Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• [CF=CH]-Gly 9, from benzothiazolyl fluoroaminosulfones (Scheme 2) [24][25]. The Julia–Kocienski olefination of 3-alkoxypropanal 7 with phthalimido sulfone 6 afforded the corresponding monofluoroalkene 8 as a (Z):(E) mixture (54:46). Removal of the benzyl group using titanium tetrachloride gave the

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• proceeds only at elevated temperatures (50 °C), that may account for relatively low yields of products 62. Furthermore, the reaction of sulfone 63 with lithium (trimethylsilyl)acetylide furnished only enoxime 64. Apparently, the application of more convenient and selective nitrosoalkene sources (e.g., TBS

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• glycosylations have now even been described in materials chemistry. Here they provide an extremely efficient way to functionalize hydroxy-terminated self-assembled monolayers (SAM) on gold (Scheme 37). First the surface was incubated with divinyl sulfone (DVS) in a basic aqueous buffer (pH 11) followed by

Urea–hydrogen peroxide prompted the selective and controlled oxidation of thioglycosides into sulfoxides and sulfones

• Adesh Kumar Singh,
• Varsha Tiwari,
• Kunj Bihari Mishra,
• Surabhi Gupta and
• Jeyakumar Kandasamy

Beilstein J. Org. Chem. 2017, 13, 1139–1144, doi:10.3762/bjoc.13.113

• controlled oxidation of thioglycosides to glycosyl sulfoxides and sulfones selectively by altering the reaction conditions. It is also observed that thioglycoside oxidation suffers from low yields, poor selectivity (i.e., sulfoxide vs sulfone), use of inconvenient reaction conditions and expensive oxidants

• as dichloromethane and acetonitrile gave a negligible amount of corresponding sulfoxide (1a) while no sulfone (1b) was detected at room temperature even after 6 hours (Table 1, entries 1 and 2). However, protic solvents such as methanol, ethanol, tert-butanol and acetic acid were found to be

• was driven to completion with the desired sulfoxide (1b) in 92% yield within 2 h at 60 °C (Table 1, entry 9). It is also worth noting that less than 5% of the corresponding sulfone was detected in the crude product by 1H NMR under these conditions. Considering the importance of glycosyl sulfones, we

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• protocol is successfully used with various electron-deficient substituted phenyl groups (15b–e) and with heterocycles (15f–h). The double-bond of cyanopyrrolidine 14l is preserved from the hydroboration reaction (15l). Olefins bearing bulky ester, sulfone or amide groups afforded good to excellent yields

New syntheses of (±)-tashiromine and (±)-epitashiromine via enaminone intermediates

• Darren L. Riley,
• Joseph P. Michael and
• Charles B. de Koning

Beilstein J. Org. Chem. 2016, 12, 2609–2613, doi:10.3762/bjoc.12.256

• approach most commonly comprise a nitrogen atom in a pyrrolidine or piperidine ring conjugated at C-2 through an exocyclic vinyl fragment to an ester (vinylogous urethane) or another electron-withdrawing substituent (usually ketone, nitrile, nitro or sulfone). When suitable carbon chains bearing terminal

Opportunities and challenges for direct C–H functionalization of piperazines

• Zhishi Ye,
• Kristen E. Gettys and
• Mingji Dai

Beilstein J. Org. Chem. 2016, 12, 702–715, doi:10.3762/bjoc.12.70

• % yield with Ir(ppy)3 as the catalyst [63]. In another report, MacMillan et al. showed that under similar photoredox conditions, 87 could couple with vinyl sulfone 90 to provide α-vinylation product 91 in 74% yield with excellent E/Z selectivity [65]. They also discovered that piperazine 87 could couple

Facile synthesis of 4H-chromene derivatives via base-mediated annulation of ortho-hydroxychalcones and 2-bromoallyl sulfones

• Srinivas Thadkapally,
• Athira C. Kunjachan and
• Rajeev S. Menon

Beilstein J. Org. Chem. 2016, 12, 16–21, doi:10.3762/bjoc.12.3

• that such problems may be circumvented by developing a synthetic surrogate for the sensitive allenyl sulfones. Investigations along this direction led to the discovery that the easily prepared 2-bromoallyl sulfones 2a,b function as allenyl sulfone surrogates in the presence of cesium carbonate (Scheme

• b) [24]. Similarly, treatment of 2a with salicylaldehyde furnished the 3-sulfonyl-2H-chromene derivative 4 in 69% yield (Scheme 1, path c) [24]. The formation of allenyl sulfone 5 and propargyl sulfone 6 in the reaction of 2a with cesium carbonate indicated that 5 is an intermediate in the above

• , stability, and ease of preparation, ortho-hydroxychalcones were considered to be a suitable choice for this purpose. A pilot reaction between the o-hydroxychalcone 7a and bromoallyl sulfone 2a in the presence of 2 equivalents of cesium carbonate in acetonitrile afforded the 4H-chromene derivative 8aa in 61

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

• alcohol was converted to the corresponding silyl ether. Next, alkylation of the metalated sulfone with allylic chloride 51 afforded alcohol 52 after desilylation. Subsequent desulfonylation with sodium amalgam and Jones oxidation of the primary alcohol furnished carboxylic acid 53. The corresponding

• allenic sulfone [44] which, upon conjugate addition of diethyl amine followed by hydrolysis afforded a β-ketosulfone. For the following ring closure, the primary alcohol was desilylated and converted to the corresponding allylic carbonate 71. The cyclononene structure 72 was then assembled via a palladium

• -catalyzed and base-mediated cyclization of carbonate 71 [45]. Reductive cleavage of the sulfone using aluminium amalgam afforded a ketone, which was converted to an exocyclic double bond by treatment with Tebbe’s reagent [42]. In order to convert the methoxy acetal to the corresponding lactone, without

Beyond catalyst deactivation: cross-metathesis involving olefins containing N-heteroaromatics

• Kevin Lafaye,
• Cyril Bosset,
• Lionel Nicolas,
• Amandine Guérinot and
• Janine Cossy

Beilstein J. Org. Chem. 2015, 11, 2223–2241, doi:10.3762/bjoc.11.241

• of 2,6-disubstituted pyridine 60 was treated with GI, the expected macrocycle 61 was obtained (51%) together with the dimeric cyclophane 62 (20%). The authors explained that the sulfone moieties facilitated the RCM by steering the alkenyl chains into a favorable conformation, but it also may be

• hypothesized that the steric hindrance caused by the sulfone groups might reduce the ability of the nitrogen atom in deactivating the ruthenium catalyst. A desulfonylation followed by a hydrogenation of the double bond afforded normuscopyridine (Scheme 23). Other syntheses of cyclophanes using RCM were

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

• using catalysts 1 and 2 [32]. The tetraallyl derivative, prepared from 142 by an allylation protocol, was subjected to a RRM sequence in the presence of the catalyst 1 to produce propellane derivative 144 containing an oxa-bowl moiety. In another sequence [33], the alkenylation of sulfone 145 gave the

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

• Ramberg–Bäcklund reaction [10] and they can be alkylated via carbanion chemistry. Moreover, they are suitable synthons in Diels–Alder (DA) reactions [11][12][13][14]. In view of various applications of sulfone derivatives, we envisioned a new synthetic strategy based on ring-rearrangement metathesis (RRM

• polycycles by RRM [27][28] as a key step, here we conceive unique examples where cis and trans ring junctions are produced in the RRM reactions. Results and Discussion Strategy Our retrosynthetic strategy to diverse sulfone derivatives is shown in Figure 1. The target sulfone derivatives 1 could be

• synthesized from the functionalized tricyclic sulfone 2 by RRM sequence. The sulfone 2 may be prepared from the dimesylate 3, which in turn, can be assembled from the known anhydride 4 via reduction followed by mesylation of the resulting diol. Compound 4 could be prepared via DA reaction starting with

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

• ) in quantitative yield. Next, bis-sulfone 239 was reacted with 5-bromo-1-pentene (240) in the presence of NaH to give an inseparable mixture of cis and trans-sulfones 241a and 241b, respectively. An RCM sequence of these sulfones in the presence of the G-I (12) catalyst gave cyclophane 243 (51%) and

• %). Similar reaction conditions were employed with the dimeric product 242, to generate the macrocyclic pyridinophane 245 (64%). It is interesting to note that when the same strategy was applied with a benzene analogue, dipentenylation of bis-sulfone 246 gave compounds 247 and 248, which were easily separable

• by column chromatography [174]. Moreover, it was observed that cis-sulfone generates the monomeric cyclophane 249 during the metathesis as confirmed by single crystal X-ray diffraction data while the trans-sulfone gave the dimer 252. Finally, the desulfonylation followed by the hydrogenation sequence

Regioselective synthesis of chiral dimethyl-bis(ethylenedithio)tetrathiafulvalene sulfones

• Flavia Pop and
• Narcis Avarvari

Beilstein J. Org. Chem. 2015, 11, 1105–1111, doi:10.3762/bjoc.11.124

• aerial oxidation of the chiral dithiolates generated from the propionitrile-protected precursors. Both enantiomers crystallize in the orthorhombic chiral space group P212121. They show a boat-type conformation of the TTF moiety, a rather rigid dithiin sulfone ring and the methyl groups in a bisequatorial

• that the oxidation of the outer sulfur atoms into sulfoxide or sulfone should only moderately influence the oxidation potential and thus provide more stable radical cation species. In order to access chiral precursors with controlled stereochemistry we decided to investigate the sulfoxidation of the DM

• elemental analysis, which are all concordant, the definite proof for the sulfone structure of 1 has been provided by single crystal X-ray diffraction analysis. Single crystals of the two enantiomers (S,S)-1 and (R,R)-1 were obtained by slow evaporation from dichloromethane/pentane or dichloromethane

Hetero-Diels–Alder reactions of hetaryl and aryl thioketones with acetylenic dienophiles

• Grzegorz Mlostoń,
• Paulina Grzelak,
• Maciej Mikina,
• Anthony Linden and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2015, 11, 576–582, doi:10.3762/bjoc.11.63

• ESI mass spectra as well as the elemental analysis confirmed the molecular formula C19H16SO6, which corresponds with the structure of the sulfone 6a obtained in 90% yield (Scheme 4). Based on this result, the intermediate product observed in the mixture after 3 h can be proposed as the corresponding

Synthesis of nanodiamond derivatives carrying amino functions and quantification by a modified Kaiser test

• Gerald Jarre,
• Steffen Heyer,
• Elisabeth Memmel,
• Thomas Meinhardt and
• Anke Krueger

Beilstein J. Org. Chem. 2014, 10, 2729–2737, doi:10.3762/bjoc.10.288

• nitrogen and sulfur content. All analytical methods yield comparable results around 0.2 mmol g−1. The further reaction depicted in Scheme 1 enables the formation of an aromatic amine at the 2-position of the ring by the oxidation of the thioethers and subsequent substitution of the sulfone by an amino

• carried out using gaseous ammonia and hence the isolation and purification of the reaction product 11 is very simple. As expected the intensity of the sulfone related IR bands decreases upon amination (but does not vanish as only the SO2Me group in 2-position is exchanged) and new signals corresponding to

• amino functions (1590 and ~3450 cm−1) appear in the spectrum. Furthermore, the sulfur content of the material is reduced to one half of the original value. This shows that the reaction occurs with high efficiency as the remaining sulfur stems from the conserved sulfone group. From these results it is

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

• accomplished through a one-pot Swern oxidation/Wittig olefination protocol followed by hydrogenation to give ketone 127. For further extension of the carbon chain and installation of the trisubstituted double bond, a modified Julia olefination with imidazole sulfone 128 was employed [100][101][102]. Thus

• , reaction of ketone 127 with the lithium anion of sulfone 128 and treatment of the obtained β-hydroxysulfone with SmI2 led to olefin 129 as a 2:1 mixture of E/Z-isomers. After reduction of the tert-butyl ester to the primary alcohol, the E/Z-isomers could be separated chromatographically. Cleavage of the

• accessed from (S)-glycidol. The assembly of the two cyclic building blocks and the Roche ester derived middle fragment under formation of the trans-double bonds would utilize phosphonamide and sulfone anion coupling strategy, respectively. A similar strategy was employed for the assembly of ambruticin S

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

• -benzyloxyhex-5-enal [30], oxidative degradation of aromatics and subsequent lactonization [31], and a two-carbon homologation of an enantiopure C4-building block with a metallated sulfone [32]. A combinatorial biosynthetic approach to D- and L-amicetose has also recently been established by combining different

Synthetic scope and DFT analysis of the chiral binap–gold(I) complex-catalyzed 1,3-dipolar cycloaddition of azlactones with alkenes

• María Martín-Rodríguez,
• Luis M. Castelló,
• Carmen Nájera,
• José M. Sansano,
• Olatz Larrañaga,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2013, 9, 2422–2433, doi:10.3762/bjoc.9.280

• sulfone, trans-1,2-bis(phenylsulfonyl)ethylene, chalcone, crotonaldehyde and cinnamaldehyde at the same reaction conditions [36]. Another drawback was the poor reactivity observed when α-substituted azlactones were used as starting material in the named reaction with NPM. However, the alanine-derived 4

Sequential Diels–Alder/[3,3]-sigmatropic rearrangement reactions of β-nitrostyrene with 3-methyl-1,3-pentadiene

• Peter A. Wade,
• Alma Pipic,
• Matthias Zeller and
• Panagiota Tsetsakos

Beilstein J. Org. Chem. 2013, 9, 2137–2146, doi:10.3762/bjoc.9.251

• . Nitronic ester 26c with a sulfone group (Hammett σp 0.68) [20] at the C(I) position rearranges at 80 °C to 28b whereas analogous nitronic ester 26d with phenacyl group, a less powerful W-group (Hammett σp 0.43) [20], requires 120 °C for rearrangement to 28c [2]. The [3,3]-sigmatropic rearrangement of 26a

• similar bicyclic transition state must be involved [2]. The high reactivity of nitronic ester 30 is presumably due to the combined presence of a C(I) sulfone group and a C(IV) methyl group. In particular, the presence of an electron-attracting substituent at C(I) appears to have a greater accelerative

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• (52) and cytochalasin L-696,474 (78) diverged. For 78, another five steps were necessary to form the isoindolinone 74. After oxidation of the primary alcohol with Dess–Martin periodinane, the obtained aldehyde was coupled with the readily available N-phenyltetrazole sulfone 75 via a Julia–Kocienski

Stereoselective synthesis of the C79–C97 fragment of symbiodinolide

• Hiroyoshi Takamura,
• Takayuki Fujiwara,
• Isao Kadota and
• Daisuke Uemura

Beilstein J. Org. Chem. 2013, 9, 1931–1935, doi:10.3762/bjoc.9.228

• Julia–Kocienski olefination as the coupling reaction. The new retrosynthetic analysis of the C79–C97 fragment 8 is described in Scheme 2. We envisaged that the diol 8 could be synthesized by the Julia–Kocienski olefination [12][13][14] between aldehyde 9 and 1-phenyl-1H-tetrazol-5-yl (PT)-sulfone 10 and

• /Mo(VI) [23] to yield PT-sulfone 23. The TBDPS protecting group of 23 was transformed to the TBS group in two steps to provide PT-sulfone 24. With the coupling precursors aldehyde 20 and PT-sulfones 23 and 24 in hand, we next examined the Julia–Kocienski olefination [12][13][14] of these compounds

• (Table 1). Deprotonation of the PT-sulfone 23 with KHMDS, followed by addition of the aldehyde 20, gave rise to the desired coupling product (E)-25 along with (Z)-25 in 27% combined yield at a 3.5:1 diastereomeric ratio (Table 1, entry 1). When NaHMDS was used as the base, the chemical yield was improved

Ethyl diazoacetate synthesis in flow

• Mariëlle M. E. Delville,
• Jan C. M. van Hest and
• Floris P. J. T. Rutjes

Beilstein J. Org. Chem. 2013, 9, 1813–1818, doi:10.3762/bjoc.9.211

• elimination of the sulfone substituent. Additionally, Ley et al. [19] recently prepared a range of α-hydroxy acids in flow starting from the corresponding amino acids, involving diazotization of the amine to the diazonium salt in a biphasic system. Inspired by Ley’s approach, which is significantly more atom

Dipolar addition to cyclic vinyl sulfones leading to dual conformation tricycles

• Steven S. Y. Wong,
• Michael G. Brant,
• Christopher Barr,
• Allen G. Oliver and
• Jeremy E. Wulff

Beilstein J. Org. Chem. 2013, 9, 1419–1425, doi:10.3762/bjoc.9.159

• coupling partners for these cycloadditions, and in many cases the reaction rate can be enhanced through the addition of a Lewis acid that can coordinate to the carbonyl function, thereby lowering the energy of the olefin LUMO. By contrast, vinyl sulfones (with the exception of simple aryl vinyl sulfone

• species [13][14][15][16][17][18][19][20][21]) have been less-frequently employed as acceptors in 1,3-dipolar cycloadditions [22][23][24][25]. Indeed, we are only aware of a single prior example of a cyclic alkyl vinyl sulfone participating in a dipolar addition with an azomethine ylide [26]. In part, this

• lack of reactivity is due to a poor orbital overlap between the sulfone and olefin functions [27][28][29]; while vinyl sulfones are electrophilic (due to the inductive effects of the sulfone group), their LUMO cannot be as easily perturbed by the addition of a Lewis acid. We previously described the