Young Ho Rhee

Beilstein J. Org. Chem. 2011, 7, 740–743, doi:10.3762/bjoc.7.84

• in the formal synthesis of clavukerin A was explored. We first investigated the cyclization–hydrogenation strategy (path A in Scheme 4). Deprotection of 4 and the aldol condensation of the resulting diketone under basic conditions proceeded smoothly to give the enone 2 in good yield. However

• completion of the formal synthesis of clavukerin A. In summary, a formal synthesis of racemic clavukerin A was accomplished via the gold(I)-catalyzed cycloisomerization of a 3-methoxy-1,6-enyne as the key strategy and stereoselective Rh-catalyzed hydrogenation. Notably, the gold(I)-catalyzed reaction was

• analysis. Preparation of compound 5. Synthesis of the cycloheptenone 4. Completion of the formal synthesis of clavukerin A. Supporting Information Supporting Information File 144: Experimental section for the preparation of compounds 2–12, and 1H and 13C NMR spectra for all new compounds

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

• -methylmorpholine N-oxide (NMO) in acetone) to yield 28 and final deprotection (MeOH–HCl) gave the imino-D-allitol 29 as the HCl salt. Formal synthesis of (2S,3R,4S)-3,4-dihydroxyproline (30) starting from 24 was carried identically by RCM to afford 27 and subsequent conversion of 28 to 30 was achieved in several

• ). Synthesis of 1,4-dideoxy-1,4-imino-D-allitol (29) and formal synthesis of (2S,3R,4S)-3,4-dihydroxyproline (30). Synthesis of iminocyclitols 35 and 36. Total synthesis of iminocyclitols 40 and 44. Synthesis of 2,5-dideoxy-2,5-imino-D-mannitol [(+)-DMDP] (49) and (−)-bulgecinine (50). Synthesis of

• dihydroxylation with simultaneous deprotection of (+)-22 gave the final product (−)-23 in good yield. In an interesting work by Rao and co-workers [54] a Grignard reaction was employed to design the diene with desired stereochemistry for the synthesis of 1,4-dideoxy-1,4-imino-D-allitol (29) and the formal

Gold-catalyzed heterocyclizations in alkynyl- and allenyl-β-lactams

• Benito Alcaide and
• Pedro Almendros

Beilstein J. Org. Chem. 2011, 7, 622–630, doi:10.3762/bjoc.7.73

• starting materials were mostly unreacted in the case of cyclohexene substrates and partly decomposed in the case of cyclopentene substrates. This method allows an expedient formal synthesis of indolizidine 167B. Oxycyclizations Transition metal-assisted intramolecular addition of oxygen nucleophiles across

A review of new developments in the Friedel–Crafts alkylation – From green chemistry to asymmetric catalysis

• Magnus Rueping and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2010, 6, No. 6, doi:10.3762/bjoc.6.6

• “on water”. Reductive FC alkylation of arenes with benzaldehyde and acetophenone catalyzed by the Ir-carbene complex 33. Formal synthesis of 1,1-diarylalkanes from benzyl alcohols and styrenes. (A) Mo-catalyzed hydroarylation of styrenes and cyclohexenes. (B) Hydroalkylation–cyclization cascade

Recent progress on the total synthesis of acetogenins from Annonaceae

• Nianguang Li,
• Zhihao Shi,
• Yuping Tang,
• Jianwei Chen and
• Xiang Li

Beilstein J. Org. Chem. 2008, 4, No. 48, doi:10.3762/bjoc.4.48

• completed the synthesis of 71a. The diastereomeric structure 71b was also synthesized following the same route but using the (2R)-10,2-camphorsultam. In 2004, the full details of this total synthesis were reported [44]. In 2005, Donohoe’s group [45] reported the formal synthesis of (+)-cis-solamin using