Solution-phase automated synthesis of an α-amino aldehyde as a versatile intermediate

• Hisashi Masui,
• Sae Yosugi,
• Shinichiro Fuse and
• Takashi Takahashi

Beilstein J. Org. Chem. 2017, 13, 106–110, doi:10.3762/bjoc.13.13

• developed solution-phase automated synthesizer, ChemKonzert [9]. Protected α-amino aldehydes are versatile intermediates for the synthesis of vicinal amino alcohols and important building blocks for various bioactive natural products [10][11][12]. In particular, Garner’s aldehyde (4a) is very useful as a

Iodination of carbohydrate-derived 1,2-oxazines to enantiopure 5-iodo-3,6-dihydro-2H-1,2-oxazines and subsequent palladium-catalyzed cross-coupling reactions

• Michal Medvecký,
• Igor Linder,
• Luise Schefzig,
• Hans-Ulrich Reissig and
• Reinhold Zimmer

Beilstein J. Org. Chem. 2016, 12, 2898–2905, doi:10.3762/bjoc.12.289

• modifications and synthetic applications of 1,2-oxazines 3 including the preparation of seven-membered N,O-heterocycles by ring enlargement [5], functionalization of the enol ether unit [6][7][8][9][10][11], and N,O-cleavage reactions leading to amino alcohols [8][10][12], pyrroles [13] or α,β-unsaturated β

• proceeded well and afforded the expected 5-(1,2,3-triazolyl)-substituted 1,2-oxazine syn-26 in moderate yield (54%). Hydrogenolysis belongs to the well-established transformations of 1,2-oxazines, often successfully leading to valuable compounds including 1,4-amino alcohols or pyrrolidine derivatives. We

• -oxazines that after cleavage of the N–O bond provide the corresponding amino alcohols. In the second reaction step, the hydrogen attacks the C=C bond mainly from the less hindered side (here trans to the fairly bulky 3-dioxolanyl group) leading to the preferred configuration of anti-30a as depicted in

β-Amino functionalization of cinnamic Weinreb amides in ionic liquid

• Yi-Ning Wang,
• Guo-Xiang Sun and
• Gang Qi

Beilstein J. Org. Chem. 2016, 12, 2372–2377, doi:10.3762/bjoc.12.231

• towards the preparation of β-amino carbonyl compounds is the Mannich reaction [8][9]. However, there are few reported methods specifically focused on this target, which include oxidation of γ-amino alcohols [10], hydrolysis of 1,3-oxazines [11], rearrangement of 2,3-aziridinio alcohols [12], etc. N

Synthesis and NMR studies of malonyl-linked glycoconjugates of N-(2-aminoethyl)glycine. Building blocks for the construction of combinatorial glycopeptide libraries

• Markus Nörrlinger,
• Sven Hafner and
• Thomas Ziegler

Beilstein J. Org. Chem. 2016, 12, 1939–1948, doi:10.3762/bjoc.12.183

• either simple alkyl chains [15][16], amino alcohols [17][18] or 1,2,3-triazoles [19][20][21]. These building blocks were used for automated SPOT synthesis on a cellulose surface in order to construct complex glycoconjugates which are able to specifically bind to lectins [15][18][20]. In continuation of

A chiral analog of the bicyclic guanidine TBD: synthesis, structure and Brønsted base catalysis

• Mariano Goldberg,
• Denis Sartakov,
• Jan W. Bats,
• Michael Bolte and
• Michael W. Göbel

Beilstein J. Org. Chem. 2016, 12, 1870–1876, doi:10.3762/bjoc.12.176

• ][16][17] or from their reduction products, chiral α-amino alcohols [9][18]. In contrast, our approach used the racemic ester rac-12 of β-phenylalanine, easily accessible in a Knoevenagel-type condensation of benzaldehyde 11, ammonium acetate and malonic acid, followed by esterification (Scheme 1) [20

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

• ligands are air and moisture-stable, the free ligands are prone to hydrolysis and oxidation. Especially SimplePHOX ligands, although they are readily prepared from amino alcohols in just two steps, suffer from these problems resulting in low yields and difficult purification steps. We therefore decided to

One-pot synthesis of enantiomerically pure N-protected allylic amines from N-protected α-amino esters

• Gastón Silveira-Dorta,
• Sergio J. Álvarez-Méndez,
• Víctor S. Martín and
• José M. Padrón

Beilstein J. Org. Chem. 2016, 12, 957–962, doi:10.3762/bjoc.12.94

• unstable to manipulate. As part of our interest in the synthesis of nitrogen-containing bioactive molecules [15], we developed a simplified version of the Reetz protocol [11] for the synthesis of enantiomerically pure anti-β-amino alcohols [16]. The process circumvents the problem of the instability of the

• our one-pot procedure to obtain enantiomerically pure anti-β-amino alcohols, we selected N,N-dibenzyl amino esters as starting material. We also investigated whether the method we developed could be applied to serine and threonine derivatives without protection of the hydroxy groups. Results and

• mixture. In the one-pot synthesis of anti-β-amino alcohols, the best results were achieved when the reactions were run in Et2O [16]. A fine tuning of the reducing agent was also necessary to obtain the desired products. Our first goal was to study the outcome of the reaction in terms of solvent and the

Self and directed assembly: people and molecules

• Tony D. James

Beilstein J. Org. Chem. 2016, 12, 391–405, doi:10.3762/bjoc.12.42

• the enantiomeric excess of the original scalemic mixture of binol (diol) or amine (Figure 15). The three-component system was very versatile and we could use the complexes to determine the enantiomeric excess (ee) of amines [69][70], diamines [71], amino alcohols [72], hydroxylamines [73] and diols

Organocatalytic asymmetric Henry reaction of 1H-pyrrole-2,3-diones with bifunctional amine-thiourea catalysts bearing multiple hydrogen-bond donors

• Ming-Liang Zhang,
• Deng-Feng Yue,
• Zhen-Hua Wang,
• Yuan Luo,
• Xiao-Ying Xu,
• Xiao-Mei Zhang and
• Wei-Cheng Yuan

Beilstein J. Org. Chem. 2016, 12, 295–300, doi:10.3762/bjoc.12.31

• amino-alcohols, amino acids and carbonyl compounds [15]. Much attention has been devoted to the development of an efficient catalytic asymmetric version of this reaction from readily accessible nitroalkanes and carbonyl compounds [16], such as aldehydes [17][18][19], α-ketoesters [20], α

Copper-catalyzed asymmetric conjugate addition of organometallic reagents to extended Michael acceptors

• Thibault E. Schmid,
• Sammy Drissi-Amraoui,
• Christophe Crévisy,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2015, 11, 2418–2434, doi:10.3762/bjoc.11.263

• variety of unsymmetrical NHC precursors [25]. With this new methodology in hand, Mauduit and co-workers synthesized several bidentate chiral NHC precursors, using amino acids and amino alcohols as starting materials, and tested them in copper-catalyzed ACA [26]. Leucine-based L5 displayed the best

Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

• Tor E. Kristensen

Beilstein J. Org. Chem. 2015, 11, 446–468, doi:10.3762/bjoc.11.51

• related compounds, such as various amino alcohols and the thiol-functional amino acid cysteine. While the basic methodology underlying this approach has been known for decades, it has evolved through recent developments connected to amino acid-derived chiral organocatalysts to become a more widely

• more elaborate procedures for chemoselective O-acylation reactions, spur its further development, and finally to chronicle the informative, but poorly documented history of its development. Keywords: amino alcohols; chemoselectivity; DOPA; hydroxyamino acids; hydroxyproline; O-acylation

• be distinctly preferable to other, including newer and more widely publicized, preparatory strategies for chemical manipulation of amino alcohols and other functionally related substances. Review The historical development of acidic chemoselective O-acylation procedures for hydroxyamino acids The

Stereoselective cathodic synthesis of 8-substituted (1R,3R,4S)-menthylamines

• Carolin Edinger,
• Jörn Kulisch and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2015, 11, 294–301, doi:10.3762/bjoc.11.34

• [19] are used as precursors for chiral β-amino alcohols. As precursors for α-chiral primary amines, fenchone [20] and camphor [21][22] are typically employed. Furthermore, optically pure dehydroabietylamine is readily available and applicable without further modification [23][24][25]. Among the

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

• quinone 116 afforded esters 117. This method was also applied to the synthesis of esters 117a–c from amino alcohols (Scheme 25) [115][116]. Different conditions were proposed for the cross-dehydrogenative C–O coupling of aldehydes with alcohols and phenols catalyzed by N-heterocyclic carbenes (118, 129

Multicomponent versus domino reactions: One-pot free-radical synthesis of β-amino-ethers and β-amino-alcohols

• Bianca Rossi,
• Nadia Pastori,
• Simona Prosperini and
• Carlo Punta

Beilstein J. Org. Chem. 2015, 11, 66–73, doi:10.3762/bjoc.11.10

• imines through a ring opening of the ether (Scheme 2, entry c) [30]. Even though it is interesting by itself, this domino reaction limits the general approach towards the synthesis of a wider range of β-amino-alcohols and ethers. The importance of these derivatives is well-documented. They are the key

Stereoselective synthesis of perillaldehyde-based chiral β-amino acid derivatives through conjugate addition of lithium amides

• Zsolt Szakonyi,
• Reijo Sillanpää and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2014, 10, 2738–2742, doi:10.3762/bjoc.10.289

• -pinene and verbenone, have frequently been used as starting materials for the preparation of chiral reagents and as unique synthons in asymmetric syntheses of β-amino acids and 1,3-amino alcohols, which in turn can be applied as chiral additives, catalysts or building blocks [17][28][29][30][31][32][33

Synthesis of aromatic glycoconjugates. Building blocks for the construction of combinatorial glycopeptide libraries

• Markus Nörrlinger and
• Thomas Ziegler

Beilstein J. Org. Chem. 2014, 10, 2453–2460, doi:10.3762/bjoc.10.256

• focus was on glycosylated amino acid building blocks derived from aspartic acid and from the PNA-like N-(2-aminoethyl)glycine (AEG) backbone to which the sugar moieties were attached through either simple alkyl chains [5][6], amino alcohols [7][8] or 1,2,3-triazoles [9][10][11]. These building blocks

One-pot stereoselective synthesis of α,β-differentiated diamino esters via the sequence of aminochlorination, aziridination and intermolecular S_N2 reaction

• Yiwen Xiong,
• Ping Qian,
• Chenhui Cao,
• Haibo Mei,
• Jianlin Han,
• Guigen Li and
• Yi Pan

Beilstein J. Org. Chem. 2014, 10, 1802–1807, doi:10.3762/bjoc.10.189

• corresponding β,γ-amino alcohols and vicinal diamines. α,β-Diamino acid derivatives have been served as organocatalysts, chiral ligands, chiral auxiliaries for asymmertric synthesis [10][11][12], as well as synthetic fragments for peptides and natural products [13]. Mannich-type addition reactions of α-amino

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

• system. Indeed, a number of previously reported PHOX ligands derived from tert-leucinol were shown to provide superior enantioselectivities compared to their analogues obtained from less bulky amino alcohols [54][57][59]. However, the arylation carried out in the presence of L3 proceeded much more

Synthesis of 1-[bis(trifluoromethyl)phosphine]-1’-oxazolinylferrocene ligands and their application in regio- and enantioselective Pd-catalyzed allylic alkylation of monosubstituted allyl substrates

• Zeng-Wei Lai,
• Rong-Fei Yang,
• Ke-Yin Ye,
• Hongbin Sun and
• Shu-Li You

Beilstein J. Org. Chem. 2014, 10, 1261–1266, doi:10.3762/bjoc.10.126

• (COCl)2 and then chiral amino alcohols yielded the amide intermediates which were transformed to their corresponding 1-bromo-1’-oxazolinylferrocenes 3. Eventually, lithium–bromide exchange of 3 with n-BuLi at −78 °C, followed by quenching with P(OPh)3, provided the phosphonite intermediates which were

Homogeneous and heterogeneous photoredox-catalyzed hydroxymethylation of ketones and keto esters: catalyst screening, chemoselectivity and dilution effects

• Axel G. Griesbeck and
• Melissa Reckenthäler

Beilstein J. Org. Chem. 2014, 10, 1143–1150, doi:10.3762/bjoc.10.114

• product without the need of sacrificial components. The latter process proceeds with a high degree of atom economy [16]. We have recently demonstrated this for the azido-hydroperoxidation of alkenes, a convenient method for the synthesis of 1,2-amino alcohols [17][18]. In the field of C–C coupling

• contrast to that, photochemical redox activation is possible in the presence of titanium(IV) catalysts [19][20][21][22]. As shown in a series of papers by Sato and coworkers, carbonyl compounds 1 as well as imines couple with methanol to give the 1,2-diols or 1,2-amino alcohols, respectively, when

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

• -isomer over the 1,5-isomer [85]. In 2010, Nenajdenko et al. described an Ugi/Click-approach using chiral isocyanoazides, which in turn were derived from L-amino alcohols [85]. The Ugi-products were obtained in good yields, with high diastereoselectivity (de >99%). A follow-up Click reaction using 10 mol

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

• overcoming separation difficulties usually associated to triphenylphosphine oxide. Keywords: amino acids; asymmetric synthesis; cyclodehydration; hydroxypiperidines; natural products; one-pot; Introduction 1,2-Amino alcohols of the type A (Figure 1) represent a frequent core motif of many pharmacologically

• 5e (along with 30% of reisolated starting material), illustrating the tendency of reagent 6 to attack the side chain ester moiety. Synthesis of syn-amino alcohols C Already the NaBH4 reduction (in MeOH at −40/0 °C) of ketones 7a and 7b and subsequent hydrogenolysis of the Cbz-group in one-pot

• delivered the syn-amino alcohols 9a and 9b in good diastereomeric ratios (around 11:1 syn/anti, compare Scheme 4). In contrast the NaBH4 reduction of ketone 7c under identical conditions gave diol 9c without any selectivity (dr = 1.3:1). To our delight, reduction of the ketones 7a and 7b with L-Selectride

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

• ]. We have recently reviewed the literature on the synthesis of 1,2-vicinal amino alcohols [53]. Use of Garner’s aldehyde for the synthesis of non-natural amino acids through ethynylglycine has been reviewed [54]. In the following section, significant findings in the use of 1 as an electrophile and

• synthesis. Simple addition reactions to the carbonyl group give access to vicinal amino alcohols, important building blocks for many natural products. Another possibility for carbon chain elongation are olefination reactions, which often lead to epimerization of the α-stereocenter. As with the alkylations

A one-pot synthesis of 3-trifluoromethyl-2-isoxazolines from trifluoromethyl aldoxime

• Raoni S. B. Gonçalves,
• Michael Dos Santos,
• Guillaume Bernadat,
• Danièle Bonnet-Delpon and
• Benoit Crousse

Beilstein J. Org. Chem. 2013, 9, 2387–2394, doi:10.3762/bjoc.9.275

• yield the corresponding trifluoromethylated γ-amino alcohols. Keywords: aldoxime; amino alcohol; fluorine; isoxazole; isoxazoline; organo-fluorine; Introduction 2-Isoxazolines are five-membered heterocyclic compounds that have been widely applied in medicinal and organic chemistry. This nucleus is

• supply a variety of organic functionalities including γ-amino alcohols [12], β-amino acids [13], β-hydroxy ketones [14][15] and β-hydroxy nitriles [14][15]. Fluorinated compounds play a central role in different branches of chemistry [16]. The incorporation of a fluorine atom into bioactive molecules

• order to prepare the corresponding trifluoromethylated γ-amino alcohols. The major and almost the only route to synthesize these amino alcohols is the reduction of β-aminocarbonyl compounds prepared from Mannich-type reactions [46][47][48]. The ring opening of 2-methyl-3-trifluoromethylisoxazolines by

Direct electrophilic N-trifluoromethylthiolation of amines with trifluoromethanesulfenamide

• Sébastien Alazet,
• Kevin Ollivier and
• Thierry Billard

Beilstein J. Org. Chem. 2013, 9, 2354–2357, doi:10.3762/bjoc.9.270

• volatility, some compounds (3h and 3i) have not been isolated. Imines can be also trifluoromethylthiolated in good yields (3m). Even if our first developed method is compatible with primary amines [37], they can also react under these new conditions, as illustrated with the aniline (3n). Amino alcohols and