Direct C(sp³)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

• Siyu Wang,
• Lianyou Zheng,
• Shutao Wang,
• Shulin Ning,
• Zhuoqi Zhang and
• Jinbao Xiang

Beilstein J. Org. Chem. 2021, 17, 2505–2510, doi:10.3762/bjoc.17.167

• precursors have also been widely explored in the past decades. These reactions typically proceed under the catalysis of a nucleophilic tertiary amine or phosphine, and no metal catalysts are needed, which makes this strategy more synthetically useful for the construction of allyl-substituted scaffolds

• MBH-derived allyl bromides (Scheme 1d) [30]. This reaction was assumed to involve the deprotonation of the initially formed 2-methylpyridinium salt by base to generate an N-allyl enamine intermediate, which undergoes a 3-aza-Cope rearrangement to give the allyl-substituted products. To the best of our

Copper-catalyzed monoselective C–H amination of ferrocenes with alkylamines

• Zhen-Sheng Jia,
• Qiang Yue,
• Ya Li,
• Xue-Tao Xu,
• Kun Zhang and
• Bing-Feng Shi

Beilstein J. Org. Chem. 2021, 17, 2488–2495, doi:10.3762/bjoc.17.165

• ferrocenes with alkynes by using an unprecedented half-sandwich Sc catalyst [36]. Very recently, Shi and Zhang demonstrated a Cp*Co-catalyzed ortho-C–H allylation of ferrocenes assisted by thioamide using allyl carbonates and vinylcyclopropanes as allylating partners [37]. Meanwhile, Zhang and co-authors

Targeting active site residues and structural anchoring positions in terpene synthases

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 2441–2449, doi:10.3762/bjoc.17.161

• (GFPP, C25) for sesterterpene biosynthesis. Type I terpene synthases (TPSs) activate these acyclic molecules by the abstraction of diphosphate to produce a reactive allyl cation that can initiate a cascade reaction through typical carbocation chemistry, including cyclisation reactions by intramolecular

• overall structures are very similar and constitute an α-helical fold that was first described for the FPP synthase (FPPS) from chicken (Gallus gallus) [10]. A helix G break first observed in tobacco 5-epi-aristolochene synthase with a nearby main chain carbonyl group stabilises the allyl cation of the

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• Jin’s one step dihydroxylation–oxidation protocol using a NaIO4/(cat.) OsO4 system. Allylation of the resulting aldehyde 74 was best performed under Brown’s protocol at low temperature utilizing a chiral allyl reagent prepared from allylmagnesium bromide and (+)-B-chloro-diisopinocampheylborane. By this

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• –halide complex compound 3 (Scheme 1). Review Cyclization reactions involving stoichiometric amounts of Hg(II) salts Cyclization involving alkenes (>C=C<) In 1900 and 1901, the Sand and Biilmann group had first reported the Hg(II)-mediated cyclization of allyl alcohol using Hg(II) nitrate (Hg(NO3)2) in

• cyclization of γ-hydroxyalkene derivative 187 as an intermediate stage to give a mixture of diastereomeric 2,5-disubstituted tetrahydrofurans 188a and 188b (Scheme 58) [119]. Later for the total synthesis of ventiloquinone J (194), a Hg(II)-salt-catalyzed intramolecular cyclization reaction of the ortho-allyl

• the racemic naphthohydroquinone hongconin (197) starting from the ortho-allyl alcohol derivative 195. The starting material was cyclized using a Hg(II) salts to get an inseparable mixture of products 196a and 196b in the ratio of 1:5 [121]. The synthetic route proceeded by benzylic alcohol ortho

Base-free enantioselective S_N2 alkylation of 2-oxindoles via bifunctional phase-transfer catalysis

• Mili Litvajova,
• Emiliano Sorrentino,
• Brendan Twamley and
• Stephen J. Connon

Beilstein J. Org. Chem. 2021, 17, 2287–2294, doi:10.3762/bjoc.17.146

• delight, relatively electron-rich benzyl bromides were able to afford products in high yields and with improved product ee – up to 90% (Table 2, entries 8 and 9). Attention then switched to non-benzyl bromide-based electrophiles – however, use of allyl iodide was able to furnish product 10Aj with only 51

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• have been provided by the group of Jacobsen in the nucleophilic addition of indoles 17 to pyranones 62 (Scheme 14a) [71], as well as in the enantioselective synthesis of α-allyl amino esters 67 by the reaction of α-chloro amino acid derivatives 65 with allyltin and allylsilane 66 nucleophiles [72

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• ]. In this context, Tambar developed a δ-selective C(sp3)–H allylation of aliphatic amides 64 using allyl chlorides 65 under visible light photoredox nickel catalysis (Scheme 34) [112]. The optimized reaction conditions exhibited good tolerance to a variety of substitutions on the allyl chloride

Chemical syntheses and salient features of azulene-containing homo- and copolymers

• Vijayendra S. Shetti

Beilstein J. Org. Chem. 2021, 17, 2164–2185, doi:10.3762/bjoc.17.139

• by using [Pd(allyl)Cl]2 and JackiePhos as a ligand to obtain the polymer 30 in 52% yield. The deprotection of the N-Boc functionality led to the formation of poly[2,6-aminoazulene] 31 in excellent yields (Scheme 7C). The N-Boc-protected polymer 30 possessed good solubility in organic solvents and its

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• used with TFAA to obtain diallyl intermediate 127. The latter undergoes a [3,3]-sigmatropic reaction to afford allyl (2-allylindol-3-yl)sulfide 128, which is oxidized by m-CPBA to sulfine 124. Repetition of the steps along with indole addition led to the desired products. Here the absence of a β

Preparation of mono-substituted malonic acid half oxyesters (SMAHOs)

• Tania Xavier,
• Sylvie Condon,
• Christophe Pichon,
• Erwan Le Gall and
• Marc Presset

Beilstein J. Org. Chem. 2021, 17, 2085–2094, doi:10.3762/bjoc.17.135

• primary activated alkyl halides such as allyl (3bf, 81%) or benzyl (3bh, 76%), but lower with a base-sensitive propargyl group (3bg, 58%). More functionalized lateral chains like a chlorobutyl group could be introduced efficiently (3bj, 91%) and the use of protected aminated or hydroxylated derivatives

• . SMAHOs bearing classical ester groups could be obtained in moderate yields (iPr: 51%; Bn: 53%; allyl: 52%) and the use of less nucleophilic alcohols such as t-BuOH, 2,2,2-trifluoroethanol, (−)-menthol, and phenol led to decreased yields (37%, 34%, 28%, and 17%, respectively). More functionalized alcohols

Enantioenriched α-substituted glutamates/pyroglutamates via enantioselective cyclopropenimine-catalyzed Michael addition of amino ester imines

• Zara M. Seibel,
• Jeffrey S. Bandar and
• Tristan H. Lambert

Beilstein J. Org. Chem. 2021, 17, 2077–2084, doi:10.3762/bjoc.17.134

• isopropyl completely suppressed reactivity (Table 2, entry 8). On the other hand, allyl (Table 2, entry 9) and propargyl (Table 2, entry 10) groups proved to viable substituents, leading to the products in good yield and high enantioselectivities. Of course, these two functional groups provide convenient

A study on selective transformation of norbornadiene into fluorinated cyclopentane-fused isoxazolines

• Zsanett Benke,
• Attila M. Remete and
• Loránd Kiss

Beilstein J. Org. Chem. 2021, 17, 2051–2066, doi:10.3762/bjoc.17.132

• the selectivity of olefin bonds during a CM reaction [38][39][40][41][42][43]. Investigations of various types of olefins in CM, such as substituted and functionalized styrenes, unsaturated tertiary alcohols, olefins with quaternary carbon centers, acrylates, allyl ethers or allyl acetates gave a

• used in our CM steps. CM reactions of compound (±)-4 were investigated first. With 4-bromo-3,3,4,4-tetrafluorobut-1-ene and allyl 2,2,2-trifluoroacetate, no CM product was observed. However, CM reactions with 1,1,1,3,3,3-hexafluoropropan-2-yl acrylate (7c) were successful (Scheme 1 and Table 1). When

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• temperatures. Allyl groups provided a valid alternative and could be removed with palladium chloride at 60 °C in 4 hours [90]. Chemical synthesis grants full control over the polymer length, avoiding non-uniform dispersions of MW obtained by polymerization. Polymers with virtually any possible pattern of

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• (III) salts and AlMe3 as a base for the regioselective ortho functionalization of aromatic secondary amides has been recently reported [121]. The reaction is performed with 1–2 mol % of CrCl3 or Cr(aca)3, a stoichiometric amount of AlMe3 and bromoalkynes (Scheme 15B), allyl bromide or 1,4-dihydro-1,4

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• peptide–carbohydrate conjugation was achieved using tryptophan-containing peptides 29 and sugar-containing allyl carbonates 30 in chemo- and site-selective manners using a pyridyl directing group. The optimized reaction conditions entailed the use of dimanganese decacarbonyl as the catalyst and sodium

Electron-rich triarylphosphines as nucleophilic catalysts for oxa-Michael reactions

• Susanne M. Fischer,
• Simon Renner,
• A. Daniel Boese and
• Christian Slugovc

Beilstein J. Org. Chem. 2021, 17, 1689–1697, doi:10.3762/bjoc.17.117

• h but TMTPP is again a distinctly better catalyst providing 73% conversion after 1 h and almost full conversion (98%) after 24 h. Allyl alcohol (c) is more reactive than 1-propanol as conversions with all catalysts at all conditions are slightly higher. Most importantly, the TMTPP-catalyzed reaction

• than those presented here can be achieved [22][23]. Switching to the weaker Michael acceptor acrylamide (E = −23.54 for N,N-dimethylacrylamide) [19], no useful conversions on any account were obtained. However, TMTPP performs best, giving 61 and 74% conversions with 1-propanol (b) and allyl alcohol (c

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• engage in a retarding radical pathway with the olefin to generate an allyl radical species via H abstraction. TBC acts on this species through hydrogen atom transfer to regenerate the olefin double bond and allows its reentry into the productive catalytic cycle (a repair chain step), thereby allowing the

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

• Jie Zheng,
• Shuyu Meng and
• Quanrui Wang

Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104

• reaction leading to the 4-allyl-substituted tetrahydronaphthalen-2-ol 14ai in 65% yield. On comparing the results from the anisole-type nucleophiles or thiophene with that from furans, it was observed that the reactions with furans furnished predominantly trans-14af and trans-14ag with a high degree of

• carbon-nucleophile. As expected, the 4-allyl-substituted tetrahydronaphthalen-2-ol 14ai was obtained, again, as a mixture of cis/trans-isomers in a ratio of 44:56. This example demonstrates the general synthetic utility of this cascade protocol. Encouraged by the success of using 13a as the substrate

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• ′-ketonucloside 1 with trimethylsulfoxonium iodide in DMSO afforded the spironucleoside 2, which in turn was converted to the TIPDS-protected 2′-(pyrimidin-1-yl)methyl-/2′-(purin-9-yl)methylarabinofuranosyluracil derivatives 3a–f by nucleophilic epoxide ring opening with thymine, N-benzoyladenine, 6-O-allyl-N

• oligonucleotides [42]. Pedersen and Nielsen [35] synthesized a double-headed nucleoside with two different nucleobases, i.e., 2′-deoxy-2′-(thymine-1-yl)ethyluridine (11) (Scheme 3). The oxidative cleavage of the allyl group in TIPDS-protected 2-allyl-2-deoxyuridine 8 gave the TIPDS-protected hydroxynucleoside 9 as

• -(2-(thymine-1-yl)ethyl)thymidine (118) with an additional nucleobase at the 5′-(S)-C-position of thymidine. Double-headed nucleoside 118 was synthesized starting from 3′-tert-butyldiphenylsilyl (TBDPS)-protected thymidine 115 which was converted into the pixylated 5′(S)-C-allyl-substituted nucleoside

Design, synthesis and photophysical properties of novel star-shaped truxene-based heterocycles utilizing ring-closing metathesis, Clauson–Kaas, Van Leusen and Ullmann-type reactions as key tools

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2021, 17, 1374–1384, doi:10.3762/bjoc.17.96

• , compound 2 was subjected to nitration followed by reduction to deliver triaminotruxene 4 in excellent yield. Later, compound 4 was subjected to six-fold N-allylation in the presence of NaH/allyl bromide to provide the required compound 3 which was directly treated with G-I catalyst (9) to afford the

• ) and allyl bromide (0.48 mL, 5.52 mmol) at 0 °C under nitrogen atmosphere. The mixture was stirred at rt for 12 h. After completion of the reaction (TLC monitoring), the reaction mixture was quenched with saturated NH4Cl and the aqueous layer was extracted with EtOAc (50 mL × 3), dried over Na2SO4. The

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• , when the allylation was performed in the presence of indium metal, in a saturated aqueous solution of sodium bromide, a mixture of the bromoallylation and allylation products 25 and 26, respectively, were obtained [69]. The addition of the allyl unit to the imines proceeded with total facial

• diastereoselectivity, producing also preferably diastereoisomers with anti relative configuration. According to the mechanism depicted on Scheme 8, the allyl unit reacted at γ-position, taking place the addition to the Si face of the imines with RS configuration. The bromoallylated product 24 was obtained as a mixture

• took place to the Re face of imines with (Z,SS)-configuration (Scheme 27). The cycloaddition of chiral sulfinyl imines (RS)-14 with 2-(trimethysilylmethyl)allyl acetate (91) could also be promoted by Pd(0) to give methylenepyrrolidines 92. The group of Stockman demonstrated that Pd(PPh3)4 was the best

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• ][33]. The racemization occurs during allyl transfer as a result of 2-oxonia-Cope rearrangement through a 3,3-sigmatropic shift, which plays a crucial role during the reaction, as shown in Scheme 7. The Prins cyclization between alcohol (R)-35 and aldehyde 36 was investigated under different Lewis acid

• variety of the Prins-cyclized products. The allyl metalation, followed by intramolecular Sakurai cyclization (IMSC) provides an efficient route to a variety of tetrahydropyran derivatives, as described by Marko and Leroy [68][69]. In these approaches, an initial ene reaction between an aldehyde 139 and

• Scheme 49. Unlike allyl- and vinylsilanes, as discussed earlier, Furman and co-workers introduced a new concept of synthesizing 211 utilizing silyl-Prins cyclization of propargylsilane 209 and aldehyde 210 in the presence of TMSOTf [93]. The oxocarbenium ion was intramolecularly trapped by the olefin

Manganese/bipyridine-catalyzed non-directed C(sp³)–H bromination using NBS and TMSN₃

• Kumar Sneh,
• Takeru Torigoe and
• Yoichiro Kuninobu

Beilstein J. Org. Chem. 2021, 17, 885–890, doi:10.3762/bjoc.17.74

• gram scale. The introduced bromine atom can be converted into fluorine and allyl groups. Keywords: bromination; C–H transformation; hydrogen abstraction; manganese; radical; Introduction Organic halides are versatile precursors for various synthetic protocols and are frequently used to introduce a

• functionalized upon the introduction of other functional groups, such as fluorine and allyl groups. We hope that this C(sp3)–H bromination reaction will become a useful method to synthesize organic compounds with bromine atom(s). Several examples of C(sp3)–H halogenation. Substrate scope. a80 °C. b45 min. c4 h