Recent advances in copper-catalyzed asymmetric coupling reactions

• Fengtao Zhou and
• Qian Cai

Beilstein J. Org. Chem. 2015, 11, 2600–2615, doi:10.3762/bjoc.11.280

• -dimethylbutyrate. In this reaction, only one diastereoisomer was formed during the Ullmann coupling and the auxiliary is easily prepared and removed by hydrolysis after the coupling reaction (Scheme 3). In 2007, Breit et al. [22] employed a chiral tether to link two aryl halides for the enantioselective synthesis

• )hexopyranose derivatives. Preparation of 3,3’-disubstituted MeO-BIPHEP derivatives. Enantioselective synthesis of trans-4,5,9,10-tetrahydroxy-9,10-dihydrophenanthrene. Copper-catalyzed coupling of oxazoline-substituted aromatics to afford biaryl products with high diastereomeric purity. Total synthesis of O

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• centres (Scheme 41). Sakurai and co-workers have successfully established an enantioselective synthesis of the C3-symmetric chiral trimethylsumanene through a Pd-catalyzed cyclotrimerization and the RRM protocol as key steps [45]. Here compound 207 reacted with catalyst 1 in the presence of ethylene (24

The enantioselective synthesis of (S)-(+)-mianserin and (S)-(+)-epinastine

• Piotr Roszkowski,
• Jan. K. Maurin and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2015, 11, 1509–1513, doi:10.3762/bjoc.11.164

• pharmacological tests for antidepresant activity [1][2][3], it is still administered as a racemate probably due to the fact that no serious adverse effects have been recorded for the (R)-enantiomer. Interestingly, no enantioselective synthesis of mianserin has been developed so far. The synthesis of racemic

• auxiliary was described by the Czarnocki group [7]. For the commercial manufacture of mianserin enantiomers both the above mentioned processes are rather unjustified economically and the most advantageous method could be the enantioselective synthesis. Considering our experience in asymmetric synthesis of

• more active form [9]. In a key step in the enantioselective synthesis of mianserin and epinastine we applied the asymmetric reduction of the prochiral imine by asymmetric hydrogen transfer reaction (ATH) [10][11][12][13][14]. The proposed strategy could be used for the preparation of the title

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• , Shair and co-workers [196] have reported the enantioselective synthesis of (−)-longithorone A by using a conventional synthesis to realize the proposed biosynthesis, which was put forward by Schmitz involving an intermolecular and an intramolecular DA reaction of two [12]paracyclophanequinone [197

Enantioselective synthesis of polyhydroxyindolizidinone and quinolizidinone derivatives from a common precursor

• Nemai Saha and
• Shital K. Chattopadhyay

Beilstein J. Org. Chem. 2014, 10, 3104–3110, doi:10.3762/bjoc.10.327

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• oxidation used in the preparation of the poison frog alkaloid 195C [80]. Preparation of iminosugars using an electrochemical approach [81]. The electrosynthetic preparation of α-L-fucosidase inhibitors [84][85]. Enantioselective synthesis of the anaesthetic ropivacaine 85 [71]. The preparation of

First chemoenzymatic stereodivergent synthesis of both enantiomers of promethazine and ethopropazine

• Paweł Borowiecki,
• Daniel Paprocki and
• Maciej Dranka

Beilstein J. Org. Chem. 2014, 10, 3038–3055, doi:10.3762/bjoc.10.322

• straightforward approach for the preparation of optically active promethazine and ethopropazine molecules, respectively. Results and Discussion Herein, we wish to present an original chemoenzymatic procedure for the enantioselective synthesis of promethazine 9 and ethopropazine 10. Most of our efforts during

Formal total syntheses of classic natural product target molecules via palladium-catalyzed enantioselective alkylation

• Yiyang Liu,
• Marc Liniger,
• Ryan M. McFadden,
• Jenny L. Roizen,
• Jacquie Malette,
• Corey M. Reeves,
• Douglas C. Behenna,
• Masaki Seto,
• Jimin Kim,
• Justin T. Mohr,
• Scott C. Virgil and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2014, 10, 2501–2512, doi:10.3762/bjoc.10.261

• enantioselective synthesis of the (4aS,8aR,8S)-hydrolilolidone core 37 [63][64] present in aspidospermine (36), and thus a formal total synthesis of the alkaloid itself, intercepting Stork’s classic route [61]. One precursor described in the core synthesis is enone 38, which bears the quaternary stereocenter 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

• , respectively, and subsequent conversion of the primary adducts [35]. The enantioselective synthesis of α-phosphonosulfonic acids as squalene inhibitors, as discussed later in this review, was achieved using similar reactions – asymmetric alkylation of an α-sulfo phosphonamide and asymmetric α-sulfuration of an

• converted exclusively into various sterols, such as cholesterol, by a multi-step pathway [78]. The α-phosphono sulfonate 19 was found to be a potent inhibitor of squalene synthase, however, only the racemic version was originally tested. Biller and co-workers designed an enantioselective synthesis of 19

Stereoselective synthesis of carbocyclic analogues of the nucleoside Q precursor (PreQ₀)

• Sabin Llona-Minguez and
• Simon P. Mackay

Beilstein J. Org. Chem. 2014, 10, 1333–1338, doi:10.3762/bjoc.10.135

• diastereoselectivity [36], but since initially we did not require an enantioselective synthesis and the Zhou method employed rather expensive reagents, we investigated a simpler and cheaper route to access both cis- and trans-isomers. We envisioned a stereoselective synthesis that would potentially allow for the

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

A convenient enantioselective decarboxylative aldol reaction to access chiral α-hydroxy esters using β-keto acids

• Zhiqiang Duan,
• Jianlin Han,
• Ping Qian,
• Zirui Zhang,
• Yi Wang and
• Yi Pan

Beilstein J. Org. Chem. 2014, 10, 969–974, doi:10.3762/bjoc.10.95

• and aliphatic α-keto esters. The possible mechanism is rationalized. Keywords: enantioselective synthesis; hydroxy esters; scandium; Introduction The catalytic enantioselective construction of tertiary carbon centres is a major challenge in organic chemistry. The nucleophilic attack of carbonyls

Primary-tertiary diamine-catalyzed Michael addition of ketones to isatylidenemalononitrile derivatives

• Akshay Kumar and
• Swapandeep Singh Chimni

Beilstein J. Org. Chem. 2014, 10, 929–935, doi:10.3762/bjoc.10.91

• attention as novel substrates for the enantioselective synthesis of 3,3'-disubstituted oxindoles [18][19][20][21][22]. The organocatalytic Michael addition of ketones to isatylidenemalononitriles via enamine-catalysis has emerged as a useful tool for the synthesis of 3,3'-disubstituted oxindoles, which

Aza-Diels–Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome

• Amitabh Jha,
• Ting-Yi Chou,
• Zainab ALJaroudi,
• Bobby D. Ellis and
• T. Stanley Cameron

Beilstein J. Org. Chem. 2014, 10, 848–857, doi:10.3762/bjoc.10.81

• and strongly basic conditions [19]. Kang et al. achieved a highly enantioselective synthesis of an isoindolo[2,1-a]quinoline derivative by affecting an intramolecular ring closure on (E)-3-(2-(isoindolin-2-yl)phenyl)acrylaldehyde using camphorsulfonic acid and a chiral pyrrolidine organocatalyst [20

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

• Wageningen, The Netherlands 10.3762/bjoc.10.71 Abstract Virgin females of the parasitoid wasp Trichogramma turkestanica produce minute amounts of a sex pheromone, the identity of which has not been fully established. The enantioselective synthesis of a putative component of this pheromone, (6S,8S,10S

Synthesis of (2S,3R)-3-amino-2-hydroxydecanoic acid and its enantiomer: a non-proteinogenic amino acid segment of the linear pentapeptide microginin

• Rajendra S. Rohokale and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2014, 10, 667–671, doi:10.3762/bjoc.10.59

• anticancer drug taxol [9]. Due to the biological importance of (2S,3R)-AHDA, the enantioselective synthesis of its chiral core is a challenge task. This fact led to several approaches for the stereoselective synthesis of (2S,3R)-AHDA including (i) the enantioselective introduction of amino- and hydroxy

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

Organocatalytic asymmetric fluorination of α-chloroaldehydes involving kinetic resolution

• Kazutaka Shibatomi,
• Takuya Okimi,
• Yoshiyuki Abe,
• Akira Narayama,
• Nami Nakamura and
• Seiji Iwasa

Beilstein J. Org. Chem. 2014, 10, 323–331, doi:10.3762/bjoc.10.30

• the fluorination of α-branched aldehydes [7]. During the course of our study on the enantioselective construction of such fluorinated stereogenic centers, we developed a method for the enantioselective synthesis of α-chloro-α-fluoroaldehydes via the organocatalytic α-fluorination of α-alkyl-α

• (Scheme 1) [8]. These results suggested that kinetic resolution of the starting aldehydes was involved in this asymmetric fluorination. To collect further information on the reaction mechanism, we sought to determine the absolute configuration of 4a. Recently, we reported the enantioselective synthesis of

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• anti-elimination was invoked to account for the observed experimental outcome (Scheme 29d). A complementary approach for the enantioselective synthesis of 3,4-disubstituted pyrrolidines was recently reported by Bandini and co-workers [72]. Intramolecular hydroalkylation of allylic alcohols with

A combined continuous microflow photochemistry and asymmetric organocatalysis approach for the enantioselective synthesis of tetrahydroquinolines

• Erli Sugiono and
• Magnus Rueping

Beilstein J. Org. Chem. 2013, 9, 2457–2462, doi:10.3762/bjoc.9.284

Towards stereochemical control: A short formal enantioselective total synthesis of pumiliotoxins 251D and 237A

• Jie Zhang,
• Hong-Kui Zhang and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2013, 9, 2358–2366, doi:10.3762/bjoc.9.271

• , Lanzhou 730000, P. R. China 10.3762/bjoc.9.271 Abstract A concise enantioselective synthesis of the advanced intermediate 5 for the synthesis of pumiliotoxins (Gallagher’s intermediate) is described. The synthesis started from the regio- and trans-diastereoselective (dr = 98:2) reductive 3-butenylation

• consisting of ozonolysis and reductive dehydroxylation provided the indolizidine derivative 5, which completed the formal enantioselective total synthesis of pumiliotoxins 251D and 237A. Keywords: enantioselective synthesis; Grignard reagent; pumiliotoxin 237A; pumiliotoxin 251D; reductive dehydroxylation

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

• R-(+) form, the S-(−) form or the racemate leading to the conclusion that an enantioselective synthesis leading to solely S-(−)-amlodipine would be beneficial only if economically feasible [67]. An alternative strategy to this molecule begins with an interesting aza-Diels–Alder reaction between the

• racemic quinuclidinol. However, an improved approach makes use of a Noyori-type asymmetric reduction employing a BINAP ligated RuCl2 and a chiral diamine to yield the desired (R)-quinuclidine in high yield and enantioselectivity [78]. The enantioselective synthesis of the tetrahydroisoquinoline fragment

Gold(I)-catalyzed enantioselective cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2013, 9, 2250–2264, doi:10.3762/bjoc.9.264

• (Scheme 1). In 2009, the same group extended the utility of this asymmetric cyclopropanation reaction to an intramolecular process that allows the enantioselective synthesis of polycarbocyclic products embedding seven or eight-membered rings [42]. Curiously, the catalytic system based on DTBM-Segphos

• core of frondosins (for example, 5a), in 68% yield and 90% ee (Scheme 4). Since this bicyclic enone was previously elaborated into frondosin A and B, the approach represented a streamlined formal enantioselective synthesis of both molecules. Analogous to other transition metals from groups eight to

Synthesis of enantiomerically pure N-(2,3-dihydroxypropyl)arylamides via oxidative esterification

• Akula Raghunadh,
• Satish S More,
• T. Krishna Chaitanya,
• Yadla Sateesh Kumar,
• Suresh Babu Meruva,
• L. Vaikunta Rao and
• U. K. Syam Kumar

Beilstein J. Org. Chem. 2013, 9, 2129–2136, doi:10.3762/bjoc.9.250

• to facilitate these reactions [10][11][12][13][14][15][16][17][18]. Herein we describe a highly enantioselective synthesis of (S) and (R)-N-(2,3-dihydroxypropyl)arylamides [19][20][21][22] in a two-step process in overall good yields by oxidative esterification of the corresponding aryl aldehydes

• purifications and showed a chiral HPLC purity of 100% with retention of configuration. Conclusion A highly enantioselective synthesis of (S) and (R)-isomers of N-(2,3-dihydroxypropyl)arylamides was developed with high overall yields. We report the nitrogen heterocyclic carbene catalyzed enantioselective ring

A concise enantioselective synthesis of the guaiane sesquiterpene (−)-oxyphyllol

• Martin Zahel and
• Peter Metz

Beilstein J. Org. Chem. 2013, 9, 2028–2032, doi:10.3762/bjoc.9.239

• ; Introduction The hydroazulene framework is present in many natural products that are often associated with interesting biological properties [1][2]. The guaiane sesquiterpene (−)-oxyphyllol (1) has been isolated from the roots of the Thai medicinal plant Phyllanthus oxyphyllus [3]. A recent enantioselective

• synthesis of the unnatural enantiomer of 1 enabled a structural revision of this compound and established its relative and absolute configuration as depicted in Figure 1 [4]. During the total synthesis of (−)-9-deoxyenglerin A, compound 1 had already been prepared enantiomerically pure in 14 steps starting