Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• Technology, Guangzhou 510006, P. R. China 10.3762/bjoc.21.151 Abstract Enantioselective desymmetrization is employed as a powerful tool for the creation of chiral centers. Within this scope, the enantioselective desymmetrization of prochiral 1,3-diols, which generates chiral centers by enantioselective

• functionalization of one hydroxy group, offers beneficial procedures for accessing diverse structural motifs. In this review, we highlight a curated compilation of publications, focusing on the applications of enantioselective desymmetrization of prochiral 1,3-diols in the synthesis of natural products and

• biologically active molecules. Based on the reaction types, three strategies are discussed: enzymatic acylation, transition-metal-catalyzed acylation, and local desymmetrization. Keywords: asymmetric synthesis; desymmetrization; 1,3-diols; natural product; total synthesis; Introduction Natural products

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• ]. Diarylborinic acids have been shown to provide exclusive catalytic performance in the site-selective monofunctionalization of various 1,2- and 1,3-diols [60], as well as in the regioselective glycosylation of polyhydroxyglycosyl acceptors via base-promoted deprotonation of a specific hydroxy group involved in

• addition, 2-amino-2-deoxy-1,3-diols were successfully employed as glycosyl acceptors, as exemplified by the use of GlcN-derived lactol 42, which was reacted with the 2N-Troc-protected GalN phosphite donor 47 in the presence of borinic acid catalyst to give the β,α-1,1'-linked disaccharide 48 (Scheme 4) [63

4,6-Diaryl-5,5-difluoro-1,3-dioxanes as chiral dopants for liquid crystal compositions

• Maurice Médebielle,
• Peer Kirsch,
• Jérémy Merad,
• Carolina von Essen,
• Clemens Kühn and
• Andreas Ruhl

Beilstein J. Org. Chem. 2024, 20, 2940–2945, doi:10.3762/bjoc.20.246

• still remain elusive and are not well understood [29]. Recently we have become interested in the preparation of racemic [30] anti- and highly enantioenriched 2,2-difluoro-1,3-diols [30][31][32] through an acylative double catalytic kinetic resolution (DoCKR) process [33]. While the 1,3-diol motif is

• found in some natural products [34] with some fluorinated analogues [35][36], this motif is rarely found in LCs [37][38][39]. Based on these observations and literature data, we embarked in the synthesis and evaluation of enantiomerically pure acetals derived from anti-2,2-difluoro-1,3-diols as

Stereoselective synthesis and transformation of pinane-based 2-amino-1,3-diols

• Ákos Bajtel,
• Mounir Raji,
• Matti Haukka,
• Ferenc Fülöp and
• Zsolt Szakonyi

Beilstein J. Org. Chem. 2021, 17, 983–990, doi:10.3762/bjoc.17.80

• , POB 35, 40351 Jyväskylä, Finland Stereochemistry Research Group of the Hungarian Academy of Sciences, H-6720 Szeged, Eötvös u. 6, Hungary, Interdisciplinary Centre of Natural Products, University of Szeged, Szeged, Hungary 10.3762/bjoc.17.80 Abstract A library of pinane-based 2-amino-1,3-diols was

• -amino-1,3-diols, which underwent a regioselective ring closure with formaldehyde or benzaldehyde delivering pinane-condensed oxazolidines. During the preparation of 2-phenyliminooxazolidine, an interesting ring–ring tautomerism was observed in CDCl3. Keywords: 2-amino-1,2-diol; monoterpene; oxazolidin

• the regioisomers of potential monoterpenic 2-amino-1,3-diols [29][30][31][32][33]. These trifunctionalized terpenoids may also possess diverse biological activities and could successfully applied as chiral catalysts in enantioselective transformations [34]. In the present study, our aim was to

The B & B approach: Ball-milling conjugation of dextran with phenylboronic acid (PBA)-functionalized BODIPY

• Patrizia Andreozzi,
• Lorenza Tamberi,
• Elisamaria Tasca,
• Gina Elena Giacomazzo,
• Marta Martinez,
• Mirko Severi,
• Marco Marradi,
• Stefano Cicchi,
• Sergio Moya,
• Giacomo Biagiotti and
• Barbara Richichi

Beilstein J. Org. Chem. 2020, 16, 2272–2281, doi:10.3762/bjoc.16.188

• related esters are relevant synthetic building blocks widely employed as cross-coupling reagents [14] as well as protecting groups for polyols and diamines [15][16]. Moreover, the reversible covalent interaction of boronic acids with specifically oriented cis-1,2 and 1,3-diols has been successfully

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• , or disulfonates of alkane-1,3-diols with sodium sulfide. The intramolecular substitution of 3-mercaptoalkyl halides or sulfonates is a similar strategy for the preparation of thietanes [12][13][14]. Alternatively, inter- and intramolecular photochemical [2 + 2] cycloadditions (thia-Paternò–Büchi

• )-1-tosylazetidine (22) with sodium sulfide followed by the detosylation with Mg in MeOH afforded 1,6-thiazaspiro[3.3]heptane (24) [36] (Scheme 4). 2.1.2 Synthesis via double nucleophilic displacements of disulfonates of alkane-1,3-diols: Considering that 6-amino-3-azaspiro[3.3]heptane was evaluated

• thietanes. Indeed, the direct cyclization of the 3-mercaptopropan-1-ol unit in 60 with Ph3P(OEt)2 as a reagent was realized in the synthesis of the spirothietane derivative 61 [44] (Scheme 14). Also, 1,3-diols were considered as precursors of γ-mercaptoalkanols. A Japanese group developed a new method to

Application of chiral 2-isoxazoline for the synthesis of syn-1,3-diol analogs

• Juanjuan Feng,
• Tianyu Li,
• Jiaxin Zhang and
• Peng Jiao

Beilstein J. Org. Chem. 2019, 15, 1840–1847, doi:10.3762/bjoc.15.179

• methods using Claisen condensation. (b) Our new method using cycloaddition. Attempted oxidations of 4. Preparations of 16 and related syn-1,3-diol compounds. Attempted oxidations of 6'. Attempted selective protections of internal 1,3-hydroxy groups: (a) acetonizations of 1,3-diols; (b) removal of co

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

• the same potency as N,N-dimethylsphingosine (DMS) being completely inactive toward hSphK1. 2-Amino-1,3-diols A 2-amino-1,3-dihydroxypropyl fragment 12 of sphingosine and ceramides of the required 2S,3R configuration can also originate from the aziridine alcohol, e.g., (2S,1'R,1''R)-87 prepared from

• synthesized from aziridine-2-methanols either by functionalization at C3 (Scheme 12 and Scheme 13) or by opening of the aziridine ring to form 2-amino-1,3-diols 12 (Schemes 22–24) combined with the removal of the secondary hydroxy group when simple amino acids (R = alkyl, aryl) are to be prepared. For the

Ionic liquids as transesterification catalysts: applications for the synthesis of linear and cyclic organic carbonates

• Maurizio Selva,
• Alvise Perosa,
• Sandro Guidi and
• Lisa Cattelan

Beilstein J. Org. Chem. 2016, 12, 1911–1924, doi:10.3762/bjoc.12.181

• corresponding cyclic carbonates, while 1,3-diols, depending on their structures, could yield both, cyclic or acyclic carbonates, such as the ones shown in Scheme 19 [75]. There is no direct relation of the performance of these IL-catalysts to their basicity. Curiously, it should be noted that the activity of

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

• . Disappointingly, the product (E)-4a was obtained in low yield although in excellent (dia)stereoselectivity. In the synthesis of anti-2-amino-1,3-diols, we reported earlier that the addition of DIBAL-H must be done necessarily in two portions [16]. Thus, fine-tuning of the reduction conditions was required in

Recent advances in copper-catalyzed asymmetric coupling reactions

• Fengtao Zhou and
• Qian Cai

Beilstein J. Org. Chem. 2015, 11, 2600–2615, doi:10.3762/bjoc.11.280

• -halophenoxyl)-1,3-diols by the same group [54]. However, the palladium catalytic systems suffered from limited substrate scope and poor efficiency and enantioselectivity for the formation of quaternary stereocenters. Recently, Cai et al. carried out such couplings using a CuI/cyclized diamine catalytic system

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

• method to synthesize protected syn-1,3-diols by performing intramolecular conjugate additions to a series of α,β-unsaturated esters and amides [71] (Scheme 8). Upon treatment of 24 with KHMDS and benzyaldehyde, a hemiacetal forms which provides the alkoxide nucleophile for the DCA reaction. These

A new intermediate in the Prins reaction

• Shinichi Yamabe,
• Takeshi Fukuda and
• Shoko Yamazaki

Beilstein J. Org. Chem. 2013, 9, 476–485, doi:10.3762/bjoc.9.51

• reactions were investigated by the use of DFT calculations. A model composed of R–CH=CH2 + H3O+(H2O)13 + (H2C=O)2, R = Me and Ph, was adopted to trace reaction paths. For both alkenes, the concerted path forming 1,3-diols was obtained as the rate determining step (TS1). TS stands for a transition state

Aryl nitrile oxide cycloaddition reactions in the presence of pinacol boronic acid ester

• Sarah L. Harding,
• Sebastian M. Marcuccio and
• G. Paul Savage

Beilstein J. Org. Chem. 2012, 8, 606–612, doi:10.3762/bjoc.8.67

• alkenes [15], alkynes [16][17], and benzyne [18][19], to give Δ2-isoxazolines and isoxazoles. These are interesting sources of bioactive compounds in their own right, but isoxazoles are particularly valuable for their latent functionality as β-hydroxyketones, β-aminoalcohols, 1,3-diols, and a range of

Synthesis of 2-amino-3-arylpropan-1-ols and 1-(2,3-diaminopropyl)-1,2,3-triazoles and evaluation of their antimalarial activity

• Matthias D’hooghe,
• Stéphanie Vandekerckhove,
• Karen Mollet,
• Karel Vervisch,
• Stijn Dekeukeleire,
• Liesbeth Lehoucq,
• Carmen Lategan,
• Peter J. Smith,
• Kelly Chibale and
• Norbert De Kimpe

Beilstein J. Org. Chem. 2011, 7, 1745–1752, doi:10.3762/bjoc.7.205

• variety of 2-amino-3-arylpropan-1-ols, anti-2-amino-3-aryl-3-methoxypropan-1-ols and anti-2-amino-1-arylpropan-1,3-diols were prepared selectively through elaboration of trans-4-aryl-3-chloro-β-lactams. In addition, a number of 2-(azidomethyl)aziridines was converted into novel 2-[(1,2,3-triazol-1-yl

• ). Furthermore, in order to provide access to the class of 2-aminopropan-1,3-diols, aziridines 7 were evaluated for the first time as substrates for a water-induced aziridine ring opening in an acidic medium. Thus, treatment of trans-2-aryl-3-(hydroxymethyl)aziridines 7 with one equiv of para-toluenesulfonic

• acid in a H2O/THF (1/1) solvent system [32] furnished novel anti-2-amino-1-arylpropan-1,3-diols 9a–d in good yields after 3 h at 40 °C, again in a regio- and stereospecific way (Scheme 1). The observed regio- and stereoselectivity in aminopropanols 8 and 9 can be rationalized by considering the ring