Synthesis of the B-seco limonoid core scaffold

• Hanna Bruss,
• Hannah Schuster,
• Rémi Martinez,
• Markus Kaiser,
• Andrey P. Antonchick and
• Herbert Waldmann

Beilstein J. Org. Chem. 2014, 10, 194–208, doi:10.3762/bjoc.10.15

• the thermodynamic enolate of 2-methylcyclohexanone (5) and the bicyclic electrophile 12 (Scheme 2). A challenging synthetic problem appears to be the construction of the stereochemically dense trans-fused C–D ring system 12, which possesses four stereogenic centers including two contiguous asymmetric

• (−)-quinic acid (16) according to the route reported by Arthurs et al. [40] with minor modifications. After Baylis–Hillman reaction and subsequent silylation of the resulting free primary hydroxy group, substrate-controlled α-methylation of the lithium enolate proceeded with full stereocontrol [41][42

• tosylation of the primary alcohols in 19, 20 and 22 gave suitable electrophiles for the planned O-alkylation with the thermodynamic enolate of 2-methylcyclohexanone. However, under various conditions (NaH/15-crown-5/THF; t-BuOK/18-crown-6/THF/DMPU; KHMDS/THF) [44][45], the intended O-alkylation to yield the

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

• -catalyzed cyclopropanation of silyl-enol-diazo compound 101 and Boc-protected pyrrole 147 resulted in the formation of intermediate cis-divinylcyclopropane 148, that rearranged under the reaction conditions to give the corresponding highly substituted bridged cycloheptadiene 149. Deprotection of the enolate

• acid was converted to the corresponding anhydride, which could be reduced to the alcohol using NaBH4, followed by reoxidation with DMP to yield aldehyde 154. Attachment of furanone enolate 155 [134][135], followed by reoxidation yielded tricycle 156. Deprotection of the amine and the MOM-protected

• TMSCN [159][160][161], followed by protonation of the TMS-enolate and esterification of the intermediate acyl cyanide yielding allyl ester 191. This ester was transferred into the corresponding carboxylic acid, followed by formation of the acid chloride. The chloride was displaced with an azide, which

Four-component reaction of cyclic amines, 2-aminobenzothiazole, aromatic aldehydes and acetylenedicarboxylate

• Hong Gao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 2934–2939, doi:10.3762/bjoc.9.330

• aldehydes also gave the morpholinium 2-pyrrolidinon-3-olates 2b–2e (Table 2, entries 2–5) in 65–87% yields, respectively. The formation of morpholinium 2-pyrrolidinon-3-olates 2a–2e clearly indicated that the reaction initially gave the expected 3-hydroxy-2-pyrrolidinone, which in turn converted to enolate

Diastereoselectivity in the Staudinger reaction of pentafluorosulfanylaldimines and ketimines

• Alexander Penger,
• Cortney N. von Hahmann,
• Alexander S. Filatov and
• John T. Welch

Beilstein J. Org. Chem. 2013, 9, 2675–2680, doi:10.3762/bjoc.9.303

• increases the acidity of the α-proton of the imine 5 and of the iminium ion intermediate B formed on the initial nucleophilic attack of the imine on the ketene as illustrated in Scheme 4. The ring closure step requires bond formation between the iminium ion carbon and the enolate carbon B to be particularly

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

• one step. An example recently published by us combines RCM of butenoates 2 with a base-induced highly stereoselective ring opening of the transient metathesis products 4, furnishing exclusively Z,E-dienes 3 [24]. We assume that the reaction proceeds via formation of an enolate 5, followed by

• co-solvent, together with toluene. Under these conditions, reproducible yields in the range between 67% and 78% were obtained (Table 2, entries 1–3). The alcohol is believed to protonate the Cu-enolate formed upon conjugate addition, resulting in the ketone and a Cu-alkoxide, which is then reduced

• with silane to regenerate the Cu-hydride. Alternatively, the Cu-enolate might enter a competing catalytic cycle by reacting with silane, furnishing a silyl enol ether and the catalytically active Cu-hydride species. The silyl enol ether is inert to protonation by tert-butanol, and therefore the

Synthesis of the spiroketal core of integramycin

• Evgeny. V. Prusov

Beilstein J. Org. Chem. 2013, 9, 2446–2450, doi:10.3762/bjoc.9.282

• by an intramolecular Diels–Alder cycloaddition. The installation of the tetramic acid moiety would proceed via Lassey–Dickmann condensation with subsequent introduction of the 5-hydroxy group by oxidation of the corresponding vinylogous enolate. Herein a straightforward synthesis of the C16–C35

• treatment with sodium periodate furnished pure 13. The primary hydroxy group was selectively converted to alkyl iodide by using Ph3P/I2/imidazole conditions [10]. Then the protected iodide 14 was subjected to Myers alkylation [11] reaction with an excess of enolate to install the last required stereocenter

Oxidative 3,3,3-trifluoropropylation of arylaldehydes

• Akari Ikeda,
• Masaaki Omote,
• Shiho Nomura,
• Miyuu Tanaka,
• Atsushi Tarui,
• Kazuyuki Sato and
• Akira Ando

Beilstein J. Org. Chem. 2013, 9, 2417–2421, doi:10.3762/bjoc.9.279

• the enolate intermediate, which is generated during the reaction, intermolecularly extracted the benzylic deuterium of 4. To further investigate the reaction mechanism, 4a was exposed to basic conditions to observe whether or not the isomerization of 4a to 3a would occur. Indeed, the treatment of 4a

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• in Scheme 7. The intermediate 67, which contains all of the carbon atoms of the natural product, was synthesized in eight steps starting from the advanced building blocks 64, 65 and 66. Selective deprotonation and trapping the so-formed enolate with phenylselenyl chloride gave an intermediate

• four steps to give aldehyde 86, which was reacted with the lithium enolate of lactam 87 to furnish the aldol adduct 88 (Scheme 10). Oxidation of the secondary alcohol to the corresponding ketone and selective selenation with phenylselenyl chloride gave 89. Following the reported sequence for the

Synthesis of enantiomerically pure (2S,3S)-5,5,5-trifluoroisoleucine and (2R,3S)-5,5,5-trifluoro-allo-isoleucine

• Holger Erdbrink,
• Elisabeth K. Nyakatura,
• Susanne Huhmann,
• Ulla I. M. Gerling,
• Dieter Lentz,
• Beate Koksch and
• Constantin Czekelius

Beilstein J. Org. Chem. 2013, 9, 2009–2014, doi:10.3762/bjoc.9.236

• protocol reported by Wang and Resnick from commercially available 4,4,4-trifluorobutanoic acid by diastereoselective enolate alkylation followed by reduction with lithium borohydride (Scheme 1) [18]. Fluorinated alcohol 1 was transformed into the corresponding tosylate ester 2 and subsequently reacted with

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• yields amine radical cation 14, which is converted to α-amino radical 17. Conjugated addition of 17 to methyl vinyl ketone produces radical 79, which is reduced by the Ru(I) or Ir(II) complex with concomitant regeneration of the Ru(II) or Ir(III) complex. Protonation of the resulting enolate furnishes

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

• determined. Conversion of iso-C17 acid 6 to the N-acyloxazolidinone 28 was achieved using pivalyl chloride/LiCl [62] and (S)-4-benzyloxazolidinone. Diastereoselective methylation [63] of the chelated Z-enolate, derived from deprotonation of 28, using NaHMDS, followed by addition of iodomethane, yielded 29 as

• sources [1] including the myxobacterium Stigmatella aurantiaca [21][65], and the oral bacterium Veillonella parvula [66], although the absolute configuration has not been reported. Diastereoselective hydroxylation [67] of the chelated Z-enolate derived from 28 using the Davis oxaziridine [68] afforded the

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• boron enolate-based strategy using the N-acetylthiazolidinethione 58 (Scheme 14) for its high reported diastereoselectivity with aliphatic aldehydes and its avoidance of toxic tin reagents [61]. The reaction of the brightly colored 58 with but-3-enal proceeded in moderate yield, with an initial

• recognized that reaction of the enolate of ester 45, a compound previously synthesized in just two steps, and subsequent oxidation could give the β-ketoester 61. Decarboxylation of this compound would provide rapid access to the key iodocyclization substrate 55. Aldehyde 62 was prepared by reduction of the

• . Ozonolysis of the pendant olefin afforded aldehyde 75 in high yield. Following the prior procedure, the lithium enolate of TMS ester 64 was reacted with aldehyde 75, and the mixture of diastereomeric alcohols was oxidized to the β-ketoester 76 (Scheme 20). This substrate did not appear to be prone to

Exploration of an epoxidation–ring-opening strategy for the synthesis of lyconadin A and discovery of an unexpected Payne rearrangement

• Brad M. Loertscher,
• Yu Zhang and
• Steven L. Castle

Beilstein J. Org. Chem. 2013, 9, 1179–1184, doi:10.3762/bjoc.9.132

• mesylate derived from known alcohol 9 [24] (Scheme 2). Then, coupling of methyl γ-hydroxybutyrate (10) [25] with lithiated (+)-pseudoephedrine afforded amide 11 in excellent yield. Selective silylation of the primary alcohol of 11 delivered substrate 12. Alkylation of the enolate derived from 12 with 8

Synthesis of the tetracyclic core of Illicium sesquiterpenes using an organocatalyzed asymmetric Robinson annulation

• Lynnie Trzoss,
• Jing Xu,
• Michelle H. Lacoske and
• Emmanuel A. Theodorakis

Beilstein J. Org. Chem. 2013, 9, 1135–1140, doi:10.3762/bjoc.9.126

• under Meerwein’s conditions to afford β-ketoester 17. Treatment of 17 with TMSOTf/Et3N followed by enolate alkylation [82] under TBAF/MeI conditions afforded the desired C-5 quaternary center of 18 as a single isomer (35% over four steps). Global reduction of 18 with lithium aluminium hydride produced

Tandem dinucleophilic cyclization of cyclohexane-1,3-diones with pyridinium salts

• Mostafa Kiamehr,
• Firouz Matloubi Moghaddam,
• Satenik Mkrtchyan,
• Volodymyr Semeniuchenko,
• Linda Supe,
• Alexander Villinger,
• Peter Langer and
• Viktor O. Iaroshenko

Beilstein J. Org. Chem. 2013, 9, 1119–1126, doi:10.3762/bjoc.9.124

• -diketone deprotonation and nucleophilic attack of potassium 3-oxocyclohex-1-enolate on pyridinium cation, which yields an intermediate with a new C–C bond, and this is a key stage in the reaction. The C–O bond formation can be excluded in the initial stage (see Supporting Information File 2 for the

• + regioselective reaction is inherent. Intrigued by this discrepancy, we computed the full reaction mechanism for cation 2a+ with potassium 3-oxocyclohex-1-enolate in the presence of potassium cation and hydrogencarbonate anion as base. We included HCO3− in our computation, both because it has only five atoms and

• of the hydrogencarbonate anion, the latter is exchanged with iodine in the salt of 2a, and an initial complex consisting of 2a+HCO3− with potassium 3-oxocyclohex-1-enolate is assembled (intermediate 9). Nucleophilic attack yields intermediate 11 through TS 10. The latter TS was first localized

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• adduct 62 to the action of potassium carbonate, in a mixture of acetonitrile and tert-butanol under reflux, leads to tricyclic thiochromanone 63 in high yield [32]. This transformation involves attack of the ketone enolate on the thiocarbonyl group of the nearby xanthate, followed by substitution of the

Recent advances in transition-metal-catalyzed intermolecular carbomagnesiation and carbozincation

• Kei Murakami and
• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 278–302, doi:10.3762/bjoc.9.34

• indanones (Scheme 4) [59]. Phenylrhodation of 1g first proceeds to form 1A. A subsequent intramolecular 1,4-hydrogen shift gives 1B, which smoothly undergoes an intramolecular 1,4-addition to yield 1C. Finally, transmetalation from the phenylzinc reagent to rhodium enolate 1C affords zinc enolate 1h, which

A new synthetic protocol for coumarin amino acid

• Xinyi Xu,
• Xiaosong Hu and
• Jiangyun Wang

Beilstein J. Org. Chem. 2013, 9, 254–259, doi:10.3762/bjoc.9.30

• coumarinylacetic acid, which was then reduced to an alcohol by borane-dimethyl sulfide. After the phenolic hydroxy group was protected with a tert-butyl(dimethyl)silyl group, the alcohol was converted into a bromide and was used to alkylate a glycine enolate synthon to afford an imine. All the protecting groups

Development of peptidomimetic ligands of Pro-Leu-Gly-NH₂ as allosteric modulators of the dopamine D₂ receptor

• Swapna Bhagwanth,
• Ram K. Mishra and
• Rodney L. Johnson

Beilstein J. Org. Chem. 2013, 9, 204–214, doi:10.3762/bjoc.9.24

• hexafluorophosphate (HATU) as the coupling reagent in order to provide the primary carboxamide intermediate, which could be deprotected to give 48. The lithium enolate of Seebach’s oxazolidinone 30 served as the starting material for the stereoselective synthesis of ethylene-linked biproline derivative 50. The nature

• oxazolidinones 56 and 57, which served as precursors to the corresponding novel (R,R)-α,α’-biproline 58 and meso-α,α’-biproline 59 [57]. In contrast, the reaction of the more electrophilic alkylating agent glycol bistriflate with the enolate of 30 provided the desired dimer 55, which after acid hydrolysis of the

Alternaric acid: formal synthesis and related studies

• Michael C. Slade and
• Jeffrey S. Johnson

Beilstein J. Org. Chem. 2013, 9, 166–172, doi:10.3762/bjoc.9.19

• coupling product 12 was in 50% combined yield of all four possible diastereomers: 3.6:1 syn-/anti-selectivity and ~1.7:1 facial selectivity were observed. Thus, under these conditions both the control of enolate geometry as well as facial selectivity with respect to the aldehyde were incomplete. The four

• the silyl glyoxylate-based three-component coupling reaction: while this aldehyde directly affords the substructure of the natural product target, it is unable to adequately control the facial selectivity of the approach of the glycolate enolate revealed after nucleophile addition/[1,2]-Brook [33

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

• a C-2 phenyl substituent. The synthesis of flavans and flavones generally involves treatment of acetophenone (7) with a base to give enolate 8, which undergoes a Knoevenagel condensation with salicylaldehyde (5) to yield a chalcone 9. These chalcone derivatives are then cyclized by using various

• and co-workers achieved the synthesis of flavone 11 relying on the reaction of salicylaldehyde (5) and an enolate derived from acetophenone (7, Scheme 5) [20]. To begin, chalcone 9 was prepared in 85% yield by the Knoevenagel reaction of salicylaldehyde (5) and acetophenone (7) in the presence of KOH

• used. Chromane derivatives from the reactions of salicylaldehyde and enolate equivalents derived from malononitrile and its derivatives The one-pot reaction of salicylaldehyde and malononitrile has proved to be an efficient method for the synthesis of 2-iminochromene derivatives. In general such

Asymmetric synthesis of γ-chloro-α,β-diamino- and β,γ-aziridino-α-aminoacylpyrrolidines and -piperidines via stereoselective Mannich-type additions of N-(diphenylmethylene)glycinamides across α-chloro-N-sulfinylimines

• Gert Callebaut,
• Sven Mangelinckx,
• Pieter Van der Veken,
• Karl W. Törnroos,
• Koen Augustyns and
• Norbert De Kimpe

Beilstein J. Org. Chem. 2012, 8, 2124–2131, doi:10.3762/bjoc.8.239

• the glycinamides 4, as compared to the reaction with glycine esters, is attributed to the α-coordinating ability of the chlorine atom with the lithium of the incoming enolate as depicted in transition state TS-6b. The coordinating α-chloro atom in TS-6b overrides the chelation of the sulfinyl oxygen

• ,β-diaminocarboxylamides 5. aYield in parentheses results from the use of LDA instead of LiHMDS. Transition-state model for reaction of the Z-enolate of glycinamides 4 in the Mannich-type addition across chiral α-chloro-N-p-toluenesulfinyl aldimines 3. Synthesis of N-sulfinyl-β,γ-aziridino-α-amino

Design and synthesis of quasi-diastereomeric molecules with unchanging central, regenerating axial and switchable helical chirality via cleavage and formation of Ni(II)–O and Ni(II)–N coordination bonds

• Vadim A. Soloshonok,
• José Luis Aceña,
• Hisanori Ueki and
• Jianlin Han

Beilstein J. Org. Chem. 2012, 8, 1920–1928, doi:10.3762/bjoc.8.223

• of target complexes 19/20. It is interesting to note that the acetophenone module-derived compound 14a gave the expected enolate 16a; however, its further oxidation lead mostly to decomposition, suggesting higher instability of intermediate derivatives of type 17 and 18 [48]. Also, the benzophenone

Approaches to α-amino acids via rearrangement to electron-deficient nitrogen: Beckmann and Hofmann rearrangements of appropriate carboxyl-protected substrates

• Sosale Chandrasekhar and
• V. Mohana Rao

Beilstein J. Org. Chem. 2012, 8, 1393–1399, doi:10.3762/bjoc.8.161

• preparation of 1 is also presented herein). Ketone 1 was α-alkylated in high yields to various 2 via sodium hydride deprotonation and reaction of the resulting enolate with a variety of alkyl bromides or iodides. Alkyl derivatives 2 may be converted conventionally to the corresponding oximes 3. The Beckmann

• transformation of 1 to 5 indicates that 1 functions as a glycine enolate equivalent with the benzoylamino group in 5 being introduced in umpolung fashion (reaction involves the migration to an electrophilic nitrogen center). Hofmann rearrangement approach Our strategy was based on the known ethyl

• trioxaadamantylacetate 6 (Scheme 2) [15]. Alkylation of this compound was accomplished via initial deprotonation with lithium hexamethyldisilazide in THF at −78 °C [19]. The resulting enolate was reacted with various alkyl bromides or iodides, initially at −78 °C and then at room temperature over 6–8 h. The α-alkyl

Asymmetric organocatalytic decarboxylative Mannich reaction using β-keto acids: A new protocol for the synthesis of chiral β-amino ketones

• Chunhui Jiang,
• Fangrui Zhong and
• Yixin Lu

Beilstein J. Org. Chem. 2012, 8, 1279–1283, doi:10.3762/bjoc.8.144

• aryl methyl ketones, we wondered whether β-keto acids could serve as an enolate equivalent to aryl methyl ketones upon decarboxylation (Scheme 1). The proposed addition–decarboxylation sequence is consistent with current mechanistic understanding [31][35][37][38]. However, we cannot exclude an

• alternative decarboxylation–addition pathway at this stage. In fact, in sharp contrast to the popular use of malonic acid half thioesters (MAHTs) as an ester enolate equivalent in enantioselective decarboxylative additions [39], the employment of β-keto acids as a reaction partner in decarboxylative processes