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

• enantioselectivities for both electron-rich and electron-poor N-benzoylarylimines, aliphatic N-benzoylimines, and bulkier N-carboxyalkylimines. However, less sterically hindered N-carboxyalkyl- and N-carbamoylimines showed a significant drop in both enantioselectivity and yield. The observed enantioselectivity was

• ,β-unsaturated imines 9. However, with ethynylimines 12, the enantioselectivity dropped to a modest level. In addition, the reaction with sterically hindered tertiary allylboronates, such as the chiral (R)-α-cyclohexyl-α-methyl-allylboronate required the use of catalytic amounts of zinc tert-butoxide

• (Scheme 6). The study explored a broad range of p-methoxyphenyl (PMP)imines derived from aryl, heteroaryl and alkyl aldehydes (including ethyl glyoxylate), demonstrating yields of 57–98% and high enantioselectivity of 90–98%. Screening of aldehyde and amine components indicated that the method is

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• . Mild enolization of thioesters allows for the generation of Michael adducts with good yields and stereoselectivities. Reactions in a ball mill afford product formation with similar efficacy to solution-phase reactions but with slightly reduced enantioselectivity, yet they yield products in just one

• Discussion Based on our previous experiences with low-reactive Michael acceptors [29], initial attempts were carried out using bifunctional squaramides, derivatives of cinchona. However, up to 45% yield of the desired product was obtained with poor enantioselectivity (14%, Scheme 2). Considering the

• product with 93% ee after 24 h, while the bifunctional primary amine-thiourea catalysts (system B) required 4 days to provide an adduct with similar enantioselectivity. Prolonged reaction time is in general the innate nature of organocatalytic reactions employing iminium activation approaches. With the

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• Drawing inspiration from linear free energy relationships, MLR models, pioneered by Norrby and co-workers [83] and later further developed by Sigman and co-workers [69][82], are commonly used for the prediction of enantioselectivity. In such models, the substrates, catalysts, and other relevant reaction

• is insufficient to represent steric substituent properties. Instead, the authors used Sterimol parameters [84] as steric descriptors (Figure 5), showing superior correlations towards the enantioselectivity for a multitude of organocatalytic reactions. Sterimol parameters are calculated from a given

• descriptors for the prediction of the enantioselectivity for several previously reported reactions, showing improved prediction performance compared to non-Boltzmann-weighted Sterimol parameters. Apart from considering parameters of the entire conformer ensemble, it has been shown that informative models can

Factors influencing the performance of organocatalysts immobilised on solid supports: A review

• Zsuzsanna Fehér,
• Dóra Richter,
• Gyula Dargó and
• József Kupai

Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183

• spaces. The confinement of the heterogeneous version of cinchona amine and thiourea catalysts was reported, leading to improved enantioselectivity values in the Michael addition of nitromethane (5) to chalcone (6) through modification of the pore size of mesoporous silica 8 or 9 (Scheme 2) [63]. Thus

• , for cinchona thiourea, enantioselectivity not only increased with reduced pore size but even reached the level of the homogeneous catalyst when the support pore size was reduced to 6.3 nm. This resulted in obtaining the (R)-configured product 7 with 63% yield and 93% ee, as opposed to a 55% yield and

• , experiments were conducted. It was discovered that the nanoparticles themselves catalysed the formation of the racemic product in the absence of the thiourea catalyst. This finding elucidates the relatively poor enantioselectivity observed in reactions catalysed by the magnetic nanoparticle-supported

Chiral bifunctional sulfide-catalyzed enantioselective bromolactonizations of α- and β-substituted 5-hexenoic acids

• Sao Sumida,
• Ken Okuno,
• Taiki Mori,
• Yasuaki Furuya and
• Seiji Shirakawa

Beilstein J. Org. Chem. 2024, 20, 1794–1799, doi:10.3762/bjoc.20.158

• ; enantioselectivity; halogenation; lactones; organocatalysis; Introduction Catalytic asymmetric halolactonizations of alkenoic acids are powerful methods for the preparation of important chiral lactones in enantioenriched forms [1][2][3][4][5][6][7][8][9][10][11]. A wide variety of chiral catalysts have been applied

• bifunctional sulfide (S)-1a (10 mol %) bearing a hydroxy group. This reaction yielded the desired δ-valerolactone product 3a with good yield and enantioselectivity [83% yield, 86:14 enantiomeric ratio (er)]. We further tested the reaction of 2a with a hydroxy-protected sulfide catalyst (S)-4 under the same

• conditions to evaluate the importance of the bifunctional design of the hydroxy-type chiral sulfide catalyst (S)-1a. As expected, the use of the hydroxy-protected catalyst (S)-4 produced 3a with significantly lower enantioselectivity (51:49 er). This outcome clearly underscores the crucial role of the

Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones

• Pooja Goyal,
• Akhil K. Dubey,
• Raghunath Chowdhury and
• Amey Wadawale

Beilstein J. Org. Chem. 2024, 20, 1518–1526, doi:10.3762/bjoc.20.136

• File 1), the catalyst I imparted the highest enantioselectivity (74% ee) of the Michael product 3aa (Table 1, entry 1). Different solvents (see details in Supporting Information File 1) were screened for the test reaction using 15 mol % of catalyst I. Among them, CHCl3 turned out to be the optimal

• solvent, as the product 3aa was isolated in reproducible yield (77%) and enantioselectivity 74% ee (Table 1, entry 3). Next, we explored a variety of achiral and/or chiral Brønsted acids A1–6 as additives in order to increase the yield and the enantioselectivity of the reaction (Table 1, entries 4–9). A

• marked increase in both the yield and enantioselectivity of the product 3aa were observed. Among the screened Brønsted acids A1–6, the combination of 15 mol % of the catalyst I and 30 mol % of (±)-mandelic acid (A5) was found to be superior in terms of enantioselectivity (92% ee) of the product 3aa

Towards an asymmetric β-selective addition of azlactones to allenoates

• Behzad Nasiri,
• Ghaffar Pasdar,
• Paul Zebrowski,
• Katharina Röser,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1504–1509, doi:10.3762/bjoc.20.134

• the use of 3 equiv Cs2CO3 in toluene (0.05 M) at room temperature as the best-suited conditions (Table 1, entry 13), allowing for the synthesis of 5a in moderate yield (61%) and enantioselectivity (81:19 er). With optimized conditions for the synthesis of enantioenriched (−)-5a at hand, we next

• investigated the generality of this protocol. As outlined in Scheme 2, differently substituted allenoates were reasonably well tolerated (see products 5a–d), albeit some erosion in enantioselectivity was observed when using a tert-butyl ester containing allenoate (product 5d). Various α-arylmethyl-substituted

• steric bulk (5p) leads to a somewhat lower enantioselectivity, while the methoxy-substituent does not have a strong impact on the yield. It should, however, be stated that some of the methoxy-containing products, i.e., the α-alkyl-substituted 5j and 5k tend to undergo partial nucleophilic ring opening by

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• enantioselective intramolecular Cannizzaro reaction of aryl and alkyl glyoxals 1a–h and alcohol 2 using trisoxazoline (TOX) ligand (4)/copper catalysts to furnish the requisite mandelic esters 3a–h in good yields (greater than 90%) and high enantioselectivity. This was observed in the wide substrate scope as

• enantioselectivity of the resultant product (Scheme 1). A one-pot oxidation–Cannizzaro reaction of aryl methyl ketones to mandelic acid derivatives was observed in the presences of ytterbium triflate as the catalyst. The intramolecular reaction sequence employed a SeO2/Yb(OTf)3 combination to affect the in-situ

• % enantioselectivity. They employed a double asymmetric induction with (+)/(−)-menthol (12), and CuX2 bis(oxazoline) catalyst where the corresponding chiral mandelate ester 13 was obtained in 81% yield and high selectivity (90% de) (Scheme 6). The proposed mechanism of the reaction is depicted below. Hong et al

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• followed by a sequential Jones oxidation. The overall method displays a broad scope and good enantioselectivity, favoring the (R) enantiomer. The applicability of the protocol is highlighted by the efficient enantioselective syntheses of the selective phosphodiesterase-4-inhibitor rolipram and the

• temperature gave the NH-unprotected γ-lactam 5a and the drug (R)-rolipram 5b in 79% and 97% yields, respectively, with excellent enantioselectivity. Hydrolysis of γ-lactam 5a in 6 N HCl aqueous solution at 100 °C for 10 hours then led to the formation of (R)-baclofen hydrochloride (6) in 76% yield (Scheme 6

• ). The total yields were determined to be 49% for (R)-baclofen hydrochloride (6) and 61% (R)-rolipram (5b) from starting pyrrolidine 1d. Determination of the absolute stereochemistry of the Heck adducts/lactams and rationalization of the enantioselectivity The absolute stereochemistry of the products was

Evaluation of the enantioselectivity of new chiral ligands based on imidazolidin-4-one derivatives

• Jan Bartáček,
• Karel Chlumský,
• Jan Mrkvička,
• Lucie Paloušová,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2024, 20, 684–691, doi:10.3762/bjoc.20.62

• based on derivatives of imidazolidin-4-one were synthesised and characterised. The catalytic activity and enantioselectivity of their corresponding copper(II) complexes were studied in asymmetric Henry reactions. It was found that the enantioselectivity of these catalysts is overall very high and

• enhanced economic efficiency, eco-friendly practices, and reduced waste. Catalysts with the highest enantioselectivity have been employed in the synthesis of essential chiral intermediates for drug production, such as amprenavir [12], rivaroxaban [13][14], linezolid [13] and salmeterol [7]. Therefore

• donor ability to pyridine. This change reduces the ring size within the ligand structure, potentially increasing the space available for coordinating reacting species, thereby possibly enhancing catalytic activity and enantioselectivity. We also aimed to assess the impact of alkyl groups at the 5

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• cooperative catalytic effect of the two Cr(III) units. Control experiments without K+, or in the presence of competitive crown ether presented a reduced conversion rate and enantioselectivity, proving the conformation change in the reactivity of the system. Anion responsive tweezers The main types of anion

• higher activity and enantioselectivity due to the preorganization of the Cr(III) catalytic centers enabling bimetallic catalysis compared to the more flexible arrangement of the salen in the open form. The tweezers could be opened by breaking the thioether–rhodium bond with a combination of Cl− and CO

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• -workers found a reversal of enantioselectivity that can be controlled by choice of solvent, which they rationalized by invoking a solvent induced change in ion-pairs [6]. In another study by Agbossou-Niedercorn, Michon, and co-workers, they found that chiral alcohols do not impact enantioselectivity [7

Chiral phosphoric acid-catalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles

• Yumei Wang,
• Guangzhu Wang,
• Yanping Zhu and
• Kaiwu Dong

Beilstein J. Org. Chem. 2024, 20, 205–211, doi:10.3762/bjoc.20.20

• excellent yield and enantioselectivity. Keywords: asymmetric organocatalysis; chiral Brønsted acid; 3,3-difluoroindoline; Hantzsch ester; transfer hydrogenation; Introduction The introduction of fluoro atoms into organic molecules can alter their lipophilicity, solubility, metabolic stability, and

• relatively strict reaction conditions (up to 150 bar H2). In 2022, Liu’s group reported an asymmetric hydrogenation of 3H-indoles catalyzed by a chiral Mn complex, which showed good yield and enantioselectivity [25]. In addition to metal catalysis for the enantioselective reduction, asymmetric

• , synthesized in situ from a chiral boron phosphate complex with water, for asymmetric indole reduction (Scheme 1b) [30]. The mild reaction conditions, low catalyst loading, and high enantioselectivity rendered this transformation an attractive approach to synthesize optically active indolines. However, these

Anion–π catalysis on carbon allotropes

• M. Ángeles Gutiérrez López,
• Mei-Ling Tan,
• Giacomo Renno,
• Augustina Jozeliūnaitė,
• J. Jonathan Nué-Martinez,
• Javier Lopez-Andarias,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2023, 19, 1881–1894, doi:10.3762/bjoc.19.140

• diastereoselectivity ratio with exo/endo21/20 = 1.9 nearly doubled. The same was true for the enantioselectivity, which increased from 23% ee for control 20 to 55% ee for anion–π catalyst 21. These results were in support that stabilization of the intrinsically disfavored exo transition state VII on the polarizable

• surface of carbon allotropes can increase diastereo- and enantioselectivity of Diels–Alder reactions. The direct formation of 1,3-nonadjacent stereocenters is a topic of concern in asymmetric catalysis [67]. To explore compatibility with anion–π catalysis, the addition of ethyl 2-cyano-2-phenylacetate (28

• ) to 2-chloroacrylonitrile (29) was selected (Figure 5) [68]. In the presence of 5 mol % of the best fullerene catalyst 21, conversion into dicyanide 30 reached 72% within 5 days at ambient temperature [67]. While enantioselectivity was negligible, dr 5.3:1 was the best diastereoselectivity among all

A novel recyclable organocatalyst for the gram-scale enantioselective synthesis of (S)-baclofen

• Gyula Dargó,
• Dóra Erdélyi,
• Balázs Molnár,
• Péter Kisszékelyi,
• Zsófia Garádi and
• József Kupai

Beilstein J. Org. Chem. 2023, 19, 1811–1824, doi:10.3762/bjoc.19.133

• ). Based on the literature [36], Meldrum’s acid has a low solubility in non-polar solvents, resulting in diminished enantioselectivity. Furthermore, in our case, the application of polar solvents would not be favorable due to the low solubility of the lipophilic organocatalyst in these solvents

• ) [37]. In a similar manner as the former Michael addition, a solvent screening was carried out in the previously well-established four solvents: CPME, 2-MeTHF, anisole, and toluene (Table 4, entries 1–4). Based on the solvent screening, high yields and good enantioselectivity can be achieved in anisole

• and toluene, while using 2-MeTHF drastically decreased the enantioselectivity. From the perspective of green chemistry, anisole would be more favorable, but toluene is also a distinctly better alternative to the other solvents (e.g., DCM) commonly used in Michael additions. Another critical aspect

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• , resulting in good to excellent yields and enantioselectivity. This groundbreaking work opened up new possibilities for the practical application of photoredox catalysis in large-scale industrial processes, as it provided a more accessible and cost-effective catalyst system that could be readily utilized for

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• sulfur reagents resulted in thiolated products 92 up to 99% ee, in the presence of quinidine as the organocatalyst (Scheme 38) [72]. For the study of enantioselectivity of products, different N-substituted oxindoles with H, Me, phenyl, and benzyl groups were investigated. As the size of N-protecting

• groups increased, the percentage of enantioselectivity decreased, where in the case of NH-oxindoles, the product was achieved with only 6% ee. Another sulfenylation at the 3-position of unprotected oxindoles with N-(phenylthio)phthalimide was reported by Feng et al. [73]. A chiral N,N′-dioxide-Sc(OTf)3

• with N-(arylthio)phthalimide 14 and N-chlorophthalimide (96) under phase-transfer conditions was developed by Maruoka and co-workers (Scheme 39) [74]. The presence of chiral bifunctional catalysts C and D with the amide, or sulfonamide moieties could improve the enantioselectivity. Also, the

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• . The hydrosilylation of aryl, alkyl, and cyclic ketones could be accomplished with excellent yields (Scheme 35) [48]. In 2011, Gawley and co-worker reported an excellent reactivity and enantioselectivity of a C2-symmetric NHC–Cu(I) complex for the catalytic hydrosilylation of a variety of carbonyl

• enantioselectivity, using NHC–Cu(I) complexes generated in situ from chiral imidazolium salts containing possible chelating functional group(s). For example, the conjugate addition of Grignard reagents to 3-methyl- and 3-ethylcyclohexenones in the presence of the C2-symmetric chiral NHC–copper complex catalyst

• use of an azolium salt with a sterically bulky alkyl substituent such as N-CHRR (e.g., NCHPh2 in 123) on the azolium ring results in a marked increase in the enantioselectivity of the ACA reaction. Thus, a new functionalized azolium salt 123 was prepared and used in combination with Cu(OTf)2 as

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• dihydropyrans (DHPs) and aldehydes in the presence of Zn(II) (Scheme 37) [102]. The method has good enantioselectivity and functional group tolerance and provides a practical and economical route towards a series of enantiopure α-substituted DHPs through CDC, through an in situ NaBH4 reduction two-step sequence

• may provide completely new insights into this issue. In addition, CDC reactions involving ether α-C(sp3)–H bonds are rarely enantioselective, although examples of enantioselectivity have been reported for some similar CDC reactions of amines, and future developments will undoubtedly bridge this

Acetaldehyde in the Enders triple cascade reaction via acetaldehyde dimethyl acetal

• Alessandro Brusa,
• Debora Iapadre,
• Maria Edith Casacchia,
• Alessio Carioscia,
• Giuliana Giorgianni,
• Giandomenico Magagnano,
• Fabio Pesciaioli and
• Armando Carlone

Beilstein J. Org. Chem. 2023, 19, 1243–1250, doi:10.3762/bjoc.19.92

• enantioselectivity. Keywords: acetaldehyde; acetaldehyde dimethyl acetal; cascade reaction; multicomponent reaction; organocatalysis; Introduction Multicomponent reactions (MCRs) are chemical processes that involve three or more compounds, in which the product contains all the atoms of the reagents, except for

• nitroalkene derivatives with low reagent excess and high enantioselectivity; this reaction represents the first step in the Enders triple cascade catalytic cycle. The use of acetaldehyde in a two-component cascade reaction was previously reported by Enders [27]; however, the scope of this reaction is limited

Radical ligand transfer: a general strategy for radical functionalization

• David T. Nemoto Jr,
• Kang-Jie Bian,
• Shih-Chieh Kao and
• Julian G. West

Beilstein J. Org. Chem. 2023, 19, 1225–1233, doi:10.3762/bjoc.19.90

• ) azide complex, reducing the iron catalyst back to the starting Fe(II) state. Organic azides can be formed in moderate to high enantioselectivity using this approach; however, the scope is largely limited to benzylic products, a result in line with Groves’ finding that benzylic acid substrates perform

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• -substituted indoles. The authors also tried the reaction with C3-substituted indoles to functionalize the C2 position. However, a very low enantioselectivity was achieved in the latter case (Scheme 10) [35]. Lin and co-workers designed a planar chiral phosphoric acid containing a [2.2]paracyclophane moiety

• yields and enantioselectivity. The catalyst P13 was an even far superior catalyst than conventional BINOL and SPINOL-derived phosphoric acids. The substrate scope was investigated by varying substituents in the carbocyclic ring of indole 4. Changing the β-aryl and α-substituents in the styryl-derived

• as the nucleophile. This reaction afforded (bis(indolyl)methyl)benzenesulfonamide derivatives 43 but no promising enantioselectivity was achieved for most of the products (Scheme 12) [37]. In 2019, You, Yuan and co-workers reported another enantioefficient aza-Friedel–Crafts reaction between N

Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors

• Brigita Mudráková,
• Renata Marcia de Figueiredo,
• Jean-Marc Campagne and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65

• derivatives using HBF4 or CF3SO3H (see Supporting Information File 1 for more details). The corresponding tandem products were isolated in medium to good yields as mixtures of diastereomers and high enantiomeric purities were recorded for selected tandem products. The enantioselectivity of this reaction is

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• imines 25 (Scheme 6). The authors also demonstrated the enantioselective aminoalkylation, using chiral diamines as ligands. The introduction of chiral diamines in the metal complex produced the aminoalkylated products enantioselectivity with good ratio of enantiomeric excess. The plausible mechanism

• containing bioactive molecules (Scheme 10). To attain enantioselectivity a chiral phosphine oxide (43)-ligated Ni–Al bimetallic catalyst was used that was critical in improving the reactivity and controlling the selectivity of the reaction. Further, based on deuterium labelling experiments, KIE studies, and

• elimination delivers the desired product 44 via the intermediate 49 (Scheme 10b). It was proposed that the enantioselectivity was mainly due to the C–C reductive elimination of the R-pathway, which is lower in energy than the S-pathway. Remote C–H alkylation Several remarkable studies have been reported for