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

• tetrahydropyran 92 as key intermediate of the synthesis. Oxidation of 92 and heating to 220 ºC resulted in a concurrent selenoxide elimination and Claisen rearrangement to give 93 via intermediate 81. Face-selective Simmons–Smith cyclopropanation, reduction of both carbonyl groups, and chemoselective oxidation of

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

• lactam, together with an acylimine. This was removed under acidic conditions to furnish aldehyde 143. Tebbe olefination [127] installed the missing double bond in 144. Oxymercuration [128] followed by reductive biphasic demercurization [129] furnished the remaining tetrahydropyran ring, yielding 145

• of the amide under basic conditions. Cyclization and Ley–Griffith oxidation [150] took place, followed by deprotection of the alcohol to give spiro-oxindole 176. The formation of the remaining tetrahydropyran was much in line with Fukuyama’s synthesis, utilizing the same oxymercuration/reductive

Glycosylation efficiencies on different solid supports using a hydrogenolysis-labile linker

• Mayeul Collot,
• Steffen Eller,
• Markus Weishaupt and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 97–105, doi:10.3762/bjoc.9.13

• site, which was obtained by removal of the tetrahydropyran (THP) protecting group after coupling to the solid support. A terephthalic chromophore was incorporated into the linker to facilitate the UV detection during HPLC analysis or purification. The linker was directly attached to chloro

Regio- and stereoselective oxidation of unactivated C–H bonds with Rhodococcus rhodochrous

• Elaine O’Reilly,
• Suzanne J. Aitken,
• Gideon Grogan,
• Paul P. Kelly,
• Nicholas J. Turner and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2012, 8, 496–500, doi:10.3762/bjoc.8.56

• isomers in yields of up to 26%. Most interestingly, 2-(4-nitrobenzyloxy)tetrahydrofuran and 2-(4-nitrobenzyloxy)tetrahydropyran were transformed in high yields to the 4-hydroxylated and 5-hydroxylated products, respectively. Keywords: biocatalysis; cytochrome P450; hydroxylation; Rhodococcus rhodochrous

• isomers 4 and 5 as the major products. We initially examined the regioselectivity of the biohydroxylation of tetrahydropyran (THP) derivative 3a and found that an inseparable mixture of hydroxylated products was obtained. Studies have shown that minor alterations in substrate structure can strongly affect

Efficient, highly diastereoselective MS 4 Å-promoted one-pot, three-component synthesis of 2,6-disubstituted-4-tosyloxytetrahydropyrans via Prins cyclization

• Naseem Ahmed and
• Naveen Kumar Konduru

Beilstein J. Org. Chem. 2012, 8, 177–185, doi:10.3762/bjoc.8.19

• yields (72–96%) within short reaction times (20–90 min). The MS 4 Å-promoted synthesis proved to be versatile enough to provide an array of symmetrical and unsymmetrical tetrahydropyran derivatives in economical manner. Furthermore, cleavage of the 4-tosyl group under mild conditions afforded 4

• phorboxazoles (A and B) [1], (−)-centrolobine [2], GEX1A/herboxidiene [3], bryostatins [4], and pheromones [5] (Figure 1). Tetrahydropyran derivatives are also used as materials in photographic films [6] and host–guest chemistry [7]. In particular, 2,4,6-trisubstituted tetrahydropyrans have tremendous

• applications in pharmaceuticals and are widely present in biologically active core structures such as 4-oxygenated, 4-halogenated, 4-sulfonyl- and 4-azido/amidotetrahydropyrans [8][9][10][11]. Various applications of tetrahydropyran derivatives have inspired organic chemists to develop their efficient

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• available heteroatom-substituted propargyl alcohols 10 has been developed by Aponick and co-workers [22]. For the formation of tetrahydropyran analogs 13 and 15, the gold(I)-catalyzed cyclization of monoallylic diols 12 and 14 is an efficient method (Scheme 2) [23][24]. In addition to common organic

• tetrahydropyran 24 were produced by an efficient gold(I) chloride catalyzed cycloisomerization of 2-alkynyl-1,5-diol 22 [28]. A plausible mechanism for the gold-catalyzed transformation of dioxabicyclo[4.2.1]ketal 25 to tetrahydropyran 31 is outlined in Scheme 5. The gold catalyst activates one of the oxygen

Homoallylic amines by reductive inter- and intramolecular coupling of allenes and nitriles

• Peter Wipf and
• Marija D. Manojlovic

Beilstein J. Org. Chem. 2011, 7, 824–830, doi:10.3762/bjoc.7.94

• intermolecular reaction using dimethylzinc in toluene for the transmetalation step. These new experiments produced results similar to the reactions in the presence of zinc chloride (Table 2). Next, we investigated the scope of the intramolecular reaction (Table 4). Both tetrahydrofuran and tetrahydropyran

• equatorial position, placing the electronegative carbamate substituent and the C–O bond in the tetrahydropyran ring into a gauche orientation (Figure 1). We propose a chelated transition state for the formation of 19, 21, and 23 (Scheme 3). After the initial hydrozirconation and transmetallation with

A comparative study of the Au-catalyzed cyclization of hydroxy-substituted allylic alcohols and ethers

• Berenger Biannic,
• Thomas Ghebreghiorgis and
• Aaron Aponick

Beilstein J. Org. Chem. 2011, 7, 802–807, doi:10.3762/bjoc.7.91

• corresponding ethers. Additionally, it is reported that Reaxa QuadraPureTM MPA is an efficient scavenging reagent that halts the reaction progress. Keywords: allylic alcohol; allylic ether; Au-catalyzed; SN2'; tetrahydropyran; Introduction Saturated oxygen heterocycles are found in a wide variety of

The preparation of 3-substituted-1,5-dibromopentanes as precursors to heteracyclohexanes

• Bryan Ringstrand,
• Martin Oltmanns,
• Jeffrey A. Batt,
• Aleksandra Jankowiak,
• Richard P. Denicola and
• Piotr Kaszynski

Beilstein J. Org. Chem. 2011, 7, 386–393, doi:10.3762/bjoc.7.49

• the Wittig olefination of tetrahydro-4H-pyran-4-one range from 35–75% [41][42][43]. The third route (Method 2C) begins from tetrahydropyran-4-carboxylic acid: The acid chloride is reacted with a Grignard reagent, and the resulting ketone reduced under Wolff–Kischner conditions. Typical yields for this

• and 3b are volatile so care should be exercised during evaporation of solvent to ensure maximum yields. Negishi coupling of tetrahydropyran 3e with propylzinc chloride following a general literature method [45] using PEPPSI-IR as the Pd(0) source gave tetrahydropyran 3d in 69% yield. Tetrahydropyran

• prepared exclusively starting from tetrahydro-4H-pyran-4-one in overall yields averaging about 20% (three steps, entries 6 and 7). For comparison Table 2 includes the preparation of dibromides I (R = aryl) involving Heck-type arylation (entry 8) and dibromides I (R = alkyl) starting from tetrahydropyran-4

A novel and efficient method to prepare 2-aryltetrahydrofuran-2-ylphosphonic acids

• Vsevolod V. Komissarov,
• Anatoly M. Kritzyn and
• Jouko J. Vepsäläinen

Beilstein J. Org. Chem. 2010, 6, No. 63, doi:10.3762/bjoc.6.63

• [18]. The length of hydrocarbon chain is also of major importance, since cyclic tetrahydropyran derivatives are not formed in the case of arylpentanones 9a,b under the same conditions as those used for the synthesis of furans 2 (Scheme 3). According to the NMR spectra, the only phosphorus containing

• reaction is the anchimeric assistance of the P=O group. We have also demonstrated that the tetrahydropyran analogs of the title phosphonic acids were not formed under similar conditions. Experimental General remarks. 1H, 13C and 31P NMR spectra were recorded on a Bruker Avance 500 DRX instrument at 500 MHz

Prins fluorination cyclisations: Preparation of 4-fluoro-pyran and -piperidine heterocycles

• Guillaume G. Launay,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2010, 6, No. 41, doi:10.3762/bjoc.6.41

• accelerated under microwave conditions. X-ray crystal structure of syn-5a. X-ray crystal structure of the major bicyclic tetrahydropyran diastereoisomer 9b. X-ray crystal structure of the minor anti-piperidine product 14d. The C–F bond forming Prins reaction leading to 4-fluoropyrans [10]. Ring opening

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

• -THF, adjacent tetrahydrofuran-tetrahydropyran (THF-THP), nonadjacent THF-THP, mono-THP, and acetogenins containing only γ-lactones. These compounds are known to exhibit a broad range of biological activities, the precedent for which came from early South American populations, who used extracts of

• [23][24]. In 1996, Tanaka’s group [25] reported the total synthesis of two possible diastereomers (8′R)- and (8′S)-8a to confirm the stereochemistry of the C-8′ hydroxyl group (Scheme 2). Their synthetic approach started from 1-iodododecane (9) and 5-(tetrahydropyran-2-yloxy)pent-1-yne (10

Methods for the synthesis of polyhydroxylated piperidines by diastereoselective dihydroxylation: Exploitation in the two-directional synthesis of aza-C-linked disaccharide derivatives

• Andrew Kennedy,
• Adam Nelson and
• Alexis Perry

Beilstein J. Org. Chem. 2005, 1, No. 2, doi:10.1186/1860-5397-1-2

• , as we have demonstrated for C-substituted monosaccharide[34] and C-linked disaccharide mimetics,[35][36][37] a wide range of stereochemically diverse aza-C-linked disaccharide analogues could be prepared (see piperidine ring systems A-D and tetrahydropyran ring systems d, d' and e).† († In this

• paper, the final products are labelled according the configuration of the piperidine (A-D) and tetrahydropyran (d, d' or e) ring systems. Note that the ring systems d and d' are enantiomeric.) Results and discussion Synthesis of substrates for model dihydroxylation reactions Methods for the

• by comparison of their 500 MHz 1H NMR spectra with those of the corresponding piperidine and tetrahydropyran model compounds (see Table 2). The outcome of the dihydroxylation of the bis-allylic alcohol 31 depended on the reagent used. Although dihydroxylation anti to the hydroxyl group in the