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

• of pyronyl ethers is useful in itself, the ability to introduce an unsaturated group onto the oxygen, leading to a pyronyl enol ether, would have additional value. This is a highly unusual motif found in some marine polyketide natural products (such as compound 1, Figure 1). Conjugate addition to α,β

Molecular architecture with carbohydrate functionalized β-peptides adopting 3₁₄-helical conformation

• Nitin J. Pawar,
• Navdeep S. Sidhu,
• George M. Sheldrick,
• Dilip D. Dhavale and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2014, 10, 948–955, doi:10.3762/bjoc.10.93

• attracted interest due to their use as structural elements as peptidomimetics [38][39], oligosaccharide mimetics [40][41] and induction of secondary structures [42][43][44][45][46]. Carbohydrate-derived β-amino acids used in this study were obtained by conjugate addition (Michael addition) of ammonia to a

• ]. Thus, preparation of the glucose derived β3-amino acid, the corresponding starting material ethyl (methyl 2,3,4-tri-O-benzyl-6,7-dideoxy-α-D-gluco-oct-6-enopyranoside)uronate (9a) was prepared from D-glucose as reported earlier [54]. Conjugate addition of ammonia to the α,β-unsaturated ester 9a

Asymmetric total synthesis of a putative sex pheromone component from the parasitoid wasp Trichogramma turkestanica

• Danny Geerdink,
• Jeffrey Buter,
• Teris A. van Beek and
• Adriaan J. Minnaard

Beilstein J. Org. Chem. 2014, 10, 761–766, doi:10.3762/bjoc.10.71

• )-4,6,8,10-tetramethyltrideca-2E,4E-dien-1-ol (2), is reported as a contribution to this identification. Catalytic asymmetric conjugate addition of methylmagnesium bromide and stereoselective Horner–Wadsworth–Emmons olefinations are used as the key steps, and 2 was obtained in 16 steps with an overall yield

• strategies is available for the synthesis of deoxypropionates [7][8][9][10][11][12][13][14][15]. Our approach [16] is based on copper-catalyzed asymmetric conjugate addition of methylmagnesium bromide to α,β-unsaturated thioesters and has proven its versatility [17][18][19]. Arrays of up to eight methyl

• substituents have been constructed [20]. Starting from 3, the first conjugate addition using (R,SFe)-L1 afforded 4, as expected in high yield and excellent enantiomeric excess (Scheme 1). Reduction with DIBALH, followed by Horner–Wadsworth–Emmons olefination and again asymmetric conjugate addition gave 6 in 77

Phosphinate-containing heterocycles: A mini-review

• Olivier Berger and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2014, 10, 732–740, doi:10.3762/bjoc.10.67

• cyclization through conjugate addition of ethyl 7-(ethoxy-H-phosphinoyl)-3-methyl-2-heptenoate (48) in the presence of potassium tert-butoxide (Scheme 20) [28]. A phosphorino[3’,4’:4,5]furo[2,3-d]-1,3-dioxole 51 was synthesized in 36% yield by Tattersall and coworkers by realizing a double Arbuzov-type

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

• achieved by the conjugate addition of cyanide [78]. Reduction of the newly introduced nitrile yielded the unexpected stable pentacycle 77. Formation of the missing methyl group (compound 78) could be achieved using forcing Wolff–Kishner-conditions. Benzoate formation and global oxidation [79][80] finally

• to give tricycle 111. The enol ether moiety was reduced using NaCNBH3, followed by allylic Riley oxidation and PCC-mediated enone formation. Copper-catalyzed conjugate addition in the presence of TMSCl [105] yielded silyl enol ether 112. Subsequent introduction of the side chain in 113 via a Claisen

• detected in the human body after cocaine consumption. It can be degradatively accessed from cocaine through pyrolysis, cocaine congeners can be prepared via conjugate addition afterwards [113][114]. Boc-protected pyrrole 127 was subjected to rhodium-catalyzed cyclopropanation with vinyldiazo compound 128

Organobase-catalyzed three-component reactions for the synthesis of 4H-2-aminopyrans, condensed pyrans and polysubstituted benzenes

• Moustafa Sherief Moustafa,
• Saleh Mohammed Al-Mousawi,
• Maghraby Ali Selim,
• Ahmed Mohamed Mosallam and
• Mohamed Hilmy Elnagdi

Beilstein J. Org. Chem. 2014, 10, 141–149, doi:10.3762/bjoc.10.11

• generated using a one-pot reaction involving condensation of ethyl propiolate (4a) with benzylidenemalononitrile (7a) in the presence of L-proline (5) (Scheme 4) [4]. It is believed that the pathway followed in this process involves conjugate addition of proline to the propiolate to yield adduct 6 which

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• conjugate addition [93], and a recent synthesis of lucentamycin A was achieved using this strategy [94]. Epoxidation of A leads to a highly functional intermediate C, which has been used in the synthesis of manzacidin B [95]. Among the plethora of olefination reactions, the Wittig [96][97] and Horner

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

• 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

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• noted that both enantiomers were required for physiological profiling at the discovery stage). Next, a 1,2-syn diastereoselective reduction of enaminoester 2.81 occurs with high diastereocontrol imposed by the convexed presentation of the substrate for the formal conjugate addition and subsequent

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

• diastereoselective synthesis of lactonamycinone (214) employing a Diels–Alder reaction [162][163]. In 2010, Tastuta completed the first total synthesis of lactonamycin (215) by using a sequential conjugate addition, a stereoselective glycosylation reaction and a Michael–Dieckmann-type cyclization [164]. The recently

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

• conjugate addition reactions. Recently, the MacMillan group has nicely expanded the scope of the reactions to include addition of the radicals to aryl rings (Scheme 27) [100]. Using Ir(ppy)3 as the photocatalyst and a 26 W fluorescent light bulb as the light source, cyclic amines with a variety of ring

Synthesis and antibacterial activity of monocyclic 3-carboxamide tetramic acids

• Yong-Chul Jeong and
• Mark G. Moloney

Beilstein J. Org. Chem. 2013, 9, 1899–1906, doi:10.3762/bjoc.9.224

• pyroglutamates by a conjugate addition of amines [22]. Tautomerism Tautomerism in tricarbonyl 3-acyltetramate systems is known to be complex and strongly dependent on the identity of the side chain acyl group [23]. 3-Acyl (X = CH2) [10][24][25], 3-carboxamide (X = NH) [8][10] and 3-alkoxycarbonyl (X = O

Asymmetric allylic alkylation of Morita–Baylis–Hillman carbonates with α-fluoro-β-keto esters

• Lin Yan,
• Zhiqiang Han,
• Bo Zhu,
• Caiyun Yang,
• Choon-Hong Tan and
• Zhiyong Jiang

Beilstein J. Org. Chem. 2013, 9, 1853–1857, doi:10.3762/bjoc.9.216

• conjugate addition and Mannich reaction of α-fluoro-β-ketoesters with excellent results [38][39][40]. Herein, we wish to report the first allylic alkylation of MBH carbonates with α-fluoro-β-ketoesters in excellent enantioselectivities and moderate diastereoselectivities, furnishing enantiopure fluorinated

Zinc–gold cooperative catalysis for the direct alkynylation of benzofurans

• Yifan Li and
• Jérôme Waser

Beilstein J. Org. Chem. 2013, 9, 1763–1767, doi:10.3762/bjoc.9.204

• reaction could proceed either via π-activation of the triple bond by the gold catalyst followed by conjugate addition of the benzofuran, α-elimination and 1,2-shift, or oxidative addition of TIPS-EBX (8) onto the gold catalyst (either at the Au(I) or Au(0) oxidation level) followed by electrophilic

Synthesis of the reported structure of piperazirum using a nitro-Mannich reaction as the key stereochemical determining step

• James C. Anderson,
• Andreas S. Kalogirou,
• Michael J. Porter and
• Graham J. Tizzard

Beilstein J. Org. Chem. 2013, 9, 1737–1744, doi:10.3762/bjoc.9.200

• available from a Henry reaction [50], imine 14 from the condensation of p-anisidine and isobutyraldehyde, and the process can easily be made asymmetric [45]. Conjugate addition of hydride to 13 and subsequent trapping of the nitronate anion with freshly prepared imine 14 in THF gave β-nitroamine 15 in 64

Gold-catalyzed intermolecular coupling of sulfonylacetylene with allyl ethers: [3,3]- and [1,3]-rearrangements

• Jungho Jun,
• Hyu-Suk Yeom,
• Jun-Hyun An and
• Seunghoon Shin

Beilstein J. Org. Chem. 2013, 9, 1724–1729, doi:10.3762/bjoc.9.198

• -substituted alkynes underwent an efficient intermolecular carboalkoxylation with allyl ethers via a tandem conjugate addition and a [3,3]-sigmatropic rearrangement [10][11][12]. Preliminary results in the above studies [5][9] have demonstrated that a polarizing effect of the sulfonyl substituent on the alkyne

A scalable synthesis of the (S)-4-(tert-butyl)-2-(pyridin-2-yl)-4,5-dihydrooxazole ((S)-t-BuPyOx) ligand

• Hideki Shimizu,
• Jeffrey C. Holder and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2013, 9, 1637–1642, doi:10.3762/bjoc.9.187

• ][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. Recently, our laboratory reported the catalytic asymmetric conjugate addition of arylboronic acids to cyclic, β,β-disubstituted enones utilizing (S)-t-BuPyOx (1) as the chiral ligand (Figure 1) [24]. This robust reaction is

Bioinspired total synthesis of katsumadain A by organocatalytic enantioselective 1,4-conjugate addition

• Yongguang Wang,
• Ruiyang Bao,
• Shengdian Huang and
• Yefeng Tang

Beilstein J. Org. Chem. 2013, 9, 1601–1606, doi:10.3762/bjoc.9.182

• neuraminidase (NA) inhibitor, was synthesized by using a bioinspired, organocatalytic enantioselective 1,4-conjugate addition of styryl-2-pyranone with cinnamaldehyde, followed by a tandem Horner–Wadsworth–Emmons/oxa Michael addition. Keywords: bioinspired synthesis; catalysis; katsumadain A; natural product

• ; organocatalytic 1,4-conjugate addition; Introduction 2-Pyranone is a privilege structure that is often present in natural products and pharmaceuticals, many of which exhibit diverse molecular architectures and biological profiles [1][2]. For example, katsumadain A (1) and B (2), which were isolated from Alpinia

• the way for their application in further biomedical investigations. Biosynthetically, katsumadain A is assumed to be derived from styryl-2-pyranone 3 and alnustone (4) [9] through a 1,6-conjugate addition/oxa-Michael addition cascade reaction (path a, Scheme 1). Indeed, both 3 and 4 are known natural

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

• the C13 hydroxy group via conjugate addition to the δ-hydroxy-α,β-enone 49 (Figure 5). Although the diastereoselectivity of this reaction using substrates with a chiral center at the hydroxy group had not been investigated in the published study, substitution at the carbinol position was reportedly

Methylidynetrisphosphonates: Promising C₁ building block for the design of phosphate mimetics

• Vadim D. Romanenko and
• Valery P. Kukhar

Beilstein J. Org. Chem. 2013, 9, 991–1001, doi:10.3762/bjoc.9.114

• 12a–f a three-step protocol including synthesis of alkylidene-1,1-bisphosphonates 11 from tetraethyl methylenebisphosphonate (10), phosphinylation and oxidation has been developed (Scheme 6) [26]. Propargyl-substituted trisphosphonate 15 was prepared by conjugate addition of sodium acetylide to

Diastereoselective synthesis of nitroso acetals from (S,E)-γ-aminated nitroalkenes via multicomponent [4 + 2]/[3 + 2] cycloadditions promoted by LiCl or LiClO₄

• Leandro Lara de Carvalho,
• Robert Alan Burrow and
• Vera Lúcia Patrocinio Pereira

Beilstein J. Org. Chem. 2013, 9, 838–845, doi:10.3762/bjoc.9.96

• besides conjugate addition [19] make them useful chiral building blocks for diastereoselective synthesis. Experimental General EtOH, MeOH, 2-propanol, toluene, LiClO4, LiCl, methyl vinyl ketone, ethyl vinyl ether, methyl acrylate and acrylonitrile were purchased from Aldrich, Acros or Merck and were used

A versatile and efficient approach for the synthesis of chiral 1,3-nitroamines and 1,3-diamines via conjugate addition to new (S,E)-γ-aminated nitroalkenes derived from L-α-amino acids

• Vera Lúcia Patrocinio Pereira,
• André Luiz da Silva Moura,
• Daniel Pais Pires Vieira,
• Leandro Lara de Carvalho,
• Eliz Regina Bueno Torres and
• Jeronimo da Silva Costa

Beilstein J. Org. Chem. 2013, 9, 832–837, doi:10.3762/bjoc.9.95

• yields of 68–88%. The conjugate addition of hydride, methoxide, nitronate and azide nucleophiles to 2a–c led to the corresponding chiral 1,3-nitroamines in 74–90% yield. The conjugate addition of cyanide anion to 2a,b was followed by HNO2 elimination affording chiral aminated acrylonitriles (73–98%). On

• derivatives by the use of chiral metal and organocatalysts [55][56]. In contrast, chiral 1,3-nitroamines, despite constituting direct precursors of chiral 1,3-diamines, are scarcely synthesized by conjugate addition of nitroalkanes to nitroalkenes. Chiral 1,3-diamines present extraordinary opportunities in

• analysis showed that the stereochemical integrity of 2 was preserved throughout the synthetic process. Next, the reactivity of the new chiral nitroalkenes was investigated with respect to the conjugate addition of hydride, nitronate, methoxide, cyanide, and azide anions in addition to benzylamine aiming to

Efficient synthesis of β’-amino-α,β-unsaturated ketones

• Isabelle Abrunhosa-Thomas,
• Aurélie Plas,
• Nishanth Kandepedu,
• Pierre Chalard and
• Yves Troin

Beilstein J. Org. Chem. 2013, 9, 486–495, doi:10.3762/bjoc.9.52

• nucleophilic addition reaction of Grignard reagents to N-carbamoyl β-amino Weinreb amides (Scheme 2) [18]. Conjugate addition of (R)-N-benzyl-N-methylbenzylamide to methyl cinnamate under basic conditions led to β–aminoester 5 with high diastereoselectivity (dr >94%) [11][12]. Subsequent transformation 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

• bearing a directing group; (3) cyclopropenes; (4) unactivated alkynes or alkenes; and (5) substrates that have two carbon–carbon unsaturated bonds (allenes, dienes, enynes, or diynes). Review Carbomagnesiation and carbozincation of electron-deficient alkynes Since conjugate addition reactions of

Flow photochemistry: Old light through new windows

• Jonathan P. Knowles,
• Luke D. Elliott and
• Kevin I. Booker-Milburn

Beilstein J. Org. Chem. 2012, 8, 2025–2052, doi:10.3762/bjoc.8.229