Cobalt‐Catalyzed Enantioselective Synthesis of Chiral gem‐Bis(boryl)alkanes

We report an asymmetric synthesis of enantioenriched gem‐bis(boryl)alkanes in an enantioselective diborylation of 1,1‐disubstituted alkenes catalyzed by Co(acac)₂/(R)‐DM‐segphos. A range of activated and unactivated alkenes underwent this asymmetric diborylation in the presence of cyclooctene as a hydrogen acceptor, affording the corresponding gem‐bis(boryl)alkanes with high enantioselectivity. The synthetic utility of these chiral organoboronate compounds was demonstrated through several stereospecific derivatizations and the synthesis of sesquiterpene and sesquiterpenoid natural products.     

Hydrogen Atom Transfer-Mediated Domino Cyclisation Reaction to Access (Spiro)Quinazolinones

A radical domino cyclisation reaction of N-cyanamide alkenes, mediated by hydrogen atom transfer (HAT) has been developed. This method, using PhSiH₃ and catalytic Fe(acac)₃, allows for the synthesis of challenging (spiro)quinazolinone scaffolds from simple, tractable (hetero)aryl carboxylic acid and cyanamide building blocks.     

Chelating Group Enabled Palladium-Catalyzed Regiodivergent Carbonylative Synthesis of 2,3-Dihydroquinolin-4(1H)-ones

A new procedure on palladium-catalyzed carbonylative cyclization of N-(2-pyridyl)sulfonyl (N-SO₂Py)-2-iodoanilines with terminal alkenes has been developed for the rapid construction of dihydroquinolin-4(1H)-one scaffolds. Enabled by the chelating group and using benzene-1,3,5-triyl triformate (TFBen) as the CO source, both aromatic and aliphatic alkenes were smoothly transformed into the corresponding 2,3-dihydroquinolin-4(1H)-ones in good yields with excellent regioselectivities. Notably, the reaction of aromatic alkenes produces 2-aryl-2,3-dihydroquinolin-4(1H)-ones, while 3-alkyl-2,3-dihydroquinolin-4(1H)-ones were obtained when aliphatic alkenes were used. This protocol has been applied in the synthesis of antitumor agent A as well.     

Photocatalyzed Borylcyclopropanation of Alkenes with a (Diborylmethyl)iodide Reagent

Cyclopropane skeletons play a prominent role in the development of organic synthesis and pharmaceutical chemistry. Herein, we report the design and synthesis of a stable, multifunctional (diborylmethyl)iodide reagent (CHI(Bpin)₂) for the photoinduced cyclopropanation of alkenes, providing an array of 1,2-substituted cyclopropylboronates in good yields. This α-haloboronic ester can be readily synthesized on a multigram scale from commercially available starting materials. Furthermore, the protocol displays high chemo- and diastereoselectivity, excellent functional-group tolerance, and allows for late-stage borylcyclopropanation of complex molecules. Mechanistic studies reveal that the borylcyclopropanation proceeds through a radical addition/polar cyclization pathway mediated by the photocatalyst fac-Ir(ppy)₃ and visible light.     

Cover Picture: Methylation of Unactivated Alkenes with Engineered Methyltransferases To Generate Non-natural Terpenoids (Angew. Chem. Int. Ed. 26/2023)

Terpenoids are built from isoprene building blocks and have numerous biological functions. Selective late-stage modification of their carbon scaffold has the potential to optimize or transform their biological activities. However, the synthesis of terpenoids with a non-natural carbon scaffold is often a challenging endeavor because of the complexity of these molecules. Herein we report the identification and engineering of (S)-adenosyl-l -methionine-dependent sterol methyltransferases for selective C-methylation of linear terpenoids. The engineered enzyme catalyzes selective methylation of unactivated alkenes in mono-, sesqui- and diterpenoids to produce C₁₁, C₁₆ and C₂₁ derivatives. Preparative conversion and product isolation reveals that this biocatalyst performs C−C bond formation with high chemo- and regioselectivity. The alkene methylation most likely proceeds via a carbocation intermediate and regioselective deprotonation. This method opens new avenues for modifying the carbon scaffold of alkenes in general and terpenoids in particular.     

Organocatalyzed arylalkylation of activated alkenes via decarboxylation of PhI(O2CR)2: efficient synthesis of oxindoles

A novel organocatalyzed arylalkylation of activated alkenes has been developed. This reaction was initiated from the decomposition of PhI(O₂CR)₂ to generate alkyl radical, followed by addition to alkenes. Then the formed radical was trapped by aromatic ring to generate the cyclized products. This method presents an efficient road to synthesis of a variety of oxindoles.     

Synthesis and Application of Poly(diallyldimethylammonium tribromide)as a Novel Polymeric Brominating Agent

In this study, the synthesis and applications of a new supported tribromide reagent based on poly(diallyldimethylammonium chloride) is reported. This supported tribromide is used in α‐bromoacetalization of ketones, bromination of alkenes and regioselective bromination of activated aromatic compounds. This method is mild and no Br₂ and HBr were used. Other advantages of this reagent are stability, high efficiency, simple filtera‐ bility and reusability.     

Absolute Rate Constants for the Addition of Cyanomethyl (·CH2CN) and (tert-Butoxy)carbonylmethyl (·CH2CO2C(CH3)3) radicals to alkenes in solution

Absolute rate constants and their temperature dependence were determined by time-resolved electron spin resonance for the addition of the radicals ·CH₂CN and ·CH₂CO₂C(CH₃)₃ to a variety of mono- and 1,1-disubstituted and to selected 1,2- and trisubstituted alkenes in acetonitrile solution. To alkenes CH₂?CXY, ·CH₂CN adds at the unsubstituted C-atom with rate constants ranging from 3.3·10³ M ^?1S ^?1 (ethene) to 2.4·10⁶ M ^?1S ^?1 (1,1-diphenylethene) at 278 K, and the frequency factors are in the narrow range of log (A/M ^?1S ^?1) = 8.7 ± 0.3. ·CH₂CO₂C(CH₃)₃ shows a very similar reactivity with rate constants at 296 K ranging from 1.1·10⁴ M ^?1S ^?1 (ethene) to 10⁷ M ^?1S ^?1 (1,1-diphenylethene) and frequency factors log (A/M ^?1S ^?1) = 8.4 ± 0.1. For both radicals, the rate constants and the activation energies for addition to CH₂?CXY correlate well with the overall reaction enthalpy. In contrast to the expectation of an electro- or ambiphilic behavior, polar alkene-substituent effects are not clearly expressed, but some deviations from the enthalpy correlations point to a weak electrophilicity of the radicals. The rate constants for the addition to 1,2- and to trisubstituted alkenes reveal additional steric substituent effects. Self-termination rate data for the title radicals and spectral properties of their adducts to the alkenes are also given.     

Oxydifluoromethylation of Alkenes by Photoredox Catalysis: Simple Synthesis of CF2H‐Containing Alcohols

We have developed a novel and simple protocol for the direct incorporation of a difluoromethyl (CF₂H) group into alkenes by visible‐light‐driven photoredox catalysis. The use of fac‐[Ir(ppy)₃] (ppy=2‐pyridylphenyl) photocatalyst and shelf‐stable Hu's reagent, N‐tosyl‐S‐difluoromethyl‐S‐phenylsulfoximine, as a CF₂H source is the key to success. The well‐designed photoredox system achieves synthesis of not only β‐CF₂H‐substituted alcohols but also ethers and an ester from alkenes through solvolytic processes. The present method allows a single‐step and regioselective formation of C(sp³)–CF₂H and C(sp³)?O bonds from C=C moiety in alkenes, such as hydroxydifluoromethylation, regardless of terminal or internal alkenes. Moreover, this methodology tolerates a variety of functional groups.     

Polystyrene‐Supported (Catecholato)oxorhenium Complexes: Catalysts for Alcohol Oxidation with DMSO and for Deoxygenation of Epoxides to Alkenes with Triphenylphosphine

Polymer‐supported catalysts offer practical advantages for organic synthesis, such as improved product isolation, ease of catalyst recycling, and compatibility with parallel solution‐phase techniques. We have developed the (carboxypolystyrene‐catecholato)rhenium catalyst 2 derived from tyramine (=4‐(2‐aminoethyl)phenol), which is effective for alcohol oxidation with dimethylsulfoxide (DMSO) and for epoxide deoxygenation with triphenylphosphine. The supported [Re(catecholato)]catalyst 2 is air‐ and moisture‐stable and can be recovered and used repeatedly without decreasing activity. The procedures work with non‐halogenated solvents (toluene). DMSO for Re‐catalyzed alcohol oxidation is inexpensive and safer for transport and storage than commonly used peroxide reagents. The oxidation procedure was best suited for aliphatic alcohols, and the mild conditions were compatible with unprotected functional groups, such as those of alkenes, phenols, nitro compounds, and ketones (see Tables 1 and 2). Selective oxidation of secondary alcohols in the presence of primary alcohols was possible, and with longer reaction time, primary alcohols were converted to aldehydes without overoxidation. Epoxides (oxirans) were catalytically deoxygenated to alkenes with this catalyst and Ph₃P (see Table 3). Alkyloxiranes were converted to the alkenes with retention of configuration, while partial isomerization was observed in the deoxygenation of cis‐stilbene oxide ( cis‐1,2‐diphenyloxirane). These studies indicate that supported [Re(catecholato)] complexes are effective catalysts for O‐atom‐transfer reactions, and are well suited for applications in organic synthesis.     

Pd(0)/iodide salt-mediated Heck reaction of aryl nonaflates: Application to the synthesis of 2-(1-alkenyl)phenylphosphonates

Iodide salt, such as NaI, KI or n-Bu₄NI (TBAI), rather than bromide or chloride salt, was found to play a key role in the Pd(0)-catalyzed Heck reaction of aryl nonaflates and terminal alkenes. In the presence of PdCl₂(PPh₃)₂, NaI or TBAI in DMF, a class of 2-(1-alkenyl)phenylphosphonates was first synthesized via the reaction of o-phosphonylphenyl nonaflates with alkenes, the yields, regioselectivities and stereoselectivities were much dependent on the nature of the substituents. In case of the aryl nonaflates without bearing the sterically hindered phosphonyl group with the alkenes, the reactions proceeded more smoothly under the same conditions, leading to the linear products regioselectively in good to excellent yields. A rationale for this reaction is discussed.     

A Planar‐Chiral Rhodium(III) Catalyst with a Sterically Demanding Cyclopentadienyl Ligand and Its Application in the Enantioselective Synthesis of Dihydroisoquinolones

The rapid development of enantioselective C?H activation reactions has created a demand for new types of catalysts. Herein, we report the synthesis of a novel planar‐chiral rhodium catalyst [(C₅H₂^tBu₂CH₂^tBu)RhI₂]₂ in two steps from commercially available [(cod)RhCl]₂ and tert‐butylacetylene. Pure enantiomers of the catalyst were obtained through separation of its diastereomeric adducts with natural (S)‐proline. The catalyst promoted enantioselective reactions of aryl hydroxamic acids with strained alkenes to give dihydroisoquinolones in high yields (up to 97 %) and with good stereoselectivity (up to 95 % ee).     

Osmium(III) and Osmium(V) Complexes Bearing a Macrocyclic Ligand: A Simple and Efficient Catalytic System for cis‐Dihydroxylation of Alkenes with Hydrogen Peroxide

A simple protocol that uses [Os^III(OH)(H₂O)(L ‐N₄Me₂)](PF₆)₂ ( 1 ; L ‐N₄Me₂=N,N′‐dimethyl‐2,11‐diaza[3.3](2,6)pyridinophane) as a catalyst and H₂O₂ as a terminal oxidant for efficient cis‐1,2‐dihydroxylation of alkenes is presented. Unfunctionalized (or aliphatic) alkenes and alkenes/styrenes containing electron‐withdrawing groups are selectively oxidized to the corresponding vicinal diols in good to excellent yields (46–99 %). In the catalytic reactions, the stoichiometry of alkene:H₂O₂ is 1:1, and thus the oxidant efficiency is very high. For the dihydroxylation of cyclohexene, the catalytic amount of 1 can be reduced to 0.01 mol % to achieve a very high turnover number of 5500. The active oxidant is identified as the Os^V(O)(OH) species ( 2 ), which is formed via the hydroperoxide adduct, an Os^III(OOH) species. The active oxidant 2 is successfully isolated and crystallographically characterized.     

Catalysis of hydrosilylation part XVIII. Pt(PPh3)2(CH2CH2) – a versatile catalyst for hydrosilylation of olefins

Pt(PPh₃)₂(CH₂?CH₂) appeared to be a versatile catalyst in hydrosilylation of alkenes (with 5–22 C atoms) as well as of functionalized alkenes such as allyl chloride, allylamine, allyl methacrylate and vinylsilanes. In comparison with a well-known Speier catalyst or with Pt(PPh₃)₄, this complex is characterized by a very high effectiveness (activity and selectivity) and relative resistance to oxygenation and it may be applied in recycling runs with a minor induction period. The catalytic processes examined are of great industrial importance since they lead to a synthesis of alkylsilanes, disilylethanes and silane coupling agents.     

B(C6F5)3-Catalyzed E-Selective Isomerization of Alkenes

Herein, we report the B(C₆F₅)₃-catalyzed E-selective isomerization of alkenes. The transition-metal-free method is applicable across a diverse array of readily accessible substrates, giving access to a broad range of synthetically useful products containing versatile stereodefined internal alkenes. The reaction mechanism was investigated by using synthetic and computational methods.     

Glycosylsulfenyl- und (Glycosylthio)sulfenyl-halogenide (Halogeno- bzw. Halogenothio-(1-thioglycoside)): Herstellung und Umsetzung mit Alkenen

Glycosylsulfenyl snf (Glycosylthio) sulfenyl Halides (Halogeno and Halogenothio 1-Thioglycosides, Resp.): Preparation and Reaction with Alkenes The disulfides 11–17 and 20 were prepared from 7, 9 , and 18 via the dithiocarbonates 8, 10 , and 19 , respectively (Scheme 2). The structure of 11 and of 13 was established by X-ray analysis. Chlorolysis (SO₂Cl₂) of 11 gave mostly the sulfenyl chloride 24 , characterized as the sulfenamide 26 , a small amount of 21 , characterized as the (glycosylthio)sulfenamide 23 , and the glycosyl chloride 27 (Scheme 3). Bromolysis of 11 followed by treatment of the crude with PhNH₂ yielded only 28 . Chlorolysis of the diglycosyl disulfide 13 , however, gave mostly the (glycosylthio)sulfenyl chloride 21 and 27 , besides 24 . Bromolysis of 13 (→ 22 and traces of 25 ) followed by treatment with PhNH₂ gave an even higher proportion of 23 . Similarly, 20 led to 29 and hence to 30 . In solution (CH₂Cl₂), the sulfenyl chloride 24 decomposes faster than the (thio)sulfenyl chloride 21 , and both interconvert. Addition of crude 24 to styrene (?78°) yielded the chloro-sulfide 31 and some 37 , both in low yields. The product of the addition of 24 to l-methylcyclohexene was transformed into the triol 32 . Silyl ethers of allylic alcohols reacted with 24 only at room temperature, yielding, after desilylation, isomer mixtures 33 and 34 , and pure 35 . Much higher yields were achieved for the addition of (thio)sulfenyl halides yielding halogeno-disulfides. Good diastereoselctivites were only obtained with 21 , its cyclohexylidene-protected analogue, and 22 , and this only in the addition to styrene (→ 36, 37, 38 ), to (E)-disubstituted alkenes (→ 46, 48, 49a/b, 50a/b, 53 ), and to trisubstituted alkenes (→ 47, 51, 52, 54, 55 ). Other monosubstituted alkenes (→ 41–45 ) and (Z)-hex-2-ene (→ 49c/d,50c/d ) reacted with low diastereoselectivities. Where structurally possible, a stereospecific trans-addition was observed; regioselectivity was observed in the addition to mono- and trisubstituted alkenes and to derivatives of allyl alcohols. The absolute configuration of the 2-chloro-disulfides was either established by X-ray analysis ( 47a ) or determined by transforming (LiAlH₄) the chloro-disulfides into known thiiranes (Scheme 5). Thus, 37, 48 , and the mixture of 49a/b and 50a/b gave the thiiranes 56, 61 , and 64 , respectively, in good-to-acceptable yields (Scheme 5). Harsher conditions transformed 56 into the thiols 57 and 58 . Similarly, 61 gave 62 . The enantiomeric excesses of these thiols were determined by GC analysis of their esters obtained with (?)-camphanoyl chloride. Addition of 21 to {[(E)-hex-2-enyl]oxy}trimethylsilane, followed by LiAlH₄ reduction and desilylation, gave the known 66 (63%, e.e. 74%). The diastereoselectivity of the addition of 21 to trans-disubstituted and trisubstituted alkenes is rationalized by assuming a preferred conformation of the (thio)sulfenyl chloride and destabilizing steric interactions with one of the alkene substituents, while the diastereoselectivity of the addition to styrene is explained by postulating a stabilizing interaction between the phenyl ring and the C(1)–S substituent (Fig.4).     

An Alkene‐Promoted Borane‐Catalyzed Highly Stereoselective Hydrogenation of Alkynes to Give Z‐ and E‐Alkenes

The stereoselective hydrogenation of alkynes to alkenes is an extremely useful transformation in synthetic chemistry. Despite numerous reports for the synthesis of Z‐alkenes, the hydrogenation of alkynes to give E‐alkenes is still not well resolved. In particular, selective preparation of both Z‐ and E‐alkenes by the same catalytic hydrogenation system using molecular H₂ has rarely been reported. In this paper, a novel strategy of using simple alkenes as promoters for the HB(C₆F₅)₂‐catalyzed metal‐free hydrogenation of alkynes was adopted. Significantly, both Z‐ and E‐alkenes can be furnished by hydrogenation with molecular H₂ in high yields with excellent stereoselectivities. Further experimental and theoretical mechanistic studies suggest that interactions between H and F atoms of the alkene promoter, borane intermediate, and H₂ play an essential role in promoting the hydrogenolysis reaction.     

Radical Cyclization Reactions via Manganese(III) Acetate Leading to 2‐Thienyl‐Substituted Dihydrofuran Compounds

The 2‐thienyl‐substituted 4,5‐dihydrofuran derivatives 3 – 8 were obtained by the radical cyclization reaction of 1,3‐dicarbonyl compounds 1a – 1f with 2‐thienyl‐substituted conjugated alkenes 2a – 2e by using [Mn(OAc)₃] (Tables 1–5). In this study, reactions of 1,3‐dicarbonyl compounds 1a – 1e with alkenes 2a – 2c gave 4,5‐dihydrofuran derivatives 3 – 5 in high yields (Tables 1–3). Also the cyclic alkenes 2d and 2e gave the dihydrobenzofuran compounds, i.e., 6 and 7 in good yields (Table 4). Interestingly, the reaction of benzoylacetone (=1‐phenylbutane‐1,3‐dione; 1f ) with some alkenes gave two products due to generation of two stable carbocation intermediates (Table 5).     

Absolute Rate Constants for the Addition of Benzyl (PhĊH2) and Cumyl (PhĊMe2) Radicals to Alkenes in Solution

Absolute rate constants and their temperature dependence were determined by time-resolved electron spin resonance for the addition of the radicals Ph?H₂ and Ph?Me₂ to a variety of alkenes in toluene solution. To vinyl monomers CH₂=CXY, Ph?H₂ adds at the unsubstituted C-atom with rate constants ranging from 14 M ^?1S ^?1 (ethoxyethene) to 6.7 · 10³ M ^?1S ^?1 (4-vinylpyridine) at 296 K, and the frequency factors are in the narrow range of log (A/M ^?1S ^?1) = 8.6 ± 0.3, whereas the activation energy varies with the substituents from ca. 51 kJ/mol to ca. 26 kJ/mol. The rate constants and the activation energies increase both with increasing exothermicity of the reaction and with increasing electron affinity of the alkenes and are mainly controlled by the reaction enthalpy, but are markedly influenced also by nucleophilic polar effects for electron-deficient substrates. For 1,2-disubstituted and trisubstituted alkenes, the rate constants are affected by additional steric substituent effects. To acrylate and styrenes, Ph?Me₂ adds with rate constants similar to those of Ph?H₂, and the reactivity is controlled by the same factors. A comparison with relative-rate data shows that reaction enthalpy and polar effects also dominate the copolymerization behavior of the styrene propagation radical.     

Homogeneous [RuIII(Me3tacn)Cl3]‐Catalyzed Alkene cis‐Dihydroxylation with Aqueous Hydrogen Peroxide

A simple and green method that uses [Ru(Me₃tacn)Cl₃] ( 1 ; Me₃tacn=N,N′,N′′‐trimethyl‐1,4,7‐triazacyclononane) as catalyst, aqueous H₂O₂ as the terminal oxidant, and Al₂O₃ and NaCl as additives is effective in the cis‐dihydroxylation of alkenes in aqueous tert‐butanol. Unfunctionalized alkenes, including cycloalkenes, aliphatic alkenes, and styrenes (14 examples) were selectively oxidized to their corresponding cis‐diols in good to excellent yield (70–96 %) based on substrate conversions of up to 100 %. The preparation of cis‐1,2‐cycloheptanediol (119 g, 91 % yield) and cis‐1,2‐cyclooctanediol (128 g, 92 % yield) from cycloheptene and cyclooctene, respectively, on the 1‐mol scale can be achieved by scaling up the reaction without modification. Results from Hammett correlation studies on the competitive oxidation of para‐substituted styrenes (ρ=?0.97, R=0.988) and the detection of the cycloadduct [(Me₃tacn)ClRuHO₂(C₈H₁₄)]⁺ by ESI‐MS for the 1 ‐catalyzed oxidation of cyclooctene to cis‐1,2‐cyclooctanediol are similar to those of the stoichiometric oxidation of alkenes by cis‐[(Me₃tacn)(CF₃CO₂)Ru^VIO₂]⁺ through [3+2] cycloaddition (W.‐P. Yip, W.‐Y. Yu, N. Zhu, C.‐M. Che, J. Am. Chem. Soc. 2005 , 127, 14239).