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

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• , respectively, in moderate to excellent yields. The reaction with the erythro isomer resulted in a single diastereomer 48a whereas no selectivity was observed for the threo isomer. Based on this diastereoselective MCR, the group of Banfi developed an Ugi-Joullié 3-CR with carboxylic acids, chiral bicyclic

• yields and in high diastereomeric excess (de 70–96%) [60]. It is worth noting that deprotection of the acetal-group allows modulation of rigidity and polarity of the final molecules. Our group reported a highly diastereoselective Ugi-MCR towards 3,4-alkyl-substituted prolyl mimics by reacting several

• several pharmaceutical compounds such as antipsychotics, anticonvulsants, local anaesthetics or analgesics [131]. An interesting diastereoselective multicomponent approach towards such six-membered pipecolic acid-based analogues was described by Maison et al. [128] Although this work is closely related to

A catalyst-free multicomponent domino sequence for the diastereoselective synthesis of (E)-3-[2-arylcarbonyl-3-(arylamino)allyl]chromen-4-ones

• Pitchaimani Prasanna,
• Pethaiah Gunasekaran,
• Subbu Perumal and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2014, 10, 459–465, doi:10.3762/bjoc.10.43

• and in a diastereoselective transformation. This transformation generates one C–C and one C–N bond and presumably proceeds via a reaction sequence comprising a Michael-type addition–elimination reaction, a nucleophilic attack of an enamine to a carbonyl reminiscent of one of the steps of the Bayllis

• developed a facile three-component diastereoselective synthesis of novel (E)-3-[2-arylcarbonyl-3-(arylamino)allyl]-4H-chromen-4-ones containing chromone and β-enaminoketone structural fragments from simple, readily available starting materials in a one-pot operation and in good to excellent yields. This

Self-assembly of metallosupramolecular rhombi from chiral concave 9,9’-spirobifluorene-derived bis(pyridine) ligands

• Rainer Hovorka,
• Sophie Hytteballe,
• Torsten Piehler,
• Georg Meyer-Eppler,
• Filip Topić,
• Kari Rissanen,
• Marianne Engeser and
• Arne Lützen

Beilstein J. Org. Chem. 2014, 10, 432–441, doi:10.3762/bjoc.10.40

• -recognising [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] or a self-discriminating manner [19][20][21][22][23][24][25][26][27]. As part of our ongoing programme to develop general guidelines for the diastereoselective self-assembly of metallosupramolecular aggregates, we have recently started a

• of self-discrimination. Analysis of the 1H NMR spectra provides versatile information: first, the self-assembly is not completely diastereoselective, since a number of additional signals are visible in the spectrum of the aggregates obtained from (rac)-3. Second, the self-assembly does not happen in

• . Interestingly, these self-assembly processes proceed with significant diastereoselective self-sorting via preferred narcissistic self-recognition amplifying the formation of the homochiral assemblies by a factor of approximately three. Together with the results obtained for further bis(pyridine) ligands derived

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• Abstract A concise (5 to 6 steps), stereodivergent, highly diastereoselective (dr up to >19:1 for both stereoisomers) and scalable synthesis (up to 14 g) of cis- and trans-2-substituted 3-piperidinols, a core motif in numerous bioactive compounds, is presented. This sequence allowed an efficient synthesis

Boron-substituted 1,3-dienes and heterodienes as key elements in multicomponent processes

• Ludovic Eberlin,
• Fabien Tripoteau,
• François Carreaux,
• Andrew Whiting and
• Bertrand Carboni

Beilstein J. Org. Chem. 2014, 10, 237–250, doi:10.3762/bjoc.10.19

• finally elimination of boryl and boroxy groups. Four C–B bonds were converted into two C–C and one C=C bonds with total stereocontrol in each step (Scheme 16) [58]. 1-Boron-substituted 1,3-heterodienes 1-Oxo-4-borono-1,3-dienes In 2003, first examples of a novel diastereoselective routes to α

• 1,3-diene in a tandem cycloaddition [4 + 2]/allylboration sequence. Lewis acid catalyst in the tandem cycloaddition [4 + 2]/allylboration sequence. Synthesis of an advanced precursor of clerodin. Intramolecular Diels–Alder/allylboration sequence. Diastereoselective Diels–Alder reaction with N

Synthesis of the B-seco limonoid core scaffold

• Hanna Bruss,
• Hannah Schuster,
• Rémi Martinez,
• Markus Kaiser,
• Andrey P. Antonchick and
• Herbert Waldmann

Beilstein J. Org. Chem. 2014, 10, 194–208, doi:10.3762/bjoc.10.15

• taxoid building block. Regioselective protection of the less hindered ketone in 80 and diastereoselective hydrogenation of the double bond could be achieved in a known one-pot procedure [54][55] affording the cis-hydrindanone and providing the desired stereochemistry at C4 and C5. Ozonolytic cleavage of

Stereoselectively fluorinated N-heterocycles: a brief survey

• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2013, 9, 2696–2708, doi:10.3762/bjoc.9.306

• ]-Wittig rearrangement, a diastereoselective epoxidation, and a microwave assisted transannular epoxide opening reaction. It is also noteworthy that the starting material 55 contains an extraneous fluorine atom which is deleted during the synthetic sequence; this approach takes advantage of the often low

• cost and ready availability of perfluorinated building blocks. It should be noted, however, that access to enantiopure targets is not straightforward via the building block approach. Such targets may be better obtained through diastereoselective or enantioselective fluorination methods, and examples of

• these types of approaches are examined in the following sections. 6.3 Diastereoselective fluorocyclisation The use of fluorocyclisation processes for the production of heterocycles and carbocycles has attracted considerable attention in recent years. Such processes have the advantage of forming multiple

Diastereoselectivity in the Staudinger reaction of pentafluorosulfanylaldimines and ketimines

• Alexander Penger,
• Cortney N. von Hahmann,
• Alexander S. Filatov and
• John T. Welch

Beilstein J. Org. Chem. 2013, 9, 2675–2680, doi:10.3762/bjoc.9.303

• stereochemistry. Optimization of β-lactam synthesis will require a better understanding of the nature of the competing, undesirable reactions and enable utilization of this unique construct in further synthetic transformations. The product β-lactams are a useful entrée to the diastereoselective synthesis of

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

• -selectivity (Table 1, entry 20). Olefination of Garner’s aldehyde Olefination of 1 provides an easy access to chiral 2-aminohomoallylic alcohols A (Scheme 24). The intermediate can be derivatized further, thus providing a route for greater molecular diversity. Diastereoselective dihydroxylation of A with OsO4

• leads to triols B, which have been utilized in the syntheses of calyculins family [83][84], D-ribo-phytosphingosine [85], and radicamine [86][87]. If the R-group in A is an ester, diastereoselective Michael addition leads to structures C [88][89][90][91][92]. Kainic acid was synthesized using such

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

• deuterated compounds 14a,b permitted to confirm the anti-diastereoselective hydroamination of the double bond. (Scheme 5b). Interestingly, although 14 represents a likely intermediate of the reaction course, when it was treated with various Brønsted and Lewis acids, the expected product 16 was not observed

Stereodivergent synthesis of jaspine B and its isomers using a carbohydrate-derived alkoxyallene as C₃-building block

• Volker M. Schmiedel,
• Stefano Stefani and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2013, 9, 2564–2569, doi:10.3762/bjoc.9.291

• indicates that a (partial) epimerization at C-4 occurs under the reaction conditions employed. The diastereoselective reduction of the carbonyl group with L-selectride afforded the α-azidotetrahydrofuranones 9 and 10 in 66% yield over three steps. Subsequent hydrogenolysis of 9 and 10 afforded a mixture of

Bidirectional cross metathesis and ring-closing metathesis/ring opening of a C₂-symmetric building block: a strategy for the synthesis of decanolide natural products

• Bernd Schmidt and
• Oliver Kunz

Beilstein J. Org. Chem. 2013, 9, 2544–2555, doi:10.3762/bjoc.9.289

• -membered ring lactones stagonolide E and curvulide A were synthesized using a bidirectional olefin-metathesis functionalization of the terminal double bonds. Key steps are (i) a site-selective cross metathesis, (ii) a highly diastereoselective extended tethered RCM to furnish a (Z,E)-configured dienyl

Synthetic scope and DFT analysis of the chiral binap–gold(I) complex-catalyzed 1,3-dipolar cycloaddition of azlactones with alkenes

• María Martín-Rodríguez,
• Luis M. Castelló,
• Carmen Nájera,
• José M. Sansano,
• Olatz Larrañaga,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2013, 9, 2422–2433, doi:10.3762/bjoc.9.280

• enantioselective and/or diastereoselective processes have been focussed on the elaboration of enantiomerically enriched new non-proteinogenic α-amino acids, such as Michael-type additions [6][7], transition metal-catalyzed allylations [8], Mannich-type additions [9], aldol-type reactions [10], and for other

• -methyloxazole-5-one 10, surprisingly, reacted at 25 and at 0 °C with tert-butyl acrylate yielding cycloadduct 11 in good yields and moderate to good enantioselections (Scheme 6). If we compare this result with previous ones obtained using α-imino esters, this last diastereoselective cycloaddition exhibited an

Towards stereochemical control: A short formal enantioselective total synthesis of pumiliotoxins 251D and 237A

• Jie Zhang,
• Hong-Kui Zhang and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2013, 9, 2358–2366, doi:10.3762/bjoc.9.271

• , Lanzhou 730000, P. R. China 10.3762/bjoc.9.271 Abstract A concise enantioselective synthesis of the advanced intermediate 5 for the synthesis of pumiliotoxins (Gallagher’s intermediate) is described. The synthesis started from the regio- and trans-diastereoselective (dr = 98:2) reductive 3-butenylation

• ][31], among them L-proline and its derivative were used as popular precursors from the pool of chiral compounds [13][14][15][18][19][20][21][22]. Herein, we report a concise diastereoselective synthesis of (8S,8aS)-5 starting from (R)-3-(tert-butyldimethylsilyloxy)glutarimide 14, a versatile building

• minor diastereomer. Similar results have been reported by Nubbemeyer [27] and Li [8]. In view of the fruitless efforts of Nubbemeyer [27] and Li [8] in inversing the diastereoselectivity of the methylation reaction of keto-lactam 7, an alternative approach was envisaged. To develop a diastereoselective

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

• noted that both enantiomers were required for physiological profiling at the discovery stage). Next, a 1,2-syn diastereoselective reduction of enaminoester 2.81 occurs with high diastereocontrol imposed by the convexed presentation of the substrate for the formal conjugate addition and subsequent

Gold(I)-catalyzed enantioselective cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2013, 9, 2250–2264, doi:10.3762/bjoc.9.264

• ]. Further studies revealed that the scope of the methodology could be significantly broadened by using a gold catalyst such as Au9/AgSbF6 [58]. In general, the reactions are completely diastereoselective, affording bicyclo[5.3.0]decane products (14 and/or 14’) that result from an exo-like approach of the

Gold(I)-catalyzed 6-endo hydroxycyclization of 7-substituted-1,6-enynes

• Ana M. Sanjuán,
• Alberto Martínez,
• Patricia García-García,
• Manuel A. Fernández-Rodríguez and
• Roberto Sanz

Beilstein J. Org. Chem. 2013, 9, 2242–2249, doi:10.3762/bjoc.9.263

• expected [10][11][12] the terminal enyne 1l (R = H) underwent exclusively the 5-exo cyclization leading to the corresponding alcohol 8l in 55% yield (Table 2, entry 12). At this point we wondered if the cyclization would be diastereoselective, so we prepared enynes 1m by reacting 2-(phenylethynyl

Gold-catalyzed glycosidation for the synthesis of trisaccharides by applying the armed–disarmed strategy

• Abhijeet K. Kayastha and
• Srinivas Hotha

Beilstein J. Org. Chem. 2013, 9, 2147–2155, doi:10.3762/bjoc.9.252

• -catalyzed glycosidations [22][23][24][25][26][27][28]. Propargyl mannopyranosides as glycosyl donors are ideal for investigating armed–disarmed strategies for the synthesis of oligosaccharides, because the gold-catalyzed glycosidation proceeds in a highly 1,2-trans diastereoselective fashion [22