Chiral phosphoric acid-catalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles

• Yumei Wang,
• Guangzhu Wang,
• Yanping Zhu and
• Kaiwu Dong

Beilstein J. Org. Chem. 2024, 20, 205–211, doi:10.3762/bjoc.20.20

• asymmetric reduction studies focused on alkyl or aryl-substituted 3H-indoles whereas the synthesis of chiral difluorinated indole derivatives could have potential applications in pharmaceutical chemistry. Herein, an organocatalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles to obtain fluorinated 3H

• aryl ring smoothly underwent this asymmetric reduction, affording the desired indolines in 95–99% yield and 90–96% ee within 3 hours. Replacing the 3,3-difluoro substituents by two methyl groups in the starting indole as well as the alkyne part by a phenyl group, the reaction still gave good results

• spectroscopy and the ee values were determined by chiral HPLC. Structures of bioactive fluorinated indole derivatives. Proposed mechanism for the transfer hydrogenation reaction. Synthesis of chiral indolines via asymmetric reduction. Substrate scope of 3,3-difluoro-3H-indoles. Experiment at 2 mmol scale

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• -catalysed asymmetric reduction of propargylic ketones and the proposed mechanism. H-B-9-BBN-catalysed C–F esterification of alkyl fluorides and the proposed mechanism. H-B-9-BBN-catalysed 1,4-hydroboration of enones and the proposed mechanism. Boric acid-promoted reduction of esters, lactones, and

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

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

• removal of the silyl protecting group, followed by a carboxylation and acylation gave 13. Koide’s group [13] reported a second-generation route to 13, which utilized the Corey–Bakshi–Shibata chiral oxazaborolidine catalyst 21 [20] for the asymmetric reduction of the THP-protected 5-hydroxy-3-pentyn-2-one

• . Unfortunately, all attempted 1,4-reduction conditions afforded an inseparable mixture of trans-54 as the major product along with minor amounts of the desired cis-55. Alternatively, the asymmetric reduction of the 2-acylfuran 56 using the Corey–Bakshi–Shibata reagent (21) [30] gave the alcohol 57 in a high

• the spliceostatins/thailanstatins or to couple the subfragments of these molecules (Table 2). The most common route to the (2Z,4S)-4-acetoxy-2-butenoic acid fragment relies on the cis-reduction of 4-acetoxy-2-pentynoic acid; the most efficient of these routes utilizes a Noyori asymmetric reduction of

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• of a poly-ʟ-valine 6 coated graphite cathode for asymmetric electrochemical reductions in two consecutive reports. In the first communication, they carried out the asymmetric reduction of prochiral activated olefins 5 and 8, affording 7 and 9 with optical yields of 25% and 43%, respectively (Scheme 3

• ) [23]. In the second report, the same electrode was applied for the asymmetric reduction of prochiral carbonyl compounds 10a and 12a, oximes 14 and gem-dibromo compounds 16 (Scheme 4). Among all of these the highest optical yield (16.6%) was obtained in the reduction of gem-dibromide substrates 16 to

• asymmetric reduction of 135 using enolate reductase that afforded the corresponding chiral acid 136 in 95% yield and 95% ee. It has been shown that the cofactor NADH is oxidized during this process and can be regenerated using methyl viologen 137 as a reductive mediator (Scheme 43) [78]. In 1997, Yoneyama

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

• isolated from fungi of the genus Acremonium. Here, we present the asymmetric total synthesis of acremine F which hinges on a modestly enantioselective dihydroxylation and a subsequent kinetic resolution via a highly selective asymmetric reduction. Chemoselective oxidation of acremine F gave access to

Catalytic asymmetric oxo-Diels–Alder reactions with chiral atropisomeric biphenyl diols

• Chi-Tung Yeung,
• Wesley Ting Kwok Chan,
• Wai-Sum Lo,
• Ga-Lai Law and
• Wing-Tak Wong

Beilstein J. Org. Chem. 2019, 15, 955–962, doi:10.3762/bjoc.15.92

• to that for 1 and 2 [37]. Asymmetric reduction of the carbonyl group of 2’-bromobenzophenone (a) with borane dimethyl sulfide in the presence of (S)-(−)-2-methyl-CBS-oxazaborolidine catalyst gave (S)-(2-bromophenyl)(phenyl)methanol (S)-b in 93% yield and 94% ee (Scheme 2 and Figure S1 in Supporting

• , different from the synthesis of catalyst 3, asymmetric reduction of the corresponding ketone, (2-bromophenyl)(mesityl)methanone c, using (S)-(–)-2-methyl-CBS-oxazaborolidine as the catalyst resulted in a very low enantioselectivity (<15% ee) of the product, (2-bromophenyl)(mesityl)methanol (d, Scheme 3

• diols 3, 4 and 6 with axial chiralities controlled by their corresponding additional asymmetric carbon centers were synthesized; despite having the same biphenyl scaffold, their highly enantioselective intermediates b, d and g were obtained with different strategies: asymmetric reduction with

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

• concentrations [11]. There have been few contributions on the total synthesis of strongylodiols [12][13] employing alkynylation of an unsaturated aliphatic aldehyde catalyzed by Trost’s pro-phenol ligand [12][14], β-elimination of epoxy chloride [15], Noyori’s asymmetric reduction of ynones [16], diyne addition

• 25 and 25a was oxidized under Dess–Martin conditions to give the prochiral ene–yne–one 17 in 87% yield. The ketone 17 was then subjected to a stereoselective asymmetric reduction [23][29][30][31] in the presence of (S)-CBS as the catalyst to yield the chiral propargylic alcohol 25 with 92% ee (Scheme

A general and atom-efficient continuous-flow approach to prepare amines, amides and imines via reactive N-chloramines

• Katherine E. Jolley,
• Michael R. Chapman and
• A. John Blacker

Beilstein J. Org. Chem. 2018, 14, 2220–2228, doi:10.3762/bjoc.14.196

• use of heated CSTRs would be useful to explore. The formation of both imines 20 and 21 are of interest as an asymmetric reduction would give an optically pure amine. To demonstrate this, imine 20, formed in situ, underwent asymmetric-transfer hydrogenation in both batch and flow modes, using [IrCp*Cl2

Stereoselective synthesis of hernandulcin, peroxylippidulcine A, lippidulcines A, B and C and taste evaluation

• Marco G. Rigamonti and
• Francesco G. Gatti

Beilstein J. Org. Chem. 2015, 11, 2117–2124, doi:10.3762/bjoc.11.228

• noteworthy that in this case the Corey asymmetric reduction of the carbonyl group is completely regioselective in favour of the exocyclic carbonyl group. To knowledge of the authors, just another example has been reported with a similar regioselectivity [37]. Then, lippidulcine C ([α]D +92.1° (c 1.1, CHCl3

The enantioselective synthesis of (S)-(+)-mianserin and (S)-(+)-epinastine

• Piotr Roszkowski,
• Jan. K. Maurin and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2015, 11, 1509–1513, doi:10.3762/bjoc.11.164

• /bjoc.11.164 Abstract A simple enantioselective synthetic procedure for the preparation of mianserin and epinastine in optically pure form is described. The key step in the synthetic pathway is the asymmetric reduction of the cyclic imine using asymmetric transfer hydrogenation conditions. Keywords

• more active form [9]. In a key step in the enantioselective synthesis of mianserin and epinastine we applied the asymmetric reduction of the prochiral imine by asymmetric hydrogen transfer reaction (ATH) [10][11][12][13][14]. The proposed strategy could be used for the preparation of the title

• analysis of compound (S)-7. Enantioselective synthesis of (S)-(+)-mianserin. Enantioselective synthesis of (S)-(+)-epinastine. The asymmetric reduction imine 6 by asymmetric transfer hydrogenationa. Supporting Information Supporting Information File 26: Experimental procedures, spectroscopic and

An intramolecular C–N cross-coupling of β-enaminones: a simple and efficient way to precursors of some alkaloids of Galipea officinalis

• Hana Doušová,
• Radim Horák,
• Zdeňka Růžičková and
• Petr Šimůnek

Beilstein J. Org. Chem. 2015, 11, 884–892, doi:10.3762/bjoc.11.99

• ]. As part of our ongoing interest in the preparation of polarized ethylenes and their application in organic synthesis, we have been attracted by the procedure published by Zhou [30]. Here, the authors used heterocyclic enaminone 1b as the reactant for an asymmetric reduction followed by N-methylation

• S28), similarly to the situation found for peptide type of bonding [55]. Conclusion An asymmetric reduction of suitably substituted 2-aroylmethylidene-1,2,3,4-tetrahydroquinolines is one of the possible routes to tetrahydroquinoline alkaloids of Galipea officinalis. The methodology, however, suffered

Synthesis of chiral N-phosphinyl α-imino esters and their application in asymmetric synthesis of α-amino esters by reduction

• Yiwen Xiong,
• Haibo Mei,
• Lingmin Wu,
• Jianlin Han,
• Yi Pan and
• Guigen Li

Beilstein J. Org. Chem. 2014, 10, 653–659, doi:10.3762/bjoc.10.57

• -substituent led to lower yield due to steric effects (Table 2, entry 7). Besides, the reaction with ethyl ester also worked well and resulted in a slightly lower yield (Table 2, entry 11). Optimization of the asymmetric reduction reaction conditions Then, the obtained chiral N-phosphinyl α-imino esters were

• temperature influenced the reaction obviously, and raising the temperature to −40 °C reduces the yield to 89% and the diastereoselectivity to 87:13 (Table 3, entry 14). Scope of the asymmetric reduction reaction After getting the optimized reduction conditions, several chiral N-phosphinyl α-imino esters

• result the free α-amino esters. Experimental General procedure for the asymmetric reduction of N-phophinyl α-imino esters: A reaction vial under argon was charged with L-Selectride (0.3 mmol) with THF (2.5 mL). The reaction mixture was then cooled to −78 °C for 10 min. Meanwhile, α-imino ester 3 (0.15

New hydrogen-bonding organocatalysts: Chiral cyclophosphazanes and phosphorus amides as catalysts for asymmetric Michael additions

• Helge Klare,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2014, 10, 224–236, doi:10.3762/bjoc.10.18

• ; Chakravarty et al. [24] tested an ansa-bridged BINOL-based PV-cyclodiphosphazane in the asymmetric reduction of acetophenone with BH3 (5–8% ee), while Gade et al. [25] recently introduced BINOL-based PIII-cyclodiphosphazane ligands to transition-metal catalysis (up to 84% ee). We anticipated that by

A combined continuous microflow photochemistry and asymmetric organocatalysis approach for the enantioselective synthesis of tetrahydroquinolines

• Erli Sugiono and
• Magnus Rueping

Beilstein J. Org. Chem. 2013, 9, 2457–2462, doi:10.3762/bjoc.9.284

• and subsequent asymmetric reduction to afford the corresponding tetrahydroquinolines in good yields and high enantioselectivities. Conclusion In conclusion, we have demonstrated the great potential of a new continuous-flow microreactor system for the photocyclization–reduction cascade of 2

• photocyclization–reduction cascade. Optimization of the Brønsted acid catalyzed transfer hydrogenation of quinolines.a Scope of the continuous-flow photocyclization–asymmetric reduction domino sequence.a

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• racemic quinuclidinol. However, an improved approach makes use of a Noyori-type asymmetric reduction employing a BINAP ligated RuCl2 and a chiral diamine to yield the desired (R)-quinuclidine in high yield and enantioselectivity [78]. The enantioselective synthesis of the tetrahydroisoquinoline fragment

Asymmetric synthesis of a highly functionalized bicyclo[3.2.2]nonene derivative

• Toshiki Tabuchi,
• Daisuke Urabe and
• Masayuki Inoue

Beilstein J. Org. Chem. 2013, 9, 655–663, doi:10.3762/bjoc.9.74

• heptenone 12 [17][18][19][20][21]. The more thermodynamically stable silyl enol ether 13 was regioselectively formed from 12 under Holton’s conditions [22], and DDQ-mediated oxidation of 13 resulted in the formation of α,β-unsaturated ketone 14. Asymmetric reduction of ketone 14 was in turn realized by

Continuous-flow catalytic asymmetric hydrogenations: Reaction optimization using FTIR inline analysis

• Magnus Rueping,
• Teerawut Bootwicha and
• Erli Sugiono

Beilstein J. Org. Chem. 2012, 8, 300–307, doi:10.3762/bjoc.8.32

• : asymmetric reduction; binolphosphoric acid; Brønsted acid; Hantzsch dihydropyridine; IR spectroscopy; real-time analysis; Introduction In recent years, a growing interest in microreactor technology has been seen in the scientific community and the development of microfabricated reaction systems is actively

• decided to extend its scope to the reduction of quinoxalines 7 (Table 5) [107]. The asymmetric reduction of quinoxalines is typically more difficult to achieve. Using the optimized conditions for the fast inline reaction, we found that the continuous-flow reduction could be performed using 10 mol

Achiral bis-imine in combination with CoCl₂: A remarkable effect on enantioselectivity of lipase-mediated acetylation of racemic secondary alcohol

• K. Arunkumar,
• M. Appi Reddy,
• T. Sravan Kumar,
• B. Vijaya Kumar,
• K. B. Chandrasekhar,
• P. Rajender Kumar and
• Manojit Pal

Beilstein J. Org. Chem. 2010, 6, 1174–1179, doi:10.3762/bjoc.6.134

• associated with Alzheimer’s and Parkinson’s disease. Thus the enantiopure acetate (R)-5 was treated with excess of dimethylamine in toluene to afford the desired (S)-8 [(S)-rivastigmine] in 60% yield (final step, Scheme 5). Notably, the earlier method for the synthesis of (S)-8 involved asymmetric reduction

Concise methods for the synthesis of chiral polyoxazolines and their application in asymmetric hydrosilylation

• Wei Jie Li,
• Zun Le Xu and
• Sheng Xiang Qiu

Beilstein J. Org. Chem. 2010, 6, No. 29, doi:10.3762/bjoc.6.29

• aromatic ketones with various polyoxazoline ligands Enantiomerically pure chiral alcohols are key intermediates in the synthesis of numerous biologically active molecules [22]. For this reason, much effort has been made over the last 30 years to develop efficient techniques for asymmetric reduction of

Synthesis of (3R,5R)-harzialactone A and its (3R,5S)-isomer

• Gowravaram Sabitha,
• Rangavajjula Srinivas,
• Sukant K. Das and
• Jhillu S. Yadav

Beilstein J. Org. Chem. 2010, 6, No. 8, doi:10.3762/bjoc.6.8

• earlier. The IR absorption at 1774 cm−1 indicates the presence of δ-lactone system. The synthesis of (3R,5S)-2 was also accomplished in an identical manner from 4 (Scheme 3). The substrate hydroxyl directed asymmetric reduction with Me4NBH(OAc)3 [15][16] was performed at 0 °C to afford the anti diol 11 as

Diastereoselective and enantioselective reduction of tetralin- 1,4-dione

• E. Peter Kündig and
• Alvaro Enriquez-Garcia

Beilstein J. Org. Chem. 2008, 4, No. 37, doi:10.3762/bjoc.4.37

• efficient highly diastereoselective one-step reduction of both carbonyl functions in 2 have not been realized, enrichment of one or the other diastereoisomer by choice of reducing agent is feasible and acceptable yields of pure diastereoisomers can be obtained. Enantioselective bis-reduction of 2 Asymmetric

• reduction of dione 2 was probed next. This was carried out successfully as shown in Scheme 4 and gave, after two recrystallizations from diisopropylether, (−)-(1R,4R)-tetralin-1,4-diol (R,R-7) in 72% yield and 99% ee [8]. Only small amounts (ca. 7%) of the cis stereoisomer 6 were detected by 1H NMR in the

Total synthesis of the indolizidine alkaloid tashiromine

• Stephen P. Marsden and
• Alison D. McElhinney

Beilstein J. Org. Chem. 2008, 4, No. 8, doi:10.1186/1860-5397-4-8

• potentially act as nucleophiles themselves in the acidic medium of the electrophilic cyclisation, and the investigation of such chemoselectivity issues provided a further impetus for this study. Acylsilane 13 was therefore prepared from propargyl alcohol in four steps then subjected to asymmetric reduction

Asymmetric aza-Diels- Alder reaction of Danishefsky's diene with imines in a chiral reaction medium

• Bruce Pégot,
• Olivier Nguyen Van Buu,
• Didier Gori and
• Giang Vo-Thanh

Beilstein J. Org. Chem. 2006, 2, No. 18, doi:10.1186/1860-5397-2-18

• very important for chirality transfer. This had already been reported by Colonna and co-workers[34][35] in the borohydride asymmetric reduction of carbonyl compounds using a chiral phase transfer catalyst. This observation is supported by our studies in the asymmetric Baylis-Hillman reaction.[25] Thus