Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• -1,3-diamine 132 in 57% yield. The ring-closing metathesis of 121 (R1 = allyl, from Scheme 25) provided pure N-cyclohexenyl imine 135 in 98% yield. Asymmetric alkylation of imine-carbanion In 2023, a team of Huang and Yan [44] presented a novel approach towards synthetically important homoallylic α

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• evidence [60]. The synthetic route was designed in such a way that intercept both Ryu’s intermediate (+)-69 [50] and Hatakeyama’s intermediate (+)-82b [22] (Scheme 12 and Scheme 13). In this approach, the asymmetric alkylation of 96 with alkyne 95 under Carreira’s conditions [61][62][63] afforded (−)-98 in

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• and his group developed an electrochemical strategy for the asymmetric alkylation of 2-acylimidazole derivatives 94 with substituted para-methylphenols 95 using Ni(OAc)2 as a Lewis acid catalyst in presence of chiral diamine ligand 96 (Scheme 34) [71]. Based on their detailed mechanistic studies, the

A novel and practical asymmetric synthesis of eptazocine hydrobromide

• Ruipeng Li,
• Zhenren Liu,
• Liang Chen,
• Jing Pan,
• Kuaile Lin and
• Weicheng Zhou

Beilstein J. Org. Chem. 2018, 14, 2340–2347, doi:10.3762/bjoc.14.209

• alkaloid-derived catalysts was identified as the best one for asymmetric alkylation of 1-methyl-7-methoxy-2-tetralone (2) with 1,5-dibromopentane. The products I-13a and I-13b were isolated in a ratio of 79:21 and in 77.8% yield (Scheme 2). Encouraged by the previous studies and relevant works [15][16], we

• are engaged in the development of a concise and efficient asymmetric synthetic route for eptazocine hydrobromide (1), with the same material and catalyst. Results and Discussion Herein, we developed a new, practical and resolution-free preparation of 1 (Scheme 3) using the asymmetric alkylation of 2

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• our group. These were applied to the asymmetric alkylation reaction of benzophenone imine of glycine ester which has become one of the benchmark reactions for examining the performance of new phase-transfer catalysts [36]. Later in 2010, Shirakawa and Shimizu reported the synthesis of novel inherently

• asymmetric alkylation of tert-butyl glycinate benzophenone Schiff base 3 with alkyl halides 4 in a toluene–50% KOH biphasic system (Scheme 1). The corresponding α-alkyl-α-amino acid derivatives 5 were obtained in excellent yields with very low enantioselectivities (up to 9%). This is the first example of

• chiral calix[4]arene derivatives 9–15 (Figure 2) bearing secondary amides at lower rim have been designed as catalysts and employed in the asymmetric alkylation of N-(diphenylmethylene)glycine esters. Among them, α-methylbenzylamine-derived calixarene-methoxy-triamide 12 afforded the (R)-benzylated

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• bearing a N-enoyl sultam moiety 84 instead. A 3-key step strategy involving a copper-mediated reduction, a transmetalation and an asymmetric alkylation was adopted for the preparation of monofluoroalkenes 85 (Scheme 16). After some synthetic modifications, Fmoc-Orn(Ns)-ψ[(Z)-CF=CH]-Orn(Ns) [48], Fmoc-Lys

• reduction, transmetalation and asymmetric alkylation by Fujii and co-workers. Synthesis of (E)-monofluoroalkene-based dipeptide isostere by Fujii and co-workers. Diastereoselective synthesis of MeOCO-Val-ψ[(Z)-CF=C]-Pro isostere by Chang and co-workers. Asymmetric synthesis of Fmoc-Ala-ψ[(Z)-CF=C]-Pro by

Synthesis of 2-aminosuberic acid derivatives as components of some histone deacetylase inhibiting cyclic tetrapeptides

• Shital Kumar Chattopadhyay,
• Suman Sil and
• Jyoti Prasad Mukherjee

Beilstein J. Org. Chem. 2017, 13, 2153–2156, doi:10.3762/bjoc.13.214

• to provide the desired 2-aminoheptenoic acid derivative 11. Several syntheses of this important amino acid have appeared which include Lubell’s palladium-catalyzed allylation [15], Riera’s asymmetric epoxidation protocol [16], Rich’s enolate amination [17] and Hruby’s asymmetric alkylation [18] of a

Spiro-fused carbohydrate oxazoline ligands: Synthesis and application as enantio-discrimination agents in asymmetric allylic alkylation

• Jochen Kraft,
• Martin Golkowski and
• Thomas Ziegler

Beilstein J. Org. Chem. 2016, 12, 166–171, doi:10.3762/bjoc.12.18

• asymmetric alkylation. Results and Discussion We started our synthesis from readily available 3,4,5-tri-O-benzyl-1,2-O-isopropylidene-β-D-fructopyranose (1) [18] and 3,4,5-tri-O-benzyl-1,2-O-isopropylidene-β-D-psicopyranose (2) [19], respectively (Scheme 1). Deprotection of the isopropylidene group under

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

• formation of C–C bonds. Here we describe the asymmetric alkylation of alkylzirconium species to racemic 3,6-dihydro-2H-pyrans. Two systems were examined: 3-chloro-3,6-dihydro-2H-pyran using linear optimization (45–93% ee, up to 33% yield, 5 examples) and 3,6-dihydro-2H-pyran-3-yl diethyl phosphate with the

• mechanistic diversity in Cu-catalysed asymmetric alkylation reactions to racemic starting materials. DoE from 3,6-dihydro-2H-pyran-3-yl diethyl phosphate (2d). Conditions: 4-phenyl-1-butene (2.5 equiv), Cp2ZrHCl (2.0 equiv), 2d (1.0 equiv), CuL* as specified (0.1 equiv), additive as specified (1.0 equiv or

• ), 3-chloro-3,6-dihydro-2H-pyran 2a (1.0 equiv), CuCl (10 mol %), D (10 mol %), AgClO4 (10 mol %), B(OiPr)3 (1.0 equiv), in CH2Cl2 (2.0 mL), room temperature. Isolated yield. ee determined by HPLC or GC. For more information see Supporting Information File 1. Asymmetric alkylation to 3-chloro-3,6

Multivalent polyglycerol supported imidazolidin-4-one organocatalysts for enantioselective Friedel–Crafts alkylations

• Tommaso Pecchioli,
• Manoj Kumar Muthyala,
• Rainer Haag and
• Mathias Christmann

Beilstein J. Org. Chem. 2015, 11, 730–738, doi:10.3762/bjoc.11.83

• the asymmetric alkylation reaction. The experiment showed constant enantiomeric ratios although decreased activity and yields were observed. The lower yields exhibited after each cycle might be attributed to the decreased solubility of the recovered polymer. For the same reason, early attempts using

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

• control the stereoselectivity. We envisioned that an alternative way of constructing this motif would again make use of our recently developed palladium-catalyzed asymmetric alkylation of lactam enolates. The formal synthesis of (+)-quebrachamine commenced with benzoyl lactam 50 (Scheme 13), which was

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

• diastereoselectivity and further hydrolyzed to the corresponding enantiomerically pure α-substituted phosphonic acids 33 [22][29][30]. Other asymmetric alkylation methodologies using chiral phosphonamides were reported by the groups of Denmark [3][4] and Steglich [7]. Remarkably, the alkylation of α-dithioalkylimino

• , 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

• based on an asymmetric sulfuration (route A) or asymmetric alkylation (route B) of a chiral phosphorus carbanion (Scheme 12) [36]. Deprotonation of (R,R)-28a and alkylation with 3-(3’-phenoxyphenyl)propyl iodide (96) gave 97. Sulfuration of the Li anion of 97 with tetramethylthiuram disulfide provided

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

• approach are available [22][42][43][44][45][46][47][48]. In recent years methodologies were developed for the asymmetric alkylation. Livinghouse and Wolfe have reported an enantioselective method for the preparation of chiral tertiary phosphine–boranes starting from a racemic secondary phosphine borane

• used to carry out an asymmetric alkylation reaction (Scheme 4). The monoalkylation of phosphine–borane complex 15 was performed in the presence of the Cinchona alkaloid ammonium salt 16 [50]. However, the enantioselectivity of the reaction was low. Imamoto et al. prepared a new tetraphosphine ligand 19

• metal-catalyzed reaction was faster than the achiral base-mediated alkylation of 36a. Bisphosphines 37 were also reported with high enantiomeric excesses. The procedure is mainly restricted to benzylic halides but also allowed for the asymmetric alkylation with ethyl bromide. All the phosphines were

Non-cross-linked polystyrene-supported 2-imidazolidinone chiral auxiliary: synthesis and application in asymmetric alkylation reactions

• Quynh Pham Bao Nguyen and
• Taek Hyeon Kim

Beilstein J. Org. Chem. 2013, 9, 2113–2119, doi:10.3762/bjoc.9.248

• Quynh Pham Bao Nguyen Taek Hyeon Kim School of Applied Chemistry and Center for Functional Nano Fine Chemicals, Chonnam National University, Gwangju 500-757, Republic of Korea 10.3762/bjoc.9.248 Abstract Asymmetric alkylation reactions using non-cross-linked polystyrene (NCPS)-supported 2

• -imidazolidinone chiral auxiliaries were successfully investigated with excellent diastereocontrol (>99% de). The recovery and the recycling of this soluble polymer-supported chiral auxiliary were achieved in order to produce highly optical pure carboxylic acids. Keywords: asymmetric alkylation; chiral

• solid phase and solution phase synthesis, non-cross-linked soluble polymer supports have attracted great interest because of some advantages such as high reactivity, easy analysis and purification of products [6][7][8][9][10][11][12]. Asymmetric alkylation reactions using polymer-supported chiral

One-pot tandem cyclization of enantiopure asymmetric cis-2,5-disubstituted pyrrolidines: Facile access to chiral 10-heteroazatriquinanes

• Ping-An Wang,
• Sheng-Yong Zhang and
• Henri B. Kagan

Beilstein J. Org. Chem. 2013, 9, 265–269, doi:10.3762/bjoc.9.32

• (Figure 5), and they have investigated their catalytic activities in asymmetric alkylation reactions for producing enantiomerically enriched amino acids. The synthesis of these quaternary ammonium ions follows a diversity-oriented approach wherein the tandem inter-[4 + 2]/intra-[3 + 2] cycloaddition of

Mechanochemistry assisted asymmetric organocatalysis: A sustainable approach

• Pankaj Chauhan and
• Swapandeep Singh Chimni

Beilstein J. Org. Chem. 2012, 8, 2132–2141, doi:10.3762/bjoc.8.240

• by milling protected glycine hydrochloride 21 and diphenylmethanimine (20), under solvent-free conditions (Scheme 11) [62]. The asymmetric alkylation of glycine imine 22 was carried out by using a phase-transfer catalyst under basic conditions in a ball-mill. The Schiff base reacted rapidly with

• Michael reaction assisted by pestle and mortar grinding. C-2 symmetric thiourea catalysed enantioselective MBH reaction. Quinine-catalysed ring opening of meso-anhydride by ball-milling. Ball-milling-assisted (A) synthesis of glycine schiff bases and (B) their organocatalytic asymmetric alkylation

Asymmetric one-pot sequential Friedel–Crafts-type alkylation and α-oxyamination catalyzed by a peptide and an enzyme

• Kengo Akagawa,
• Ryota Umezawa and
• Kazuaki Kudo

Beilstein J. Org. Chem. 2012, 8, 1333–1337, doi:10.3762/bjoc.8.152

• they often have chiral carbon chains attached to indole rings. A Friedel–Crafts-type asymmetric alkylation (FCAA) to indoles is a versatile method for synthesizing such chiral indole derivatives. To date, a number of FCAA reactions by either metal catalysts or organocatalysts have been reported [4][5

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

A two step synthesis of a key unit B precursor of cryptophycins by asymmetric hydrogenation

• Benedikt Sammet,
• Mathilde Brax and
• Norbert Sewald

Beilstein J. Org. Chem. 2011, 7, 243–245, doi:10.3762/bjoc.7.32

• sulfate. A completely different route to unit B precursor 8 (Scheme 2) is based on a phase transfer catalyst (PTC) mediated asymmetric alkylation. However, the required cinchonine derived chiral catalyst is not commercially available [9]. Results and Discussion We envisaged a two step synthesis for the

Enantioselective nucleophilic difluoromethylation of aromatic aldehydes with Me₃SiCF₂SO₂Ph and PhSO₂CF₂H reagents catalyzed by chiral quaternary ammonium salts

• Chuanfa Ni,
• Fang Wang and
• Jinbo Hu

Beilstein J. Org. Chem. 2008, 4, No. 21, doi:10.3762/bjoc.4.21

• the benzyl ring afforded the product with good ee, though the unsubstituted one gave a significantly low ee (Table 2, entries 12 and 14). Although the 9-anthracenylmethyl and 2,3,4-trifluorobenzyl functionality were found to be quite useful for asymmetric alkylation of tert-butylglycinate Schiff base