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

• Ishmael B. Masesane Zelalem Yibralign Desta Department of Chemistry, University of Botswana, Private Bag 00704, Gaborone, Botswana 10.3762/bjoc.8.244 Abstract The reported methodologies for the synthesis of chromane derivatives through the reaction of salicylaldehyde and enolates are discussed

• . The enolates and their equivalents involved in the reactions discussed in this article were derived from ketones, nitroalkanes, malononitrile and α,β-unsaturated compounds. Keywords: acetophenone; chromane; enolates; malononitrile; Michael addition; salicylaldehyde; Introduction The chromane

• ][16][17]. Among the reported methodologies for the synthesis of chromane derivatives, the reaction of salicylaldehyde and enolates or their equivalents has gained a prominent position. The key features of the synthesis of chromane derivatives by the reaction of salicylaldehyde and enolates are

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

• potency of analogous α,β-diaminocarboxylamides exists [15]. The synthesis of chiral α,β-diaminocarboxylic acid derivatives by asymmetric Mannich-type addition of enolates across activated imines, e.g., N-sulfinylimines [16][17][18][19][20], is one of the most common and versatile methods in organic

• -chloro-α,β-diaminocarboxyl esters obtained by Mannich-type addition of E-enolates derived from glycine esters across imines 3 [20]. The monosubstituted tertiary amide enolates obtained by deprotonation of N-(diphenylmethylene)glycinamides 4 are expected to have the Z-geometry in which A(1,3) interactions

• are minimized and Li-chelation stabilizes the conformation (Scheme 3), regardless of the base that was used [30][31]. Reaction of the Z-enolates via a cyclic chelated six-membered chairlike transition-state model TS-6a, would have resulted in anti-addition products anti-5 in analogy with our

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

• enolates 16, in the presence of relatively strong bases (KOt-Bu), is an established step in general methods for homologation of the glycine moiety by alkyl halide alkylation [27][50][51][52][53], aldol [29][33][36][37] and Michael [28][31][34][35][38][39][43][44][45][46][47] addition reactions. The

• following oxidation step of the enolates 16 in the presence of atmospheric oxygen, is less studied [48]; however, plausible key transformations can be deduced based on the closely related results on the well-established general oxidation of enolates [55][56][57][58][59][60][61][62][63][64] and glycine

• -derived enolates [65][66][67][68][69][70], in particular, under similar conditions. Thus, the ionized form of α-hydroxy intermediate 17 can undergo the cleavage of the glycine C–N bond [65][68][69][70] resulting in the formation of neutral complex 18. Previously, we demonstrated that in situ formed

Palladium-catalyzed substitution of (coumarinyl)methyl acetates with C-, N-, and S-nucleophiles

• Kalicharan Chattopadhyay,
• Erik Fenster,
• Alexander J. Grenning and
• Jon A. Tunge

Beilstein J. Org. Chem. 2012, 8, 1200–1207, doi:10.3762/bjoc.8.133

• hydroxymethylcoumarins, we chose to investigate their decarboxylative couplings of enolates. We have previously shown that decarboxylative benzylation (DcB) is a useful method for the addition of less-stabilized enolate anions to a benzyl functionality [46][53][54][55]. Thus, we envisioned being able to add various

• ketone enolates to the exo-methyl position of the coumarin core by this method (Table 1). Screening of reaction conditions showed that, in contrast to common decarboxylative benzylation conditions (Table 1,entries 1 and 2) under which nonpolar solvents give the best DcB, the selective mono-alkylation of

• conditions (5 mol % Pd(PPh3)4, MeCN, rt, Table 1, entry 3), a variety of enolate nucleophiles could be selectively coupled with coumarin electrophiles (Scheme 2). For example, acetone, acetophenone and 1,1,1-trimethylacetone enolates can all be generated and coupled with the coumarin electrophile

Facile isomerization of silyl enol ethers catalyzed by triflic imide and its application to one-pot isomerization–(2 + 2) cycloaddition

• Kazato Inanaga,
• Yu Ogawa,
• Yuuki Nagamoto,
• Akihiro Daigaku,
• Hidetoshi Tokuyama,
• Yoshiji Takemoto and
• Kiyosei Takasu

Beilstein J. Org. Chem. 2012, 8, 658–661, doi:10.3762/bjoc.8.73

• sequence, Tf2NH catalyzes both of the reactions. Keywords: isomerization; one-pot reaction; organocatalysis; silyl enol ethers; triflic imide; Introduction Silyl enol ethers, which are isolable equivalents of metal enolates, are useful and important intermediates in synthetic chemistry [1][2][3]. They

N-Heterocyclic carbene/Brønsted acid cooperative catalysis as a powerful tool in organic synthesis

• Rob De Vreese and
• Matthias D’hooghe

Beilstein J. Org. Chem. 2012, 8, 398–402, doi:10.3762/bjoc.8.43

• -lactam to γ-lactam ring expansions [29][30], aziridine ring openings followed by cyclization with enolates [31], palladium-catalyzed cyclizations [32], cycloadditions [33], multicomponent reactions [34], and even NHC catalysis [35][36]. Nevertheless, the methodology developed by Rovis indisputably

Synthetic approaches to multifunctional indenes

• Neus Mesquida,
• Sara López-Pérez,
• Immaculada Dinarès and
• Ermitas Alcalde

Beilstein J. Org. Chem. 2011, 7, 1739–1744, doi:10.3762/bjoc.7.204

• enolates, which needs to be considered when adjusting the reaction conditions [25]; and (ii) the chemical response of indanoles towards dehydration [6][18] to give the desired endo-olefin 3, which should be favored with the presence of a methyl group at the indene 2-position. Results and Discussion We

Continuous-flow enantioselective α-aminoxylation of aldehydes catalyzed by a polystyrene-immobilized hydroxyproline

• Xacobe C. Cambeiro,
• Rafael Martín-Rapún,
• Pedro O. Miranda,
• Sonia Sayalero,
• Esther Alza,
• Patricia Llanes and
• Miquel A. Pericàs

Beilstein J. Org. Chem. 2011, 7, 1486–1493, doi:10.3762/bjoc.7.172

• preformed enolates, both with the use of chiral auxiliaries (chiral, enantiopure enolates and achiral oxidizing agents, or achiral enolates and chiral, enantiopure oxidizing agents) [3][4][5] and by Mukaiyama-type catalytic processes involving preformed achiral enolate equivalents and achiral oxidants, with

• chiral enantiopure Lewis acids as catalysts [6][7][8][9][10][11]. Worth noting is the contribution made by Yamamoto et al., who introduced the use of nitrosobenzene as an electrophilic source of oxygen in the aminoxylation of preformed tin enolates catalyzed by a chiral, silver-based Lewis acid [12

Directed aromatic functionalization in natural-product synthesis: Fredericamycin A, nothapodytine B, and topopyrones B and D

• Charles Dylan Turner and
• Marco A. Ciufolini

Beilstein J. Org. Chem. 2011, 7, 1475–1485, doi:10.3762/bjoc.7.171

• issue for which no solution existed at that time: The arylation of stabilized enolates. Indeed, the retrosynthetic analysis illustrated in Scheme 1 suggests that 1 could result from the cyclization of 3, which in turn would ensue through the union of fragments 4 and 5. These two subunits were prepared

• ]. In the years since, Pd-mediated arylation reactions of enolates have been extensively developed and improved, especially by Buchwald [40][41][42][43] and Hartwig [44][45][46]. Nothapodytine Our group cultivates a long-standing interest in furan chemistry, especially in connection with a process that

Development of the titanium–TADDOLate-catalyzed asymmetric fluorination of β-ketoesters

• Lukas Hintermann,
• Mauro Perseghini and
• Antonio Togni

Beilstein J. Org. Chem. 2011, 7, 1421–1435, doi:10.3762/bjoc.7.166

• reactions were developed, before Differding and Lang found the first stoichiometric asymmetric fluorination of β-ketoester enolates with a chiral N–F (N-fluoroamine) reagent in 1988 [21]. Later work by Davis [22][23], Takeuchi [24] and their respective coworkers extended this chemistry, while Haufe and

• halogenating agents [58][59][60][61][62]. These reactions can be slow due to rate-limiting enolization of the substrate, thus enolates or enolate equivalents are often preferred as substrates [58]. If activated methylene derivatives are mixed with a strong halogenating agent, the enol portion of the tautomeric

• ][64][65]. Preparative halogenations of 1,3-dicarbonyl substrates at ambient temperatures are relatively slow and it is more common to halogenate their alkali enolates instead [58]. From studies on the electrophilic fluorination with N–F reagents, it is known that some β-carbonyl compounds are α

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

• chelated enolates and subsequent oxidation/Passerini reaction. This protocol works with both, aldehyde and ketone intermediates, as long as the ketones are activated by electron-withdrawing groups. In principle Ugi reactions are also possible, allowing the generation of diamino acid derivatives. Keywords

• : amino acids; chelated enolates; epoxides; Passerini reactions; Ugi reactions; Introduction Multicomponent reactions (MCR) are a very popular and powerful tool in modern organic synthesis [1][2][3][4]. Besides a wide range of heterocycle syntheses [5] and catalytic cross coupling reactions [6], the

• by chelated enolate Claisen rearrangement [22][23] or transition metal-catalyzed allylic alkylation of chelated enolates [24] and subsequent oxidative cleavage of the γ–δ-unsaturated amino acids obtained. Results and Discussion An alternative approach is based on regioselective ring opening of

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

• tertiary thiols, the majority (for example, those involving epoxide opening or electrophilic attack on thio-substituted enolates) lead to thiols carrying further functionality in some form. Tertiary thiols without further functionality are still challenging, with organolithium-based alkylations and

Shelf-stable electrophilic trifluoromethylating reagents: A brief historical perspective

• Norio Shibata,
• Andrej Matsnev and
• Dominique Cahard

Beilstein J. Org. Chem. 2010, 6, No. 65, doi:10.3762/bjoc.6.65

• % yield [17]. In 2008–2009, we found that chiral nonracemic cinchona alkaloids and guanidines act as Brønsted bases to generate ammonium or guanidinium enolates for the enantioselective electrophilic trifluoromethylation of β-keto esters with Umemoto reagents with good enantioselectivities in the range 60

Fused bicyclic piperidines and dihydropyridines by dearomatising cyclisation of the enolates of nicotinyl-substituted esters and ketones

• Heloise Brice,
• Jonathan Clayden and
• Stuart D. Hamilton

Beilstein J. Org. Chem. 2010, 6, No. 22, doi:10.3762/bjoc.6.22

• scope of the dearomatisation can be extended to much less reactive nucleophiles with a more electron deficient aromatic acceptor [39][40][41]. Thus enolates of glycine esters 1 carrying isonicotinoyl or nicotinoyl N-substituents cyclise readily to yield bicyclic amino acid derivatives 2 (Scheme 1a for

• presence of an alcohol [41] (Scheme 1b). In this paper we report the results of cyclising the enolates of ester and ketones tethered to a nicotinyl nucleus via chains which do not incorporate an amide linkage. The starting materials for these cyclisations do not benefit from the favourable conformational

• potassium enolates are more reactive than the lithium enolate and compete too well with N-acylation. We surmised that effective cyclisation onto the acylpyridinium species, avoiding the N- vs. C-acylation problem, might be made possible by decreasing the reactivity of the enolate still further, transforming

Recent progress on the total synthesis of acetogenins from Annonaceae

• Nianguang Li,
• Zhihao Shi,
• Yuping Tang,
• Jianwei Chen and
• Xiang Li

Beilstein J. Org. Chem. 2008, 4, No. 48, doi:10.3762/bjoc.4.48

C₂-symmetric bisamidines: Chiral Brønsted bases catalysing the Diels- Alder reaction of anthrones

• Deniz Akalay,
• Gerd Dürner,
• Jan W. Bats and
• Michael W. Göbel

Beilstein J. Org. Chem. 2008, 4, No. 28, doi:10.3762/bjoc.4.28

• mechanistic rationalisation is proposed in Scheme 4. The catalyst deprotonates the anthrone in the initial step. This assumption is supported by the pKa values of compounds 2a (10, [7][8]) and 8·H+ (~11, [6]). Furthermore, the appearance of the yellow color of enolates (1·H+) shows significant proton transfer

Stereoselective α-fluoroamide and α-fluoro- γ-lactone synthesis by an asymmetric zwitterionic aza-Claisen rearrangement

• Kenny Tenza,
• Julian S. Northen,
• David O'Hagan and
• Alexandra M. Z. Slawin

Beilstein J. Org. Chem. 2005, 1, No. 13, doi:10.1186/1860-5397-1-13

• Background Asymmetric introduction of fluorine α-to a carbonyl has become popular recently, largely because the direct fluorination of enolates by asymmetric electrophilic fluorinating reagents has improved, and as a result such compounds are becoming attractive synthons. We have sought an alternative but

• reagents, either using asymmetric enolates, [3][4] asymmetric fluorinating reagents[5][6] or asymmetric Lewis acids.[7][8][9] Most recently organocatalysis mediated asymmetric fluorinations have been explored[10] and this has resulted in the efficient preparation of α-fluoroaldehydes in high enantiomeric