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

• method to synthesize protected syn-1,3-diols by performing intramolecular conjugate additions to a series of α,β-unsaturated esters and amides [71] (Scheme 8). Upon treatment of 24 with KHMDS and benzyaldehyde, a hemiacetal forms which provides the alkoxide nucleophile for the DCA reaction. These

• ). Molander and Harris developed the samarium(II) iodide-mediated cyclization of α,β-unsaturated esters and amides [167] (Scheme 20). Previous methods for the cyclization of alkyl halides and α,β-unsaturated carbonyl systems include: (1) tin-mediated radical cyclization [168] or (2) nucleophilc cyclization

Copper-catalyzed cascade reactions of α,β-unsaturated esters with keto esters

• Zhengning Li,
• Chongnian Wang and
• Zengchang Li

Beilstein J. Org. Chem. 2015, 11, 213–218, doi:10.3762/bjoc.11.23

• Zhengning Li Chongnian Wang Zengchang Li College of Environmental and Chemical Engineering, Dalian University, Dalian 116622, China 10.3762/bjoc.11.23 Abstract A copper-catalyzed cascade reaction of α,β-unsaturated esters with keto esters is reported. It features a copper-catalyzed reductive

• -lactone and more catalyst or longer reaction times were needed to obtain a reasonable yield of lactones (Table 5, entry 1 vs Table 4, entry 1; Table 5, entry 6 vs Table 4, entry 4). Conclusion In conclusion, a novel copper-catalyzed three-component cascade reaction among α,β-unsaturated esters, keto

• esters and a silane was developed. The reaction involves conjugate addition of copper hydride, generated in situ, to α,β-unsaturated esters, followed by the aldolization with a keto ester and lactonization. It gives γ-carboxymethyl-γ-lactones and δ-carboxymethyl-δ-lactones in high yields, and provides a

Stereoselective synthesis of perillaldehyde-based chiral β-amino acid derivatives through conjugate addition of lithium amides

• Zsolt Szakonyi,
• Reijo Sillanpää and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2014, 10, 2738–2742, doi:10.3762/bjoc.10.289

• achiral anhydrides followed by Curtius degradation [18][19][20]. The highly stereoselective Michael addition of lithium amide-type nucleophiles to α,β-unsaturated esters also proved to be a very efficient and useful method for the preparation of alicyclic β-amino acids in homochiral form [21][22

• ]. Generally, in these transformations, the source of chirality is served by chiral lithium amides, and there are only few examples where chiral α,β-unsaturated esters are applied [23][24][25][26][27]. Easily obtainable chiral monoterpenes, such as (+)-3-carene as well as all the enantiomers of pulegone, α

• ][34]. From this aspect, chiral, monoterpene-based α,β-unsaturated esters might be excellent starting materials, in which the natural monoterpene skeleton may serve as the chiral origin for the stereoselective construction of the β-amino acid moiety. Our present aim was the synthesis of new, limonene

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

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

• high level of stereocontrol (Scheme 4) [37][38][39][40]. Thus, vicinal and quartenary carbon centers can be obtained in high diasteromeric purity by conjugate additions of allyl, crotyl, and cinnamyl-derived anions to Michael acceptors such as enones, lactones, lactams, and α,β-unsaturated esters

• used for limited exploratory studies. Cyclopropanation and aziridination The cyclopropanation of α,β-unsaturated esters and lactones using chiral phosphonamide reagents is a special case of the conjugate addition–enolate alkylation sequence. The application of chloroallyl phosphonamides such as (trans

• cyclopropane 50a. Starting with (cis,R,R)-47b, the isomeric exo,endo product 50b is obtained as major isomer. The cyclopropanation reaction tolerates a wide range of Michael acceptor subtrates such as enones, lactones, lactams, and acyclic α,β-unsaturated esters. The obtained products can easily be cleaved to

One-pot stereoselective synthesis of α,β-differentiated diamino esters via the sequence of aminochlorination, aziridination and intermolecular S_N2 reaction

• Yiwen Xiong,
• Ping Qian,
• Chenhui Cao,
• Haibo Mei,
• Jianlin Han,
• Guigen Li and
• Yi Pan

Beilstein J. Org. Chem. 2014, 10, 1802–1807, doi:10.3762/bjoc.10.189

• access for the generation of α,β-diamino esters, which usually employ palladium or osmium as catalysts [23][24][25]. The electrophilic diamination reaction is an alternative methodology [26][27][28], which makes use of α,β-unsaturated esters as starting materials to form imidazoline diamine derivatives

• with α,β-unsaturated esters as starting materials. On the initial reaction step the cinnamic ester underwent a copper(II) trifluoromethanesulfonate-catalyzed aminohalogenation reaction with TsNCl2 as nitrogen source. After being quenched by saturated sodium sulfite, the resulting mixture was stirred

• with benzylamine. Various α,β-unsaturated esters were studied to evaluate the yield and stereochemical outcome of these reactions (Table 3). As shown in Table 3, almost all of the tested substrates worked well under the optimized conditions giving rise to the corresponding α,β-diamino ester products

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

• -peptide incorporation of sugar-β-amino acids are described providing the saccharide units as amino acid side chain. The respective sugar-β-amino acids are accessible by Michael addition of ammonia to sugar units derivatized as α,β-unsaturated esters. Three sugar units were incorporated in β-peptide

• conformation, thereby organizing the D-glucose, D-galactose or D-xylose carbohydrate epitopes on one face of the helix. Results and Discussion Synthesis of carbohydrate-β3-amino acids Key step for the synthesis of β3-sugar amino acids is the Michael addition of ammonia to α,β-unsaturated esters [47][48][49][50

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• several substituents and enolates 33 can be generated from methyl- or ethyl vinyl ketone, the corresponding α,β-unsaturated esters being unreactive. Enamines 34 arise from cyclic or linear C3–C5 ketones, acetophenones and β-diketones. It is noteworthy, that the reactions are highly regiospecific for

Additive-assisted regioselective 1,3-dipolar cycloaddition of azomethine ylides with benzylideneacetone

• Chuqin Peng,
• Jiwei Ren,
• Jun-An Xiao,
• Honggang Zhang,
• Hua Yang and
• Yiming Luo

Beilstein J. Org. Chem. 2014, 10, 352–360, doi:10.3762/bjoc.10.33

• with various dipolarophiles, such as α,β-unsaturated esters [21][22][23][24][25], dienones [26][27], α,β-unsaturated ketones [28][29][30], unsaturated aryl ketones [31][32][33] and electron-poor alkenes [34][35][36][37][38][39]. Among the studied α,β-unsaturated enones for 1,3-dipolar cycloaddition

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

• reversed to >10:1 favouring adduct 68 [105]. α,β-Unsaturated esters can be synthesized from stabilized ylides. Reaction of 1 with ylide 69 is E-selective. Depending on the solvent, the E/Z-ratio can vary from 3:1 (in MeOH) [106] to 100:0 (THF [107] or benzene [108]). Since stabilized ylides are less

• reactive compared to their non-stabilized counterparts, they tend to epimerize the existing chiral center of 1 a lot less, if at all (pKaH value of 69 in DMSO is 8.5 compared to the pKa value of Ph3(Me)PBr, which is 22.5) [109]. Another method to prepare α,β-unsaturated esters is the Horner–Wadsworth

Palladium(II)-catalyzed Heck reaction of aryl halides and arylboronic acids with olefins under mild conditions

• Tanveer Mahamadali Shaikh and
• Fung-E Hong

Beilstein J. Org. Chem. 2013, 9, 1578–1588, doi:10.3762/bjoc.9.180

• ) was examined with different vinyl esters to determine the scope of this procedure. The results are given in Table 2, entries 18–20. Notably, the performances were in agreement with the previous expectations and yields are excellent in the preparation of α,β–unsaturated esters. The corresponding α,β

• -unsaturated esters 3o–3q were obtained in 90–95% yields, respectively. Heck reaction of arylboronic acids with olefins The phosphine- and base-free coupling of arylboronic acids with olefins under mild reaction conditions were studied as well to broaden the scope of cross-coupling reactions. To search for 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

• well tolerated for the reaction using γ-hydroxy-α,β-enones. Although the presence of chirality at the δ-position allows for diastereoselective intramolecular oxy-Michael addition of hemiacetal-derived alkoxides into α,β-unsaturated esters, the extension of this reaction to ketones was not successful

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

• under different protocols in which the stereoselectivity of the reaction can be introduced through the use of a chiral catalyst [9][10] (Lewis acid, Brønsted acids, L-proline, Cinchona alkaloids derivatives, thioureas, etc.), or by the addition of chiral amines to α,β-unsaturated esters [11][12] or the

Efficient synthesis of 1,3-diaryl-4-halo-1H-pyrazoles from 3-arylsydnones and 2-aryl-1,1-dihalo-1-alkenes

• Yiwen Yang,
• Chunxiang Kuang,
• Hui Jin,
• Qing Yang and
• Zhongkui Zhang

Beilstein J. Org. Chem. 2011, 7, 1656–1662, doi:10.3762/bjoc.7.195

• ], alkenyl arenes [19], 1,3-dienes [20][21], α,β-unsaturated esters [19][22] and nitriles [23], phosphane oxides [24] or with alkynyl silanes [18], stannanes [18][25][26], arenes [27][28], esters [29][30][31][32][33], boronic esters [34][35]. However, the cycloaddition of sydnones with 1,1-dihaloalkenes is

Application of the diastereoselective photodeconjugation of α,β-unsaturated esters to the synthesis of gymnastatin H

• Ludovic Raffier and
• Olivier Piva

Beilstein J. Org. Chem. 2011, 7, 151–155, doi:10.3762/bjoc.7.21

• configuration of the C-6 centre of the target molecule was controlled. Keywords: amide; diastereoselective protonation; dienol; isomerisation; Wittig reaction; Introduction The photodeconjugation of α,β-unsaturated esters 1 – which bear at least one hydrogen atom on γ-position – allows a straightforward

Catalytic synthesis of (E)-α,β-unsaturated esters from aldehydes and 1,1-diethoxyethylene

• Rubén Manzano,
• Lidia Ozores,
• Andreas Job,
• Lars Rodefeld and
• Benjamin List

Beilstein J. Org. Chem. 2009, 5, No. 3, doi:10.3762/bjoc.5.3

• high yielding synthesis of α,β-unsaturated esters from aldehydes and 1,1-diethoxyethylene was developed. Keywords: 1,1-diethoxyethylene; α,β-unsaturated esters; Introduction A number of reactions transforming aldehydes into α,β-unsaturated esters have been developed and especially Wittig reaction

• leads to the formation of water and CO2 as the only by-products (Scheme 1, eq 3) [23][24]. Here we describe as a new approach, the boronic acid-catalyzed condensation of ketene dialkyl acetal with aldehydes to furnish α,β-unsaturated esters in good yields and reliably high (E)-stereoselectivities

• reaction was stirred at the same temperature for 12 h. The solvent was removed under vacuum, and the crude material was purified by flash chromatography to afford the pure product (silica gel, hexane/EtOAc 95/5). Conversions of aldehydes into α,β-unsaturated esters. A plausible mechanism. Selected results

The role of an aromatic group in remote chiral induction during conjugate addition of α-sulfonylallylic carbanions to ethyl crotonate

• Shlomo Levinger,
• Ranjeet Nair and
• Alfred Hassner

Beilstein J. Org. Chem. 2008, 4, No. 32, doi:10.3762/bjoc.4.32

• -sulfonylallylic carbanions to open-chain α,β-unsaturated esters, which has been shown to proceed anti-diastereoselectively [2][13] and with the N(1)R*,3S*,4R* relative configuration predominating [1], we assign our major and minor products structures 3 and 4 respectively (showing in Scheme 1 only one enantiomer

Efficient 1,4-addition of α-substituted fluoro(phenylsulfonyl)methane derivatives to α,β-unsaturated compounds

• G. K. Surya Prakash,
• Xiaoming Zhao,
• Sujith Chacko,
• Fang Wang,
• Habiba Vaghoo and
• George A. Olah

Beilstein J. Org. Chem. 2008, 4, No. 17, doi:10.3762/bjoc.4.17

• -addition to α,β-unsaturated esters, ketones, sulfone, nitriles and propynoates. Supporting Information Supporting Information File 83: Experimental procedures, full spectroscopic data and spectra. Supporting Information File 84: Spectra. Acknowledgements Support of our work by the Loker Hydrocarbon

Flexible synthetic routes to poison- frog alkaloids of the 5,8-disubstituted indolizidine- class I: synthesis of common lactam chiral building blocks and application to the synthesis of (-)-203A, (-)-205A, and (-)-219F

• Naoki Toyooka,
• Dejun Zhou,
• Hideo Nemoto,
• H. Martin Garraffo,
• Thomas F. Spande and
• John W. Daly

Beilstein J. Org. Chem. 2007, 3, No. 29, doi:10.1186/1860-5397-3-29

• and 8 with Super-Hydride gave the corresponding alcohols (9, 10) in good yield. Swern oxidation of 9 or 10 followed by Horner-Emmons reaction of the resulting aldehydes afforded the α,β-unsaturated esters (11, 12) each in 97% yield. Hydrogenation of the double bond in 11 or 12 over 20% Pd(OH)2 and