CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• a superacid [78]. When allylic alcohol 99 was ionized with SbF5 in SO2ClF at −78 °C, the corresponding α-(trifluoromethyl)allylcarbenium ion 100 was formed. The carbons atoms C1 and C2 exhibited very different chemical shifts, δC1 = 157 ppm and δC2 = 290 ppm, which are to be compared to the

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• disubstituted alkene 13 in refluxing diglyme or triglyme at 190 °C (Scheme 7) [23]. The method has been widely used for the difluorocyclopropanation of allylic alcohol derivatives [24], steroids [25], and N-Boc-protected enamides [26]. Boron-substituted difluorocyclopropanes 16 can be also obtained from 12

Benzothiazolium salts as reagents for the deoxygenative perfluoroalkylthiolation of alcohols

• Armin Ariamajd,
• Nils J. Gerwien,
• Benjamin Schwabe,
• Stefan Dix and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2021, 17, 83–88, doi:10.3762/bjoc.17.8

• converted into thioether 3i in 81% yield, although the allylic alcohol 2j was less efficient (13% yield of 3j). The primary aliphatic (pentafluoroethyl) thioether 3k could also be obtained in the reaction between alcohol 2k and BT-SC2F5, however, with this less activated substrate, the thionoester 4k was

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• products. We were forced to conclude that the rather complex structure of 3 was incompatible with the Jacobsen catalytic system. Since the one-step difluorination method (Scheme 1) was unsuccessful, we decided to pursue a stepwise fluorination approach [26][27] (Scheme 2). Thus, the allylic alcohol 7 [28

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• manipulation of the C-4 and C-6 protecting groups gave the secondary allylic alcohol 71, which underwent an epoxidation with mCPBA to give 72. A second sequence of C-4/C-6 protection, manipulation, and oxidation gave the aldehyde 73. The disadvantages of this route include the overall length (13 or 14 steps

• ketals. The protection of the C-4 hydroxy group, hydrolysis of the acetonide, and selective tosylation of the 1° alcohol were prerequisites for the generation of the C-5–C-6 bond. To this end, the reaction of 82 with the ylide generated from trimethylsulfonium iodide gave the allylic alcohol 83. The

• with a 6:1 diastereoselectivity. The Red-Al reduction of 94, protection of the 2° alcohol, and reduction of the enoate to an allylic alcohol were prerequisites for the stereoselective 2,3-sigmatropic selenoxide rearrangement to generate 95. Further protecting group manipulation and Johnson–Lemieux

Azidophosphonium salt-directed chemoselective synthesis of (E)/(Z)-cinnamyl-1H-triazoles and regiospecific access to bromomethylcoumarins from Morita–Baylis–Hillman adducts

• Soundararajan Karthikeyan,
• Radha Krishnan Shobana,
• Kamarajapurathu Raju Subimol,
• J. Helen Ratna Monica and
• Ayyanoth Karthik Krishna Kumar

Beilstein J. Org. Chem. 2020, 16, 1579–1587, doi:10.3762/bjoc.16.130

• attack on the AzPS by the allylic alcohol of the MBH adduct Ia. Subsequently, the azide ion undergoes a nucleophilic attack on the allylic carbon atom of the oxyphosphonium intermediate IIa and generates the 2-azidoalkene IIIa. Interestingly, the consecutive nucleophilic attack by the azido ion smoothly

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• metathesis between the formed propargylic derivative and an appropriate allylic alcohol promoted by the Grubbs second-generation catalyst, finally produced in high yield (85%) the intermediate diene 6, as an essential building block for the southern fragment (Scheme 9). Several other asymmetric transition

• -metathesis, and a one-pot, two-step stereoselective conjugated allylic alcohol substitution (Scheme 26). It should be emphasized that in this convergent synthesis of (−)-exiguolide, the authors achieved a rigorous stereocontrol of both the exocyclic and endocyclic double bond geometries, as well as the

• propargylic derivative and the allylic alcohol in the synthesis of the southern fragment of des-epoxy-amphidinolide N. Synthetic route to amphidinolide N (6a). Synthesis of the stereoisomeric precursors of amphidinolide V (7a and 7b) through alkyne ring-closing metathesis and enyne metathesis as the key steps

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• chemoselective carbonyl reduction to obtain the corresponding allylic alcohol derivative 36 was achieved in 92% under Luche reduction conditions employing NaBH4/CeCl3 in MeOH/DCM, resulting in the selective synthesis of the syn-alcohol, as a consequence of the formation of the equatorial alcohol favored by

Chiral terpene auxiliaries V: Synthesis of new chiral γ-hydroxyphosphine oxides derived from α-pinene

• Anna Kmieciak and
• Marek P. Krzemiński

Beilstein J. Org. Chem. 2019, 15, 2493–2499, doi:10.3762/bjoc.15.242

• sodium carbonate to give (+)-3-methyleneverbanone (5) in 57% yield from 3. α,β-Unsaturated ketone 5 was exclusively reduced to allylic alcohol (1R,2R,4S,5R)-3-methyleneneoisoverbanol (6), using the Luche method [24]. 1,2-Reduction of enone 5 was achieved with sodium borohydride in the presence of cerium

• (III) chloride in methanol in 88% yield (Scheme 1). The synthesis of allylic alcohol 11, a regioisomer of 6, started again from (1R)-α-pinene (1, Scheme 2). Hydroboration of (1R)-α-pinene with borane–dimethyl sulfide adduct (BMS) and crystallization of the product diisopinocampheylborane (dIpc2BH, 84

• to the allylic alcohol. Thus, Claisen condensation of 8 with ethyl formate gave β-hydroxyenone 9, which was subjected to transaldolization with formaldehyde producing the corresponding 4-methyleneisopinocamphone (10) in 83% yield. Luche reduction of the latter compound provided (1R,2R,3R,5R)-4

Synthesis of acremines A, B and F and studies on the bisacremines

• Nils Winter and
• Dirk Trauner

Beilstein J. Org. Chem. 2019, 15, 2271–2276, doi:10.3762/bjoc.15.219

• later stage the optical purity could be improved (see below). Diol protection gave dioxolane 14, which underwent Saegusa oxidation to afford enone 15. Subsequent α-iodination gave access to α-iodoenone 16, which could be stereoselectively reduced under Corey–Itsuno conditions to yield allylic alcohol 17

• biogenetic precursor of acremines A (1) and B (2), we wanted to access these antifungal derivatives through selective oxidations. Indeed, treatment of 5 with IBX preferentially oxidized the C1-allylic alcohol, giving 1 in respectable yield. Prolonged treatment (9 h) of 5 with a large excess of IBX oxidized

• elimination of the tertiary allylic alcohol to the unstable triene 6. As we were able to observe elimination as well as acetate incorporation into the molecule the desired cation was clearly formed under a variety of conditions. Nevertheless, none of these could affect the desired cyclization. Attempts to

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• cationic polyene cyclization, transition-metal- or photocatalyst-mediated radical polyene cyclization [72]. The key to such transformation is to install a proper initiator within the substrate such as an allylic alcohol, an acetal, an aziridine, an N-acetal, a hydroxylactam, or a 1,3-dicarbonyl moiety. van

• and reacted with 3,3-dimethylallyl bromide, followed by changing the protecting group from MOM ether to methyl ether to provide olefin 86. Allylic oxidation of 86 followed by nucleophilic bromination of the resulting allylic alcohol gave bromide 87. Dianion displacement of the bromide of 87 gave ester

Synthesis and biological investigation of (+)-3-hydroxymethylartemisinin

• Toni Smeilus,
• Farnoush Mousavizadeh,
• Johannes Krieger,
• Xingzhao Tu,
• Marcel Kaiser and
• Athanassios Giannis

Beilstein J. Org. Chem. 2019, 15, 567–570, doi:10.3762/bjoc.15.51

• -hydroxymethylartemisinin (2, Figure 1). Results and Discussion Our synthesis (Scheme 1) started from the known and readily available aldehyde 3 [14] which was treated with the organolithium species obtained from derivative 4 [15] and n-BuLi to yield derivative 5. The latter afforded allylic alcohol 6 after reduction of

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• (Scheme 11) [60]. Sharpless epoxidation of the allylic alcohol 48 gave a 46:11:33 mixture of (S)-48, (3R,4S)-49 and (2R,3R)-50. While (S)-48 is a product of kinetic resolution, the formation of (2R,3R)-50 results from the intramolecular opening of the oxirane ring in (3R,4S)-49. After chromatographic

6’-Fluoro[4.3.0]bicyclo nucleic acid: synthesis, biophysical properties and molecular dynamics simulations

• Sibylle Frei,
• Andrei Istrate and
• Christian J. Leumann

Beilstein J. Org. Chem. 2018, 14, 3088–3097, doi:10.3762/bjoc.14.288

• . The relative configuration at C(5’) could be assigned by 1H,1H-ROESY experiments (Supporting Information File 1). Tritylation of allylic alcohol 8 with 4,4-dimethoxytrityl chloride (DMTr-Cl) afforded intermediate 9 which was subsequently phosphitylated with 2-cyanoethyl N,N

• of the nucleobase was partially removed. As a consequence an additional benzoylation step was needed to obtain the allylic alcohol 14 in high yields. Verification of the configuration at C(5’) was again accomplished by 1H,1H-ROESY experiments (Supporting Information File 1). Tritylation of the

A tutorial review of stereoretentive olefin metathesis based on ruthenium dithiolate catalysts

• Daniel S. Müller,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2018, 14, 2999–3010, doi:10.3762/bjoc.14.279

• catalyst loading Scheme 2b) [2]. Allylic alcohol (7) reacted cleanly with norbornene (1), albeit with lower stereoretention (8; 88:12 Z/E) [17]. Cyclobutenes (e.g., 9) and cyclopropenes also delivered the corresponding products with good yields and excellent selectivity (Scheme 2b) [17]. It should also be

• allylic alcohol. Allylic oxygen atoms often have an activating effect in metathesis [23]. This was confirmed by Hoveyda for stereoretentive metathesis by exposing homoallylic alcohol (product Z-45) and alkyl containing metathesis partners (products Z-46 and E-47) to standard reaction conditions [22]. All

• the reactions were inefficient emphasizing the importance of an allylic alcohol, ether or acetate group. 7 The in situ catalyst synthesis strategy Very recently, our group developed an in situ synthesis of dithiolate catalysts with the aim to avoid tedious isolation of Ru-dithiolate catalysts and to

Photocatalyic Appel reaction enabled by copper-based complexes in continuous flow

• Clémentine Minozzi,
• Jean-Christophe Grenier-Petel,
• Shawn Parisien-Collette and
• Shawn K. Collins

Beilstein J. Org. Chem. 2018, 14, 2730–2736, doi:10.3762/bjoc.14.251

• corresponding dibromide could be formed from 1,9-nonadiol (6) in quantitative yield (99%, Table 1, entry 4). A sulfur-containing alcohol 7 was smoothly converted to its bromide in 99% yield (Table 1, entry 5). An allylic alcohol 8 having a cis-olefin underwent alcohol-to-halide conversion in 89% yield and was

• % yield, Table 3, entry 2). A methyl ester 5, allylic alcohol 8 and racemic secondary alcohol 9 could all undergo conversion to their corresponding bromides in 240 min using the continuous flow protocol (Table 3, entries 3 to 5). The continuous flow protocol was also applicable to the synthesis of

Stereoselective total synthesis and structural revision of the diacetylenic diol natural products strongylodiols H and I

• Pamarthi Gangadhar,
• Sayini Ramakrishna,
• Ponneri Venkateswarlu and
• Pabbaraja Srihari

Beilstein J. Org. Chem. 2018, 14, 2313–2320, doi:10.3762/bjoc.14.206

• -selective reduction [25] of alkyne 20 was easily achieved with sodium bis(2-methoxyethoxy)aluminum hydride (Red-Al) as a hydride-transfer reagent to furnish the corresponding (E)-allylic alcohol 23. A Swern oxidation of 23 provided the corresponding aldehyde which was subjected to an addition reaction with

Heterogeneous acidic catalysts for the tetrahydropyranylation of alcohols and phenols in green ethereal solvents

• Ugo Azzena,
• Massimo Carraro,
• Gloria Modugno,
• Luisa Pisano and
• Luigi Urtis

Beilstein J. Org. Chem. 2018, 14, 1655–1659, doi:10.3762/bjoc.14.141

• isomerisation of the acid-sensitive allylic alcohol 1j [34]. To stress the usefulness of a tetrahydropyranylation reaction performed in a green ethereal solvent and in the presence of a heterogeneous acidic catalyst, we realized two one-pot procedures employing either 2-MeTHF or CPME as a solvent. Accordingly

Biocatalytic synthesis of the Green Note trans-2-hexenal in a continuous-flow microreactor

• Morten M. C. H. van Schie,
• Tiago Pedroso de Almeida,
• Gabriele Laudadio,
• Florian Tieves,
• Elena Fernández-Fueyo,
• Timothy Noël,
• Isabel W. C. E. Arends and
• Frank Hollmann

Beilstein J. Org. Chem. 2018, 14, 697–703, doi:10.3762/bjoc.14.58

• beverages. One attractive access to trans-2-hex-2-enal is the oxidation of the corresponding allylic alcohol to the aldehyde. Though at first sight an oxidation of primary alcohols to the corresponding aldehydes does not appear to be a major challenge, the methods of the state-of-the-art are mostly plagued

Novel amide-functionalized chloramphenicol base bifunctional organocatalysts for enantioselective alcoholysis of meso-cyclic anhydrides

• Lingjun Xu,
• Shuwen Han,
• Linjie Yan,
• Haifeng Wang,
• Haihui Peng and
• Fener Chen

Beilstein J. Org. Chem. 2018, 14, 309–317, doi:10.3762/bjoc.14.19

• different alcohols (Table 3). Excellent yields with high enantioselectivities were obtained in all cases. The sterically more bulky 2-propanol worked well in this reaction. Allylic alcohol, benzyl alcohol and cinnamyl alcohol were also well compatible in this bifunctional organocatalysis conditions to

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis

• Raju Cheerlavancha,
• Ahmed Ahmed,
• Yun Cheuk Leung,
• Aggie Lawer,
• Qing-Quan Liu,
• Marina Cagnes,
• Hee-Chan Jang,
• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228

• fluoride, then deoxyfluorination). We therefore sought to apply O’Hagan’s method to the target 6b (Scheme 3, boxed). Accordingly, the enantiopure allylic alcohol 27 [35] was extended through a cross-metathesis reaction to deliver the disubstituted alkene 30 (Scheme 3). Compound 30 became the substrate for

Mechanically induced oxidation of alcohols to aldehydes and ketones in ambient air: Revisiting TEMPO-assisted oxidations

• Andrea Porcheddu,
• Evelina Colacino,
• Giancarlo Cravotto,
• Francesco Delogu and
• Lidia De Luca

Beilstein J. Org. Chem. 2017, 13, 2049–2055, doi:10.3762/bjoc.13.202

• oxidative procedure was also applied to allylic alcohol derivatives. Cinnamyl alcohol (1m) was transformed into the corresponding α,β-unsaturated aldehyde in an excellent yield (96%) and with the stereochemical retention of the double bond. Encouraged by these promising results, we attempted to oxidise

Pd(OAc)₂/Ph₃P-catalyzed dimerization of isoprene and synthesis of monoterpenic heterocycles

• Dominik Kellner,
• Maximilian Weger,
• Andrea Gini and
• Olga García Mancheño

Beilstein J. Org. Chem. 2017, 13, 1807–1815, doi:10.3762/bjoc.13.175

• the tail-to-tail linkage [15][29]. Moreover, the naturally occurring head-to-tail 2-HT dimers, myrcene and ocimene, can be obtained in allylic alcohol when employing Pd(NO3)2/Ph3P/KOPh as catalytic system [30]. The head-to-head 2-HH dimer could also be prepared as major isomer under catalysis with the

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