Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• determination of the enantiomeric excess of a chiral amine based on the use of phosphorinanes derivatives. Two synthetic pathways i) the AT reaction and ii) the direct use of chlorophosphate were evaluated for the derivatization of chiral amine (or alcohol) as reported in Scheme 6. For the AT reaction (i) [23

• . However, as reported in Scheme 32-ii, some chiral phosphoramidates and thiophosphoramidates can be readily synthesized with the AT reaction in high yield (85–88%) from dimethyl phosphite or O,O-dimethyl thiophosphite [106]. When the chiral amine was functionalized with a thiol group (Scheme 32-iii), the

Synthesis and stereochemical assignments of diastereomeric Ni(II) complexes of glycine Schiff base with (R)-2-(N-{2-[N-alkyl-N-(1-phenylethyl)amino]acetyl}amino)benzophenone; a case of configurationally stable stereogenic nitrogen

• Hiroki Moriwaki,
• Daniel Resch,
• Hengguang Li,
• Iwao Ojima,
• Ryosuke Takeda,
• José Luis Aceña and
• Vadim A. Soloshonok

Beilstein J. Org. Chem. 2014, 10, 442–448, doi:10.3762/bjoc.10.41

• glycine-Ni(II) complexes is that they, along with the chiral amine residue, have a configurationally stable stereogenic nitrogen, leading to formation of two diastereomers. Consequently, stereochemical assignments of the diastereomeric products, based on crystallographic data, and sense of stereochemical

An investigation of the observed, but counter-intuitive, stereoselectivity noted during chiral amine synthesis via N-chiral-ketimines

• Thomas C. Nugent,
• Richard Vaughan Williams,
• Andrei Dragan,
• Alejandro Alvarado Méndez and
• Andrei V. Iosub

Beilstein J. Org. Chem. 2013, 9, 2103–2112, doi:10.3762/bjoc.9.247

• addition to imines [31][32] continue to be refined and relied on. Furthermore, enzymatic methods can offer competitive advantages that cannot be overlooked [33][34][35]. With this perspective, it is perhaps unsurprising that methods utilizing imines with chiral amine auxiliaries, i.e. N-chiral imines, can

• sometimes offer competitive solutions regarding the synthesis of challenging chiral amine structures [9][22]. Furthermore, it is common that alkaloid or amine containing pharmaceutical drug syntheses proceed through imine intermediates that lead to diastereomeric amine products [36][37][38][39][40]. With

• /trans ratios frequently provides unexpectedly good to excellent de for the corresponding chiral amine product. An early rationale was proposed by Harada, and invokes in situ cis-to-trans imine isomerization [51]. We were curious if conformational factors may be contributing to or even dominating the

Reactions of salicylaldehyde and enolates or their equivalents: versatile synthetic routes to chromane derivatives

• Ishmael B. Masesane and
• Zelalem Yibralign Desta

Beilstein J. Org. Chem. 2012, 8, 2166–2175, doi:10.3762/bjoc.8.244

• 27. Although Shanti and co-workers used a chiral catalyst, no data was provided on the stereoselectivity of this reaction. In a study related to that of Shanti and co-workers, Yang and co-workers used chiral amine-thiourea catalyst 31 in a three-component enantioselective reaction of salicylaldehyde

Automated three-component synthesis of a library of γ-lactams

• Erik Fenster,
• David Hill,
• Oliver Reiser and
• Jeffrey Aubé

Beilstein J. Org. Chem. 2012, 8, 1804–1813, doi:10.3762/bjoc.8.206

• calcium hydride. The maleimides 1, the aldehydes 2, the amines 3 and the chiral amine organocatalyst (A–I) were purchased from the Aldrich Chemical Co. and used without further purification. Melting points were performed by using an Optimelt (MPA100) automated melting-point system (Sanford Research

• , 0.289 mmol, 1.0 equiv) in chloroform (3 mL) at 0 °C, followed by the appropriate chiral amine (A–I) (0.0289 mmol, 0.1 equiv) and the reaction mixture was stirred at the appropriate temperature for the appropriate length of time listed in Table 1. Water was added upon completion of the reaction and the

Organocatalytic cascade aza-Michael/hemiacetal reaction between disubstituted hydrazines and α,β-unsaturated aldehydes: Highly diastereo- and enantioselective synthesis of pyrazolidine derivatives

• Zhi-Cong Geng,
• Jian Chen,
• Ning Li,
• Xiao-Fei Huang,
• Yong Zhang,
• Ya-Wen Zhang and
• Xing-Wang Wang

Beilstein J. Org. Chem. 2012, 8, 1710–1720, doi:10.3762/bjoc.8.195

• cascade aza-Michael/hemiacetal reactions between 2 and α,β-unsaturated aldehydes 3. Chiral-amine-catalyzed cascade aza-Michael/hemiacetal reaction of 2c with 3a. Optimization of the reaction of 2c and 3a catalyzed by chiral amine 1m. Substrate scope of 2 and 3 catalyzed by chiral amine 1m. Supporting

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

• most significant synthetic methods reported on chiral-amine-catalyzed tandem Michael conjugate addition of heteroatom-centered nucleophiles to α,β-unsaturated compounds followed by cyclization reactions for the enantioselective construction of functionalized chiral chromenes, thiochromenes and 1,2

• and powerful tools for the stereocontrolled access to a wide range of biologically active heterocycles in optically enriched form [29][30][31][32]. In this review we have summarized our efforts to cover various chiral-amine-catalyzed synthetic protocols leading to one-pot enantioselective synthesis of

• solvent, the test reaction provided the chiral chromenes 3 in good yields (up to 98%) and enantioselectivities (99%) at room temperature (Scheme 3). In 2009, Xu et al. [45] developed an efficient protocol for the asymmetric tandem oxa-Michael–aldol reaction using chiral amine/chiral acid organocatalyst

Organocatalytic C–H activation reactions

• Subhas Chandra Pan

Beilstein J. Org. Chem. 2012, 8, 1374–1384, doi:10.3762/bjoc.8.159

• tetrahydroquinolines by C–H activation, the authors embarked on the asymmetric transformation utilizing chiral secondary amine catalysis. After the screening of different chiral amine catalysts, solvents, and acid additives, as well as temperatures, chiral pyrrolidine catalyst 15 in combination with

A novel asymmetric synthesis of cinacalcet hydrochloride

• Veera R. Arava,
• Laxminarasimhulu Gorentla and
• Pramod K. Dubey

Beilstein J. Org. Chem. 2012, 8, 1366–1373, doi:10.3762/bjoc.8.158

• ][16][17][18][19][20]. In our quest to utilize the chiral tert-butanesulfinamides in asymmetric syntheses of chiral amine APIs in an industrial setting [21][22][23], we report a novel asymmetric synthesis of 1 (Scheme 1) based on (R)-tert-butanesulfinamide (2), which was developed and extensively

• studied by Ellman [24]. We have chosen 1-acetylnaphthalene (3) (Scheme 1) as a key starting material to produce the chiral amine center, and 3-trifluoromethylbenzaldehyde (8) as another key starting material for the preparation of the intermediates 1-(3-bromopropyl)-3-trifluoromethylbenzene (5) and 1-(3

Organocatalytic asymmetric allylic amination of Morita–Baylis–Hillman carbonates of isatins

• Hang Zhang,
• Shan-Jun Zhang,
• Qing-Qing Zhou,
• Lin Dong and
• Ying-Chun Chen

Beilstein J. Org. Chem. 2012, 8, 1241–1245, doi:10.3762/bjoc.8.139

• optimized conditions in hand, we explored a diversity of MBH carbonates derived from isatins in the reactions with protected hydroxylamine 3d by the catalysis of chiral amine 1h in chlorobenzene at 0 °C. The results are summarized in Table 2. A series of MBH carbonates 2 bearing either electron-donating or

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

• the desired product 3a with high enantioselectivity (97%, Table 1, entry 3), whereas the diastereomeric catalyst VII afforded product 3a in lower enantioselectivity (78% ee, Table 1, entry 7). These results demonstrate that the central and axial chiral elements in the chiral amine-thiourea catalyst

Development of the titanium–TADDOLate-catalyzed asymmetric fluorination of β-ketoesters

• Lukas Hintermann,
• Mauro Perseghini and
• Antonio Togni

Beilstein J. Org. Chem. 2011, 7, 1421–1435, doi:10.3762/bjoc.7.166

• catalysts [52] and small-molecule chiral amine catalysts were introduced and explored with great success [53][54][55][56]. Here we present the full range of observations on titanium-catalyzed fluorinations of β-ketoesters. The focus is on the development of the reaction and the study of factors influencing

Thermal rearrangement of tert-butylsulfinamide

• Veera Reddy Arava,
• Laxminarasimhulu Gorentla and
• Pramod Kumar Dubey

Beilstein J. Org. Chem. 2011, 7, 9–12, doi:10.3762/bjoc.7.2

• ever increasing number of methods based upon the chiral amine reagent tert-butylsulfinamide (1) (Figure 1) has become one of the most extensively used synthetic approaches for both the production and discovery of drug candidates [1]. In particular, the tert-butylsulfinyl group showed high levels of

Analogues of amphibian alkaloids: total synthesis of (5R,8S,8aS)-(−)-8-methyl- 5-pentyloctahydroindolizine (8-epi-indolizidine 209B) and [(1S,4R,9aS)-(−)-4-pentyloctahydro- 2H-quinolizin- 1-yl]methanol

• Joseph P. Michael,
• Claudia Accone,
• Charles B. de Koning and
• Christiaan W. van der Westhuyzen

Beilstein J. Org. Chem. 2008, 4, No. 5, doi:10.1186/1860-5397-4-5

• (+)-28 was less tractable than its pyrrolidinylidene counterpart, thereby necessitating modifications that included timing changes and additional protection–deprotection steps. A successful synthesis of [(1S,4R,9aS)-4-pentyloctahydro-2H-quinolizin-1-yl]methanol (−)-41 from the chiral amine tert-butyl (3R

• acylation of the chiral amine (−)-15, prepared as described in our prior work [13], with 5-bromopentanoyl chloride (obtained in two steps from δ-valerolactone) [27][28]. This afforded tert-butyl (3R)-[(5-bromopentanoyl)amino]octanoate (+)-25 in 98% yield (Scheme 3). However, subsequent cyclisation to the

• synthesis before the introduction of other incompatible functional groups (lactam, thiolactam, enaminone). The only feasible option was to go back to the chiral amine (+)-14, reduction of which with lithium aluminium hydride gave the unstable amino alcohol (+)-30 in 97% yield as long as the amine was added

The use of chiral lithium amides in the desymmetrisation of N-trialkylsilyl dimethyl sulfoximines

• Matthew J. McGrath and
• Carsten Bolm

Beilstein J. Org. Chem. 2007, 3, No. 33, doi:10.1186/1860-5397-3-33

• column indicated that adduct 2a was formed in 42% ee (Table 1, entry 4). To overcome the separation problem, N-tert-butyldiphenylsilyl dimethylsulfoximine 1b was used in place of trimethylsilyl adduct 1a and the electrophilic trap was changed to TMSCl. Under these modified conditions, the chiral amine

• mechanism involving irreversible asymmetric deprotonation to a lithiated sulfoximine followed by rapid anion quenching on addition of the electrophile appears likely. An alternative equilibration of the sulfoximine anion with the chiral amine is less probable as racemic 2b was obtained in 23% yield after