P(O)R₂-directed Pd-catalyzed C–H functionalization of biaryl derivatives to synthesize chiral phosphorous ligands

• Rong-Bin Hu,
• Hong-Li Wang,
• Hong-Yu Zhang,
• Heng Zhang,
• Yan-Na Ma and
• Shang-dong Yang

Beilstein J. Org. Chem. 2014, 10, 2071–2076, doi:10.3762/bjoc.10.215

• reported operation, the substrates of biaryl derivatives that contained phosphate with axial chirality were obtained in high yields using the Suzuki–Miyaura coupling reaction with the assistance of this versatile chiral ligand [31][32][33][34]. We used substituted naphthylboronic acid or ortho-substituted

• were successfully synthesized using the Suzuki–Miyaura coupling reaction under the assistance of a chiral ligand. Moreover, the substrates were further C–H functionalized using the P(O)Ar2 directing role with Pd salt as catalyst. Notably, the reactions took place in air atmosphere and at high

Rational design of cyclopropane-based chiral PHOX ligands for intermolecular asymmetric Heck reaction

• Marina Rubina,
• William M. Sherrill,
• Alexey Yu. Barkov and
• Michael Rubin

Beilstein J. Org. Chem. 2014, 10, 1536–1548, doi:10.3762/bjoc.10.158

• ring. As a result, the (R)-enantiomer of the product was predominantly formed, albeit with moderate enantioselectivity. Analogously, in the intermediate I5 derived from chiral ligand L2, the less bulky pseudo-axial phenyl substituent at phosphorus blocks the re-face approach even less efficiently

• ]. Intermolecular asymmetric Heck reaction by Hayashi [16]. Mechanistic rationale of asymmetric Heck reaction. Synthetic scheme for preparation of PHOX ligands with chiral cyclopropyl backbone. Conformational equilibrium in cationic arylpalladium(II) complexes with chiral ligand L1. For discussion on asymmetric

• induction imparted by chiral ligands L1 and L2 (originally published in [64]). For discussion on asymmetric induction imparted by chiral ligands L3 (originally published in [64]). Conformational equilibrium in cationic arylpalladium(II) complexes with chiral ligand L4. For discussion on asymmetric induction

Synthesis of a sucrose dimer with enone tether; a study on its functionalization

• Zbigniew Pakulski,
• Norbert Gajda,
• Magdalena Jawiczuk,
• Jadwiga Frelek,
• Piotr Cmoch and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2014, 10, 1246–1254, doi:10.3762/bjoc.10.124

• ECD data are given as the Δε' values, which are calculated in the usual manner by means of the equation Δε' = ΔA/c × d, A being the absorption, c the molar concentration of the chiral ligand, assuming 100% complexation, and d the path length of the cell. The numbering of the atoms in sucrose dimers is

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• -coupling of benzyl or alkyl halides with racemic secondary phosphines have been developed. These reactions were catalyzed by chiral platinum or ruthenium complexes. The enantioselectivity is based on a dynamic kinetic resolution. Upon reaction with the catalyst precursor containing a chiral ligand (L*), a

• electronegative fluorine atom is needed for the SNAr reaction to take place, even though the arenechromium complexes are already very electron-deficient aromatic compounds. The same group also developed a P-chiral ligand, QuinoxP 74, via deprotonation of chiral secondary phosphine borane 13d with n-butyllithium

• )-BINAP 116; a successful chiral ligand. Nickel was chosen as catalyst instead of palladium to minimize catalyst poisoning by binding of the metal with the phosphines present. After optimization, the desired chiral BINAP 116 was obtained in 77% yield. This protocol has been adopted by other research

Boron-substituted 1,3-dienes and heterodienes as key elements in multicomponent processes

• Ludovic Eberlin,
• Fabien Tripoteau,
• François Carreaux,
• Andrew Whiting and
• Bertrand Carboni

Beilstein J. Org. Chem. 2014, 10, 237–250, doi:10.3762/bjoc.10.19

• a one-pot, cycloaddition/allylboration sequence [43][44]. With (S,S)-Norphos as chiral ligand, the desired alcohol 10 was isolated in 87% yield and 71% ee (Scheme 9). In a related process, the same group reported a two-step reaction cascade interconnecting four components to afford dihydroaromatic

Multigramme synthesis and asymmetric dihydroxylation of a 4-fluorobut-2E-enoate

• James A. B. Laurenson,
• John A. Parkinson,
• Jonathan M. Percy,
• Giuseppe Rinaudo and
• Ricard Roig

Beilstein J. Org. Chem. 2013, 9, 2660–2668, doi:10.3762/bjoc.9.301

• osmium and chiral ligand contents were varied in the first instance. While the commercial AD-mixes were used, we also carried out the dihydroxylations with 1 mol % osmium/5 mol % ligand, the so-called “improved procedure”, and with 1 mol % osmium/10 mol % ligand (results summarised in Table 1). Methyl

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

• (R)-diphenyl(1-methylpyrrolidin-2-yl)methanol (50, (R)-DPMPM) [75] in toluene at 0 °C gave adducts 49 and 16 in a 4:1 ratio (anti/syn). By changing the chiral ligand to (S)-DPMPM 51 the selectivity dropped to 2:1 (anti/syn). When the addition reaction was performed in the presence of achiral N,N

Synthetic scope and DFT analysis of the chiral binap–gold(I) complex-catalyzed 1,3-dipolar cycloaddition of azlactones with alkenes

• María Martín-Rodríguez,
• Luis M. Castelló,
• Carmen Nájera,
• José M. Sansano,
• Olatz Larrañaga,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2013, 9, 2422–2433, doi:10.3762/bjoc.9.280

• efficient in asymmetric catalysis [23][24]. The high amount of gold per mole of catalyst and the chiral ligand itself make these processes somehow expensive. The relative lower cost of chiral privileged ligand Binap (versus Cy-Segphos) and the good results obtained in the 1,3-DC of α-imino esters and

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

• /kg) allowed isolation of ligand 1 in high purity and with no observed decomposition. Conclusion In conclusion, we have developed a concise, highly efficient and scalable synthesis of the chiral ligand (S)-t-BuPyOx (1) (Figure 2). Efforts to further refine the synthesis by telescoping the procedure

Cascade radical reaction of substrates with a carbon–carbon triple bond as a radical acceptor

• Hideto Miyabe,
• Ryuta Asada and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2013, 9, 1148–1155, doi:10.3762/bjoc.9.128

• moiety as an electron-deficient acceptor in the absence of a chiral ligand (Scheme 2). To control the rotamer population of substrates, Zn(OTf)2 was used as a Lewis acid to coordinate the hydroxamate ester functionality. The reactions were evaluated in CH2Cl2 at 20 °C under the tin-free iodine atom

• chiral ligand, the zinc Lewis acid accelerated the reaction of alkyne 14 with an isopropyl radical at 20 °C to give the desired cyclic product 15a in 73% yield. Under analogous reaction conditions, both cyclohexyl iodide and cyclopentyl iodide worked well to give 15b and 15c in 65% and 68% yields

• , entry 2). The secondary radicals, generated from cyclohexyl iodide or cyclopentyl iodide, reacted well to afford 15b and 15c with 85% ee and 83% ee, respectively (Table 2, entry 3 and 4). In marked contrast to the reaction in the absence of a chiral ligand (Scheme 6), the use of bulky tert-butyl iodide

Inter- and intramolecular enantioselective carbolithiation reactions

• Asier Gómez-SanJuan,
• Nuria Sotomayor and
• Esther Lete

Beilstein J. Org. Chem. 2013, 9, 313–322, doi:10.3762/bjoc.9.36

• inter- and intramolecular enantioselective carbolithiation reactions carried out in the presence of a chiral ligand for lithium, such as (−)-sparteine, to promote facial selection on a C=C bond. This is an attractive approach for the construction of new carbon–carbon bonds in an asymmetric fashion, with

• chiral ligands for lithium, thus opening new opportunities for their application in asymmetric synthesis. The naturally occurring alkaloid (−)-sparteine, which has been until recently inexpensive and commercially available, is the most widely used chiral ligand in enantioselective carbolithiation

• carbolithiation reactions. The review will not attempt to provide exhaustive coverage of the literature, but it is intended to focus on examples in which a stereogenic center is created in the chiral-ligand-mediated carbolithiation reaction of achiral substrates. Review Intermolecular carbolithiation reactions

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

• exchange and the subsequent transmetalation to zinc, and then used directly in one pot (Table 3). Lautens reported enantioselective carbozincation of alkenes using a palladium catalyst with a chiral ligand (Scheme 23) [93]. Treatment of 3g with diethylzinc in the presence of catalytic amounts of palladium

Rh(III)-catalyzed directed C–H bond amidation of ferrocenes with isocyanates

• Satoshi Takebayashi,
• Tsubasa Shizuno,
• Takashi Otani and
• Takanori Shibata

Beilstein J. Org. Chem. 2012, 8, 1844–1848, doi:10.3762/bjoc.8.212

• of chiral ferrocenyl ligands with several substitution patterns have been successfully utilized for enantioselective catalysis in both academia and industry. In particular, planar chiral 1,2-disubstituted ferrocenyl scaffolds have been extensively studied, and are among a few premier chiral ligand

A new approach toward the total synthesis of (+)-batzellaside B

• Jolanta Wierzejska,
• Shin-ichi Motogoe,
• Yuto Makino,
• Tetsuya Sengoku,
• Masaki Takahashi and
• Hidemi Yoda

Beilstein J. Org. Chem. 2012, 8, 1831–1838, doi:10.3762/bjoc.8.210

• , entry 11). The above observations clearly suggested a possibility of improving the product selectivity by lowering the reaction temperature and/or introducing an additional catalytic amount of chiral ligand. Having established the optimized conditions for the preparation of 12d-A, our next objective was

Evaluation of a chiral cubane-based Schiff base ligand in asymmetric catalysis reactions

• Kyle F. Biegasiewicz,
• Michelle L. Ingalsbe,
• Jeffrey D. St. Denis,
• James L. Gleason,
• Junming Ho,
• Michelle L. Coote,
• G. Paul Savage and
• Ronny Priefer

Beilstein J. Org. Chem. 2012, 8, 1814–1818, doi:10.3762/bjoc.8.207

• above the copper center and limits the asymmetric control with this ligand. Keywords: chiral ligand; cubane; M06L and B3LYP calculations; Michael addition; Introduction Since the initial synthesis of cubane in 1964 by Eaton and Cole [1][2], numerous studies have been undertaken on its derivatives

• evaluating this cubane-based ligand with cyclopropanation reactions. When no chiral ligand was added there was a 2.6:1 ratio of trans to cis products with no ee control. We then introduced our cubane-based chiral ligand 1 to our cyclopropanation protocol with four different copper sources (Table 1). The

• ) toluene complex, as well as Cu(OTf)2; however, we only obtained a maximum value of 12% ee with Cu(OTf) 2 in Et2O (Table 2, entry 10). The use of Et2Zn has also been used to provide excellent stereoselectivity in Michael addition reactions [21][22]. However, with our cubane-based chiral ligand 1 we did not

Synthesis of axially chiral oxazoline–carbene ligands with an N-naphthyl framework and a study of their coordination with AuCl·SMe₂

• Feijun Wang,
• Shengke Li,
• Mingliang Qu,
• Mei-Xin Zhao,
• Lian-Jun Liu and
• Min Shi

Beilstein J. Org. Chem. 2012, 8, 726–731, doi:10.3762/bjoc.8.81

• , affording the corresponding Au(I) complexes in moderate to high yields. Keywords: axially chiral ligand; gold; N-heterocyclic carbenes; N-naphthyl framework; Introduction During the past decade, with an explosive growth of asymmetric homogeneous gold catalysis in C–C, C–O, or C–N bond formations, the

• type of axially chiral ligand 7 with an N-naphthyl framework (Figure 2) instead of traditional binaphthyl framework [15]. Their palladium complexes 8 showed high stereoselectivities in asymmetric allylic arylations to achieve the kinetic resolution of Morita–Baylis–Hillman adducts, affording up to 99

Carbamate-directed benzylic lithiation for the diastereo- and enantioselective synthesis of diaryl ether atropisomers

• Abigail Page and
• Jonathan Clayden

Beilstein J. Org. Chem. 2011, 7, 1327–1333, doi:10.3762/bjoc.7.156

• on the enantioselective synthesis of diaryl ethers (a potential new class of chiral ligand having a structure related to the wide bite angle diphosphine DPEPhos) by biocatalytic oxidation or reduction, and which made use of desymmetrisation of a “pro-atropisomeric” substrate 4 to achieve the required

Directed ortho,ortho'-dimetalation of hydrobenzoin: Rapid access to hydrobenzoin derivatives useful for asymmetric synthesis

• Inhee Cho,
• Labros Meimetis,
• Lee Belding,
• Michael J. Katz,
• Travis Dudding and
• Robert Britton

Beilstein J. Org. Chem. 2011, 7, 1315–1322, doi:10.3762/bjoc.7.154

• groups. The optimization and scope of this reaction are discussed, and the utility of this process is demonstrated in the one-pot preparation of a number of chiral diols as well as a short synthesis of the chiral ligand Vivol. Keywords: chiral diol; directed ortho-metalation; hydrobenzoin; Introduction

• reactions promoted by these ligands and/or their derivatives. Although hydrobenzoin (e.g., 3) has not been utilized to the same extent, it has also demonstrated utility as both a chiral ligand [3][4][5][6][7][8] and auxiliary [9][10][11][12][13][14][15][16][17]. For example, Hall reported that the

Recent developments in gold-catalyzed cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2011, 7, 1075–1094, doi:10.3762/bjoc.7.124

• also studied enantioselective variants of this cycloaddition using gold complexes derived from this highly versatile type of chiral ligand. We found that it was possible to obtain excellent enantioselectivities with gold complexes derived from bulky phosphoramidites with anthracenyl substituents at 3

Chiral gold(I) vs chiral silver complexes as catalysts for the enantioselective synthesis of the second generation GSK-hepatitis C virus inhibitor

• María Martín-Rodríguez,
• Carmen Nájera,
• José M. Sansano,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2011, 7, 988–996, doi:10.3762/bjoc.7.111

• chiral ligand (Ra,R)-8 the enantioselectivities were low or moderate in the examples concerning AgClO4 and AgTFA (TFA = trifluoroacetate anion), respectively (Table 1, entries 5 and 7). Surprisingly, the reaction involving this chiral ligand 8 combined with AgSbF6 afforded a good yield of the

• complex (Ra,R)-8/AuTFA did not give the expected reaction product (Table 1, entry 9). The employment of this matched combination with (Ra,R)-8 was justified by the low enantioselectivity achieved through the use of (Ra,S)-8 in the same transformation (not shown in Table 1). The widely used chiral ligand

• represented in Scheme 2. The chiral ligand (Sa)-BINAP (13) was also tested in the standard reaction to access key molecule endo-5b (Scheme 3). AgClO4 was found to be the most appropriate silver salt to achieve the highest enantioselectivity (88% ee) compared to the results obtained when other silver salts

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• (Scheme 59) [174]. The first step is supposed to be an intramolecular addition of the hydroxy group to the internal carbon of the triple bond, which is similar to the mechanism mentioned above [161][163]. 6 Gold-catalyzed asymmetric addition reactions The chiral ligand used for the transition metal

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

• secondary thiol derivatives. These were prepared by diastereoselective electrophilic additions in proline-derived systems [71][72] and asymmetric alkylation of thiocarbamates in the presence of a chiral ligand [73][74]. Stereospecific functionalisation of configurationally stable lithiated thiocarbamates

Gelation or molecular recognition; is the bis-(α,β-dihydroxy ester)s motif an omnigelator?

• Peter C. Griffiths,
• David W. Knight,
• Ian R. Morgan,
• Amy Ford,
• James Brown,
• Ben Davies,
• Richard K. Heenan,
• Stephen M. King,
• Robert M. Dalgliesh,
• John Tomkinson,
• Stuart Prescott,
• Ralf Schweins and
• Alison Paul

Beilstein J. Org. Chem. 2010, 6, 1079–1088, doi:10.3762/bjoc.6.123

• (1) and two equivalents of isopropyl acrylate 2, which routinely delivered 80–85% yields of the bisenoate 3, exclusively as the (E,E)-isomer shown (Scheme 1), followed by an AD-mix double bishydroxylation with (DHQD)2PHAL as the chiral ligand [54]. The deuterated analogue 6, Scheme 2, was prepared by

Bis(oxazolines) based on glycopyranosides – steric, configurational and conformational influences on stereoselectivity

• Tobias Minuth and
• Mike M. K. Boysen

Beilstein J. Org. Chem. 2010, 6, No. 23, doi:10.3762/bjoc.6.23

• ligands for metal catalysed transformations is of crucial importance for stereoselective synthesis and is therefore an active field of research. In this context, carbohydrates are interesting, even if comparatively rarely used as starting materials for the preparation of new chiral ligand structures

Iridium-catalyzed asymmetric ring-opening reactions of oxabicyclic alkenes with secondary amine nucleophiles

• Dingqiao Yang,
• Ping Hu,
• Yuhua Long,
• Yujuan Wu,
• Heping Zeng,
• Hui Wang and
• Xiongjun Zuo

Beilstein J. Org. Chem. 2009, 5, No. 53, doi:10.3762/bjoc.5.53

• , and 4a-d. ORTEP plot for 3f. Identification of optimal chiral ligand for iridium-catalyzed asymmetric ring-opening of oxabenzonorbornadiene 1a with N-methylaniline. Proposed mechanism for the ARO of oxabenzonorbornadiene 1a with secondary amine nucleophiles. Screening conditions for iridium-catalyzed