Base-promoted isomerization of CF₃-containing allylic alcohols to the corresponding saturated ketones under metal-free conditions

• Yoko Hamada,
• Tomoko Kawasaki-Takasuka and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2017, 13, 1507–1512, doi:10.3762/bjoc.13.149

• the alkoxide 3F-Oa. In the case of 1Fb, the phenyl group worked nicely for increase of the energetic preference of 3F-Cb to 3F-Ob of about 7.9 kcal/mol. For the allylic alcohol 2Fb (R = Ph), although the ΔΔE value was small, the carbanionic species 4F-Cb was calculated to be more (or at least almost

• excess amount of CsF, the resultant product (E)-2Fb was further converted in situ to the corresponding saturated ketone (E)-5b (R = Ph). Confirmation of this process was performed by the action of DBU, resulting in 95% conversion of the starting allylic alcohol (E)-2Fb [14]. Quite recently [15], the same

• shown in Table 2, we at first checked a type of bases suitable for this isomerization in THF under reflux for 3 h. Although Et3N was appropriate in the case of isomerization of propargylic alcohols 1F [1], this was not the case for the allylic alcohol (E)-6a, forming the desired 7a only in a trace

Total synthesis of elansolids B1 and B2

• Liang-Liang Wang and
• Andreas Kirschning

Beilstein J. Org. Chem. 2017, 13, 1280–1287, doi:10.3762/bjoc.13.124

• intramolecular Diels–Alder (IMDA) cycloaddition as key step to construct the tetrahydroindane unit (Scheme 1) [7]. An enone, derived from allylic alcohol 8 served as precursor to yield tetrahydroindane 9 with excellent diastereocontrol at −25 °C. The major drawback of our first total synthesis of elansolid B1 (2

Phosphazene-catalyzed desymmetrization of cyclohexadienones by dithiane addition

• Matthew A. Horwitz,
• Elisabetta Massolo and
• Jeffrey S. Johnson

Beilstein J. Org. Chem. 2017, 13, 762–767, doi:10.3762/bjoc.13.75

• nucleophile. Mild reaction conditions allow the formation of diversely functionalized fused bicyclic lactones. The products participate in facially selective additions from the convex surface, leading to allylic alcohol derivatives. Keywords: conjugate addition; cyclohexadienones; dearomatization

• for general concern about the feasibility of easily reaching the target substructure. In order to minimize the observed side reactions, we sought to apply the deprotection conditions to allylic alcohol 3. However, both the use of NBS and HgCl2/HgO were unsuccessful. We further investigated the removal

Studies directed toward the exploitation of vicinal diols in the synthesis of (+)-nebivolol intermediates

• Runjun Devi and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2017, 13, 571–578, doi:10.3762/bjoc.13.56

•  1, method 1). For this purpose, the necessary epoxide 6 could be obtained from the parent E-allylic alcohol through Sharpless asymmetric epoxidation (SAE) [11]. However, the corresponding parent Z-allylic alcohol appears to be not suitable to provide 7 under SAE conditions [20]. This has eliminated

• the resulting crude aldehyde with Ph3P=CHCO2Et provided (E)-α,β-unsaturated ester 12 (80% over two steps). A further DIBAL-H (2.5 equiv, 0 °C) reduction of 12 delivered (E)-allylic alcohol 13 (90%) which was then dihydroxylated under Upjohn conditions to obtain triol (±)-14 (92%). With access to

Revaluation of biomass-derived furfuryl alcohol derivatives for the synthesis of carbocyclic nucleoside phosphonate analogues

• Bemba Sidi Mohamed,
• Christian Périgaud and
• Christophe Mathé

Beilstein J. Org. Chem. 2017, 13, 251–256, doi:10.3762/bjoc.13.28

• observations are in agreement with a 1,3-allylic transposition under acidic conditions. Additionally, in order to confirm the stereochemistry of the allylic alcohol in position 3’, a NOESY correlation experiment was accomplished with compound (+/−)-16 (Figure 3). We have observed a correlation between proton

First DMAP-mediated direct conversion of Morita–Baylis–Hillman alcohols into γ-ketoallylphosphonates: Synthesis of γ-aminoallylphosphonates

• Marwa Ayadi,
• Haitham Elleuch,
• Emmanuel Vrancken and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2906–2915, doi:10.3762/bjoc.12.290

• , entries 1–5), as well as five-membered cyclic MBH alcohol 1f (Table 2, entry 6). A putative reaction pathway could start from a first β-conjugate addition of DMAP onto the allylic alcohol 1a (i), followed by the elimination of the hydroxide ion that would afford the intermediate I (ii). Similarly, a

Synthesis of polyhydroxylated decalins via two consecutive one-pot reactions: 1,4-addition/aldol reaction followed by RCM/syn-dihydroxylation

• Michał Malik and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2016, 12, 2602–2608, doi:10.3762/bjoc.12.255

• most likely unstable, we decided to deprotect 20 directly before the planned one-pot procedure and use it without purification. In order to obtain (R)-10, we decided to inverse the configuration at the free hydroxy group in allylic alcohol 19 by Mitsunobu reaction. Despite the fact that the use of

Et₃B-mediated and palladium-catalyzed direct allylation of β-dicarbonyl compounds with Morita–Baylis–Hillman alcohols

• Ahlem Abidi,
• Yosra Oueslati and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2402–2409, doi:10.3762/bjoc.12.234

• further used as synthetic intermediates in numerous synthetic routes to heterocyclic compounds and molecules of biological interest [41][42]. Results and Discussion We first investigated the allylation of diethyl malonate (2a) with the allylic alcohol 1a in DMF in the presence of Pd(OAc)2 (10 mol %), PPh3

• malonate (2a), the malonate derivative 2b (pKa = 13) [29] similarly reacted with the allylic alcohol 1a in the presence of the catalytic system Pd(0)/Et3B to exclusively give the mono-allylated product 3a in 65% yield, whereas the same reaction with ethyl 3-cyano-3-oxopropanoate (2c, pKa = 10.7) [43] whose

• added successively the 1,3-dicarbonyl compound 2 (1.1 mmol), NaH (1 mmol) and an Et3B solution 1.0 M (2 to 3 mmol) in THF. The mixture was stirred for 5 to 10 min at room temperature, then the MBH allylic alcohol 1a or 1b (1 mmol) was added. The mixture was stirred and heated at 80 °C for 3 to 6 h

p-Nitrophenyl carbonate promoted ring-opening reactions of DBU and DBN affording lactam carbamates

• Madhuri Vangala and
• Ganesh P Shinde

Beilstein J. Org. Chem. 2016, 12, 2086–2092, doi:10.3762/bjoc.12.197

• . To evaluate the substrate feasibility, one phenol, an allylic alcohol and three sugar alcohols were subjected to the reaction. The 3,4-dimethylphenyl p-nitrophenyl carbonate (9a) and geranyl carbonate 10a gave the corresponding γ-lactams 9b and 10b in 62% and 46% yields, respectively. Similarly, the

Selective bromochlorination of a homoallylic alcohol for the total synthesis of (−)-anverene

• Frederick J. Seidl and
• Noah Z. Burns

Beilstein J. Org. Chem. 2016, 12, 1361–1365, doi:10.3762/bjoc.12.129

• unsaturated ester was then reduced with DiBAl–H to allylic alcohol 10, which was isolated as an unchanged 8:1 mixture of regioisomeric bromochlorides, strongly suggesting that no stereochemical or regiochemical isomerization had taken place over the previous three steps from 6. When 10 was subjected to

• two enantiomers (or pseudoenantiomers) of a substrate allylic alcohol. Tetrahalide 11 was then oxidized to the corresponding aldehyde. Installation of the vinyl bromide was found to be difficult using traditional methods. Takai olefination [14] with CHBr3 and CrBr2 resulted in significant de

NeoPHOX – a structurally tunable ligand system for asymmetric catalysis

• Jaroslav Padevět,
• Marcus G. Schrems,
• Robin Scheil and
• Andreas Pfaltz

Beilstein J. Org. Chem. 2016, 12, 1185–1195, doi:10.3762/bjoc.12.114

• various test substrates were much lower than those induced by the tert-butyloxazoline analog with the exception of the result obtained with the allylic alcohol S2 (Table 1). Surprisingly, the presence of two geminal phenyl substituents at C(5) had a negative impact on the enantioselectivity, as shown by

Synthesis of a deuterated probe for the confocal Raman microscopy imaging of squalenoyl nanomedicines

• Eric Buchy,
• Branko Vukosavljevic,
• Maike Windbergs,
• Dunja Sobot,
• Camille Dejean,
• Simona Mura,
• Patrick Couvreur and
• Didier Desmaële

Beilstein J. Org. Chem. 2016, 12, 1127–1135, doi:10.3762/bjoc.12.109

• (along with N2 and the trisyl anion) which upon condensation with squalenaldehyde 10 furnished the desired allylic alcohol 16 in 59% yield. Reduction of the hydroxy group of 16 was straightforwardly achieved in 47% yield by treatment with a large excess of thionyl chloride followed by LiAlD4 reduction

• . We next turned to the elaboration of the isopropylidene-d6 moiety. In the event, the Shapiro reaction using trisylhydrazide 14 delivered the expected allylic alcohol 21 in 70% yield. The latter afforded the deuterated ketal 22 in 52% yield, upon sequential treatment with thionyl chloride and LiAlD4

• using the van Tamelen sequence (i. 1 equiv NBS, THF, H2O; ii. K2CO3, MeOH; iii. H3IO6, Et2O) afforded the aldehyde 26 in 16% overall yield. Uneventfully, the Shapiro reaction with trisylhydrazone 14 produced the allylic alcohol 27. Thionyl chloride treatment followed by LiAlD4 reduction delivered

Efficient syntheses of climate relevant isoprene nitrates and (1R,5S)-(−)-myrtenol nitrate

• Sean P. Bew,
• Glyn D. Hiatt-Gipson,
• Graham P. Mills and
• Claire E. Reeves

Beilstein J. Org. Chem. 2016, 12, 1081–1095, doi:10.3762/bjoc.12.103

• a non-conjugated ‘isolated’ C=C bond, typical of an allylic alcohol, i.e., rac-17 (Scheme 4). Intrigued by the possibility it was the C=C bond of rac-17 that was contributing, in a negative sense, to a poor reaction outcome a ‘compare and contrast study’ using paired-up alcohols, i.e., 34 (4-hydroxy

• efficient separation of (E)-13 and (Z)-14 was not possible without recourse to analytical HPLC [9]. Nevertheless we considered it important to validate our proposed ‘halide for nitrate’ substitution by undertaking a ‘test’ reaction using silver nitrate and the allylic bromide/allylic alcohol mixture (E)-45

• -methoxybenzyloxy)-3-methylbut-2-enyl nitrate (68% yield) as stable, colourless oils. Mild oxidative cleavage of the PMB groups using DDQ in wet DCM generated the desired 1° allylic alcohol (E)-3-methyl-4-hydroxybut-2-enyl nitrate ((E)-11) and (Z)-3-methyl-4-hydroxybut-2-enyl nitrate ((Z)-12) in 62% and 53% yields

Regiodefined synthesis of brominated hydroxyanthraquinones related to proisocrinins

• Joyeeta Roy,
• Tanushree Mal,
• Supriti Jana and
• Dipakranjan Mal

Beilstein J. Org. Chem. 2016, 12, 531–536, doi:10.3762/bjoc.12.52

• lactol 34 with methylmagnesium bromide afforded diol 35 in 72% yield. Selective oxidation of the allylic alcohol group in 35 with MnO2, followed by acetylation of the secondary hydroxy group with acetyl chloride, triethylamine and DMAP furnished cyclohexenone 36 (Scheme 5). The Hauser annulation of

Study on the synthesis of the cyclopenta[f]indole core of raputindole A

• Nils Marsch,
• Mario Kock and
• Thomas Lindel

Beilstein J. Org. Chem. 2016, 12, 334–342, doi:10.3762/bjoc.12.36

• %) was synthesized by Sonogashira coupling of N-TIPS-6-iodoindoline (39) and 42. Conversion of 43 to the (Z)-allylic alcohol 44 by modified (K2CO3) Lindlar hydrogenation (47%) followed. Treatment of 44 with SnCl4 in DCM afforded cyclopenta[f]indoline 45, albeit in the rather disappointing yield of 11%. A

• moderate in both cases (33% and 29%), but already better than in the case of the SnCl4-induced cyclization of (Z)-allylic alcohol 44 (Scheme 6). We only isolated the cyclopentanones, formed from the corresponding cyclopentenyl acetates. Presumably, the propargylacetate first undergoes a [3,3]-sigmatropic

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

• coraxeniolide A (10) [12], starting from chiral (−)-Hajos–Parrish diketone (58) [39]. Based on Pfander's seminal work, the first total synthesis of a xenicane diterpenoid was then accomplished by Leumann in 2000 (Scheme 6) [40]. Starting from enantiopure (−)-Hajos–Parrish diketone (58), allylic alcohol 59 was

• allylic alcohol which was converted to the corresponding para-methoxybenzyl ether 90 using Bundle's reagent [51]. In the key step of the synthesis, the nine-membered carbocyclic ring was constructed via a ring-closing metathesis reaction. Under optimized conditions, Hoveyda–Grubbs second generation

• global reduction of the carbonyl functionalities afforded allylic alcohol 109. The precursor for the key reaction was obtained by formation of the methoxymethyl (MOM) ether from primary alcohol 109 and subsequent conversion of the allylic alcohol to stannane 110. The following 2,3-Wittig–Still

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

• , biologically relevant conditions were selected (rt, t-BuOH/H2O) and CM involving allyl sulfides that contain functional groups commonly found in DNA-intercalators and N-heteroaromatics were investigated. When a quinoline was present on the allylic sulfide, allylic alcohol was found to be the unique suitable

• partner among the tested olefins. In addition, 20 equiv of allylic alcohol were required and the CM product was obtained in a moderate 53% yield. Cross-metathesis of 81 with amide 83 or alkene 85 gave no conversion (Scheme 32). In the presence of a quinoxaline moiety on the allyl sulfide, the CM reaction

• with allylic alcohol delivered 88 in a low 31% yield and when an alkene containing a phenanthroline was used, no reaction occurred. By the light of the previously reported observations, these results could be imputed to the deactivation of the ruthenium catalyst caused by N-heteroaromatics (Scheme 33

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

• prepared from the corresponding allylic alcohol 63 by esterification with the anhydride 64 derived from cyclobutene. Later, the ester 65, on treatment with the catalyst 1 under toluene reflux conditions followed by treatment with the catalyst 2 furnished the macrolide-butenolides 66 in 42–48% yields via

Preparation of conjugated dienoates with Bestmann ylide: Towards the synthesis of zampanolide and dactylolide using a facile linchpin approach

• Jingjing Wang,
• Samuel Z. Y. Ting and
• Joanne E. Harvey

Beilstein J. Org. Chem. 2015, 11, 1815–1822, doi:10.3762/bjoc.11.197

• oct-2-en-1-ol (9b) with cinnamaldehyde (10a) was efficient and high yielding (Table 1, entry 3). Use of a Z-allylic alcohol 9c, likewise produced excellent amounts of the product dienoate (Table 1, entry 4), although a longer reaction time was required to achieve this. The Z-geometry of the allylic

• alcohol was retained, as expected. After this, the secondary allylic alcohol 9d was investigated and a reasonable yield of the product was obtained when the reaction was carried out in THF (Table 1, entry 5). A comparative reaction in toluene was also performed and found to deliver a better yield of the

Novel carbocationic rearrangements of 1-styrylpropargyl alcohols

• Christine Basmadjian,
• Fan Zhang and
• Laurent Désaubry

Beilstein J. Org. Chem. 2015, 11, 1017–1022, doi:10.3762/bjoc.11.114

• molybdenum(VI)-catalyzed etherification of allylic alcohol with a gold(I)-catalyzed intramolecular cyclization process [5][6]. During the optimization process of this synthesis, we examined several catalysts to transform allylic alcohol 1 into ether 2, including Re2O7, which is described to efficiently

Electrochemical selenium- and iodonium-initiated cyclisation of hydroxy-functionalised 1,4-dienes

• Philipp Röse,
• Steffen Emge,
• Jun-ichi Yoshida and
• Gerhard Hilt

Beilstein J. Org. Chem. 2015, 11, 174–183, doi:10.3762/bjoc.11.18

• -dienols could be generated from simple 1,3-dienes, such as 1,3-butadiene or 1-aryl-substituted 1,3-dienes 1, and TMS-protected allylic alcohol (Scheme 1) for the synthesis of 1,4-dienols of type 2. The cobalt-catalysed hydrovinylation reaction is highly regiospecific for the carbon–carbon bond formation

• ]. The synthesis of the 1,4-dienes was then accomplished utilising the cobalt-catalyst precursor and reducing conditions in the presence of zinc iodide for abstracting the bromide anions at room temperature. The TMS-protected allylic alcohol was applied in the cobalt-catalysed 1,4-hydrovinylation process

• with aryl-substituted 1,3-dienes 1a–k because the use of allylic alcohol itself led to significant lower yields (up to 30%). Only in case of buta-1,3-diene, 2,3-dimethyl-1,3-butadiene and isoprene allyl alcohol could be used directly without decreasing the yield (Table 1, entries 12–14). The results of

A modular phosphate tether-mediated divergent strategy to complex polyols

• Paul R. Hanson,
• Susanthi Jayasinghe,
• Soma Maitra,
• Cornelius N. Ndi and
• Rambabu Chegondi

Beilstein J. Org. Chem. 2014, 10, 2332–2337, doi:10.3762/bjoc.10.242

• partners. In this regard, triene 5 was first subjected to RCM in the presence of the Hoveyda–Grubbs II (HG-II) catalyst [35][36][37] in refluxing CH2Cl2, followed by solvent concentration and CM with allylic alcohol 3 in refluxing CH2Cl2 for two hours. It was observed that the use of CH2Cl2 was critical

• E- and Z-olefin geometries. Triene 5, was subjected to an RCM reaction, followed by a CM reaction with allylic alcohol 3. After removing the solvent, the CM product was treated with LiAlH4 to produce tetraol 12 in 38% yield over three reaction steps in the one-pot, sequential process (73% avg/rxn

• different tetraol 18 was generated in 23% yield over the four reaction steps in a two-pot operation (69% avg/rxn) (Scheme 3). In a similar manner, starting with triene 7, RCM and subsequent CM with allylic alcohol 3, followed by tether removal with LiAlH4, were performed to obtain tetraol 19 in 42% yield

Palladium-catalysed cyclisation of alkenols: Synthesis of oxaheterocycles as core intermediates of natural compounds

• Miroslav Palík,
• Jozef Kožíšek,
• Peter Koóš and
• Tibor Gracza

Beilstein J. Org. Chem. 2014, 10, 2077–2086, doi:10.3762/bjoc.10.216

• DIBAL-H [32] providing the known allylic alcohol in very good yield. Following protection of the primary alcohol yielded fully protected alkene-tetraol and subsequent chemoselective removal of the acetonide protecting group in one pot led to substrates 24–26. The synthesis of substrate 28 bearing a

• tertiary allylic alcohol was performed in a two-step sequence. The addition of methyllithium to ester Z-17 and following deprotection of the corresponding alcohol 27 with aqueous acetic acid afforded tetraol 28 in good yield. Substrates syn-diols 33–35 (not bearing an α-O-protected group) were prepared in

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

• amide 79 not only afforded good E/Z ratios of 87:13 to 88:12 of 73b but also provided a product that could now be separated by column chromatography (Table 1, entries 3 and 4). Reduction of amide E-73b by LiAlH4 to aldehyde 74 and further reduction under Luche conditions delivered an allylic alcohol

Selective allylic hydroxylation of acyclic terpenoids by CYP154E1 from Thermobifida fusca YX

• Anna M. Bogazkaya,
• Clemens J. von Bühler,
• Sebastian Kriening,
• Alexandrine Busch,
• Alexander Seifert,
• Jürgen Pleiss,
• Sabine Laschat and
• Vlada B. Urlacher

Beilstein J. Org. Chem. 2014, 10, 1347–1353, doi:10.3762/bjoc.10.137

• )-19), which was prepared from geraniol (1) in 93% yield [35] was treated under modified Sharpless conditions [36] with a catalytic amount of SeO2 in the presence of t-BuOOH in dichloromethane at 0 °C, to give enal (E)-20 and allylic alcohol (E)-21 in 19% and 45% yield, respectively, which were

• into neryl acetate ((Z)-19) in 87%, followed by allylic oxidation [38], to provide enal (Z)-20 and allylic alcohol (Z)-21 in 14% and 41% yield, respectively. Saponification of 8-hydroxyneryl acetate ((Z)-21) under the above mentioned conditions gave 8-hydroxynerol (4) in 73% yield (Scheme 2). Following

• (2) reached 77%, but was less selective than that of geraniol (1) resulting in the allylic alcohol 8-hydroxynerol (4, 96%) and 2,3-epoxynerol (6, 4%) as byproduct (Table 1). As expected, amino acid substitutions at position 286 changed both regio- and chemoselectivity of the wild type significantly