Preparative semiconductor photoredox catalysis: An emerging theme in organic synthesis

• David W. Manley and
• John C. Walton

Beilstein J. Org. Chem. 2015, 11, 1570–1582, doi:10.3762/bjoc.11.173

• components, decarboxylative arylations of amino acids, diastereoselective preparations of cis-cyclobutanes via [2 + 2] cycloadditions of enones, selective reductions of benzylic and α-carbonyl halides and, with fac-Ir(ppy)3, reductions of unactivated alkyl iodides [5][6][7][8]. Furthermore, the value of

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

• mianserin was originally described by Organon [4][5], and in 1999 Jackson and Subasinghe presented a method for the separation of mianserin enantiomers with (+)- or (−)-di-p-toluoyltartaric acid [6]. Later, the diastereoselective synthesis of (R)-mianserin using (S)-(−)-α-methylbenzylamine as a chiral

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• underdeveloped due to their inherently low reactivity. This review highlights the work that has been done on both diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams. Keywords: α,β-unsaturated amides; α,β-unsaturated lactams; conjugate addition

• done on the development of diastereoselective and enantioselective conjugate addition reactions using α,β-unsaturated amides and lactams. This is not an exhaustive account of all ACA reactions that employ α,β-unsaturated amides and lactams as Michael acceptors. Instead, the review aims to highlight

• review. 1 Diastereoselective conjugate additions (DCA) Though CA reactions had been studied for decades, significant progress in the development of CA reactions using α,β-unsaturated amides and lactams was not observed until the 1980s [28][29][30][31]. Initial efforts toward performing the asymmetric CA

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

• 10.3762/bjoc.11.18 Abstract The cobalt(I)-catalysed 1,4-hydrovinylation reaction of allyloxytrimethylsilane and allyl alcohol with substituted 1,3-dienes leads to hydroxy-functionalised 1,4-dienes in excellent regio- and diastereoselective fashion. Those 1,4-dienols can be converted into tetrahydrofuran

• cyclisation in moderate to good yields. The products were generated in diastereoselective fashion and the configuration of the formed diastereomer could be identified by 1H NMR experiments comparing a mixture of both diastereomers, synthesised by conventional selenoalkoxylation, with the electrochemically

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• stainless steel cathode were utilised in a flow cell set-up [35]. An important example of the scope and synthetic potential of the silyl electroauxiliary approach was reported by Yoshida (Scheme 5) in combination with a chiral auxiliary a highly diastereoselective cationic carbohydroxylation occurred [18

• -carbon bonds [11]. The influence of the amino protecting group on the “kinetic” and “thermodynamic” anodic methoxylation [16]. Example of the application of the cation pool method [17]. A thiophenyl electroauxiliary allows for regioselective anodic oxidation [32]. A diastereoselective cation

Inherently chiral calix[4]arenes via oxazoline directed ortholithiation: synthesis and probe of chiral space

• Simon A. Herbert,
• Laura J. van Laeren,
• Dominic C. Castell and
• Gareth E. Arnott

Beilstein J. Org. Chem. 2014, 10, 2751–2755, doi:10.3762/bjoc.10.291

• Simon A. Herbert Laura J. van Laeren Dominic C. Castell Gareth E. Arnott Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, Matieland 7602, South Africa 10.3762/bjoc.10.291 Abstract The diastereoselective oxazoline-directed lithiation of calix[4]arenes is

• reported with diastereoselective ratios of greater than 100:1 in some instances. Notably, it has been found that the opposite diastereomer can be accessed via this approach merely through the choice of an alkyllithium reagent. The inherently chiral oxazoline calix[4]arenes have also been preliminarily

• of diastereomers was found to be opposite to those obtained when using the other alkyllithiums. Indeed diastereoselective reversals of this type have only rarely been observed in the literature [28][29][30][31] but importantly offer the advantage of accessing both inherently chiral antipodes after

Preparation of neuroprotective condensed 1,4-benzoxazepines by regio- and diastereoselective domino Knoevenagel–[1,5]-hydride shift cyclization reaction

• László Tóth,
• Yan Fu,
• Hai Yan Zhang,
• Attila Mándi,
• Katalin E. Kövér,
• Tünde-Zita Illyés,
• Attila Kiss-Szikszai,
• Balázs Balogh,
• Tibor Kurtán,
• Sándor Antus and
• Péter Mátyus

Beilstein J. Org. Chem. 2014, 10, 2594–2602, doi:10.3762/bjoc.10.272

• Chemistry, University of Debrecen, H-4010 Debrecen, Hungary Porfirin Ltd., Mikszáth K. u. 7. III/3, 4032 Debrecen, Hungary 10.3762/bjoc.10.272 Abstract Condensed O,N-heterocycles containing tetrahydro-1,4-benzoxazepine and tetrahydroquinoline moieties were prepared by a regio- and diastereoselective domino

• cellular injuries in human neuroblastoma SH-SY5Y cells in the range of those of positive controls. Keywords: 1,4-benzoxazepine; diastereoselective domino Knoevenagel–[1,5]-hydride shift cyclization; neuroprotective; tert-amino effect; TDDFT-ECD calculation; Introduction The 1,4-benzoxazepine structural

• neuroprotective condensed 2-phenyl-1,4-benzoxazepines rac-7a,b through the diastereoselective domino Knoevenagel–1,5-hydride shift cyclization reaction rac-5→rac-7a,b from the readily available 4-aryl-2-phenyl-1,4-benzoxazepine derivative, rac-5 (Scheme 1). Ring-closure transformations involving C(sp3)–H bond

Regio- and stereoselective synthesis of new diaminocyclopentanols

• Evgeni A. Larin,
• Valeri S. Kochubei and
• Yuri M. Atroshchenko

Beilstein J. Org. Chem. 2014, 10, 2513–2520, doi:10.3762/bjoc.10.262

• aminoglycosides [7], and nucleosides containing 9H-purin-6-amine as a nucleobase portion. High levels of stereoselectivity have been observed in substrate-controlled diastereoselective epoxidation of cyclic alkenes with O- and N-allylic directing groups [20][21]. Several 3-substituted diastereomeric epoxides have

Formal total syntheses of classic natural product target molecules via palladium-catalyzed enantioselective alkylation

• Yiyang Liu,
• Marc Liniger,
• Ryan M. McFadden,
• Jenny L. Roizen,
• Jacquie Malette,
• Corey M. Reeves,
• Douglas C. Behenna,
• Masaki Seto,
• Jimin Kim,
• Justin T. Mohr,
• Scott C. Virgil and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2014, 10, 2501–2512, doi:10.3762/bjoc.10.261

• chiral glycolic acid ketal 23 (enantioenriched to 80% ee) to the more elaborate diene 24 via two diastereoselective alkylations. After a sequence of three reactions including removal of the pinacolone portion of the auxiliary, carboxylic acid 22 could be accessed. Novak’s synthesis applied a

• of which are enantioselective [54][55][56]. In Danishefsky’s approach to racemic dysidiolide, the cyclohexene ring of 30 was installed via diastereoselective Diels–Alder reaction of a transient dioxolenium dienophile and chiral vinylcyclohexene 31 [48]. Triene 31 was prepared from α-quaternary ketone

Total synthesis of the proposed structure of astakolactin

• Takayuki Tonoi,
• Keisuke Mameda,
• Moe Fujishiro,
• Yutaka Yoshinaga and
• Isamu Shiina

Beilstein J. Org. Chem. 2014, 10, 2421–2427, doi:10.3762/bjoc.10.252

• ethyl acetate to afford the adduct 19. Diastereoselective methylation of the ester enolate moiety of 19 with MeI afforded only the anti-product 20 [32][33], which was then subjected to the deprotection of the TBDPS group with HF·pyridine, followed by cleavage of the ethyl ester group in 21 to give the

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

• diastereoselective reactions including one-pot, sequential RCM/CM/H2 protocols and their applications in total synthesis of various natural products [27][28][29][30][31][32]. In addition, the scope of phosphate-tethered methods was further expanded via extensive RCM studies of different triene subunits utilizing

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• many have been applied in medicine and other fields. Using the axially chiral spirophosphine D1, Shi and co-workers accomplished highly regioselective, diastereoselective, and enantioselective [3 + 2] annulations of a series of alkylidene azlactones with allenoates (Scheme 18) [49]. Under mild

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

• a starting alkenol. The substrate scope and proposed mechanism of Pd-catalysed cyclisation reactions are also discussed. Moreover, the diastereoselective Pd-catalysed cyclisation of appropriate alkenols to tetrahydrofurans and subsequent cyclisation provided properly substituted 2,5-dioxabicyclo

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

• -monofluoroalkylphosphonic acids were synthesized by diastereoselective fluorination of phosphonamides bearing (−)-ephedrine as chiral auxiliary, originally introduced by Sting and Steglich for the synthesis of aminoalkylphosphonic acids [7] (Scheme 16). Thus, condensation of the phosphonic acid dichloride obtained from

• , which was then opened by morpholine to afford amide 167. The primary alcohol was then oxidized to the aldehyde under Swern conditions and submitted to a diastereoselective Strecker synthesis to install the amino acid moiety. Thus, condensation of the aldehyde with (R)-α-phenylglycinol followed by

• conjugate addition of methanol and lactonization. The second cyclic building block, syn-dihydropyran 188, could be synthesized by a highly diastereoselective 6-endo-trig cyclization of an allylic 1,3-diol, which was developed by Hanessian and co-workers [141]. The required allylic 1,3-diol would also be

Rational design of cyclopropane-based chiral PHOX ligands for intermolecular asymmetric Heck reaction

• Marina Rubina,
• William M. Sherrill,
• Alexey Yu. Barkov and
• Michael Rubin

Beilstein J. Org. Chem. 2014, 10, 1536–1548, doi:10.3762/bjoc.10.158

• into acyl chloride (S)-16. Subsequent acylation of (R)-phenylglycinol with (S)-16 afforded amide 17, which was subjected to cyclization in the presence of mesyl chloride and a base providing dihydrooxazole 18. Diastereoselective partial reduction of the dibromocyclopropane moiety with zinc dust in

Asymmetric Ugi 3CR on isatin-derived ketimine: synthesis of chiral 3,3-disubstituted 3-aminooxindole derivatives

• Giordano Lesma,
• Fiorella Meneghetti,
• Alessandro Sacchetti,
• Mattia Stucchi and
• Alessandra Silvani

Beilstein J. Org. Chem. 2014, 10, 1383–1389, doi:10.3762/bjoc.10.141

• created, the stereoselectivity remains a difficult task. Waiting for enantioselective versions of the Ugi reaction [29][30][31], the diastereoselective approach by using chiral material is a possible solution. In particular, amines have shown to be promising as chiral auxiliaries, even though only a few

Stereoselective synthesis of carbocyclic analogues of the nucleoside Q precursor (PreQ₀)

• Sabin Llona-Minguez and
• Simon P. Mackay

Beilstein J. Org. Chem. 2014, 10, 1333–1338, doi:10.3762/bjoc.10.135

• introduction of diverse aryl groups at the 3-position of the cyclohexane ring using commercially available arylboronic acids as building blocks, and Pd catalysis to form the new C–C bond, followed by a highly diastereoselective ketone-to-amine conversion. Others have reported on similar preparations of 3

Human dendritic cell activation induced by a permannosylated dendron containing an antigenic GM₃-lactone mimetic

• Renato Ribeiro-Viana,
• Elena Bonechi,
• Javier Rojo,
• Clara Ballerini,
• Giuseppina Comito,
• Barbara Richichi and
• Cristina Nativi

Beilstein J. Org. Chem. 2014, 10, 1317–1324, doi:10.3762/bjoc.10.133

• unit of 6 was efficiently performed relying on a totally diastereoselective inverse electron-demand [4 + 2] hetero-Diels–Alder reaction , as described in [31]. The synthesis of compound 5 is depicted in Scheme 1. The mimetic 6 was deprotected with sodium carbonate at room temperature. Without further

Amino acid motifs in natural products: synthesis of O-acylated derivatives of (2S,3S)-3-hydroxyleucine

• Oliver Ries,
• Martin Büschleb,
• Markus Granitzka,
• Dietmar Stalke and
• Christian Ducho

Beilstein J. Org. Chem. 2014, 10, 1135–1142, doi:10.3762/bjoc.10.113

• will also be useful for the synthesis of other natural products containing this amino acid. Several synthetic approaches towards (2S,3S)-3-hydroxyleucine have been established utilizing for instance diastereoselective aldol reactions [26][27][28], Sharpless epoxidation [29], asymmetric hydrogenation

• protecting group pattern. The most promising strategy to achieve these goals appeared to be a variation of the ex-chiral pool synthesis developed by Zhu and co-workers [32]. They have utilized the stereocenter of D-serine in a diastereoselective Grignard addition to protected D-serinal as the key step of

• derivative with limited stability, which was immediately converted into alcohol 4 by diastereoselective Felkin–Anh type Grignard addition with isopropyl magnesium chloride (50% yield over 2 steps from 3, dr > 95:5). However, we could not confirm that the use of diethyl ether as co-solvent in the Grignard

Synthesis of zearalenone-16-β,D-glucoside and zearalenone-16-sulfate: A tale of protecting resorcylic acid lactones for regiocontrolled conjugation

• Hannes Mikula,
• Julia Weber,
• Dennis Svatunek,
• Philipp Skrinjar,
• Gerhard Adam,
• Rudolf Krska,
• Christian Hametner and
• Johannes Fröhlich

Beilstein J. Org. Chem. 2014, 10, 1129–1134, doi:10.3762/bjoc.10.112

• using acetyl-protected glucosyl donors since diastereoselective β-conjugation, which is needed for the preparation of glucosides formed during phase II metabolism, is commonly achieved applying the participation of acyl groups at O-2 of the glycosyl donor (anchimeric effect) [30]. Lewis acid-mediated

Stereocontrolled synthesis of 5-azaspiro[2.3]hexane derivatives as conformationally “frozen” analogues of L-glutamic acid

• Beatrice Bechi,
• David Amantini,
• Cristina Tintori,
• Maurizio Botta and
• Romano di Fabio

Beilstein J. Org. Chem. 2014, 10, 1114–1120, doi:10.3762/bjoc.10.110

• rotation around the C3–C4 bond present in the azetidine derivative Ia by incorporating an appropriate spiro moiety. The cyclopropyl moiety was introduced by a diastereoselective rhodium catalyzed cyclopropanation reaction. Keywords: Amino acids; carbenes; cyclopropanation; rhodium; spiro compounds

• faces of the terminal olefin group, therefore affording both the trans and the cis pair of diasteroisomers. As expected based on data available in literature [41][42], the reaction was highly diastereoselective toward the formation of the two trans cyclopropane derivatives 20a and 20c. Furthermore, a

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• halophosphines and their weak configurational stability. P-stereogenic chlorophosphines racemize easily even at room temperature [30]. Enantiopure P-stereogenic compounds can be synthesized via a diastereoselective nucleophilic substitution at phosphorus utilizing chiral auxiliaries. Diastereomeric intermediates

• catalyzed intramolecular hydrophosphination of phosphinoalkenes. Scheme 15 shows the diastereoselective synthesis of 2,5-dimethylphospholanes 49 from 47 with a lanthanide catalyst 48 [122]. The common mechanism when using lanthanide [113] or alkaline earth metal [123] catalysts is based on the formation of

Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

• Bernd Schmidt and
• Sylvia Hauke

Beilstein J. Org. Chem. 2014, 10, 1023–1031, doi:10.3762/bjoc.10.102

• perdeuteration of an alkynoate derived from L-threonine (giving a 2,2,3,3-tetradeuterated amicetose) [26], enantioselective hydroboration of hetero Diels–Alder adducts [27], stereoconservative diazotation of L-glutamic acid [28][29], diastereoselective addition of methylmagnesium bromide to enantiopure 2

• ], respectively, which both use enantiomerically pure L-ethyl lactate (1) as the starting material (Scheme 1). The synthetic routes rely on the highly diastereoselective two-step conversion of ethyl lactate to allylic alcohol 2 [36][37] and further to the RCM precursor 3, which then undergoes RCM-isomerization to

Phosphinate-containing heterocycles: A mini-review

• Olivier Berger and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2014, 10, 732–740, doi:10.3762/bjoc.10.67

• corresponding analog of cyclic AMP, but no biological activity was reported. 1,2-Oxaphosphorines Gouverneur and coworkers have realized the synthesis of several 1,2-oxaphosphorine derivatives 53a–k using diastereoselective ring closing metathesis with 2 to 4 mol % of various catalysts (Scheme 22) [34]. During

• (trimethylsiloxy)phosphine. Diastereoselective ring-closing metathesis. 2-Ketophosphonate/benzene annulation. Tandem Kabachnik–Fields/transesterification reaction. Tandem Kabachnik–Fields/transesterification reaction with oxazolidine. Acknowledgements This material is based in part upon work supported by the

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

• starting materials, an easy modification of the auxiliary and a highly diastereoselective control. Furthermore, the phosphonyl auxiliaries can do favor in the final purification, and it did not need any column chromatography or recrystallization, which was summarized as GAP (group assisted purification