First chemoenzymatic stereodivergent synthesis of both enantiomers of promethazine and ethopropazine

• Paweł Borowiecki,
• Daniel Paprocki and
• Maciej Dranka

Beilstein J. Org. Chem. 2014, 10, 3038–3055, doi:10.3762/bjoc.10.322

• spectra of the two diastereomeric derivatives obtained (11 and 12, Scheme 2). As already exemplified by us in few other reports [72][73][74][75], the modified Mosher’s methodology is easy to carry out and to interpret, and can be successively applied toward secondary alcohols with various heterocyclic

• due to the following facts: (i) It has been empirically confirmed by Latypov et al. [76] (as a result of dynamic NMR studies) that a final prevalent conformation in the CDA-substrate system in the case of MPA esters of secondary alcohols renders the sp rotamer, in which the methoxy group, the Cα

Galactan synthesis in a single step via oligomerization of monosaccharides

• Marius Dräger and
• Amit Basu

Beilstein J. Org. Chem. 2014, 10, 2658–2663, doi:10.3762/bjoc.10.279

• , Table 2, entry 5), followed by derivatization of the products as the TBS ethers, isolable quantities of the pentasaccharide 155c were generated. Secondary alcohols such as cyclohexanol or the sterically more hindered menthol successfully underwent glycosylation to provide mono- and disaccharides, but

A green approach to the synthesis of novel phytosphingolipidyl β-cyclodextrin designed to interact with membranes

• Yong Miao,
• Florence Djedaïni-Pilard and
• Véronique Bonnet

Beilstein J. Org. Chem. 2014, 10, 2654–2657, doi:10.3762/bjoc.10.278

• hydrophobic compound bearing one primary amine, one primary alcohol and two secondary alcohols has attracted our interest (See Figure 1 ). Its amino group can be used to couple with 6-amidosuccinyl-6-desoxy-permethylated-β-CD, and thereafter, the primary alcohol can be used for the enzymatically catalyzed

• transesterification with the corresponding fatty ester, which may lead to bicatenar amphiphilic CDs. At the same time, the two remaining secondary alcohols might increase the solubility of the modified CD compounds. The aim of this work is to synthesize new bicatenar CDs using green methods described for the first

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

Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications

• Mahesh K. Lakshman,
• Manish K. Singh,
• Mukesh Kumar,
• Raghu Ram Chamala,
• Vijayender R. Yedulla,
• Domenick Wagner,
• Evan Leung,
• Lijia Yang,
• Asha Matin and
• Sadia Ahmad

Beilstein J. Org. Chem. 2014, 10, 1919–1932, doi:10.3762/bjoc.10.200

• , primary and secondary alcohols undergo reaction under generally mild reaction conditions. Correspondingly, 1-alkoxy-1H-7-azabenzotriazoles were synthesized from At-OTs. Mechanistically, there are three pathways by which these peptide-coupling agents can react with alcohols. From 31P{1H}, [18O]-labeling

Pd/C-catalyzed aerobic oxidative esterification of alcohols and aldehydes: a highly efficient microwave-assisted green protocol

• Marina Caporaso,
• Giancarlo Cravotto,
• Spyros Georgakopoulos,
• George Heropoulos,
• Katia Martina and
• Silvia Tagliapietra

Beilstein J. Org. Chem. 2014, 10, 1454–1461, doi:10.3762/bjoc.10.149

• developed for the aerobic oxidation of primary and secondary alcohols to aldehydes and ketones using Au [4][5][6][7][8], Pd [9][10][11][12], Ru [13][14][15][16] and Cu [17][18][19] supported catalysts. An elegant approach to the direct oxidative esterification of alcohols has been described in recent years

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

• both alcohols showed a diastereomeric purity of >99% by 1H NMR. Mitsunobu reaction on the secondary alcohols using DEAD or DIAD did not provide the desired azides [42][43] nor did a one-pot Appel reaction/nucleophilic substitution/Staudinger reaction protocol involving a double inversion of

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• secondary alcohols (Scheme 12). With the AT reaction, the order of addition of reagents can impact its efficacy. Usually, the phosphite or the halide source (CBrCl3) is added dropwise to a mixture of the nucleophile (amine, phenol), trialkylamine (e.g., DIPEA) and a solvent cooled at −10 °C to 5 °C

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

• are formed that are separable by chromatography or recrystallization. The protocol has proven to be effective and has become the preferred approach for the synthesis of chiral phosphines. Commonly used chiral auxiliaries are chiral secondary alcohols (for example (−)-menthol (3), endo-borneol, etc

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

• expanded the scope of this transformation to aliphatic alcohols (Scheme 3) [29]. Under these conditions, the addition of primary and secondary alcohols to aryl and alkyl olefins 4 took place efficiently, with good yield and regioselectivity. However, poor diastereoselectivity was recorded in the presence

• of secondary alcohols. The efficiency of the process relied on the stabilization of cationic [Au(III)] species by using a catalytic amount CuCl2 (16 mol %), which prevented gold deactivation via parasitic reductive side reactions [30][31]. Moreover, recent advances in the alkoxylation of olefins

• between the amino-catalyst and the electrophilic gold complex. Experiments on chiral enriched secondary alcohols suggested the anti-attack of the in situ formed enamine 117 on gold activated allylic alcohol followed by anti-elimination of water. 6 Double functionalization of olefins by oxidative

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

• obtained. Instead, the dehydrogenation product 13 was the predominant product (Table 4, entry 2). Addition of the base Na2CO3 led only to a small improvement (Table 4, entry 3). Ketone formation has previously been described in attempted DKR’s of secondary alcohols when catalyst C was used in combination

A Lewis acid-promoted Pinner reaction

• Dominik Pfaff,
• Gregor Nemecek and
• Joachim Podlech

Beilstein J. Org. Chem. 2013, 9, 1572–1577, doi:10.3762/bjoc.9.179

• identified as an imidate hydrochloride (Scheme 1). Best results in the Pinner reaction are obtained with primary or secondary alcohols and aliphatic or aromatic nitriles. A plausible mechanism (Scheme 2) starts with a protonation of the nitrile by the strong acid hydrogen chloride leading to a highly

• obtained in the Lewis acid mediated reaction of nitriles with secondary alcohols such as cyclohexanol (Table 2, entry 10). No product at all was obtained, when the tertiary alcohol 1-methylcyclohexanol (48) was exposed to these conditions (Table 2, entry 11). The Lewis acid promoted Pinner reaction is

Re₂O₇-catalyzed reaction of hemiacetals and aldehydes with O-, S-, and C-nucleophiles

• Wantanee Sittiwong,
• Michael W. Richardson,
• Charles E. Schiaffo,
• Thomas J. Fisher and
• Patrick H. Dussault

Beilstein J. Org. Chem. 2013, 9, 1526–1532, doi:10.3762/bjoc.9.174

• , tetrahydropyranol 4a and the O-t-butyldimethylsilyl ether of the latter (4b). While good yields of acetals were obtained from the reaction with primary or secondary alcohols, or t-butyl hydroperoxide, acetalization with phenol proceeded in poor yield. Attempted acetalizations of 2,3,4,6-tetrabenzylglucose, the

Structures of the reaction products of the AZADO radical with TCNQF₄ or thiourea

• Hideto Suzuki,
• Yuta Kawahara,
• Hiroki Akutsu,
• Jun-ichi Yamada and
• Shin’ichi Nakatsuji

Beilstein J. Org. Chem. 2013, 9, 1487–1491, doi:10.3762/bjoc.9.169

• including oxygen [1]. Sometimes, however, the merit turns out to be a drawback by limiting its properties and reactivity. For example, 1 is inefficient in the oxidation of sterically hindered secondary alcohols. The AZADO radical (2) [2] is an intriguing nitroxide radical with adamantane-like structure and

Reductions of aldehydes and ketones with a readily available N-heterocyclic carbene borane and acetic acid

• Vladimir Lamm,
• Xiangcheng Pan,
• Tsuyoshi Taniguchi and
• Dennis P. Curran

Beilstein J. Org. Chem. 2013, 9, 675–680, doi:10.3762/bjoc.9.76

• procedure was not changed. Under these conditions, ketones 20–25 were reduced to the corresponding secondary alcohols 27–33 in good yields (Table 2). Reductions of 4-tert-butylcyclohexanone (21) and 4-phenyl-2-butanone (22) needed only 1 equiv of acetic acid (as with aldehydes), while the other substrates

Synthesis and stability study of a new major metabolite of γ-hydroxybutyric acid

• Ida Nymann Petersen,
• Jesper Langgaard Kristensen,
• Christian Tortzen,
• Torben Breindahl and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2013, 9, 641–646, doi:10.3762/bjoc.9.72

• , isobutyroyl or pivaloyl protection groups [21][22][23]. Alternatively, the use of bromo-derivative 10 (Scheme 2), which is easily synthesised in two steps from glucuronolactone [14][24] has been shown to glucuronidate primary and secondary alcohols under Koenigs–Knorr conditions [7][8][25][26]. Due to the

Enantioselective reduction of ketoimines promoted by easily available (S)-proline derivatives

• Martina Bonsignore,
• Maurizio Benaglia,
• Laura Raimondi,
• Manuel Orlandi and
• Giuseppe Celentano

Beilstein J. Org. Chem. 2013, 9, 633–640, doi:10.3762/bjoc.9.71

• trichlorosilane allowed the formation of secondary alcohols with high levels of enantioselection (up to 97%, Scheme 1), which was strongly influenced both by the carboxylic group at the α-position and the 2,4,6-triethylphenyl group at the 5-position in the proline ring. It must be noted, however, that the

Chemoenzymatic synthesis and biological evaluation of enantiomerically enriched 1-(β-hydroxypropyl)imidazolium- and triazolium-based ionic liquids

• Paweł Borowiecki,
• Małgorzata Milner-Krawczyk and
• Jan Plenkiewicz

Beilstein J. Org. Chem. 2013, 9, 516–525, doi:10.3762/bjoc.9.56

• ). Next, these compounds were used as a new type of substrate in lipase-catalyzed transesterification, yielding both enantiomers with good optical purity. The syntheses of the secondary alcohols (±)-3a and (±)-3b were accomplished by the addition of imidazole (2a) or 1,2,4-triazole (2b) to 1,2-propylene

• diastereomeric esters prepared from the separated enantiomers of the alcohols (+)-5a or (+)-5b and (R)- and (S)-enantiomers of methoxyphenylacetic acid (MPA, Mosher reagent) (Scheme 2). The utility of this method applied to secondary alcohols possessing heterocyclic azole rings has been demonstrated by us

• previously [58]. The absolute configuration of the substrate is deduced by interpretation of the signs of the ΔδRS values, by using an empirical model that assumes that in MPA esters of secondary alcohols, the most representative conformer has the methoxy group of MPA, the carbonyl group, and a proton bonded

Reactions of salicylaldehyde and enolates or their equivalents: versatile synthetic routes to chromane derivatives

• Ishmael B. Masesane and
• Zelalem Yibralign Desta

Beilstein J. Org. Chem. 2012, 8, 2166–2175, doi:10.3762/bjoc.8.244

• corresponding 2-aminochromene derivatives 22 and 37 in 92 and 82% yields respectively (Scheme 13) [26]. It is instructive to note that TBBDA is a versatile reagent in organic synthesis and has been reported to be efficient in oxidation of primary and secondary alcohols [27], in bromination of aromatic compounds

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

• the primary and secondary alcohols 99 by first coupling the enynol 96 with different propargyl chlorides 97 to the allenynols 98 (Scheme 24) [78][79]. These latter derivatives were then reduced by either LiAlH4 or LiAlH3(OCH3) to provide the substituted bisallenes 99 in yields between 50 and 75

The crystal structure of the Dess–Martin periodinane

• Albert Schröckeneder,
• Desiree Stichnoth,
• Peter Mayer and
• Dirk Trauner

Beilstein J. Org. Chem. 2012, 8, 1523–1527, doi:10.3762/bjoc.8.172

• periodinane; halogen bonds; hypervalent iodine; oxidant; Introduction The so-called Dess–Martin periodinane (DMP, 1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one, 1) has emerged as one of the most useful reagents for the oxidation of primary and secondary alcohols to the corresponding aldehydes and

Reduction of benzylic alcohols and α-hydroxycarbonyl compounds by hydriodic acid in a biphasic reaction medium

• Michael Dobmeier,
• Josef M. Herrmann,
• Dieter Lenoir and
• Burkhard König

Beilstein J. Org. Chem. 2012, 8, 330–336, doi:10.3762/bjoc.8.36

• , secondary alcohols give best results, while others may react less efficiently. We have reinvestigated the long-known reduction of benzylic alcohols and α-hydroxycarbonyl compounds by hydriodic acid [22][23][24][25][26][27][28][29][30][31][32]. The method has been reported for a variety of alcohols, but

Efficient and selective chemical transformations under flow conditions: The combination of supported catalysts and supercritical fluids

• M. Isabel Burguete,
• Eduardo García-Verdugo and
• Santiago V. Luis

Beilstein J. Org. Chem. 2011, 7, 1347–1359, doi:10.3762/bjoc.7.159

• . Different examples can be found, in this regard, in the literature. The most common transformations are the kinetic resolution (KR) of secondary alcohols. For example, Matsuda has reported the use of the commercially available supported lipase Novozym 435 for the kinetic resolution of aromatic and

Cyclization of 5-hexynoic acid to 3-alkoxy-2-cyclohexenones

• Anne T. Hylden,
• Eric J. Uzelac,
• Zeljko Ostojic,
• Ting-Ting Wu,
• Keely L. Sacry,
• Krista L. Sacry,
• Lin Xi and
• T. Nicholas Jones

Beilstein J. Org. Chem. 2011, 7, 1323–1326, doi:10.3762/bjoc.7.155

• formed from esterification of unreacted oxalyl chloride with excess alcohol nucleophiles, and thus a basic hydrolysis step was added to our work-up procedure. Secondary alcohols required heating to 90 °C following addition of the alcohol nucleophile to promote product formation. IR and NMR spectral data

A straightforward approach towards combined α-amino and α-hydroxy acids based on Passerini reactions

• Ameer F. Zahoor,
• Sarah Thies and
• Uli Kazmaier

Beilstein J. Org. Chem. 2011, 7, 1299–1303, doi:10.3762/bjoc.7.151

• epoxides, followed by oxidation of the hydroxy amino acid formed. While aryl-substituted epoxides react preferentially at the benzylic position giving rise to the terminal primary alcohols [25], the corresponding alkyl-substituted epoxides provide secondary alcohols 1 by nucleophilic attack of the enolate