Synthesis of bicyclo[3.1.0]hexanones via 1,3-dipolar cycloaddition of diazoalkanes to homochiral α-sulfinyl-2-cyclopentenones

The reactions of diazomethane, diazoethane, and (trimethylsilyl)diazomethane with (S)-2-p-tolylsulfinylcyclopent-2-en-1-one have been studied. The sulfinyl group increases the reactivity and controls the π-facial and endo/exo selectivities. The π-facial selectivity can be inverted in the presence of Yb(OTf)₃, which makes possible the stereodivergent synthesis of both diastereoisomeric pyrazolines. Completely stereoselective denitrogenation of optically pure pyrazolines into cyclopropanes was achieved under substoichiometric Yb(OTf)₃ catalysis.     

The Mechanism of Copper-Catalyzed Trifunctionalization of Terminal Allenes

A highly selective copper-catalyzed trifunctionalization of allenes has been established based on diborylation/cyanation with bis(pinacolato)diboron (B₂pin₂) and N-cyano-N-phenyl-p-toluenesulfonamide (NCTS). The Cu-catalyzed trifunctionalization of terminal allenes is composed of three catalytic reactions (first borocupration, electrophilic cyanation, and second borocupration) that provide a densely functionalized product with regio-, chemo- and diastereoselectivity. Allene substrates have multiple reaction-sites, and the selectivities are determined by the suitable interactions (e.g., electronic and steric demands) between the catalyst and substrates. We employed DFT calculations to understand the cascade copper-catalyzed trifunctionalization of terminal allenes, providing densely-functionalized organic molecules with outstanding regio-, chemo- and diastereoselectivity in high yields. The selectivity challenges presented by cumulated π-systems are addressed by systematic computational studies; these give insight to the catalytic multiple-functionalization strategies and explain the high selectivities that we see for these reactions.     

SN2’ versus SN2 Reactivity: Control of Regioselectivity in Conversions of Baylis–Hillman Adducts

TiCl₄‐induced Baylis–Hillman reactions of α,β‐unsaturated carbonyl compounds with aldehydes yield the (Z)‐2‐(chloromethyl)vinyl carbonyl compounds 5 , which react with 1,4‐diazabicyclo[2.2.2]octane (DABCO), quinuclidine, and pyridines to give the allylammonium ions 6 . Their combination with less than one equivalent of the potassium salts of stabilized carbanions (e.g. malonate) yields methylene derivatives 8 under kinetically controlled conditions (S_N2’ reactions). When more than one equivalent of the carbanions is used, a second S_N2’ reaction converts 8 into their thermodynamically more stable allyl isomers 9 . The second‐order rate constants for the reactions of 6 with carbanions have been determined photometrically in DMSO. With these rate constants and the previously reported nucleophile‐specific parameters N and s for the stabilized carbanions, the correlation log k (20 °C)=s(N + E) allowed us to calculate the electrophilicity parameters E for the allylammonium ions 6 (?19<E <?18). The kinetic data indicate the S_N2’ reactions to proceed via an addition–elimination mechanism with a rate‐determining addition step.     

Reaction of transition metal carbonyls with heterocyclic systems—III: SN2′-type reaction of complexed π-allyl systems

A proposition regarding the capability of a complex π-allyl system to undergo a displacement reaction was advanced (eqn 2) and examined experimentally. A unique structural feature of this system is the four rather than three C atoms which intervene between the displaced and entering groups. The experiment was carried out using lactone 1c which is internally complexed and was properly labelled with deuterium. The product of its reaction with aniline has been found to be rearranged with respect to the D label, thus substantiating an S_N2′-type mechanism in a complexed π-allyl system (eqn 2). From an intramolecular comparison study of the reactivity of an allyl and complexed π-allyl system in S_N2′-type displacement reactions using compound 10, it was concluded that the latter is more reactive than the former. Furthermore, the π-allyl lactone 12, in which the displaced and entering groups are separated by three C atoms, was also found to undergo a displacement reaction.     

Azo‐Coupling Reactions of Para‐X‐Benzenediazonium Cations with 3‐Ethoxythiophene in Acetonitrile

Kinetic studies for the azo‐coupling reactions of 3‐ethoxythiophene 1 with a series of 4‐X‐substituted diazonium cations 2a‐e (X = OCH₃, CH₃, H, Cl, and NO₂) have been investigated in acetonitrile at 20°C. The second‐order rate constants have been employed to determine the nucleophilicity parameters N and s of the thiophene 1 according the Mayr equation. Thus, the nucleophile‐specific parameters N and s of thiophene 1 have been derived and compared with the reactivities of other C‐nucleophiles in acetonitrile (pyrroles, furan, indoles, etc.). The Yukawa–Tsuno plot resulted in an excellent correlation (R² = 0.9980) with an r value of 0.89, suggesting that the nonlinear Hammett plot observed in the present work is due to resonance demand of the π–electron donor substituent of on the –N₂⁺ moiety. Importantly, using the concept of global electrophilicity (ω) proposed by Parr, we successfully predict the electrophilicity parameters E of seven substituted diazonium cations whose experimental data are available.     

Dinuclear Pd(II) and Pt(II) compounds bearing a bridging π-conjugated moiety: synthesis and reactivity toward alkynes and isocyanides

Abstract

Dinuclear Pd(II) halides that contain bridging π-conjugated groups, trans,trans-[(PR₃)₂(X)Pd–Y–Pd(X)(PR₃)₂] (X?=?Br; YH₂ = terpyridine, fluorenone, benzil, benzthiadiazole), were prepared by the oxidative addition of corresponding dihalo π-conjugated reagents to [Pd(styrene)(PR₃)₂]. Similar reactions involving dihalobenzil, dihalobithiophene, or dihaloterthiophene afforded dinuclear Pt(II) halides containing bridging π-conjugated groups. Additionally, when the dihalosilole derivatives {2,5-dibromo-1,1-dimethyl (or diphenyl)-3,4-diphenylsilole} reacted with [Pd(styrene)(PR₃)₂], mono or dinuclear Pd(II) complexes bearing a dimethyl (or diphenyl)-3,4-diphenylsilole group were obtained. π-Conjugation extension reactions of dinuclear bithiophene-bridged Pd(II) halides with HC≡C–R {R?=?SiPh₃, C(O)OMe} in the presence of CuI and HNEt₂ led to the unexpected formation of bis(acetylide) Pd(II) complexes of the form, [Pd(C≡C–R)₂(PR₃)₂] and bithiophene. In contrast, treatment of the dinuclear Pd(II) halides with two equiv of organic isocyanide resulted in isocyanide insertion into the Pd???C bonds to afford π-conjugation-extended dinuclear Pd(II) compounds bearing a π-conjugated moiety.     

Nucleophilic substitution at the pyridine ring. Kinetics of the reaction of 2-chloro-3,5-dinitropyridine with arylthiolates in methanol

The reaction rates of 2-chloro-3,5-dinitropyridine 1 with a series of arylthiolates 2a-h in methanol have been measured at 25°C. The products are the corresponding 2-thioaryl-3,5-dinitropyridine 3a-h. Good Hammett correlation with ρ value −1.19 was obtained suggesting an elimination-addition mechanism S_NAr and the formation of Meisenheimer-like intermediates. Plot of log k₂ vs. pK_a values of arylthiols gave straight line with β=0.38 indicating that the π-bond breaking in the pyridine ring is so much advanced over bond making between the nucleophile and the carbon that bears the chlorine atom. Excellent correlation between log k₂ and log K (carbon basicity of arylthiolates) was obtained. © 1997 John Wiley & Sons. Inc. Int J Chem Kinet 29: 515–521, 1997.     

Transition-Metal-Free Coupling of Polyfluorinated Arenes and Functionalized,Masked Aryl Nucleophiles

A chemoselective C(sp²)−C(sp²) coupling of sufficiently electron-deficient fluorinated arenes and functionalized N-aryl-N’-silyldiazenes as masked aryl nucleophiles is reported. The fluoride-promoted transformation involves the in situ generation of the aryl nucleophile decorated with various sensitive functional groups followed by a stepwise nucleophilic aromatic substitution (S_NAr). These reactions typically proceed at room temperature within minutes. This catalytic process allows for the functionalization of both coupling partners, furnishing highly fluorinated biaryls in good yields.     

Enantioselectivity and cis/trans-Selectivity in Dirhodium(II)-Catalyzed addition of diazoacetates to olefins

The Rh¹¹-catalyzed carbenoid addition of diazoacetates to olefins was investigated with [Rh₂{(4S)-phox}₄] ( 1 ;phox = tetrakis[(4S)-tetrahydro-4-phenyloxazol-2-one]), [Rh₂{(2S)-mepy}₄] ( 2 ; mepy = tetrakis[methyl (2S)-tetrahydro-5-oxopyrrole-2-carboxylate]), and [Rh₂(OAc)₄] ( 3 ). While catalysis with 2 and 3 afford preferentially trans-cyclopropanecarboxylates, the cis-isomers are the major products with 1 . In general, the enantioselectivities achieved with 1 and 2 are comparable. Additions catalyzed by 1 are strongly sensitive to steric effects. Highly substituted olefins afford cyclopropanes in only poor yield. The preferential cis-selectivity observed in reactions catalyzed by 1 is attributed to dominant interactions between the ligand of the catalyst and the substituents of both olefin and diazoacetate, which overrule the steric interactions between olefin and diazoacetate in the transition state for carbene transfer.     

Kinetics and mechanism of mercuration of N-(substituted benzylidene)-4-toluidines

In order to investigate the mechanism of mercuration reaction of substituted ben-zylideneanilines, kinetic measurements of these reactions at different temperatures (40-60℃) inmethanol-l,4-dioxane (1/1, V/V) were carried out and Hammett ρ value for C-phenyl substituentsof-0.61 for the N-(substituted benzylidene)-4-toluidine series was obtained. Thermodynamicparameters E_a, △S~≠ were obtained for the reaction of different. N-(substituted benzylidene)-4-toluidines. It was found that this ortho-mercuration was brought about by an internal cyclometal-lation process involving the imino-moiety.     

Amination by nucleophilic substitution and addition in solution: Substituents effect on changes in activation parameters

Changes in the activation parameters of amination along mechanisms S _N 2, S _N Ar, Ad _N and in reactions with acyl group transfer may serve as an additional investigation method for these reactions in solution. The approximation utilizes the substituents effect in benzene and pyridine derivatives on the changes in the activation parameters ΔX ^≠ (X = H, S, G) in the framework of equations of Hammett’s type for the estimation of the resulting reaction constants δΔX ^≠. The single linear dependences of the reaction constants of internal enthalpy δΔH _int ^≠ on the reaction constants δΔG ^≠ and Hammett’s ρ show that the substituents effect in the leaving and non-leaving groups and in the nucleophiles on the amination mechanisms is governed by the δΔH _int ^≠ , when unique stage of the process determines its rate.     

New Optically Active Bis‐Heterocycles Derived from (S)‐Proline

Enantiomerically pure bis‐heterocycles containing a (S)‐proline moiety have been prepared starting from (S)‐N‐benzylprolinehydrazide ( 2b ). The reactions with isothiocyanates or butyl isocyanate in refluxing MeOH led to the corresponding thiosemicarbazide 5 and semicarbazide 9 with a N‐benzylprolinoyl residue. The structure of the tert‐butyl derivative 5d was established by X‐ray crystallography. Base‐catalyzed cyclization of 5 and 9 led to (S)‐3‐(pyrrolidin‐2‐yl)‐1H‐1,2,4‐triazole‐5(4H)‐thiones 6 and the corresponding 5(4H)‐one 8 , respectively, whereas, in concentrated H₂SO₄, compounds 5 undergo cyclization to give (S)‐5‐amino‐2‐(pyrrolidin‐2‐yl)‐1,3,4‐thiadiazoles 7 . Furthermore, 2b reacted with hexane‐2,5‐dione in boiling ⁱPrOH to yield the (S)‐N‐(2,5‐dimethylpyrrol‐1‐yl)prolinamide 10 . In the case of the bis‐heterocycle 8 , treatment with HCOONH₄ and Pd/C in MeOH gave the debenzylated product 12 .     

Kinetic Studies of Donor–Acceptor Cyclopropanes: The Influence of Structural and Electronic Properties on the Reactivity

The kinetics of (3+2) cycloaddition reactions of 18 different donor–acceptor cyclopropanes with the same aldehyde were studied by in situ NMR spectroscopy. Increasing the electron density of the donor residue accelerates the reaction by a factor of up to 50 compared to the standard system (donor group=phenyl), whereas electron‐withdrawing substituents slow down the reaction by a factor up to 660. This behavior is in agreement with the Hammett substituent parameter σ. The obtained rate constants from the (3+2) cycloadditions correlate well with data from additionally studied (3+n) cycloadditions with a nitrone (n=3) and an isobenzofuran (n=4). A comparison of the kinetic data with the bond lengths in the cyclopropane (obtained by X‐ray diffraction and computation), or the ¹H and ¹³C NMR shifts, revealed no correlation. However, the computed relaxed force constants of donor–acceptor cyclopropanes proved to be a good indicator for the reactivity of the three‐membered ring.     

Computational Analysis of Mesomerism in para-Substituted mer-NCN Pincer Platinum(II) Complexes,Including its Relationships with Hammett σp Substituent Parameters

Density Functional Theory studies of square-planar Pt^II pincer structures, (4-Z-NCN)PtCl ([4-Z-NCN]⁻=[4-Z-2,6-(Me₂NCH₂)₂C₆H₂-N,C,N]⁻, Z=H, NO₂, CF₃, CO₂H, CHO, Cl, Br, I, F, SMe, SiMe₃, tBu, OH, NH₂, NMe₂), enable characterisation of mesomerism for the pincer-Pt interaction. Relationships between Hammett σ_p substituent parameters of Z and DFT data obtained from NBO6 and AOMix computation are used to probe the interaction of the 5d_yz orbital of platinum with π-orbitals of the arene ring. Analogous computation for 2,6-(Me₂CH₂)₂C₆H₃Z (Z=H, CF₃, CHO, Cl, Br, I, F, SMe, SiMe₃, tBu, OH, NH₂) and (4-H-NCN)PtZ allows an estimation of the relative substituent effects of “(CH₂NMe₂)₂PtZ” on π-delocalisation in the pincer system.     

Functionalization of Piperidine Derivatives for the Site-Selective and Stereoselective Synthesis of Positional Analogues of Methylphenidate

Rhodium-catalyzed C−H insertions and cyclopropanations of donor/acceptor carbenes have been used for the synthesis of positional analogues of methylphenidate. The site selectivity is controlled by the catalyst and the amine protecting group. C−H functionalization of N-Boc-piperidine using Rh₂(R-TCPTAD)₄, or N-brosyl-piperidine using Rh₂(R-TPPTTL)₄ generated 2-substitited analogues. In contrast, when N-α-oxoarylacetyl-piperidines were used in combination with Rh₂(S-2-Cl-5-BrTPCP)₄, the C−H functionalization produced 4-susbstiuted analogues. Finally, the 3-substituted analogues were prepared indirectly by cyclopropanation of N-Boc-tetrahydropyridine followed by reductive regio- and stereoselective ring-opening of the cyclopropanes.     

Nonlinear Brønsted and Hammett Correlations Associated with Reactions of 4‐Chloro‐7‐nitrobenzofurazan with Anilines in Dimethyl Sulfoxide Solution

The kinetics and mechanism of nucleophilic aromatic substitution reactions of 4‐chloro‐7‐nitrobenzofurazan 1 with 4‐X‐substituted anilines 2a–g (X = OH, OCH₃, CH₃, H, I, Cl, and CN) are investigated in a dimethyl sulfoxide (Me₂SO) solution at 25°C. The Hammett plot of log k₁ versus σ is nonlinear for all the anilines studied due to positive deviations of the electron‐donating substituents. However, the corresponding Yukawa–Tsuno plot resulted in a good linear correlation with σ+r (σ⁺?σ). The corresponding Brønsted‐type plot is also nonlinear, i.e., the slope (β_nuc) changes from 1.60 to 0.56 as the basicity of anilines decreases. These results indicate a change in a mechanism from a polar S_NAr process for less basic nucleophiles (X = I, Cl, and CN) to a single electron transfer for more basic nucleophiles (X = OH, OCH₃, and CH₃). The satisfactory log k₁ versus E^o correlation obtained for the reactions of 1 with anilines 2a–d in the present system is consistent with the proposed mechanism. Interestingly, the β_nuc = 1.60 value measured for 1 in Me₂SO reflects one of the highest coefficients Brønsted ever observed for S_NAr reactions. © 2013 Wiley Periodicals, Inc. Int J Chem Kinet 45: 152–160, 2013     

Bis(4‐nitro­phenyl) di­sulfide at 150 K,a three‐dimensional framework built from C—H⋯O hydrogen bonds and aromatic π⋯π stacking interactions

In the title compound, (4‐O₂NC₆H₄)₂S₂ or C₁₂H₈N₂O₄S₂, the mol­ecules lie across twofold rotation axes. A single type of C—H?O hydrogen bond, with C?O = 3.394 (3) Å and C—H?O = 158°, links the mol­ecules into continuous two‐dimensional sheets built from a single type of R⁴₄(44) ring. These sheets are linked by aromatic π?π stacking interactions to form a continuous three‐dimensional framework.     

Fe or FeNO Catalysis? A Quantum Chemical Investigation of the [Fe(CO)3(NO)]−‐Catalyzed Cloke–Wilson Rearrangement

A quantum chemical investigation of the Bu₄N[Fe(CO)₃(NO)]‐catalyzed Cloke–Wilson rearrangement of vinyl cyclopropanes is reported. It was found that allylic C?C bond activation can proceed through a S_N2′ or S_N2‐type mechanism. The application of the recently reported intrinsic bond orbital (IBO) method for all structures indicated that one Fe?N π bond is directly involved. Further analysis showed that during the reaction oxidation occurs at the NO ligand exclusively.     

The α‐effect exhibited in gas‐phase SN2@N and SN2@C reactions

In order to explore the existence of α‐effect in gas‐phase S_N2@N reactions, and to compare its similarity and difference with its counterpart in S_N2@C reactions, we have carried out a theoretical study on the reactivity of six α‐oxy‐Nus (FO^?, ClO^?, BrO^?, HOO^?, HSO^?, H₂NO^?) in the S_N2 reactions toward NR₂Cl (R = H, Me) and RCl (R = Me, i‐Pr) using the G2(+)_M theory. An enhanced reactivity induced by the α‐atom is found in all examined systems. The magnitude of the α‐effect in the reactions of NR₂Cl (R = H, Me) is generally smaller than that in the corresponding S_N2 reaction, but their variation trend with the identity of α‐atom is very similar. The origin of the α‐effect of the S_N2@N reactions is discussed in terms of activation strain analysis and thermodynamic analysis, indicating that the α‐effect in the S_N2@N reactions largely arises from transition state stabilization, and the “hyper‐reactivity” of these α‐Nus is also accompanied by an enhanced thermodynamic stability of products from the n_(N) → σ*_(O?Y) negative hyperconjugation. Meanwhile, it is found that the reactivity of oxy‐Nus in the S_N2 reactions toward NMe₂Cl is lower than toward i‐PrCl, which is different from previous experiments, that is, the S_N2 reactions of NH₂Cl is more facile than MeCl. © 2013 Wiley Periodicals, Inc.     

Supramolecular structures of bis‐thionooxalamic acid esters derived from (±)‐cyclohexane‐1,2‐diamine and (±)‐1,2‐diphenylethylenediamine

The bis‐thionooxalamic acid esters trans‐(±)‐diethyl N,N′‐(cyclohexane‐1,2‐diyl)bis(2‐thiooxamate), C₁₄H₂₂N₂O₄S₂, and (±)‐N,N′‐diethyl (1,2‐diphenylethane‐1,2‐diyl)bis(2‐thiooxamate), C₂₂H₂₄N₂O₄S₂, both consist of conformationally flexible molecules which adopt similar conformations with approximate C₂ rotational symmetry. The thioamide and ester parts of the thiooxamate group are significantly twisted along the central C—C bond, with the S=C—C=O torsion angles in the range 30.94 (19)–44.77 (19)°. The twisted s‐cis conformation of the thionooxamide groups facilitates assembly of molecules into a one‐dimensional polymeric structure via intermolecular three‐center C=S...NH...O=C hydrogen bonds and C—H...O interactions formed between molecules of the opposite chirality.