Copper-catalyzed stereoselective conjugate addition of alkylboranes to alkynoates

• Takamichi Wakamatsu,
• Kazunori Nagao,
• Hirohisa Ohmiya and
• Masaya Sawamura

Beilstein J. Org. Chem. 2015, 11, 2444–2450, doi:10.3762/bjoc.11.265

• . Keywords: alkylborane; alkynoate; conjugate addition; copper; multisubstituted alkene; Introduction Copper-mediated conjugate additions of organometallic reagents to alkynoates are powerful tools for the synthesis of multisubstituted alkenes [1][2][3][4][5][6][7][8]. Because of their broad availability

• and their compatibility with a multitude of functional groups, organoboron compounds are especially popular organometallic reagents. Recently, Yamamoto and co-workers developed copper-catalyzed conjugate additions of aryl- and allylboron compounds to alkynoates [9][10], but alkylboron compounds have

Copper-catalysed asymmetric allylic alkylation of alkylzirconocenes to racemic 3,6-dihydro-2H-pyrans

• Emeline Rideau and
• Stephen P. Fletcher

Beilstein J. Org. Chem. 2015, 11, 2435–2443, doi:10.3762/bjoc.11.264

• ][17][18]. We have developed Cu-catalysed asymmetric conjugate additions of alkylzirconium reagents generated in situ by hydrometallation of terminal alkenes [19][20][21][22][23][24][25], and recently demonstrated that zirconium nucleophiles may undergo highly enantioselective copper-catalysed AAAs to

Copper-catalyzed asymmetric conjugate addition of organometallic reagents to extended Michael acceptors

• Thibault E. Schmid,
• Sammy Drissi-Amraoui,
• Christophe Crévisy,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2015, 11, 2418–2434, doi:10.3762/bjoc.11.263

• control of the regio- and enantioselectivity of the addition. The aim of this review is to report recent breakthroughs achieved in this challenging field. Keywords: conjugate additions; electron-deficient alkenes; enantioselective catalysis; extended Michael acceptors; organometallic nucleophiles

• provided dramatic breakthroughs during the last two decades. This review aims to describe the early examples and recent advances in copper-catalyzed asymmetric conjugate additions of organometallic reagents to extended Michael acceptors. First, seminal reports dealing with the reactivity of extended

• reaction product. The selective 1,6-addition of cuprates onto extended Michael acceptors featuring a terminal C–C triple bond prompted research groups to investigate thoroughly the mechanism of this reaction [11][12][13]. Notably, the 1,6-conjugate additions onto Michael acceptors involving copper reagents

Copper catalysis in organic synthesis

• Sherry R. Chemler

Beilstein J. Org. Chem. 2015, 11, 2252–2253, doi:10.3762/bjoc.11.244

• been published in 2014. In point of fact, there has been a steady increase in publications on this topic since 1988. In the late 1980’s and early 1990’s, the topics centered on copper nitrene reactivity (e.g., aziridination), copper carbene chemistry, conjugate additions and cross-coupling reactions

• Ullmann and Goldberg couplings, asymmetric acetylide additions to carbonyl groups, radical alkylations and asymmetric conjugate additions as well as original contributions in the area of copper-catalyzed C–C cross-coupling, conjugate additions, allylic alkylations, alkene difunctionalizations, heterocycle

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

• review. 1 Diastereoselective conjugate additions (DCA) Though CA reactions had been studied for decades, significant progress in the development of CA reactions using α,β-unsaturated amides and lactams was not observed until the 1980s [28][29][30][31]. Initial efforts toward performing the asymmetric CA

• reactions focused on the development of diastereoselective CA reactions. These reactions were achieved by performing conjugate additions to chiral Michael acceptors that blocked one face of the double bond from the incoming nucleophile, thus preferentially producing one diastereomer over the other. The

• 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

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

• ][40]. Asymmetric conjugate additions using P-chiral phosphonamides were reported by Denmark [2][3][4] and Hua [5][6], with remarkable differences in selectivity depending on the configuration of the P-stereogenic center (Scheme 5). Thus, the addition of the Li-anion of trans-40a to cyclic enones 41

A tandem Mannich addition–palladium catalyzed ring-closing route toward 4-substituted-3(2H)-furanones

• Jubi John,
• Eliza Târcoveanu,
• Peter G. Jones and
• Henning Hopf

Beilstein J. Org. Chem. 2014, 10, 1462–1470, doi:10.3762/bjoc.10.150

• economic and most importantly eco-friendly [1][2]. Conjugate addition is a very efficient tool used by synthetic chemists for the construction of carbon–carbon or carbon–heteroatom bonds [3]. Much effort has been invested to develop different variants of conjugate additions, both in catalyzed and non

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

• –88% overall yield (Scheme 2). These electron-deficient nitroalkenes have exhibited excellent stereochemical stability and reactivity in conjugate additions with varied nucleophiles. The 1,3-nitroamines adducts obtained from these additions can be readily transformed into potentially useful chiral 1,3

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

• chiral nonracemic nitroalkenes 2a–c from L-leucine (1a), L-phenylalanine (1b) and L-alanine (1c), respectively, and investigate their reactivities in conjugate additions with different nucleophiles as a way of yielding chiral nonracemic 1,3-nitroamine and its corresponding 1,3-diamine derivatives

• . On the other hand, the neat benzylamine addition, or in the presence of DBU (0.5 equiv) as promoter [84], to 2a,b was unsuccessful (Table 1, entries 14 and 15). This nonreactivity can be explained on the basis of the high tendency toward reversibility presented in conjugate additions of amines to

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

• , organocatalytic enantioselective methodologies have gained much attention from many research groups worldwide [22][23][24][25][26][27][28][29]. In the meantime, organocatalytic tandem Michael conjugate additions of heteroatom-centered nucleophiles to α,β-unsaturated compounds appear as one of the most reliable

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

• conjugate additions of nucleophiles [23][24][25][26][27][28]. Kinetics of the reactions of the iminium ion 3a with the silylated ketene acetal 7a [35]. Laser flash photolytic generation of iminium ions 3a. Correlations of the reactivities of the iminium ions 3a and 3b toward nucleophiles with the

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

• ]. Due to the ambiphilic nature of the heterocyclic ring of coumarin, this core-structure undergoes a diverse array of coupling reactions, such as halogenations [25], cycloadditions [26][27][28][29][30][31][32], conjugate additions [33][34][35][36][37] and transition-metal-catalyzed C–H activation

Enantioselective Michael addition of 2-hydroxy-1,4-naphthoquinones to nitroalkenes catalyzed by binaphthyl-derived organocatalysts

• Saet Byeol Woo and
• Dae Young Kim

Beilstein J. Org. Chem. 2012, 8, 699–704, doi:10.3762/bjoc.8.78

• to the development of asymmetric conjugate additions of 1,3-dicarbonyl compounds to various Michael acceptors [27][28][29][30][31][32][33]. Recently, the groups of Du and Zhou reported a highly enantioselective Michael addition of 2-hydroxy-1,4-naphthoquinones to nitroalkenes catalyzed by chiral

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

• and co-workers postulated that poor reactivity and facial selectivity in conjugate additions with sulfur could be minimised by an intramolecular approach [47][48]. A Lewis acid-promoted sulfur migration within N-enoyl oxazolidine-2-thione substrates 56 followed by hydrolysis gave optically pure

• tertiary thiols 57 directly (Scheme 21), with only the electron rich para-methoxyphenyl substituent performing poorly. As with stereospecific nucleophilic displacement, only specific substrates are tolerated in conjugate additions, and further functionality is always required to activate the electrophilic

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

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

• as decisive for the remote transmission of chirality. Keywords: cation–π interaction; conjugate addition; diastereoselectivity; regioselectivity; remote chiral induction; Introduction Recently we have disclosed a pathway for remote asymmetric induction in conjugate additions involving lithiated α

• for preferential formation of the N(1)R*,3S*,4R* configuration in adduct 3. Conclusion The dependence of chiral induction on the identity of the aromatic nucleus attached to a remote stereogenic center in the conjugate additions of lithiated α-(phenylsulfonyl)allylic carbanions was examined. Better

An exceptional P-H phosphonite: Biphenyl- 2,2'-bisfenchylchlorophosphite and derived ligands (BIFOPs) in enantioselective copper- catalyzed 1,4-additions

• T. Kop-Weiershausen,
• J. Lex,
• J.-M. Neudörfl and
• B. Goldfuss

Beilstein J. Org. Chem. 2005, 1, No. 6, doi:10.1186/1860-5397-1-6

• -catalyzed 1,4-additions of ZnEt2 to 2-cyclohexen-1-one, this P-H phosphonite (yielding 65% ee) exceeds even the corresponding phosphite and phosphoramidite. Keywords: phosphorus ligands; chirality; biaryls; asymmetric conjugate additions; phosphoramidites; phosphites; phosphonites; X-ray analyses

• ][13][14][15][16][17][18] Such asymmetric conjugate additions of diethylzinc to enones are often highly enantioselective, especially with phosphoramidites (amidophosphites) and phosphites. [2][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] These chiral

• = fenchyl-aryl dihedral angle between C1'-C2'-C3'-O2). Monodentate phosphorus ligands, e.g. BINOL-based phosphoramidites or TADDOL-based phosphites, are highly efficient in copper catalyzed enantioselective conjugate additions. Modular phosphoramidites (R= NR'2) or phosphites (R= OR') from reactive