Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• alcohols of the structure A (Scheme 6). This alcohol can be selectively reduced either to cis- (B) or trans-allylic alcohol C. cis-Selective reduction of A can be achieved with Lindlar’s catalyst with H2 under atmospheric pressure. The thermodynamic trans-allylic alcohol C arises from the reaction of A

• with Red-Al. Both isomers B and C can also be directly accessed from 1 with the corresponding cis- and trans-vinyl nucleophiles. Allylic alcohol B can be used as an intermediate in the synthesis of various natural products or intermediates thereof. The cis-double bond allows cyclizations to five- or

• deoxynojirimycin family H [39][40][41][42][43]. The trans-allylic alcohol C contains already the functional groups of sphingosines and depending on the stereochemistry at C2 and C3, the synthesis of all four isomers can be achieved [44][45][46][47]. Isomer C leads also to the synthesis of deoxynojirimycin family H

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• between the amino-catalyst and the electrophilic gold complex. Experiments on chiral enriched secondary alcohols suggested the anti-attack of the in situ formed enamine 117 on gold activated allylic alcohol followed by anti-elimination of water. 6 Double functionalization of olefins by oxidative

Synthesis of the spiroketal core of integramycin

• Evgeny. V. Prusov

Beilstein J. Org. Chem. 2013, 9, 2446–2450, doi:10.3762/bjoc.9.282

• PMB-protected 3-hydroxypropanal via Horner–Wadsworth-Emmons olefination, reduction to the allylic alcohol and Sharples epoxidation [8] (Scheme 2). Subsequent Cu-catalyzed epoxide-opening using methylmagnesium bromide [9] produced an inseparable mixture of 1,2- and 1,3-diol products, which upon

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

• reduction, acetylation and a magnesium sulfate induced rearrangement of the epoxide to the allylic alcohol. The synthesis of cytochalasin B 52 (15 steps from 73) proceeded in a similar fashion and was highlighted in detail by Hertweck [44]. The authors state that this approach is highly diversifiable and

Gold(I)-catalysed one-pot synthesis of chromans using allylic alcohols and phenols

• Eloi Coutant,
• Paul C. Young,
• Graeme Barker and
• Ai-Lan Lee

Beilstein J. Org. Chem. 2013, 9, 1797–1806, doi:10.3762/bjoc.9.209

• . Suspecting that the moderate yield of 6 in Scheme 1 is due to the slight volatility of 6, an allylic alcohol 7 with a higher molecular weight was chosen as the model substrate in order to avoid any issues of volatility with the chroman products. As shown in Table 1, the standard conditions (50 °C, 5 equiv

• reactivity of the phenols screened, it was chosen as the model phenol in the next allylic alcohol substrate screen (Table 3) since the extra molecular weight from the t-Bu substituents should reduce any volatility issues with the chroman products [77]. At this point, we observed that the general procedure

• %, but ultimately carrying out the reaction at 90 °C in a sealed tube provides a much better yield of 83% (Table 2, entry 13). Next, the allylic alcohol scope was investigated (Table 3). Firstly, going from more hindered Cy substituents (7) to less hindered n-hexyl substituents (12) allows the reaction

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

• ]. Treatment of 20 with the sulfur ylide derived from trimethylsulfoxonium iodide [33][34] led to recovery of starting material at room temperature, but decomposition at elevated temperatures. Instead, the enone was smoothly reduced to the allylic alcohol, and a Furukawa-modified Simmons–Smith reaction [35

• rearrangement to set the geometry of the γ,δ-unsaturated double bond. In the forward direction, the allylic alcohol 44 was obtained from reaction of the alkenyllithium reagent derived from 2-bromopropene with phenylacetaldehyde (Scheme 10). In our hands, the organolithium afforded significantly higher and more

• of alkyne 50 with Schwartz’s reagent [54][55] was followed by transmetallation to zinc and nonselective addition into aldehyde 47. Oxidation of the resulting allylic alcohol mixture afforded the enone 53. Prior to the key oxy-Michael addition, it was necessary to remove the tert-butyldimethylsilyl

Anionic cascade reactions. One-pot assembly of (Z)-chloro-exo-methylenetetrahydrofurans from β-hydroxyketones

• István E. Markó and
• Florian T. Schevenels

Beilstein J. Org. Chem. 2013, 9, 1319–1325, doi:10.3762/bjoc.9.148

• proceeded faster than the expected rearrangement of the tertiary allylic alcohol (Scheme 5). To promote such an acid-catalyzed rearrangement, the (Z)-chloro-exo-methylenetetrahydrofuran 13 was treated with a catalytic amount of para-toluenesulfonic acid. To our surprise, the anti-dioxane 35 and its syn

Establishing the concept of aza-[3 + 3] annulations using enones as a key expansion of this unified strategy in alkaloid synthesis

• Aleksey I. Gerasyuto,
• Zhi-Xiong Ma,
• Grant S. Buchanan and
• Richard P. Hsung

Beilstein J. Org. Chem. 2013, 9, 1170–1178, doi:10.3762/bjoc.9.131

• amine with concomitant reduction of the alkyne revealing the olefin functionality; and (b) dehydrative condensation of this primary amine with 1,3-cyclohexanedione. Oxidation of the secondary allylic alcohol in 9 with MnO2 at ambient temperature provided enone 10 in 85% yield. We were poised to

• the TBDPS group with TBAF provided allylic alcohol 25 in 79% from 23. However, submission of 25 to the standard MnO2 oxidation procedure did not lead to enone 17, with only the starting material being recovered (Table 2). After extensive screening of various oxidation protocols, we succeeded with the

Synthesis of skeletally diverse alkaloid-like molecules: exploitation of metathesis substrates assembled from triplets of building blocks

• Sushil K. Maurya,
• Mark Dow,
• Stuart Warriner and
• Adam Nelson

Beilstein J. Org. Chem. 2013, 9, 775–785, doi:10.3762/bjoc.9.88

• , after deprotection, selective derivatisation of the product scaffolds would be possible. Synthesis of building blocks The initiating building blocks 6a and 6b were prepared by using the approach outlined in Scheme 3. The allylic alcohol 14 [19] was converted into the allylic carbonate 15 by treatment

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• by the preparation of enone 81 from allylic alcohol 80 in Scheme 17. By varying the xanthate partner, different substitution patterns and rings may then be introduced. Two examples, 83 and 86, in Scheme 17 illustrate the formation of triquinanes via bicyclic intermediate xanthates 82 and 85. The

• diquinane intermediate 87 [38]. In all of these transformations, the chiral information residing in the starting allylic alcohol 80 is transmitted, through the Claisen rearrangement, to various other centres (the ratios in Scheme 17 and following schemes refer to ratios of diastereoisomers). Very recently

• tricyclic structure 93. In this sequence too, the chirality present in the starting material 89 is initially derived from an allylic alcohol by the Claisen rearrangement and is then transmitted to the other centres. Another powerful reaction that can be associated with the radical chemistry of xanthates is

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

• hand, a reaction of longifolene with formaldehyde in acetic acid yielded the acetate of an allylic alcohol (ω-acetoxymethyl longifolene) as a major product under high-temperature conditions (Scheme 4, 140 °C, 24 h) [5]. A scheme was proposed as to the mechanism of the Prins reactions [6][7][8][9][10

• ][11][12][13][14][15][16][17][18] to afford 1,3-dioxane, 1,3-diol and allylic alcohol, where the carbocation intermediate (X) is included (Scheme 5). In the second step, X is formed. From X, two routes, (i) and (ii), are possible. In the route (i), a water molecule is linked with the cation center

Alternaric acid: formal synthesis and related studies

• Michael C. Slade and
• Jeffrey S. Johnson

Beilstein J. Org. Chem. 2013, 9, 166–172, doi:10.3762/bjoc.9.19

• began from the known allylic alcohol 21 [46], which was acetylated to afford ester 22 as prelude for reaction as a π-allyl electrophile with the Reformatsky reagent 23 derived from tert-butyl bromoacetate. The TMS-alkyne in 24 was deprotected with buffered TBAF to afford free alkyne 25, and the vinyl

Flow photochemistry: Old light through new windows

• Jonathan P. Knowles,
• Luke D. Elliott and
• Kevin I. Booker-Milburn

Beilstein J. Org. Chem. 2012, 8, 2025–2052, doi:10.3762/bjoc.8.229

Alkenes from β-lithiooxyphosphonium ylides generated by trapping α-lithiated terminal epoxides with triphenylphosphine

• David. M. Hodgson and
• Rosanne S. D. Persaud

Beilstein J. Org. Chem. 2012, 8, 1896–1900, doi:10.3762/bjoc.8.219

• with Ph3P to provide a new and direct entry to β-lithiooxyphosphonium ylides. The intermediacy of such an ylide is demonstrated by representative alkene-forming reactions with chloromethyl pivalate, benzaldehyde and CD3OD, giving a Z-allylic pivalate, a conjugated E-allylic alcohol and a partially

• [17][18]. In the event, benzaldehyde was successfully trapped to give E-allylic alcohol 7 in up to 33% yield (Scheme 4) by using LTMP (1 equiv), Ph3P (5 equiv) and LiBr (2 equiv; 24% yield in the absence of LiBr). Essentially the same yields (31% and 30%) were obtained under otherwise identical

• with epoxide 11 in the presence of Ph3P in a variety of solvents (THF, Et2O, t-BuOMe, toluene) followed by the addition of benzaldehyde was found to give allylic alcohol 7, albeit in low yields with reductive alkylation always being the dominant reaction pathway, and typically ~30% of epoxide 11 and

Stereoselective synthesis of trans-fused iridoid lactones and their identification in the parasitoid wasp Alloxysta victrix, Part I: Dihydronepetalactones

• Nicole Zimmermann,
• Robert Hilgraf,
• Lutz Lehmann,
• Daniel Ibarra and
• Wittko Francke

Beilstein J. Org. Chem. 2012, 8, 1246–1255, doi:10.3762/bjoc.8.140

• upon intramolecular aldol condensation [25][26][27]. Subsequently, the aldehyde 15 was reduced to the allylic alcohol 19 with LiAlH4 and converted into the acetate 20 [28]. Hydroboration of 20 using disiamylborane proceeded with high stereoselectivity affording 16 as a single stereoisomer [17][28

• 1 bar hydrogen pressure for 1.5 h yielded the desired product 26 as a single diastereomer. Alternative hydrogenation methods using optically active catalysts failed. In one case we investigated the hydrogenation of the endocylic double bond of the allylic alcohol 19 (Scheme 2) with one of Noyori’s

Gold(I)-catalyzed synthesis of γ-vinylbutyrolactones by intramolecular oxaallylic alkylation with alcohols

• Michel Chiarucci,
• Mirko Locritani,
• Gianpiero Cera and
• Marco Bandini

Beilstein J. Org. Chem. 2011, 7, 1198–1204, doi:10.3762/bjoc.7.139

• acids (BA) was verified by means of experimental controls with TsOH (entry 15), and also in the presence of an acid scavenger (entry 16). Here, the desired cyclic compound 2a was obtained in lower yield (64%) with concomitant substantial decomposition of the starting allylic alcohol. Such evidence

• allylic alcohol (I). In Scheme 2, the possible coordination modes for [Au+] to the allylic alcohol are reported. As a matter of fact, although we have previously demonstrated the C=C···Au interaction in the presence of allylic alcohols [16], a concomitant [Au]···OH contact cannot be ruled out [48][49

• complexes allowed the preparation of a range of functionalized malonyl esters by direct activation of the allylic alcohol by gold. The methodology appears highly chemoselective toward the allylic lactonization, with the possibility to extend the protocol also to acetate derivatives. Working hypothesis for

Amine-linked diglycosides: Synthesis facilitated by the enhanced reactivity of allylic electrophiles, and glycosidase inhibition assays

• Ian Cumpstey,
• Jens Frigell,
• Elias Pershagen,
• Tashfeen Akhtar,
• Elena Moreno-Clavijo,
• Inmaculada Robina,
• Dominic S. Alonzi and
• Terry D. Butters

Beilstein J. Org. Chem. 2011, 7, 1115–1123, doi:10.3762/bjoc.7.128

• carbohydrate into an unsaturated derivative with an allylic alcohol as leaving group [16]. After the coupling reaction, dihydroxylation of the C=C double bond would restore the carbohydrate structure (Scheme 1) [17]. As well as Mitsunobu chemistry [18], the allylic nature of the electrophile opens up the way

• unsaturated glycoside 4 to be achieved; phosphomolybdic acid [32] gave the product (α:β, 8:1) in 63% yield. Deacetylation of 4 and regioselective silylation of the primary alcohol gave the threo allylic alcohol 2. The sulfonamide nucleophiles 6, 7 and 9 were prepared from the corresponding amines 5 [33] and 8

• [34], as described previously [6], with only one equivalent of the sulfonylating agent so as to avoid bis-sulfonamide formation. Mixing equimolar equivalents of the erythro allylic alcohol 1 and the glucose-6-nosylamide 6 with DIAD and triphenylphosphine resulted in a smooth coupling reaction to give

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

• solved if the allylic alcohol leaving group did not need to be revealed directly before the cyclization event. This led us to consider the use of alternative substrates where the allylic alcohol could be deprotected under the reaction conditions, or the use of other “protecting groups” that would also

Ene–yne cross-metathesis with ruthenium carbene catalysts

• Cédric Fischmeister and
• Christian Bruneau

Beilstein J. Org. Chem. 2011, 7, 156–166, doi:10.3762/bjoc.7.22

• ][76] were prepared. One-pot EYCM followed by Brønsted acid catalyzed cyclization enabled the formation of monounsaturated cyclic amines [77]. The EYCM of homopropargylic tosylate with allylic alcohol derivatives has been used as a key step for the construction of the side chain of mycothiazole [78

Application of the diastereoselective photodeconjugation of α,β-unsaturated esters to the synthesis of gymnastatin H

• Ludovic Raffier and
• Olivier Piva

Beilstein J. Org. Chem. 2011, 7, 151–155, doi:10.3762/bjoc.7.21

• the corresponding allylic alcohol 22 followed by the oxidation with Dess–Martin periodinane (DMP) [21] afforded aldehyde 23 which was converted into the known ethyl ester (E,E)-24 by a subsequent Wittig–Horner reaction. The comparison of the optical rotation with literature data confirmed the (R

The allylic chalcogen effect in olefin metathesis

• Yuya A. Lin and
• Benjamin G. Davis

Beilstein J. Org. Chem. 2010, 6, 1219–1228, doi:10.3762/bjoc.6.140

• . When the allylic alcohol was protected with a bulky group, the catalyst reacted preferentially at the less hindered allyl ether (pathway A where R′ = H). The formation of the 4,6-bicyclic intermediate is apparently disfavored with catalyst 1a leading to largely the formation of the dihydrofuran product

• stereoselective ring-opening cross-metathesis (ROCM) (Scheme 5) [24]. The activating effect from the allylic hydroxy group in metathesis is prominent in this example. The ROCM of cyclopropene 13 with enantiomerically enriched allylic alcohol 14a is complete in 5 minutes (>98% conversion) with a high

• reaction itself. We hope to see this concept being further exploited in bioconjugation and synthetic chemistry. Allylic hydroxy activation in RCM [19]. Possible complexes generated through preassociation of allylic alcohol with ruthenium. a) Variation of olefin metathesis: CM = cross-metathesis; RCM = ring

The catalytic performance of Ru–NHC alkylidene complexes: PCy₃ versus pyridine as the dissociating ligand

• Stefan Krehl,
• Diana Geißler,
• Sylvia Hauke,
• Oliver Kunz,
• Lucia Staude and
• Bernd Schmidt

Beilstein J. Org. Chem. 2010, 6, 1188–1198, doi:10.3762/bjoc.6.136

• reactions Allylic alcohol 8 [59] was chosen to test the catalysts investigated in this study for cross metathesis activity, because allylic alcohols are known to undergo undesired “redox isomerization” in the presence of Ru metathesis catalysts in some cases with the formation of ethyl ketones [47][60

• : 304.1683; Anal. calcd for C18H24O4: C, 71.0, H, 8.0, found: C, 70.8, H, 7.7. Cross-metathesis reactions General procedure: A solution of the allylic alcohol rac-8 (139 mg, 0.5 mmol) and the corresponding acrylate 9 (5 mmol) in dry and degassed toluene (1.0 mL for 0.5 mol·L–1, 5.0 mL for 0.1 mol·L–1) was

• metathesis reactions. Cross metathesis reactions with allylic alcohol 8. RCM of acrylate 3a. RCM reactions of acrylates to unsaturated lactones.a Ring closing enyne metathesis reactions catalyzed with E and H. Cross metathesis reactions catalyzed by D, E, and H. Supporting Information Supporting Information

Redox-active tetrathiafulvalene and dithiolene compounds derived from allylic 1,4-diol rearrangement products of disubstituted 1,3-dithiole derivatives

• Filipe Vilela,
• Peter J. Skabara,
• Christopher R. Mason,
• Thomas D. J. Westgate,
• Asun Luquin,
• Simon J. Coles and
• Michael B. Hursthouse

Beilstein J. Org. Chem. 2010, 6, 1002–1014, doi:10.3762/bjoc.6.113

• further change to the remnant allylic alcohol [10]; a related mechanism has been reported for a self-coupling intermolecular reaction, which involves an intermediate allylic cation generated under acidic conditions from an electron-rich thienylmethanol derivative, where no intramolecular rearrangement

Three step synthesis of single diastereoisomers of the vicinal trifluoro motif

• Vincent A. Brunet,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2009, 5, No. 61, doi:10.3762/bjoc.5.61

• . Results and Discussion The chemistry was initiated from allylic alcohol 2 which can readily be prepared in enantiomerically pure form by hydrolytic kinetic resolution of vinyl epoxide 1 following Jacobsen’s protocol [13] (Scheme 3). Diol 2 was converted to tosyl ester 3 in a regioselective manner

• and relative stereochemistry of the crystalline threo-isomer (2R,3S,4S)-7a was confirmed by X-ray structure analysis as shown in Figure 2. With a strategy to access both stereoisomeric series of the allylic alcohol epoxides A in place, the fluorination reactions were then explored. The fluorination of

Acid- mediated reactions under microfluidic conditions: A new strategy for practical synthesis of biofunctional natural products

• Katsunori Tanaka and
• Koichi Fukase

Beilstein J. Org. Chem. 2009, 5, No. 40, doi:10.3762/bjoc.5.40

• required in a year with more than 98% purity. Namely, the preparation of 5 kg of pristane in about a week is necessary in order to supply enough material in the market. The challenging step in Scheme 1 is the acid-catalyzed dehydration of allylic alcohol 19. When the reaction was performed in 100 mg scale

• successful application of the microfluidic systems to the acid-mediated reactions during the N-glycan synthesis described above, we examined the microfluidic dehydration under the following conditions (Figure 3) [29]: Allylic alcohol 19 (1.0 M in THF) was mixed with a solution of p-TsOH (various