Amide‐Controlled Highly Selective Catalytic Borylcupration of Allenes

A novel copper‐catalyzed, highly regio‐ and stereoselective borylcupration of substituted 2,3‐allenamides with bis(pinacolato)diboron producing Z‐β‐borylated β,γ‐unsaturated enoamides has been demonstrated. Due to the unique effect of the amide‐group, perfect regio‐ and stereoselectivity and good to excellent yields have been achieved, which were rationalized by a DFT study.     

The Regio‐ and Stereoselective Synthesis of trans‐2,3‐Dihydropyridine N‐oxides and Piperidines

Reactivity N? Own : Pyridine N‐oxides can be used for the complete regio‐ and stereoselective synthesis of trans‐substituted piperidines. The sequential addition of Grignard reagents and aldehydes or ketones to pyridine N‐oxides yields a complete regio‐ and stereoselective trans 2,3‐addition reaction in high yields, and the substituted 2,3‐dihydropyridine N‐oxide can be reduced to form 2,3‐trans‐substituted piperidines (see scheme).

     

Chiral N,N′‐Dioxide‐Organocatalyzed Regio‐, Diastereo‐ and Enantioselective Michael Addition–Alkylation Reaction

A highly regio‐, diastereo‐ and enantioselective Michael addition–alkylation reaction between α‐substituted cyano ketones and (Z)‐bromonitrostyrenes has been realized by using a chiral N,N′‐dioxide as organocatalyst. A variety of substrates performed well in this reaction, and the corresponding multifunctionalized chiral 2,3‐dihydrofurans were obtained in up to 95 % yield with 95:5 dr and 93 % ee.     

2‐[2‐Methyl‐5‐nitro‐4‐(phenyl­sulfonyl­methyl)­imidazol‐1‐yl]­ethanol and 2‐methyl‐5‐nitro‐4‐phenyl­sulfonyl­methyl‐1,3‐thia­zole

The title compounds, C₁₃H₁₅N₃O₅S and C₁₁H₁₀N₂O₄S₂, respectively, both contain a phenyl­sulfonyl group connected, through a methyl­ene bridge, to either a substituted nitro­imidazole or nitro‐1,3‐thia­zole ring. In the imidazole‐containing mol­ecule, the nitro and sulfonyl groups are trans relative to the sulfonyl–methyl bond, while in the thia­zole‐containing mol­ecule, these substituents are cis. The stabilizing interactions within the crystals are also different between the two compounds.     

β‐Selective Glycosylation by Using O‐Aryl‐Protected Glycosyl Donors

New glycosyl donors have been developed that contained several para‐substituted O‐aryl protecting groups and their stereoselectivity for the glycosylation reaction was evaluated. A highly β‐selective glycosylation reaction was achieved by using thioglycosides that were protected by 4‐nitrophenyl (NP) groups, which were introduced by using the corresponding diaryliodonium triflate. Analysis of the stereoselectivities of several glycosyl donors indicated that the β‐glycosides were obtained through an S_N2‐type displacement from the corresponding α‐glycosyl triflate. The NP group could be removed by reduction of the nitro group and acylation, followed by oxidation with ceric ammonium nitrate (CAN).     

5‐exo versus 6‐endo Thiyl‐Radical Cyclizations in Organic Synthesis

Since the discovery of the radical mediated thiol‐ene and thiol‐yne reactions, these reactions have been employed in an intramolecular manner for the synthesis of sulfur‐containing heterocycles. Although closely related on a mechanistic basis, the thiol‐ene and thiol‐yne cyclization can differ greatly in regioselectivity and product distribution, with the thiol‐ene process being more predictable and thus attracting greater utilization. Herein, we review intramolecular thiyl‐radical addition reactions and the factors leading to the observed regioselectivity in examples in which both the 5‐exo and 6‐endo mode of cyclization are feasible. We highlight the applications of these important reactions for organic synthesis in the recent literature.     

Two 17‐hydroxy‐9(10→5)‐abeo‐estr‐4‐ene‐3,10‐diones

(5S,9S,17S)‐17‐Hydroxy‐9(10→5)‐abeo‐estr‐4‐ene‐3,10‐dione, C₁₈H₂₆O₃, (II), and (5R,9R,17S)‐17‐hydroxy‐9(10→5)‐abeo‐estr‐4‐ene‐3,10‐dione, C₁₈H₂₆O₃, (III), are equimolecular products of the Fe^II‐induced transposition of 10β‐hydro­peroxy‐17β‐hydroxyestr‐4‐en‐3‐one, (I). With respect to reagent mol­ecules, the configuration at C9 is retained for (II) while it is inverted in (III). The conformations of the five‐ and six‐membered rings are compared.     

Racemic and chiral 1‐[N‐(chloro­acetyl)carbamoylamino]‐2,3‐dihydro‐1H‐inden‐2‐yl chloroacetate

In the racemic crystals of (1S,2R)‐ or (1R,2S)‐1‐[N‐(chloro­acetyl)­carbamoyl­amino]‐2,3‐di­hydro‐1H‐inden‐2‐yl chloro­acetate, C₁₄H₁₄Cl₂N₂O₄, (I), the enantiomeric mol­ecules form a dimeric structure via the N—H?O cyclic hydrogen bond of the carbamoyl moieties. In the chiral crystals of (—)‐(1S,2R)‐1‐[N‐(chloro­acetyl)­carbamoyl­amino]‐2,3‐di­hydro‐1H‐inden‐2‐yl chloro­acetate, C₁₄H₁₄Cl₂N₂O₄, (II), the N—­H?O intermolecular hydrogen bond forms a zigzag chain around the twofold screw axis. The melting points and calculated densities of (I) and (II) are 446 and 396 K, and 1.481 and 1.445 Mg m^?3, respectively.     

Regio‐ and Enantio‐selective Chemo‐enzymatic C−H‐Lactonization of Decanoic Acid to (S)‐δ‐Decalactone

The conversion of saturated fatty acids to high value chiral hydroxy‐acids and lactones poses a number of synthetic challenges: the activation of unreactive C?H bonds and the need for regio‐ and stereoselectivity. Here the first example of a wild‐type cytochrome P450 monooxygenase (CYP116B46 from Tepidiphilus thermophilus) capable of enantio‐ and regioselective C5 hydroxylation of decanoic acid 1 to (S)‐5‐hydroxydecanoic acid 2 is reported. Subsequent lactonization yields (S)‐δ‐decalactone 3 , a high value fragrance compound, with greater than 90 % ee. Docking studies provide a rationale for the high regio‐ and enantioselectivity of the reaction.     

1,8‐Diazabicyclo[5.4.0]undec‐7‐ene: A Remarkable Base in the Debromination of 4‐ or 5‐Substituted N‐Benzyl α‐Bromo‐α‐p‐Toluenesulfonylglutarimide

Debromination of N‐benzyl 4‐ or 5‐substituted α‐bromo‐α‐p‐toluenesulfonylglutarimides is achieved with 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) to give the N‐benzyl 4‐ or 5‐substituted α‐p‐toluenesulfonylglutarimides. The DBU/THF system is applied to a new methodology for the synthesis of bicyclic glutarimide skeleton in moderate yields.     

20‐Di­cyano­methyl­ene‐5,8,11,14‐tetraoxa‐2,17‐di­thia­bi­cyclo­[16.4.1]­tricosa‐1(23),18,21‐triene and its mercury(II) dichloride complex

The structures of the title compound, C₂₀H₂₄N₂O₄S₂, and its mercury(II) dichloride complex, dichloro{20‐di­cyano­methyl­ene‐5,8,11,14‐tetraoxa‐2,17‐di­thia­bi­cyclo­[16.4.1]­tricosa‐1(23),18,­21‐tri­ene‐κ⁴O,κS¹⁷}mercury(II), [HgCl₂(C₂₀­H₂₄­N₂­O₄­S₂)], have been determined by X‐ray crystallographic analyses. The mercury(II) dichloride complex has two independent mol­ecules of [HgCl₂(C₂₀H₂₄N₂O₄S₂)] in the lattice. The mercury(II) ion has pentagonal bipyramidal coordination which involves one S atom, four O atoms and two Cl^? ions.     

从Baylis-Hillman溴化物方便的合成N-取代的咪唑和苯并三氮唑

在室温下, 通过Baylis-Hillman溴化物与咪唑或苯并三氮唑反应, 方便的合成了N-取代的咪唑和苯并三氮唑衍生物. 该方法的优点为操作简单, 反应条件温和, 产率高, 好的区域和立体选择性.     

(+)‐Tartaric Acid‐Catalyzed High Regio‐ and Stereoselective Aminobromination of Olefins

(+)‐Tartaric acid‐catalyzed aminobromination of α,β‐unsaturated ketones, α,β‐unsaturated esters and simple olefins utilizing TsNH₂/NBS as the nitrogen/halogen sources at room temperature without protection of inert gases achieved good yields (up to 92% yield) of vicinal haloamino products with excellent regio‐ and stereoselectivity, even just 10% of (+)‐tartaric acid was used as catalyst. The regio‐ and stereochemistry was unambiguously confirmed by X‐ray structural analysis of products 2b and 12c . The electron‐rich and deficient olefins show significant differences in activity to the aminobromination reaction and give the opposite regioselectivities. The 21 cases have been investigated which indicated that our protocol has the advantage of a large scope of olefins. Additionally, tartaric acid as catalyst has the advantage of avoiding any hazardous metals retained in products.     

Rh‐Catalyzed Reaction of Propargylic Alcohols with Aryl Boronic Acids–Switch from β‐OH Elimination to Protodemetalation

It is known that Rh‐catalyzed reaction of propargylic alcohols with aryl metallic reagents undergoes S_N2’‐type reaction affording allenes via a sequential arylmetalation and β‐OH elimination process. Here we report a Rh/Ag‐cocatalyzed reaction of propargylic alcohols with organoboronic acids affording stereo‐defined (E)‐3‐arylallylic alcohols via arylmetalation and protodemetalation with a high regio‐ and stereoselectivity under very mild conditions. The reaction exhibits a good substrate scope and the compatibility with synthetically useful functional groups with no racemization for optically active propargylic alcohols. Such a reaction may also be extended to homopropargylic alcohols with a remarkable regioselectivity and exclusive E‐stereoselectivity.     

Visible light‐induced thiol‐ene reaction: A new strategy to prepare Α,ω‐dithiol and Α,ω‐divinyl telechelic polythiolether oligomers

A new strategy is developed to prepare both α,ω‐dithiol and α,ω‐divinyl linear telechelic polythiolether oligomers by visible light induced thiol‐ene chemistry in the presence of a fac‐Ir(ppy)₃ photoredox catalyst. Polythiolether oligomers of well‐defined end groups and controlled molecular weights have been successfully synthesized at varying monomer molar ratios of 1,4‐benzenedimethanethiol (BDMT) to diethylene glycol divinyl ether (DEGVE). ¹H NMR and MALDI‐TOF MS analyses demonstrate that as‐prepared polythiolethers possess high end‐group fidelity, which is further supported by the successful polyaddition of polythiolethers bearing α,ω‐dithiol and α,ω‐divinyl groups. For example, with the α,ω‐dithiol‐ (M_n = 1900 g mol^?1, PDI = 1.25) and α,ω‐divinyl‐terminated (M_n = 2000 g mol^?1, PDI = 1.29) polythiolethers as macromonomers, the molecular weight of resulting polythiolether is up to 7700 g mol^?1 with PDI as 1.67. The reactivity of the terminal thiol group is further confirmed by the addition reaction with N‐(1‐pyrenyl)maleimide. UV‐vis spectra and fluorescene measurements suggest that fac‐Ir(ppy)₃ undergo a redox quenching process reacted with BDMT to generate thiyl free radicals. With these results, the mechanism of the thiol‐ene reaction catalyzed by photoredox catalyst is proposed. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 740–749     

Stereoselective Synthesis of 8‐Oxabicyclo[3.2.1]octane‐2,3,4,6,7‐pentols and Total Asymmetric Synthesis of 2,6‐Anhydrohepturonic Acid Derivatives and of β‐C‐manno‐Pyranosides Suitable for the Construction of (1→3)‐C,C‐Linked Trisaccharides

Enantiomerically pure (+)‐(1S,4S,5S,6S)‐6‐endo‐(benzyloxy)‐5‐exo‐{[(tert‐butyl)dimethylsilyl]oxy}‐7‐oxabicyclo[2.2.1]heptan‐2‐one ((+)‐ 5 ) and its enantiomer (−)‐ 5 , obtained readily from the Diels‐Alder addition of furan to 1‐cyanovinyl acetate, can be converted with high stereoselectivity into 8‐oxabicyclo[3.2.1]octane‐2,3,4,6,7‐pentol derivatives (see 23 – 28 in Scheme 2). A precursor of them, (1R,2S,4R,5S,6S,7R,8R)‐7‐endo‐(benzyloxy)‐8‐exo‐hydroxy‐3,9‐dioxatricyclo[4.2.1.0^2,4]non‐5‐endo‐yl benzoate ((−)‐ 19 ), is transformed into (1R,2R,5S, 6S,7R,8S)‐6‐exo,8‐endo‐bis(acetyloxy)‐2‐endo‐(benzyloxy)‐4‐oxo‐3,9‐dioxabicyclo[3.3.1]non‐7‐endo‐yl benzoate ((−)‐ 43 ) (see Scheme 5). The latter is the precursor of several protected 2,6‐anhydrohepturonic acid derivatives such as the diethyl dithioacetal (−)‐ 57 of methyl 3,5‐di‐O‐acetyl‐2,6‐anhydro‐4‐O‐benzoyl‐D ‐glycero‐D ‐galacto‐hepturonate (see Schemes 7 and 8). Hydrolysis of (−)‐ 57 provides methyl 3,5‐di‐O‐acetyl‐2,6‐anhydro‐4‐O‐benzoyl‐D ‐glycero‐D ‐galacto‐hepturonate 48 that undergoes highly diastereoselective Nozaki‐Oshima condensation with the aluminium enolate resulting from the conjugate addition of Me₂AlSPh to (1S,5S,6S,7S)‐7‐endo‐(benzyloxy)‐6‐exo‐{[(tert‐butyl)dimethylsilyl]oxy}‐8‐oxabicyclo[3.2.1]oct‐3‐en‐2‐one ((−)‐ 13 ) derived from (+)‐ 5 (Scheme 12). This generates a β‐C‐mannopyranoside, i.e., methyl (7S)‐3,5‐di‐O‐acetyl‐2,6‐anhydro‐4‐O‐benzoyl‐7‐C‐[(1R,2S,3R,4S,5R,6S,7R)‐6‐endo‐(benzyloxy)‐7‐exo‐{[(tert‐butyl)dimethylsilyl]oxy}‐4‐endo‐hydroxy‐2‐exo‐(phenylthio)‐8‐oxabicyclo[3.2.1]oct‐3‐endo‐yl]‐L ‐glycero‐D ‐manno‐heptonate ((−)‐ 70 ; see Scheme 12), that is converted into the diethyl dithioacetal (−)‐ 75 of methyl 3‐O‐acetyl‐2,6‐anhydro‐4,5‐dideoxy‐4‐C‐{[methyl (7S)‐3,5,7‐tri‐O‐acetyl‐2,6‐anhydro‐4‐O‐benzoyl‐L ‐glycero‐D ‐manno‐heptonate]‐7‐C‐yl}‐5‐C‐(phenylsulfonyl)‐L ‐glycero‐D ‐galacto‐hepturonate ( 76 ; see Scheme 13). Repeating the Nozaki‐Oshima condensation to enone (−)‐ 13 and the aldehyde resulting from hydrolysis of (−)‐ 75 , a (1→3)‐C,C‐linked trisaccharide precursor (−)‐ 77 is obtained.     

Retroracemization using new forms of Belokon's original ligand: ­intermediate NiII complexes of N‐({2‐[N‐(S)‐alkylprolylamino]phenyl}phenylmethylene)‐(S)‐phenylalanine (alkyl is 2‐picolyl, 3‐picolyl or ethyl)

In the title compounds, [N‐(phenyl{2‐[N‐(S)‐(2‐picolyl)­prolyl­amino]­phenyl}methyl­ene)‐(S)‐phenyl­alaninato]­nickel(II), [Ni(C₃₃H₃₀N₄O₃)], (I), [N‐(phenyl{2‐[N‐(S)‐(3‐picolyl)­prolyl­amino]­phenyl}methyl­ene)‐(S)‐phenyl­alaninato]­nickel(II) hemihydrate, [Ni(C₃₃H₃₀N₄O₃)]·0.5H₂O, (II), and [N‐({2‐[N‐(S)‐ethyl­prolyl­amino]­phenyl}phenyl­methyl­ene)‐(S)‐phenyl­ala­nin­ato]­nickel(II), [Ni(C₂₉H₂₉N₃O₃)], (III), the Ni^II centres have approximate square‐planar coordination geometries from N₃O donor sets. The picolyl N atoms in (I) and (II) are too remote from the metal centres to interact significantly, but the metal coordination geometries experience tetrahedral distortion and/or displacement of the metal centre from the N₃O plane. These are linked to conformational differences between the ligands of the symmetry‐independent complexes (Z′ = 2), which in turn are related to molecular packing. In (III), where a less sterically demanding ethyl group replaces the picolyl substituents, there are none of the distortions or displacements seen in (I) and (II).     

Pericyclic Transformations at the Periphery of Chromen‐4‐one (=4H‐1‐Benzopyran‐4‐one): An Unusual Preference for a 1,5‐Shift of Allylic Moieties over the Ene Reaction

Quite unlike the reported facile ene reactions on the periphery of many related heterocyclic systems, similarly disposed moieties on the periphery of the chromen‐4‐one (=4H‐1‐benzopyran‐4‐one) system fail to undergo an ene reaction and display a rather unusual preference for an overall [1,5] shift of the allylic C‐atom. Thus, heating xylene solutions of 2‐(N‐allylanilino)‐, 2‐(N‐crotylanilino)‐, and 2‐(N‐cinnamylamino)‐substituted (E)‐(oxochromenyl)propenoates 9a – c and 2‐[allyl(benzyl)amino]‐, 2‐[benzyl(crotyl)amino]‐, and 2‐[benzyl(cinnamyl)amino]‐substituted (E)‐(oxochromenyl)propenoates 16a – c in a sealed tube at 220–230° leads to a [1,5] shift of the allylic moieties (allyl, crotyl, cinnamyl), which is followed by intramolecular cyclization involving the N‐atom and the ester function, to give the 3‐allyl‐3‐crotyl‐, and 3‐cinnamyl‐substituted‐1‐phenyl‐ or 1‐benzyl‐2H‐[1]benzopyrano[2,3‐b]pyridine‐2,5(1H)‐diones 10a – c and 17a – c . The anticipated carbonyl–ene reaction in the 2‐(N‐allylanilino)‐, 2‐(N‐crotylanilino)‐, 2‐(N‐cinnamylanilino)‐, 2‐[allyl(benzyl)amino]‐, 2‐[benzyl(crotyl)amino]‐, and 2‐[benzyl(cinnamyl)amino]‐substituted 4‐oxochromene‐3‐carboxaldehydes 8a – c and 15a – c is also not observed, and these molecules remain untransformed under identical conditions. No [1,5] shifts of benzyl, phenyl, or methyl groups are observed, even in the absence of allylic moieties, though facile [1,5]‐H shift occurs in 2‐(benzylamino)‐ and 2‐(phenylamino)‐substituted (E)‐(oxochromenyl)propenoates 23a , b , which is followed by a similar intramolecular cyclization leading to the 2H‐[1]benzopyrano[2,3‐b]pyridine‐2,5(1H)‐diones 24a , b .     

1:1 Adduct of (S,S)‐4‐amino‐3,5‐bis­(1‐hydroxy­ethyl)‐1,2,4‐triazole with (S,S)‐1,2‐bis­(2‐hydroxy­propionyl)­hydrazine stabilized by eight hydrogen bonds

The structure of the cocrystallized 1:1 adduct of (S,S)‐4‐amino‐3,5‐bis­(1‐hydroxy­ethyl)‐1,2,4‐triazole and (S,S)‐1,2‐bis­(2‐hydroxy­propionyl)­hydrazine, C₆H₁₂N₄O₂·C₆H₁₂N₂O₄, has tetra­gonal symmetry. All eight O‐ and N‐bound H atoms are involved in inter­molecular hydrogen bonds, resulting in infinite zigzag chains of the triazole mol­ecules, with the hydrazine mol­ecules filling the gaps between the chains and completing a three‐dimensional hydrogen‐bonded array.     

Direct Umpolung of Glycals and Related 2,3‐Unsaturated N‐Acetylneuraminic Acid Derivatives Using Samarium Diiodide

The umpolung of glycals with samarium diiodide offers a simple route to novel carbohydrate‐derived nucleophilic reagents in a single step using a readily available reductant. The corresponding allyl samarium reagent that arises from the hexose series reacts with ketones at the C3 position with high stereoselectivity; carbon–carbon bond formation takes place only anti to the substituent at the C4 position of the dihydropyran ring. For the sialic acid series, the completely regio‐ and stereoselective coupling process of the samarium reagent occurs at the anomeric carbon atom and provides a new approach to the α‐C‐glycosides of N‐acetyl neuraminic acid.