Practical synthetic strategies towards lipophilic 6-iodotetrahydroquinolines and -dihydroquinolines

• David R. Chisholm,
• Garr-Layy Zhou,
• Ehmke Pohl,
• Roy Valentine and
• Andrew Whiting

Beilstein J. Org. Chem. 2016, 12, 1851–1862, doi:10.3762/bjoc.12.174

• [24]. Reports of aza-Michael additions occurring in water indicated that the desired 8 could be synthesised under mild conditions, and we therefore decided to adapt these published conditions to larger scale work [25][26]. Initial attempts involving a 1:1 molar mixture of o-toluidine (5) and methyl

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• chapter 1.1.1, furan rings can also be biosynthesised via oxa-Michael additions. Nonactin. Nonactin (70) is the smallest homolog of the macrotetrolides, a family of cyclic polyethers that commonly have activity as ionophore antibiotics (Scheme 11a). It is produced by Streptomyces griseus subsp. griseus

• strains. Pamamycins. Recently, the gene cluster of the macrodiolide antibiotic group of the pamamycins 73 was sequenced and the function of some of the genes studied (Figure 2) [60]. This cluster contains a NonS homolog, PamS, that was proposed to catalyse all three oxa-Michael additions that lead to

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• co-workers demonstrated that chiral lanthanum and samarium tris(BINOL) complexes (Figure 3), developed by the Shibasaki group for asymmetric Michael additions using malonates and organometallic reagents, are effective catalysts for the sequential conjugate addition of 4-tert-butyl(thiophenol) to α,β

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• the pionnering work by Trost in 2004 [26], several examples of the utility of the structurally related oxazol-4(5H)-ones (Figure 1b, X = O) have also been published, which involve mainly Michael additions (to enones [27][28], nitroalkenes [29][30], alkynones [31][32][33] and vinyl sulfones [34]), γ

• doesn’t change after the addition of nitrostyrene. 1.2.2 α-Silyloxyenones as acceptors. Among Michael acceptors, simple α,β-unsaturated esters and amides still are challenging substrates in direct Michael additions and have only been employed in few successful Michael reactions, mainly due to their

Supported bifunctional thioureas as recoverable and reusable catalysts for enantioselective nitro-Michael reactions

• José M. Andrés,
• Miriam Ceballos,
• Alicia Maestro,
• Isabel Sanz and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2016, 12, 628–635, doi:10.3762/bjoc.12.61

• organocatalysts in the stereoselective aza-Henry reaction [31]. Now we describe the results obtained in different stereoselective nitro-Michael additions promoted by these materials. Results and Discussion The ability of the supported catalysts (II–V) to promote the stereoselective nitro-Michael reaction was

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• acting through hydrogen bonding, such as thiourea, urea, squaramide, and thioamide frameworks. These have been efficiently employed in a few organocatalytic processes such as Friedel–Crafts alkylations, Michael additions, Diels–Alder reactions and aza-Henry reactions, as discussed below. Friedel–Crafts

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• ; Michael addition; Introduction Conjugate (or 1,4- or Michael) additions [1][2][3][4][5] are some of the most powerful carbon–carbon bond forming reactions in the synthetic chemist’s toolbox. These reactions have been the key step in the syntheses of numerous natural products and pharmaceutically relevant

• significant work in this area. Though, the majority of the review will focus on examples where carbon nucleophiles are utilized; there are examples where heteronucleophiles are used throughout the review. There are only a couple of examples of sulfa-Michael additions that are mentioned in this review because

• )-(+)-pseudoephedrine has emerged as a chiral auxiliary for the use in DCA reactions of α,β-unsaturated amides [49][50][51][52][53][54]. Badía and co-workers published a report where they performed aza-Michael additions to various α,β-unsaturated amides attached to (S,S)-(+)-pseudoephedrine [51] (Scheme 5

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

• carbonates, Michael additions, γ-umpolung additions, and acylations of alcohols. Keywords: asymmetric catalysis; chiral phosphine; nucleophilic; organocatalysis; organophosphorus; synthesis; Introduction During the past two decades, tertiary phosphine catalysts have been applied extensively in a wide range

• developments in nucleophilic chiral phosphine-catalyzed asymmetric reactions, including annulations of allenes, ketenes, alkynes, and Morita–Baylis–Hillman (MBH) carbonates with activated alkenes and imines, allylic substitution of MBH acetates and carbonates, Michael additions, γ-umpolung additions, and

• -RC reaction between the α,β-unsaturated imine and the enolate, followed by an SN2 reaction. 2.14 Annulations through double-Michael additions The bisphosphine-catalyzed double-Michael addition of dinucleophiles to electron-deficient alkynes provides an efficient approach for the synthesis of

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• bioactive compounds adopting phosphonamide anion technology is presented highlighting the utility of phosphonamide reagents in stereocontrolled bond-forming reactions. Methodologies utilizing phosphonamide anions in asymmetric alkylations, Michael additions, olefinations, and cyclopropanations will be

• 10–15% ee [2]. Asymmetric Michael additions using phosphonamides 28c,f, or analogs of 28 and 40, respectively, were applied in the total synthesis of acetoxycrenulide (10) [41][42], berkelic acid (15) [43], estrone (12) [44], fumonisin B2 (20) [45][46][47], methyl jasmonate (11) [48], and nudifloside

4-Hydroxy-6-alkyl-2-pyrones as nucleophilic coupling partners in Mitsunobu reactions and oxa-Michael additions

• Michael J. Burns,
• Thomas O. Ronson,
• Richard J. K. Taylor and
• Ian J. S. Fairlamb

Beilstein J. Org. Chem. 2014, 10, 1159–1165, doi:10.3762/bjoc.10.116

• using them as nucleophilic partners in oxa-Michael additions and the Mitsunobu reaction. The reactions proceed in moderate to excellent yields on a range of substrates containing useful functionality. The reactions serve as practical and valuable synthetic methods to construct complex 2-pyronyl ethers

• (Scheme 2). These more structurally complex systems also underwent Mitsunobu reaction with various alcohols in good to excellent yields (Table 1, entries 8–12). Compounds 4i–l could find further utility in the synthesis of phacelocarpus 2-pyrones in the future. Oxa-Michael additions Whilst the formation

• ., using ethyl 2-pentynoate) served to further reduce the reactivity towards addition and no product was formed even under the optimised conditions. Conclusion In conclusion, 4-hydroxy-6-alkyl-2-pyrones are effective coupling partners in Mitsunobu reactions and oxa-Michael additions. The reactions have

A catalyst-free multicomponent domino sequence for the diastereoselective synthesis of (E)-3-[2-arylcarbonyl-3-(arylamino)allyl]chromen-4-ones

• Pitchaimani Prasanna,
• Pethaiah Gunasekaran,
• Subbu Perumal and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2014, 10, 459–465, doi:10.3762/bjoc.10.43

• –Hilman condensation, and a final deoxygenation. The deoxygenation is assumed to be induced by carbon monoxide resulting from the thermal decomposition of the dimethylformamide solvent. Keywords: chromones; domino reactions; Michael additions; multicomponent reactions; transfer hydrogenation

New hydrogen-bonding organocatalysts: Chiral cyclophosphazanes and phosphorus amides as catalysts for asymmetric Michael additions

• Helge Klare,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2014, 10, 224–236, doi:10.3762/bjoc.10.18

Organocatalytic tandem Michael addition reactions: A powerful access to the enantioselective synthesis of functionalized chromenes, thiochromenes and 1,2-dihydroquinolines

• Chittaranjan Bhanja,
• Satyaban Jena,
• Sabita Nayak and
• Seetaram Mohapatra

Beilstein J. Org. Chem. 2012, 8, 1668–1694, doi:10.3762/bjoc.8.191

• organocatalysts with their percentage of conversion (% yield) and enantiomeric excess (ee) is presented in tabular form, and the best catalyst is used for the given individual scheme. Review 1 Organocatalytic oxa-Michael additions to access functionalized chromenes 1.1. Reactions of 2-hydroxybenzaldehydes with

Cyclization of ortho-hydroxycinnamates to coumarins under mild conditions: A nucleophilic organocatalysis approach

• Florian Boeck,
• Max Blazejak,
• Markus R. Anneser and
• Lukas Hintermann

Beilstein J. Org. Chem. 2012, 8, 1630–1636, doi:10.3762/bjoc.8.186

• initially thought that hydro-heteroatomic nucleophiles such as thiols, which are known to easily undergo hetero-Michael additions [38], could be suitable candidates for the screen. However, coumarin was not formed in the presence of thiols (Table 1, entry 1). We turned our attention to nucleophiles that are

Synthesis and evaluation of new guanidine-thiourea organocatalyst for the nitro-Michael reaction: Theoretical studies on mechanism and enantioselectivity

• Tatyana E. Shubina,
• Matthias Freund,
• Sebastian Schenker,
• Timothy Clark and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2012, 8, 1485–1498, doi:10.3762/bjoc.8.168

• . However, guanidine-thiourea 7 gave the product 10 only in racemic form and in moderate yield (62%, Scheme 2). The Michael additions of 2,4-pentanedione and diethylmalonate to trans-β-nitrostyrene were further explored (Scheme 3). The use of guanidine-thiourea 7 at 20 mol % in toluene at room temperature

A quantitative approach to nucleophilic organocatalysis

• Herbert Mayr,
• Sami Lakhdar,
• Biplab Maji and
• Armin R. Ofial

Beilstein J. Org. Chem. 2012, 8, 1458–1478, doi:10.3762/bjoc.8.166

• °C, silyl ketene acetal 7b in dichloromethane with c(3a-CF3CO2) = (1.7–2.5) × 10−5 M, kryptopyrrole 12a in acetonitrile with c(3a-CF3CO2) = 5.0 × 10−5 M). Comparison of calculated and experimental rate constants of electrophilic aromatic substitutions with iminium ions [56]. Aza-Michael additions of

Synthesis of chiral sulfoximine-based thioureas and their application in asymmetric organocatalysis

• Marcus Frings,
• Isabelle Thomé and
• Carsten Bolm

Beilstein J. Org. Chem. 2012, 8, 1443–1451, doi:10.3762/bjoc.8.164

• organic transformations with hydrogen bond accepting substrates. Recently, we reported the enantioselective ring opening of cyclic meso-anhydrides and asymmetric Michael additions of 1,3-dicarbonyl compounds to nitroalkenes with thiourea-based organocatalysts [48][49]. Based on those studies and in the

Catalyst-free and solvent-free Michael addition of 1,3-dicarbonyl compounds to nitroalkenes by a grinding method

• Zong-Bo Xie,
• Na Wang,
• Ming-Yu Wu,
• Ting He,
• Zhang-Gao Le and
• Xiao-Qi Yu

Beilstein J. Org. Chem. 2012, 8, 534–538, doi:10.3762/bjoc.8.61

• environmentally hazardous residues and undesirable byproducts [25][26][27][28][29][30]. As one part of our continuing efforts toward the development of green synthesis methods for Michael additions of nitroalkenes, we have previously reported an enzymatic tandem reaction to form 5-hydroxyimino-4,5-dihydrofurans

Syntheses and applications of furanyl-functionalised 2,2’:6’,2’’-terpyridines

• Jérôme Husson and
• Michael Knorr

Beilstein J. Org. Chem. 2012, 8, 379–389, doi:10.3762/bjoc.8.41

• . Unfortunately, when applied to the synthesis of furanyl-substituted tpy 12, this method leads to irreproducible results [19]. Even turning to barium hydroxide as a base (which is known to favour Michael additions [20]) did not improve the course of the reaction in a substantial manner. Therefore, basic alumina

• [19][21] was tested, since it is known to be an efficient promoter of aldol condensations and Michael additions under solvent-free conditions [22][23]. Nevertheless, the treatment of furanyl-substituted aldehydes 1, 3 and 15 did not yield the targeted diketo-intermediates, but instead the chalcones 5

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• transformations, including aza-Michael additions, hydroaminations of alkynes, Buchwald–Hartwig aminations, and allylic aminations, thereby allowing the creation of several covalent bonds in a single operation. Imine derivatives are also of high synthetic value as they may act either as electrophilic or