Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• silyl ethers 89–92 (Scheme 18), thus showcasing the synergistic relationship between Pd and Cu catalysis [43]. Driven by the success of earlier results, the authors utilized 78 for reductive couplings between ketones 93 and imines 97 as electrophiles to form unsymmetrical 1,2-diols 94–96 and 1,2-amino

• alcohols 98–100, respectively. Palladium was no longer needed for these transformations. The scope of the reaction with ketones was not limited to diaryl species and aryl ketones participated in the reaction, including those with more hindered alkyl groups (Scheme 19) [44]. This discovery was followed by a

KOt-Bu-promoted selective ring-opening N-alkylation of 2-oxazolines to access 2-aminoethyl acetates and N-substituted thiazolidinones

• Qiao Lin,
• Shiling Zhang and
• Bin Li

Beilstein J. Org. Chem. 2020, 16, 492–501, doi:10.3762/bjoc.16.44

• coordination chemistry, and also valuable protecting or directing groups in catalysis [1][2][3]. 2-Oxazolines are a readily stable class of heterocycles resistant to a range of nucleophiles, bases, or radicals [4][5], which can be easily generated from amino alcohols and carboxylic acids, and from alkenes or

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• and mono-N-methylated spiro 1,3-amino alcohols 124. The mixture was equilibrated under reflux allowing P-center inversion and an uneven mixture of diastereoisomers 125 and 127 was obtained. Treating the mixture with borane·dimethyl sulfide gave a mixture of diastereoisomers in a ratio of 2:5. The

• carbon dioxide and phenyllithium gives the phosphine ferrocene carboxylic acid 152 as the major reagent. Oxidation of the phosphine using hydrogen peroxide generated the phosphine oxide 153. In situ chlorination of the carboxylic acid followed by addition of the chiral amino alcohols gave the phosphoryl

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

• electrochemical asymmetric oxidation of 1,2-diols 74 and amino alcohols 77 in presence of a Br- mediator using Cu(OTf)2 and (R,R)-Ph-BOX 76 as the catalytic system (Scheme 29). The method enabled an asymmetric synthesis of α-hydroxycycloalkanones 75 and α-amino esters 78 along with the kinetic resolution of

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• natural products as well as compounds of commercial interest as medications. Synthetic strategies to molecules as simple as amino alcohols to as complex as indolizine alkaloids will be discussed with a special focus on stereoselectivities of key transformations. Whenever possible biological activities of

• nucleophiles to provide 9 or even by catalytic hydrogenation to form 10. Thus, biologically important fragments like vicinal amino alcohols 11 or 2-amino-1,3-propanediols 12a [Nu = OH] can be obtained in highly enantioselective procedures preserving the absolute configuration at C2. The latter compounds are

• )-13 prepared from the respective esters (Scheme 4) 5b appeared moderately active as immunostimulants [18]. Amines and amino alcohols By functionalization at C2: Synthesis of enantiomerically pure amines from 2-substituted N-(1-phenylethyl)aziridines 5–7 requires a regioselective reductive aziridine

D-Fructose-based spiro-fused PHOX ligands: synthesis and application in enantioselective allylic alkylation

• Michael R. Imrich,
• Jochen Kraft,
• Cäcilia Maichle-Mössmer and
• Thomas Ziegler

Beilstein J. Org. Chem. 2018, 14, 2082–2089, doi:10.3762/bjoc.14.182

• through their N- and P-moieties. They are usually prepared from amino acids or from the corresponding amino alcohols [9][13]. Some examples of literature-known PHOX ligands are shown in Figure 1 (1a–d). These ligands gave up to 96% ee by their application in allylic substitution with dimethyl malonate as

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• aldehydes as electrophiles [38]. Enantioselectivities of up to 84% ee were achieved by using a BINOL derivative as chiral ligand. Ever since, other types of chiral ligands including chiral Schiff bases [39], bisoxazolidines [40], 1,2-amino alcohols [41], indolinylmethanols [42], and diarylprolinols have

• allowed excellent enantioselectivities to be achieved especially in the area of aza-Reformatsky reactions. Good results have also been recently described in enantioselective catalytic Reformatsky reactions performed in the presence of various chiral 1,2-amino alcohols. For example in 2014, He and Li

• reported the synthesis of novel chiral tridentate ligands from the reaction between (1R,2S)-2-amino-1,2-diphenylethanol and substituted salicylaldehydes [43]. These chiral 1,2-amino alcohols were further investigated as ligands in the enantioselective Reformatsky reaction of aldehydes with ethyl

Quinone-catalyzed oxidative deformylation: synthesis of imines from amino alcohols

• Xinyun Liu,
• Johnny H. Phan,
• Benjamin J. Haugeberg,
• Shrikant S. Londhe and
• Michael D. Clift

Beilstein J. Org. Chem. 2017, 13, 2895–2901, doi:10.3762/bjoc.13.282

• -catalyzed oxidative deformylation of 1,2-amino alcohols is reported. A wide range of readily accessible amino alcohols and primary amines can be reacted to provide N-protected imine products. The methodology presented provides a novel organocatalytic approach for imine synthesis and demonstrates the

• common [29][30][31][32] despite the fact that these methods employ renewable resources, such as amino acids and their derivatives, as starting materials. In fact, only a few reports describing the oxidative deformylation of amino alcohols have been published [33][34][35], and in all of these reports

• stoichiometric oxidants, such as NaIO4 and Pb(OAc)4, must be employed to enable the desired transformations. Given that 1,2-amino alcohols are readily accessible from feedstock chemicals such as styrenes [36][37][38] and amino acids [39], the development of a new methodology to transform these materials into

Iodoarene-catalyzed cyclizations of N-propargylamides and β-amidoketones: synthesis of 2-oxazolines

• Somaia Kamouka and
• Wesley J. Moran

Beilstein J. Org. Chem. 2017, 13, 1823–1827, doi:10.3762/bjoc.13.177

• -oxazolines, which are valuable heterocycles found in ligand scaffolds, natural products such as the leupyrrins [18][19], and potential pharmaceuticals (Figure 1) [20][21][22]. Traditional routes to this heterocycle include the dehydration of amino alcohols with carboxylic acids, however, this process

Continuous N-alkylation reactions of amino alcohols using γ-Al₂O₃ and supercritical CO₂: unexpected formation of cyclic ureas and urethanes by reaction with CO₂

• Emilia S. Streng,
• Darren S. Lee,
• Michael W. George and
• Martyn Poliakoff

Beilstein J. Org. Chem. 2017, 13, 329–337, doi:10.3762/bjoc.13.36

• products in all cases. These results prompted us to explore the use of more functionalised amino alcohols in an attempt to access these heterocycles more cleanly and to allow us to further examine the deamination reactivity that produces 9. Diethanolamine 12 is expected to produce a cleaner cyclisation

• alcohols and simple alcohols has been achieved (Scheme 4). Using scCO2 as the solvent proved to be beneficial to the yield of cyclic N-alkylated amines, in particular for the N-alkylation step which was arrested in the absence of scCO2. The intramolecular cyclisation of the amino alcohols was favoured at

• min−1, 100 bar, when applicable 0.5 mL min−1 CO2. Diagram of the high pressure equipment used in the experiments. Target reaction – intramolecular cyclisation of 1 followed by N-methylation with methanol to yield 2b. Cyclisation and N-alkylation of 1,4- and 1,6-amino alcohols. a) Reactions

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