Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• . The stereochemistry of aza-Reformatsky reactions involving N-sulfinyl ketimines is generally explained through a six-membered transition state with the zinc coordinated to the sulfinyl oxygen atom and the enolate carbanion to the imino carbon atom. The other substituents accommodate in order to

• complex H. A subsequent addition of another molecule of BrZnCH2CO2Et to this complex results in the formation of complex I. In complex I, the double bond of the zinc enolate attacks the carbonyl group of the aldehyde providing compound J which led to the final product 50 under acidic work-up conditions

• ). Finally, good to excellent enantioselectivities (76–94% ee) combined to moderate to quantitative yields (45–99%) were reported by Matsubara and Haraguchi in the enantioselective Reformatsky reaction of aldehydes 48b–e,g–i,r–w with enolate equivalent 55 prepared from phenyl isocyanate 56 and CH2(ZnI)2 in

One-pot sequential synthesis of tetrasubstituted thiophenes via sulfur ylide-like intermediates

• Jun Ki Kim,
• Hwan Jung Lim,
• Kyung Chae Jeong and
• Seong Jun Park

Beilstein J. Org. Chem. 2018, 14, 243–252, doi:10.3762/bjoc.14.16

• to excellent yields (68% and 81%). However, a CF3 substituent, which is electron-withdrawing and might promote the keto form, provided the desired compound 8al in a low yield (14%). When the enolate was derived from 3-oxo-3-phenylpropanenitrile, 3-cyano-4-phenylthiophene 8am was obtained in a low

Gram-scale preparation of negative-type liquid crystals with a CF₂CF₂-carbocycle unit via an improved short-step synthetic protocol

• Tatsuya Kumon,
• Shohei Hashishita,
• Takumi Kida,
• Shigeyuki Yamada,
• Takashi Ishihara and
• Tsutomu Konno

Beilstein J. Org. Chem. 2018, 14, 148–154, doi:10.3762/bjoc.14.10

• addition reaction, a Michael addition reaction, giving rise to the corresponding magnesium enolate Int-L. The subsequent hydrolysis of Int-L then leads to the γ-hydroxyketone 8a', which easily tautomerizes into the more stable 5-membered hemiacetal 8a. From the above insight into the reaction mechanism, if

Volatiles from the tropical ascomycete Daldinia clavata (Hypoxylaceae, Xylariales)

• Tao Wang,
• Kathrin I. Mohr,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 135–147, doi:10.3762/bjoc.14.9

• from an α-cleavage next to the alcohol function. To verify this structural proposal for 11a, racemic 2-methylbutanal (18) was reacted in an aldol addition with the enolate anion of pentan-3-one (23) which produced a racemic mixture of all four diastereomers 11a–d (Scheme 4). All eight stereoisomers of

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• hydride to give the expected ylides 51. A subsequent intramolecular attack of the ylidic carbon atom on the carbonyl group in the Wittig reaction provided 5- or 6-membered alkenes 52 in yields of 51–69% (Scheme 35) [3]. Another example of the use of the enolate anion as a carbon nucleophilic agent was

• reported by Fuchs, who obtained 1,3-cyclohexadienes 54 by reaction of 1,3-butadienyltriphenylphosphonium bromide with enolate anions 53 derived from aldehydes or ketones in yields of 35–57% (Scheme 36). The nucleophilic attack here was directed at position 4 of the diene [11]. Hewson and MacPherson

• of cyclic alkenes in the intramolecular Wittig reaction from vinylphosphonium bromide and ketoesters as precursors of carbon nucleophiles. Synthesis of 1,3-cyclohexadienes by reaction of 1,3-butadienyltriphenylphosphonium bromide with enolate anions. Synthesis of bicyclo[3.3.0]octenes by reaction of

A Brønsted base-promoted diastereoselective dimerization of azlactones

• Danielle L. J. Pinheiro,
• Gabriel M. F. Batista,
• Pedro P. de Castro,
• Leonã S. Flores,
• Gustavo F. S. Andrade and
• Giovanni W. Amarante

Beilstein J. Org. Chem. 2017, 13, 2663–2670, doi:10.3762/bjoc.13.264

• and Mannich acceptors [20][21][22][23]. Enolate anions derived from azlactone are effective intermediates for the functionalization of α-amino acids. However, the acylation of the enolate ion by another azlactone has been less reported in the literature [24][25][26]. This transformation affords an

• stable and unreactive species (Scheme 2) [29]. Although the mechanistic details of dimerization remain to be elucidated, a plausible mechanism was proposed based on 1H NMR evidence (Figure 3). The NMR experiments revealed that KTCA reacts with CH3CN to form a basic species 3 [30]. The enolate azlactone

• shown in Figure 3. Furthermore, a six-membered ring involving the salt cation, the azlactone ring and the enolate might be involved in the addition step. Irreversible intramolecular cyclization of 4 gave 5 (for a reaction reversibility study of product 2h, see Supporting Information File 1), eventually

Diastereoselective Mannich reactions of pseudo-C₂-symmetric glutarimide with activated imines

• Tatsuya Ishikawa,
• Tomoko Kawasaki-Takasuka,
• Toshio Kubota and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2017, 13, 2473–2477, doi:10.3762/bjoc.13.244

• , Nakanarusawa 4-12-1, Hitachi 316-8511, Japan 10.3762/bjoc.13.244 Abstract As an extension of the boron enolate-based aldol reactions, the oxazolidinone-installed bisimide 1a from 3-(trifluoromethyl)glutaric acid was employed for Mannich reactions with tosylated imines 2 as electrophiles to successfully obtain

• couple of routes to get successful access to such target molecules with a variety of substituents at the 2-position [1][2][3]. Previously, the oxazolidinone-installed bisimide 1a was employed for the crossed aldol reactions by the way of boron enolate which allowed the isolation of optically active

• article. Results and Discussion On the basis of our previous study [4], the chiral glutarimide 1a was employed as the starting material and optimization of reaction conditions with benzaldehyde-based imines 2 was performed (Table 1). Lithium enolate by the action of LDA to 1a was found to be ineffective

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• nucleophile as well as asymmetric catalysis still remains to be studied in these reactions. The high efficiency and stereoselectivity of the enolate addition to nitrosoalkenes make this strategy perspective for application in total synthesis that has been recognized since 1970s. Thus, Oppolzer and co-workers

• -bromooxime 26 with lithium enolate 27 to give oxime 28 via the Michael addition to transient nitrosoalkene NSA6 [31]. Oxime adduct 28 existed predominantly in a cyclic 1,2-oxazine form (Scheme 11). Subsequent benzylation of oxime 28 and the thermal retro-[2 + 2]/[4 + 2]-cycloaddition cascade followed by

• . Diketone 30 was prepared in a straightforward manner by C-C-coupling of nitrosoalkene NSA7 (generated in situ from the corresponding α-bromooxime 31) with silyl enolate of 2-methylcyclopentanone, and subsequent deoxygenation of the resulting oxime 32 with CAN. Unfortunately, attempts to convert pentalenone

Regiodivergent condensation of 5-alkoxycarbonyl-1H-pyrrol-2,3-diones with cyclic ketazinones en route to spirocyclic scaffolds

• Alexey Yu. Dubovtsev,
• Maksim V. Dmitriev,
• Аndrey N. Maslivets and
• Michael Rubin

Beilstein J. Org. Chem. 2017, 13, 2179–2185, doi:10.3762/bjoc.13.218

• product of 1,2-addition of the C-nucleophile to the most reactive keto function and subsequent nucleophilic attack by the O-enolate on the conjugate C=C bond activated by two electron acceptors could become more preferable as compared to the alternative “normal” pathway, leading to adducts 10 and

• diastereomers (see Scheme 3 for atom numbering). This configuration was unambiguously confirmed by a single crystal X-ray crystallography of compound 12ab (CCDC 1546062) shown in Figure 1. Puzzled by this unexpected reactivity, we reasoned that the enolate moiety can be activated towards the desired

Synthesis of 2-aminosuberic acid derivatives as components of some histone deacetylase inhibiting cyclic tetrapeptides

• Shital Kumar Chattopadhyay,
• Suman Sil and
• Jyoti Prasad Mukherjee

Beilstein J. Org. Chem. 2017, 13, 2153–2156, doi:10.3762/bjoc.13.214

• to provide the desired 2-aminoheptenoic acid derivative 11. Several syntheses of this important amino acid have appeared which include Lubell’s palladium-catalyzed allylation [15], Riera’s asymmetric epoxidation protocol [16], Rich’s enolate amination [17] and Hruby’s asymmetric alkylation [18] of a

One-pot multistep mechanochemical synthesis of fluorinated pyrazolones

• Joseph L. Howard,
• William Nicholson,
• Yerbol Sagatov and
• Duncan L. Browne

Beilstein J. Org. Chem. 2017, 13, 1950–1956, doi:10.3762/bjoc.13.189

• no further improvement (Table 2, entry 5). The fluorination reaction studied here proceeds via an enolate which is aromatic and therefore is relatively facile (compared to the fluorination of other heterocyclic systems). Introduction of a mild base, such as sodium carbonate to the reaction vessel

Synthesis of benzannelated sultams by intramolecular Pd-catalyzed arylation of tertiary sulfonamides

• Valentin A. Rassadin,
• Mirko Scholz,
• Anastasiia A. Klochkova,
• Armin de Meijere and
• Victor V. Sokolov

Beilstein J. Org. Chem. 2017, 13, 1932–1939, doi:10.3762/bjoc.13.187

• the methoxycarbonyl group at C-3 under these basic conditions must be due to its reduced electrophilicity in connection with the facile enolate formation at this position. The structures of all obtained compounds were assigned on the basis of 1H and 13C NMR spectra, as well as high resolution mass

Iodoarene-catalyzed cyclizations of N-propargylamides and β-amidoketones: synthesis of 2-oxazolines

• Somaia Kamouka and
• Wesley J. Moran

Beilstein J. Org. Chem. 2017, 13, 1823–1827, doi:10.3762/bjoc.13.177

• , 6p is formed under the reaction conditions but the oxazoline ring is readily hydrolysed due to the influence of the electron-withdrawing nitro group on the aromatic ring. The mechanism of this cyclization is proposed to proceed through the formation of iodine(III)-enolate 9 followed by intramolecular

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• alone does not sufficiently catalyse and control the reaction. However, addition of Na2CO3 (leading to formation of the sodium enolate of 1 and the sodium phosphate of H) had a very pronounced effect on both, yield and enantioselectivity when using NFSI as the fluorinating agent. Again, the exact

• enolate and subsequent asymmetric α-functionalization with an electrophile (E). Reported asymmetric α-fluorination of β-ketoesters 1 using different chiral PTCs. Asymmetric α-fluorination of benzofuranones 4 with phosphonium salt PTC F1. Asymmetric α-fluorination of 1 with chiral phosphate-based catalysts

Sustainable synthesis of 3-substituted phthalides via a catalytic one-pot cascade strategy from 2-formylbenzoic acid with β-keto acids in glycerol

• Lina Jia and
• Fuzhong Han

Beilstein J. Org. Chem. 2017, 13, 1425–1429, doi:10.3762/bjoc.13.139

• demand and potential for the development of a green one-pot cascade aldol/cyclization strategy for these compounds [22]. The use of β-keto acids as ketone enolate equivalents in metal- and organocatalytic decarboxylative aldol reactions has been extensively studied and proven to be a valuable and

A speedy route to sterically encumbered, benzene-fused derivatives of privileged, naturally occurring hexahydropyrrolo[1,2-b]isoquinoline

• Olga Bakulina,
• Alexander Ivanov,
• Vitalii Suslonov,
• Dmitry Dar’in and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2017, 13, 1413–1424, doi:10.3762/bjoc.13.138

• ) N-acylation of the imine component followed by intramolecular Mannich reaction or (b) Mannich-type addition of the HPA enolate to a protonated imine component followed by intramolecular aminolysis of the cyclic anhydride moiety in Mannich adduct 13 (Scheme 3) [1]. Investigation of the CCR leading to

Switchable highly regioselective synthesis of 3,4-dihydroquinoxalin-2(1H)ones from o-phenylenediamines and aroylpyruvates

• Juraj Dobiaš,
• Marek Ondruš,
• Gabriela Addová and
• Andrej Boháč

Beilstein J. Org. Chem. 2017, 13, 1350–1360, doi:10.3762/bjoc.13.132

• partial formation of a stabilized enolate anion by DMAP deprotonation. Therefore, using DMAP activation is not recommended for EWG-substituted diamines. e) The reaction of activated ester 12d (obtained in situ after treatment of carboxylic acid 12b with HOBt/DIC, Scheme 6) and a diamine 11a–f (general

Synthesis of alkynyl-substituted camphor derivatives and their use in the preparation of paclitaxel-related compounds

• M. Fernanda N. N. Carvalho,
• Rudolf Herrmann and
• Gabriele Wagner

Beilstein J. Org. Chem. 2017, 13, 1230–1238, doi:10.3762/bjoc.13.122

• nitrogen and form the triflate or perrhenate salts. The newly formed five-membered ring in 23 is evident from the 13C NMR signals at 84.0, 90.0, 138.5, 136.0 and 125.5 ppm, and a 1H signal at 5.80 ppm. The enolate carbon is detected at 151.4 ppm in 13C NMR. Neither NMR nor IR show any evidence for carbonyl

Ultrasound-promoted organocatalytic enamine–azide [3 + 2] cycloaddition reactions for the synthesis of ((arylselanyl)phenyl-1H-1,2,3-triazol-4-yl)ketones

• Gabriel P. Costa,
• Natália Seus,
• Juliano A. Roehrs,
• Raquel G. Jacob,
• Ricardo F. Schumacher,
• Thiago Barcellos,
• Rafael Luque and
• Diego Alves

Beilstein J. Org. Chem. 2017, 13, 694–702, doi:10.3762/bjoc.13.68

• have been used for this cycloaddition reaction [20][21][22][23][24][25][26][27][28][29]. Organocatalytic approaches based on β-enamine–azide or enolate–azide cycloadditions have been employed to synthesize 1,2,3-triazole scaffolds [30][31][32]. Depending on the organocatalyst employed, different

• carbonyl compounds could successfully generate an enamine or an enolate, and these species react as dipolarophiles with organic azides in organocatalyzed 1,3-dipolar cycloadditions. Our research group has demonstrated β-enamine–azide cycloaddition reactions for the synthesis of selenium-functionalized

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• -1,3-indanodiones 77 (Scheme 26). It has been found that the intermediate 79 underwent the Stetter reaction to form the enolate intermediate 80, which next was transformed to the intermediate 81 via aldol condensation. The release of NHC gave the β-hydroxy ketone 82, which was deprotonated to enolate

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

Beilstein J. Org. Chem. 2017, 13, 348–371, doi:10.3762/bjoc.13.39

• biosynthetic cycle is KS-catalyzed chain extension. This reaction occurs by nucleophilic attack of an enolate generated by decarboxylation of an ACP-bound extender unit onto the starter unit or chain extension intermediate attached to the active site cysteine of the KS domain. The face of the enolate which is

• to yield the L-methyl. In mechanistic terms, epimerization involves removal of the C-2 proton and delivery of proton to C-2 from the opposite face of the resulting, planar enol/enolate intermediate. Monitoring by NMR of the rate of epimerization of a model C-3-ketoacyl ester (ethyl 2

• residues or alternatively abstraction by an available water molecule. The resulting enol/enolate could tautomerize spontaneously back to the original substrate or its epimer, with only the epimerized substrate possessing the required C-2 methyl stereochemistry for subsequent reduction. This epimer would

Diastereoselective anodic hetero- and homo-coupling of menthol-, 8-methylmenthol- and 8-phenylmenthol-2-alkylmalonates

• Matthias C. Letzel,
• Hans J. Schäfer and
• Roland Fröhlich

Beilstein J. Org. Chem. 2017, 13, 33–42, doi:10.3762/bjoc.13.5

• the benzyl ester 19 with lithium diisopropylamide and quenching the enolate with carbon dioxide (Scheme 2a). Benzyl 2-tert-butylmalonate (6) was prepared in good yield using a method of Krapcho et al. [18], by double deprotonation of 3,3-dimethylbutyric acid (20) with LDA and quenching the dianion

• radical have been observed [35][36][37]. In contrast, hardly any side products of that kind were obtained using menthol related auxiliaries in anodic radical coupling reactions. Products analogous to these of the radical homo-coupling above can be obtained by auxiliary controlled oxidative enolate

• obtained by auxiliary controlled oxidative enolate coupling. However, this method often requires more expensive reagents, functional groups are frequently more sensible to the used reagents and an up-scale is more difficult to perform. On the other side anodic coupling of sodium carboxylates is easy and

Synthesis of polyhydroxylated decalins via two consecutive one-pot reactions: 1,4-addition/aldol reaction followed by RCM/syn-dihydroxylation

• Michał Malik and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2016, 12, 2602–2608, doi:10.3762/bjoc.12.255

• . Then, the resulting enolate was approached by an aldehyde from the opposite side to the newly attached vinyl group. A similar stereochemical outcome of such transformation has been already reported [26][27][28][29][30][31][32][33]. Moreover, the addition of aldehyde gave rise to the anti aldol product

β-Amino functionalization of cinnamic Weinreb amides in ionic liquid

• Yi-Ning Wang,
• Guo-Xiang Sun and
• Gang Qi

Beilstein J. Org. Chem. 2016, 12, 2372–2377, doi:10.3762/bjoc.12.231

• -amino carbonyl derivatives. Surprisingly, there have been only a few successful preparations for β-amino Weinreb amides to date. One of which is the addition of the enolate of commercially available N-methoxy-N-methylacetamide to sulfinimines to generate the corresponding N-sulfinyl β-amino Weinreb

Useful access to enantiomerically pure protected inositols from carbohydrates: the aldohexos-5-uloses route

• Felicia D’Andrea,
• Giorgio Catelani,
• Lorenzo Guazzelli and
• Venerando Pistarà

Beilstein J. Org. Chem. 2016, 12, 2343–2350, doi:10.3762/bjoc.12.227

• an attempt to find an explanation of the stereochemical outcome of the reaction, we directed our attention toward the open-transition-state models. These have been proposed to explain the prevalent formation of syn products, irrespective of the enolate geometry [41], in aldol reactions performed in

• the absence of a coordinating metal center (for instance, in the case of tin and zirconium enolates, and of “naked” enolates generated from enolsilanes [42]). In the open-transition-state model, the enolate and the carbonyl group are orientated in an antiperiplanar fashion, maximazing the distance