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

Attempts to prepare an all-carbon indigoid system

• Şeref Yildizhan,
• Henning Hopf and
• Peter G. Jones

Beilstein J. Org. Chem. 2015, 11, 363–372, doi:10.3762/bjoc.11.42

• , obtained when 21 was subjected to a crossed McMurry coupling with excess acetone. In a stepwise approach, 21 was treated with either methyllithium in ether or methylmagnesium bromide in the hope of either preparing a mono- or the bis-tertiary alcohol derivative 20, which subsequently could be subjected to

Formal total syntheses of classic natural product target molecules via palladium-catalyzed enantioselective alkylation

• Yiyang Liu,
• Marc Liniger,
• Ryan M. McFadden,
• Jenny L. Roizen,
• Jacquie Malette,
• Corey M. Reeves,
• Douglas C. Behenna,
• Masaki Seto,
• Jimin Kim,
• Justin T. Mohr,
• Scott C. Virgil and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2014, 10, 2501–2512, doi:10.3762/bjoc.10.261

• , terminal alcohol silylation, and tertiary alcohol dehydration, affording methylene cyclohexane (−)-20. Treatment of this silyl ether with Jones reagent simultaneously cleaved the silyl group and oxidized the resulting alcohol, furnishing carboxylic acid (−)-12 in 65% yield. With this enantioenriched acid

Molecular recognition of isomeric protonated amino acid esters monitored by ESI-mass spectrometry

• Andrea Liesenfeld and
• Arne Lützen

Beilstein J. Org. Chem. 2014, 10, 825–831, doi:10.3762/bjoc.10.78

• Grignard reagent which was reacted with 9-fluorenone to afford tertiary alcohol 4 in 55% yield. Adopting a protocol of Tour et al. [16] led to 2-methoxy-9,9'-spirobifluorene (5) in 95% yield via acidic condensation of 4. Next, the methoxy group was cleaved quantitatively by reaction with boron tribromide

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

• . Tour [30], M. Gomberg [31], and V. Prelog [32][33] leading to (rac)-2,2’-dihydroxy-9,9’-spirobifluorene ((rac)-1) in six consecutive steps. This sequence involved a Sandmeyer-like iodination, followed by a Grignard reaction with fluorenone to furnish the corresponding tertiary alcohol. This alcohol was

Carbenoid-mediated nucleophilic “hydrolysis” of 2-(dichloromethylidene)-1,1,3,3-tetramethylindane with DMSO participation, affording access to one-sidedly overcrowded ketone and bromoalkene descendants^§

• Rudolf Knorr,
• Thomas Menke,
• Johannes Freudenreich and
• Claudio Pires

Beilstein J. Org. Chem. 2014, 10, 307–315, doi:10.3762/bjoc.10.28

• generation of dianion 37 of acid 10 (Scheme 6). Nevertheless, such one-sided shielding in the product ketone does not prevent the incorporation of a second nucleophile, affording a tertiary alcohol with a substantially impeded internal mobility. Final brominative deoxygenation of the ketones can yield

Tanzawaic acids I–L: Four new polyketides from Penicillium sp. IBWF104-06

• Louis P. Sandjo,
• Eckhard Thines,
• Till Opatz and
• Anja Schüffler

Beilstein J. Org. Chem. 2014, 10, 251–258, doi:10.3762/bjoc.10.20

• , H-18)/δC 24.2 and δH 1.63 (s, H-16)/δC 19.1) were found as well as a trisubstituted double bond (δH 5.79 (d, J = 6.1 Hz, H-14)/δC 128.0 and δC 140.9 (C-15)), an oxymethine (δH 3.75 (dd, J = 2.7, 5.8 Hz, H-13)/δC 68.0), and a tertiary alcohol (δC 76.1, C-6). A careful inspection of COSY and HMBC data

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• the resulting carbon-centered radical with oxygen. The resulting tertiary alcohol was then protected to give acetate 41. Standard functional group interconversions led to the formation of the remaining side chain using Wittig-conditions to afford olefin 42. Another series of standard functional group

The myxocoumarins A and B from Stigmatella aurantiaca strain MYX-030

• Tobias A. M. Gulder,
• Snežana Neff,
• Traugott Schüz,
• Tammo Winkler,
• René Gees and
• Bettina Böhlendorf

Beilstein J. Org. Chem. 2013, 9, 2579–2585, doi:10.3762/bjoc.9.293

• ). These signals were assigned to three methyl groups (14.0, 16.5, and 21.2 ppm), eight methylene units (22.6, 23.4, 29.2, 29.3, 29.4, 29.8, 31.8, and 38.3 ppm), a quaternary carbon at 46.5 ppm, a heteroatom-substituted quaternary carbon – most likely a tertiary alcohol – at 79.1 ppm, an ester-type

• groups to each other, to the putative ester functionality, the quaternary carbon at 46.5 ppm, and the tertiary alcohol carbon at 79.1 ppm led to the assembly of structural fragment II (F-II, Figure 2). Further substitution of the latter was obvious from HMBC cross peaks of the diastereotopic CH2 group

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

• -one (5). Synthesis of compound 18. Synthesis of hydroxylactam 18. Synthesis of tertiary alcohol 22. Synthesis of (8S,8aS)-5 and its silyl ether 23. Supporting Information Supporting Information File 488: 1H and 13C NMR of key compounds. Acknowledgments The authors are grateful to National Basic

• gave pure diastereomer 18 in 59% overall yield from 14. The trans-stereochemistry was tentatively assigned to compound 18 on the basis of our previous results, which was confirmed by the conversion of 18 into the known compound 5 (vide infra). With lactam 18 in hand, its conversion to novel tertiary

• alcohol 22 was investigated. Oxidation of alcohol 18 with an excess of Dess–Martin periodinane (DMP) in dichloromethane at room temperature for 2 h proceeded smoothly to give ketone 10 in 93% yield. It is noteworthy that keto-lactam 10 is configurational labile, and should be used immediately in the next

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• substitution pattern of the D-ring bares most of the functionalities, i.e., a secondary and a tertiary alcohol, the former of which is commonly glycosylated with 2,6-dideoxy sugars (Figure 1) [3]. These carbohydrates are of highest importance for the biological activity of anthracyclines and bind to the minor

A concise enantioselective synthesis of the guaiane sesquiterpene (−)-oxyphyllol

• Martin Zahel and
• Peter Metz

Beilstein J. Org. Chem. 2013, 9, 2028–2032, doi:10.3762/bjoc.9.239

• (−)-oxyphyllol (1) and 5, we decided to use a modification of our route to 5 for the synthesis of 1 that would also constitute a formal synthesis of the related guaiane (+)-orientalol E (2) [4][7]. As illustrated in Scheme 1, we selected tertiary alcohol 3 as a retrosynthetic precursor for 1. The acetyl group of

A practical synthesis of long-chain iso-fatty acids (iso-C₁₂–C₁₉) and related natural products

• Mark B. Richardson and
• Spencer J. Williams

Beilstein J. Org. Chem. 2013, 9, 1807–1812, doi:10.3762/bjoc.9.210

• approach to the iso-C12–C14 fatty acids 1–3 commenced from methyl undec-10-enoate (methyl undecylenate) 9. Reaction of 9 with methylmagnesium bromide afforded the tertiary alcohol 10 in 98% yield (Scheme 1). Selective reduction of the tertiary alcohol of 10 was achieved by ‘ionic hydrogenation’ with

• lactone pentadecanolide (exaltolide, 15) [57], a natural product that is produced industrially for use as a musk-odored perfumery fixative. Reaction of 15 with methylmagnesium bromide afforded the tertiary alcohol 16 in 98% yield (Scheme 2). Selective reduction of the tertiary alcohol of 16 was achieved

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

• 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

• higher yield of acetal. The Re2O7-promoted reactions were subsequently found to proceed efficiently at only 1% catalyst loading. Neither catalyst allowed etherification with a tertiary alcohol. Acetal formation As illustrated in Table 2, we next investigated acetalization of tetrahydrofuranol 3

Anionic cascade reactions. One-pot assembly of (Z)-chloro-exo-methylenetetrahydrofurans from β-hydroxyketones

• István E. Markó and
• Florian T. Schevenels

Beilstein J. Org. Chem. 2013, 9, 1319–1325, doi:10.3762/bjoc.9.148

• -derivative 36 were obtained as a 1:5 mixture of diastereoisomers that could be separated (Scheme 6). Their structure was unambiguously established by single-crystal X-ray diffraction analysis, as shown in Figure 1. Increasing the steric hindrance at the tertiary alcohol site resulted in the exclusive

• with concomitant generation of another oxonium species 47. Intramolecular capture of this electrophile by the pendant hydroxy substituent then delivers the spirocyclic adduct 48. Alternatively, reaction of the tertiary alcohol of 42 with the oxonium cation 43 affords the ketal 44. Protonation of the

• homochiral (S,S;R,R)-dimer, leading to the syn–syn product, is preferred over the heterochiral (S,R;R,S)-adduct, affording the syn–anti isomer. Increasing the steric hindrance at the tertiary alcohol center of 49 leads to prohibitive steric repulsion during the heterodimer formation. A similar facial

Asymmetric synthesis of a highly functionalized bicyclo[3.2.2]nonene derivative

• Toshiki Tabuchi,
• Daisuke Urabe and
• Masayuki Inoue

Beilstein J. Org. Chem. 2013, 9, 655–663, doi:10.3762/bjoc.9.74

• of vinylmagnesium bromide [16], provided 9. The bromoetherification of tertiary alcohol 9 by using NBS led to tetrahydrofuran 10 as a diastereomeric mixture. Next, the base-induced elimination of HBr converted 10 to diene 11, which underwent the Claisen rearrangement at 170 °C to give rise to

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

• -derived catalyst C developed by our group [7][8]. Also in other systems, such as the Matsumura-type catalysts developed by Zhang [9] of type D, the presence of a proper sterically hindered element seems to be much more decisive than the ability of the tertiary alcohol to make a possible, but not probable

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

• . Benzylic alcohols were converted in good to high yields to alkanes with increasing reactivity in the order primary (2 h) < secondary (0.5–1 h) < tertiary alcohol (15–30 min); carbonyl groups and ethers were tolerated. Diethyl tartrate was converted into diethyl succinate under the reaction conditions given

Tertiary alcohol preferred: Hydroxylation of trans-3-methyl-L-proline with proline hydroxylases

• Christian Klein and
• Wolfgang Hüttel

Beilstein J. Org. Chem. 2011, 7, 1643–1647, doi:10.3762/bjoc.7.193

• of trans-3-methyl-L-proline with the α-ketoglutarate (α-KG) dependent oxygenases, cis-3-proline hydroxylase type II and cis-4-proline hydroxylase (cis-P3H_II and cis-P4H). With cis-P3H_II, the tertiary alcohol product (3R)-3-hydroxy-3-methyl-L-proline was obtained exclusively but in reduced yield (~7

• % compared to those obtained in conversions of L-proline. Based on the cis-3-selectivity of the enzyme we assumed that the tertiary alcohol was formed. Surprisingly, the conversion with cis-P4H gave a product with the same retention time as the product of cis-P3H_II, but in much better relative yield (~110

• substituents and, consequently, a cis-configuration for the tertiary alcohol (Supporting Information File 1). Whereas the reactivity of cis-P3H_II could be expected, the shift in regioselectivity and the high activity of cis-P4H is remarkable. A certain degree of flexibility in the regioselectivity of this

High chemoselectivity in the phenol synthesis

• Matthias Rudolph,
• Melissa Q. McCreery,
• Wolfgang Frey and
• A. Stephen K. Hashmi

Beilstein J. Org. Chem. 2011, 7, 794–801, doi:10.3762/bjoc.7.90

• condensation of ester 20 and tert-butyl acetate (21) in the presence of lithium hexamethyldisilazide as the base. Ketoester 22 was obtained in 56% yield, however, the two-fold addition of 21 could not be suppressed completely and 14% of the corresponding tertiary alcohol 30 was also obtained. Reduction of the

When cyclopropenes meet gold catalysts

• Frédéric Miege,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2011, 7, 717–734, doi:10.3762/bjoc.7.82

• acted as a nucleophile, but the corresponding tertiary alcohol 9i was isolated in only modest yield (34%) (Scheme 5) [18]. Additional results were subsequently reported by Lee et al. in a full article in 2010 [19]. Due to their lower nucleophilic character compared to alcohols, phenols could not be used

Asymmetric synthesis of tertiary thiols and thioethers

• Jonathan Clayden and
• Paul MacLellan

Beilstein J. Org. Chem. 2011, 7, 582–595, doi:10.3762/bjoc.7.68

• Mitsunobu reactions, there is one example of the displacement of a tertiary alcohol by a thiol under Mitsunobu conditions in the literature. La Clair reported the synthesis of the initially assigned structure of natural product hexacyclinol (27, Figure 4) [29]. The reported synthesis entailed Mitsunobu

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• and dichloromethane selectively provides tertiary alcohol 183. In subsequent steps this imidazole is alkylated with the tetrazole containing biphenyl appendage, followed by ester hydrolysis and alkylation of the resulting carboxylate with 4-(chloromethyl)-5-methyl-2-oxo-1,3-dioxole to yield olmesartan

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33