Unconventional application of the Mitsunobu reaction: Selective flavonolignan dehydration yielding hydnocarpins

• Guozheng Huang,
• Simon Schramm,
• Jörg Heilmann,
• David Biedermann,
• Vladimír Křen and
• Michael Decker

Beilstein J. Org. Chem. 2016, 12, 662–669, doi:10.3762/bjoc.12.66

• observed yielding several products (Scheme 3). Since the cyclic hemiacetal structure (of a diketone) represents the only functional difference to the other flavanonols employed, it is obviously unstable under the conditions used. Conclusion To our knowledge, this is the first semi-synthesis of optically

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• a more rigid pre-TS assembly. Reduction of the hemiacetal 210, afforded product 212 in 90% yield and >99% ee. A mechanism for the above reaction, where the s-cis enamine attacks the electrophilic double bond of 2-hydroxynitrostyrene, was proposed (Scheme 66). In 2012, Wang and co-workers developed a

Synthesis of D-fructose-derived spirocyclic 2-substituted-2-oxazoline ribosides

• Madhuri Vangala and
• Ganesh P. Shinde

Beilstein J. Org. Chem. 2015, 11, 2289–2296, doi:10.3762/bjoc.11.249

• with nitrile solvents, providing a transient α,β-glycosyl nitrilium species that could produce an oxazolinium intermediate through the participation of the vicinal oxygen atom. In 1981, Pavia and co-workers proposed the formation of uncharacterized oxazolinium from glycosyl hemiacetal in acetonitrile

Structure and conformational analysis of spiroketals from 6-O-methyl-9(E)-hydroxyiminoerythronolide A

• Ana Čikoš,
• Irena Ćaleta,
• Dinko Žiher,
• Mark B. Vine,
• Ivaylo J. Elenkov,
• Marko Dukši,
• Dubravka Gembarovski,
• Marina Ilijaš,
• Snježana Dragojević,
• Ivica Malnar and
• Sulejman Alihodžić

Beilstein J. Org. Chem. 2015, 11, 1447–1457, doi:10.3762/bjoc.11.157

• ][46]. Most recently, in the latest revision of the reaction pathway Hassanzadeh et al. showed that this macrolide spiroketal in acid media exists in equilibrium with the 9,12-hemiacetal of erythromycin A [47]. The closely related antibiotic clarithromycin (structurally related to our starting aglycon

• 1) in acid medium does not degrade to the spiroketal but instead loses the cladinose sugar [48][49]. The degradation process terminates with decladinosyl clarithromycin in equilibrium with the 9,12-hemiacetal decladinosyl clarithromycin [50]. Unlike the acid degradation product anhydroerythromycin A

Synthesis of novel N-cyclopentenyl-lactams using the Aubé reaction

• Madhuri V. Shinde,
• Rohini S. Ople,
• Ekta Sangtani,
• Rajesh Gonnade and
• D. Srinivasa Reddy

Beilstein J. Org. Chem. 2015, 11, 1060–1067, doi:10.3762/bjoc.11.119

• between an azido alcohol and a ketone to provide lactams through an in situ-generated hemiacetal as a temporary tether. This helps the azide addition in an intramolecular fashion, followed by ring expansion (Scheme 1) [1][2][3][4]. Recently, we applied this reaction for the synthesis of sugar–lactam

Gold-catalyzed formation of pyrrolo- and indolo-oxazin-1-one derivatives: The key structure of some marine natural products

• Sultan Taskaya,
• Nurettin Menges and
• Metin Balci

Beilstein J. Org. Chem. 2015, 11, 897–905, doi:10.3762/bjoc.11.101

• addition of a carboxy group to the alkyne functionality to give methylene-oxazin-1-one derivative 7 (or 18) (Scheme 6). In the next step, the double bond is activated by π-coordination of the gold(I) catalyst. This enables a nucleophilic attack by the alcohol oxygen, which affords hemiacetal 47. In case of

• -one derivatives. Some of the exo-cyclic double bonds underwent isomerization to endo-cyclic compounds upon treatment with TFA, while some did not. DFT studies supported our findings. Moreover, cyclization reactions in the presence of alcohol formed hemiacetal derivatives after gold-catalyzed cascade

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• method to synthesize protected syn-1,3-diols by performing intramolecular conjugate additions to a series of α,β-unsaturated esters and amides [71] (Scheme 8). Upon treatment of 24 with KHMDS and benzyaldehyde, a hemiacetal forms which provides the alkoxide nucleophile for the DCA reaction. These

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

• relative to aldehyde. It is suggested that the reaction proceeds through the formation of hemiacetal from alcohol and aldehyde, which is oxidized by iodine to ester 131 or 134. In the coupling of two alcohols, one of them is initially oxidized to aldehyde by iodine. In the oxidative coupling of aldehydes

Synthesis and immunological evaluation of protein conjugates of Neisseria meningitidis X capsular polysaccharide fragments

• Laura Morelli,
• Damiano Cancogni,
• Marta Tontini,
• Alberto Nilo,
• Sara Filippini,
• Paolo Costantino,
• Maria Rosaria Romano,
• Francesco Berti,
• Roberto Adamo and
• Luigi Lay

Beilstein J. Org. Chem. 2014, 10, 2367–2376, doi:10.3762/bjoc.10.247

• -hemiacetal 6 in 81% yield (Scheme 1). The formation of the α anomer was confirmed by the doublet of H-1 at 5.23 ppm in the 1H NMR spectrum with the typical value of 1J1,2 = 3.5 Hz, and the appearance of the C-1 signal at 92.0 ppm in the 13C NMR spectrum (see Supporting Information File 1). Most importantly

• , when the hemiacetal 6 was treated with salicylchlorophosphite in pyridine at room temperature the α-H-phosphonate 7 was obtained as a single anomer in only 2 h in 62% yield. We reasoned that the occurrence of an intramolecular hydrogen bond involving the acetamido group could be the main responsible

• approaches are improved safety characteristics, enhanced rates of heat and mass transfer, simplicity and robustness in scale-up and easiness in handling the instrumentation [30][31][32][33]. For the synthesis of compound 7, two distinct solutions containing the hemiacetal 6 in pyridine and

Photorelease of phosphates: Mild methods for protecting phosphate derivatives

• Sanjeewa N. Senadheera,
• Abraham L. Yousef and
• Richard S. Givens

Beilstein J. Org. Chem. 2014, 10, 2038–2054, doi:10.3762/bjoc.10.212

• among the slowest for a photochemical heterolysis (e.g., usually not larger than μsec time constants) due to mechanistic constraints imposed by the rate determining step of a ground state hemiacetal hydrolysis, generated photochemically, that releases the substrate. Furthermore, the o-NB PPG chromophore

Reaction of selected carbohydrate aldehydes with benzylmagnesium halides: benzyl versus o-tolyl rearrangement

• Maroš Bella,
• Bohumil Steiner,
• Vratislav Langer and
• Miroslav Koóš

Beilstein J. Org. Chem. 2014, 10, 1942–1950, doi:10.3762/bjoc.10.202

• simple alkyl or aryl branched-chain sugars involves the addition of Grignard reagents. In this regard, a wide variety of Grignard reagents have been added to the free or masked (as hemiacetal) carbonyl functionalities present in the molecule of a suitable fully O-protected saccharide, thereby making

Chemistry of polyhalogenated nitrobutadienes, 14: Efficient synthesis of functionalized (Z)-2-allylidenethiazolidin-4-ones

• Viktor A. Zapol’skii,
• Jan C. Namyslo,
• Mimoza Gjikaj and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2014, 10, 1638–1644, doi:10.3762/bjoc.10.170

• . Subsequently, the thus introduced amino group attacks the carbonyl carbon of the mercaptoacetate moiety. This ring closure affords the temporary imide hemiacetal B which is then stabilized upon elimination of the corresponding alcohol to give the desired thiazolidin-4-ones 7–18 (Scheme 3). Furthermore, in

Efficient routes toward the synthesis of the D-rhamno-trisaccharide related to the A-band polysaccharide of Pseudomonas aeruginosa

• Aritra Chaudhury,
• Sajal K. Maity and
• Rina Ghosh

Beilstein J. Org. Chem. 2014, 10, 1488–1494, doi:10.3762/bjoc.10.153

• the end of the deoxygenation step. Thus, the intermediate compounds 3a and 4 were used without purification by column chromatography. Compound 2 was deoxygenated to its rhamnosyl counterpart 2a in a high yield (88%). Next, the thioglycoside was hydrolyzed to the hemiacetal 2b with trichloroisocyanuric

Pd/C-catalyzed aerobic oxidative esterification of alcohols and aldehydes: a highly efficient microwave-assisted green protocol

• Marina Caporaso,
• Giancarlo Cravotto,
• Spyros Georgakopoulos,
• George Heropoulos,
• Katia Martina and
• Silvia Tagliapietra

Beilstein J. Org. Chem. 2014, 10, 1454–1461, doi:10.3762/bjoc.10.149

• [20]. The proposed reaction pathway (Scheme 1) is based on the oxidation of the alcohol to an aldehyde, followed by conversion to the respective hemiacetal, which is further oxidized to the corresponding ester. Relatively little work has been carried out on this so far, besides some remarkable results

Molecular architecture with carbohydrate functionalized β-peptides adopting 3₁₄-helical conformation

• Nitin J. Pawar,
• Navdeep S. Sidhu,
• George M. Sheldrick,
• Dilip D. Dhavale and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2014, 10, 948–955, doi:10.3762/bjoc.10.93

• . For the galactosyl β-peptides, the hemiacetal form of the sugar units might be in equilibrium with the aldehyde form. The non-protected sugar units 4 seem to adopt better to the 314-helix conformation. Nevertheless, the galactosyl β-peptide 3 with 1,2-3,4-acetonide protection also seems sterically not

• unprotected β-glycopeptides since the equilibrium between hemiacetal and open-chain aldehyde form also does not interfere with the 314-helix secondary structure and allows further functionalization with saccharides, e.g., by reductive amination. Sketch of right-handed β-peptide helix functionalized in every

Synthesis of (2S,3R)-3-amino-2-hydroxydecanoic acid and its enantiomer: a non-proteinogenic amino acid segment of the linear pentapeptide microginin

• Rajendra S. Rohokale and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2014, 10, 667–671, doi:10.3762/bjoc.10.59

• methanol:ethyl acetate (3:2) at balloon pressure gave 4-heptyl-L-threose derivative 5a as a viscous oil in 99% yield [33]. Removal of the 1,2-acetonide group with TFA–water in 5a provided an anomeric mixture of the hemiacetal, which was directly subjected to oxidative cleavage by using sodium metaperiodate in

• hemiacetal with NaIO4 and reduction with NaBH4 gave triol 6b,which was monosilylated with TBDPSCl to give 7b. Conversion of the secondary hydroxy group in 7b to azide 8b according to the Mitsunobu protocol, and deprotection followed by oxidation of the primary hydroxy group gave azido acid 10b. Finally

New sesquiterpene hydroquinones from the Caribbean sponge Aka coralliphagum

• Qun Göthel and
• Matthias Köck

Beilstein J. Org. Chem. 2014, 10, 613–621, doi:10.3762/bjoc.10.52

• trisubstituted olefinic bonds (δ 121.7, δ 125.7, δ 131.9, δ 134.9) and a hemiacetal carbon (δ 96.2) at one terminus which differed from the acyclic side chain in 1 and 2. The remaining six carbon signals in the downfield region of the 13C NMR spectrum belonged to the tetrasubstituted aromatic ring system. In

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• ). Interestingly, the ketones 7a–d existed in an equilibrium with their cyclic hemiacetal tautomers as shown in Scheme 2. The predominant keto form possessed a clear singlet around 205–210 ppm for the quaternary carbonyl carbon and the furan form was indicated by two weak signals at 105–110 ppm for the hemiacetal

• (75%, entry 12). Synthesis of a trans-piperidinol B We initially investigated the diastereoselectivity of the reduction of the secondary benzylamino ketone 14a, which was synthesized from hydroxyketone 7a through Cbz-cleavage and basic work up (Scheme 6 and Table 4). According to 1H NMR the hemiacetal

Total synthesis of the endogenous inflammation resolving lipid resolvin D2 using a common lynchpin

• John Li,
• May May Leong,
• Alastair Stewart and
• Mark A. Rizzacasa

Beilstein J. Org. Chem. 2013, 9, 2762–2766, doi:10.3762/bjoc.9.310

• using the common linchpin phosphorus ylide derived from phosphonium salt 6 [21][22] and each of the homochiral aldehydes 5 and 7 [9]. Synthesis of vinyl iodide 4 The synthesis of fragment 4 began with the production of the aldehyde 7 as shown in Scheme 2. A Wittig reaction between hemiacetal 8 [23] and

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• convenient sources of trifluoromethyl anion [75]. H. Amii et al. reported on the use of an O-silylated hemiaminal as a cross-coupling partner for aromatic trifluoromethylation with a copper iodide/1,10-phenanthroline catalytic system [76]. Compound B was prepared from commercially available hemiacetal of

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

• well tolerated for the reaction using γ-hydroxy-α,β-enones. Although the presence of chirality at the δ-position allows for diastereoselective intramolecular oxy-Michael addition of hemiacetal-derived alkoxides into α,β-unsaturated esters, the extension of this reaction to ketones was not successful

Re₂O₇-catalyzed reaction of hemiacetals and aldehydes with O-, S-, and C-nucleophiles

• Wantanee Sittiwong,
• Michael W. Richardson,
• Charles E. Schiaffo,
• Thomas J. Fisher and
• Patrick H. Dussault

Beilstein J. Org. Chem. 2013, 9, 1526–1532, doi:10.3762/bjoc.9.174

• a Brønsted acid. Keywords: allylation; hemiacetal; O,O-acetal; O,S-thioacetal; peroxyacetal; Re2O7; S,S-acetal; Introduction The synthetically important conversions of hemiacetals to acetals, thioacetals, or homoallyl ethers are typically achieved through activation of the substrate with a strong

• oxybisacetals (Table 3). As will be described later, these apparent byproducts proved to be competent substrates for acetal formation. We next attempted to maximize the yield of acetal based upon alcohol (Table 4). Good yields were obtained at a 1:1 ratio of alcohol to hemiacetal and yields did not vary

• significantly with the rate of addition of hemiacetal. This latter observation was initially surprising given the rapidity of hemiacetal dimerization (vide supra). However, we soon realized that the bisacetal ether 11 (Table 4, entry 4) was a remarkably effective substrate. In fact, the reaction of phenethyl

Copper-catalyzed aerobic aliphatic C–H oxygenation with hydroperoxides

• Pei Chui Too,
• Ya Lin Tnay and
• Shunsuke Chiba

Beilstein J. Org. Chem. 2013, 9, 1217–1225, doi:10.3762/bjoc.9.138

• presence of Et3N (2 equiv) in DMF, the reaction proceeded at room temperature for 17 h to afford C–H oxygenation products, cyclic hemiacetal 2a and 1,4-diol 3a in 49% and 8% yields, respectively (Table 1, entry 1). It was found that addition of nitrogen ligands such as 2,2’-bipyridine and 1,10

• molecular O2 to give peroxy radical III. Probably further reaction of III with Cu(I) species gives Cu(II)-peroxide IV, which undergoes fragmentation to give aldehyde V [16][17][18], which in turn cyclizes to afford hemiacetal 2a. Protonation of Cu(II)-peroxide IV followed by the reduction of the resulting

Appel-reagent-mediated transformation of glycosyl hemiacetal derivatives into thioglycosides and glycosyl thiols

• Tamashree Ghosh,
• Abhishek Santra and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2013, 9, 974–982, doi:10.3762/bjoc.9.112

• Tamashree Ghosh Abhishek Santra Anup Kumar Misra Bose Institute, Division of Molecular Medicine, P-1/12, C.I.T. Scheme VII-M, Kolkata-700054, India, Fax: 91-33-2355 3886 10.3762/bjoc.9.112 Abstract A series of glycosyl hemiacetal derivatives have been transformed into thioglycosides and glycosyl

• carbonotrithioate. The reaction conditions are reasonably simple and yields were very good. Keywords: Appel reagent; carbon tetrabromide; glycosyl hemiacetal; glycosyl thiol; thioglycoside; triphenylphosphine; Introduction Thioglycosides (1-thiosugar) are widely used glycosyl donors in glycosylation reactions [1

• , fluoride, bromide, hemiacetal, etc.) and hence the thio functionality is often used as a temporary anomeric protecting group. Thioglycosides can act as a glycosyl donor as well as glycosyl acceptor depending on the reaction conditions (orthogonal glycosylations) [11][12]. Due to their stability towards

A new intermediate in the Prins reaction

• Shinichi Yamabe,
• Takeshi Fukuda and
• Shoko Yamazaki

Beilstein J. Org. Chem. 2013, 9, 476–485, doi:10.3762/bjoc.9.51

• . From the 1,3-diol, a bimolecular elimination (TS2) leads to the allylic alcohol as the first channel. In the second channel, the 1,3-diol was converted via TS3 into an unprecedented hemiacetal intermediate, HO–CH2–O–CH(R)–CH2–CH2–OH. This intermediate undergoes ring closure (TS4), affording the 1,3

• . Dynamical calculations of a classical trajectory using the atom-centered density matrix propagation molecular dynamics model on the four TSs were carried out, and results of IRC calculations were confirmed by them. Keywords: DFT calculations; hemiacetal intermediate; hydrogen bond; Prins reaction

• allylic alcohol, 2-buten-1-ol, here called ene-ol(Me). The other is TS3(Me) leading to an intermediate, not included in Scheme 5. This species, 3-(hydroxymethoxy)-1-butanol, called here ether(Me), has an ether moiety and is a hemiacetal. Generally, these are formed by the formal addition of an alcohol to