Endo-exo and facial stereoselectivity in the Diels-Alder reactions of 3-substituted cyclopropenes with butadiene

A computational examination of the four modes of addition in the Diels-Alder reactions of 3-substituted cyclopropene derivatives (substituents: BH(2), CH(3), SiH(3), NH(2), PH(2), OH, SH, F, and Cl) with butadiene have been carried out at the B3LYP/6-31++G(d)//HF/6-31++G(d) level. The degree of stabilization of these derivatives at the ground state correlates with the electronegativity of the substituent. This attenuation of reactivity and differences in steric interactions are the only factors needed to explain both the high facial selectivity and the differences in the endo-exo selectivity seen in these reactions. Furthermore, evidence is presented that indicates that stabilization by an interaction involving the syn C-3 hydrogen of cyclopropene and butadiene is small or irrelevant in controlling the endo-exo selectivity of the Diels-Alder reaction.     

Reactivity and stereoselectivity of the Diels-Alder reaction using cyclic dienophiles and siloxyaminobutadienes

Several bicyclic compounds were synthesized by the Diels-Alder reaction using aminodiene and a cyclic dienophile. The stereochemistries of the obtained adducts were determined by X-ray crystallography or NMR analysis. The stereoselectivity of this Diels-Alder reaction was based on the interaction of molecular orbitals between the diene and dienophile. The reactivities of these Diels-Alder reactions were estimated, and the generality of this reaction is discussed.     

Investigations of the stereoselectivity of the intramolecular Diels-Alder reaction of a spiculoic acid model system

Model linear precursors to the spiculoic acids were prepared and underwent thermally induced IMDA reactions. The configuration of C5 in the stereotriad was found to dominate any inherent endo/exo selectivity of the IMDA reaction. The isomer (2E,5S)-20 underwent the IMDA to give the spiculoic acid stereochemistry in 84% yield and 94% ds. The required stereotriads were synthesised using stereoselective substrate-controlled aldol reactions; an anti-boron aldol reaction, controlled by the π-facial preference of (S)-2-benzoyloxypentan-3-one ((S)-27) led to (5R)-(22) and a syn-titanium aldol reaction, under the stereocontrol of a chiral N-acylthiazolidinethione (42) led to (5S)-(22). Chain extension using standard Wittig, HWE and ‘modified’ Julia olefinations installed the diene and dienophile components giving the linear precursors to the IMDA reactions.     

Recyclable supported catalysts in microwave-assisted reactions: first Diels-Alder cycloaddition of a triazole ring

We describe here the first example in which a 1,2,3-triazole ring acts as a diene towards DMAD in microwave-assisted solvent-free Diels-Alder cycloadditions. The extrusion of a molecule of a nitrile affords pyrazole derivatives as the products. The yields can be markedly increased by using a recyclable supported Lewis acid catalyst, which can be reused at least five times without a decrease in the yield.     

Dihydrobenzopyran skeleton from β-lactams: a stereoselective ring opening–ring closure reaction sequence

Sodium borohydride treatment of the enantiomerically pure tricarbonyl(η⁶-arene) chromium(0) complexed β-lactam 7 promoted a stereoselective ring opening–ring closure reaction sequence leading to the novel dihydrobenzopyran derivative 9 in good yield.     

Diels-Alder reaction of sugar-derived cyclic dienophiles with cyclopentadiene. Factors affecting the reactivity and stereoselectivity

[formula: see text] A sugar-derived cyclic dienophile showed a high exo and face selectivity in the Diels-Alder reaction with cyclopentadiene. Structural modifications on the dienophile structure were made, and the outcomes of the cycloaddition reactions were investigated. These results and the spectroscopic data recorded within a series of analogues were used to analyze the factors affecting the reactivity and exo selectivity.     

Macrocyclic lactam synthesis via a ring expansion reaction: construction of the cripowellin skeleton

[reaction: see text] The cripowellin ring skeleton, a macrocyclic [2.3.5]-bicyclic ketolactam, was smoothly generated via construction of a spiro(benzazepin-cyclohexane-1,3-dione) employing oxidative cyclization as a key step and a subsequent ring expansion reaction.     

Complete facial selectivity in the Diels-Alder reaction of a 5-amino-5-carboxycyclopentadiene derivative

5-tert-Butoxycarbonylamino-5-carbethoxy-2-tert-butyldimethylsilyloxy-cyclopentadiene undergoes a Diels-Alder reaction exclusively from the face syn to the nitrogen functionality. Complete reversal of facial bias may be achieved, but at the cost of diminished reactivity, through steric shielding of the N-syn face.     

Novel ring transfer reaction of furans via intramolecular Diels-Alder reaction of allene intermediate: a new double annulation reaction

A novel ring tansfer reaction of furans to fused furans by tandem intramolecular Diels-Alder reaction and base-catalyzed ring-opening of the adducts has been developed.     

A computational study of the Diels-Alder reaction of ethyl-S-lactyl acrylate and cyclopentadiene. Origins of stereoselectivity

The eight diastereoisomeric transition structures of the Diels-Alder addition of ethyl-S-lactyl acrylate and cyclopentadiene have been investigated in the gas phase and in solution by HF, MP2, and density functional theory (B3LYP and B3PW91) methods with the 6-31G(d,p) basis set. At all levels of theory used, the s-cis transition structures are more stable than the s-trans ones. The contribution of the s-trans transition structures increases in solution and, although still small, has to be taken in consideration for correct prediction of stereoselectivity. Diastereofacial selectivity is interpreted in terms of electrostatic (weak hydrogen bonding) C=O...H(C) interactions between the carbonyl group(s) of the dienophile and cyclopentadiene in the energetically favored transition structures. Endo/exo reaction selectivity is attributed to positive orbital interactions between the diene and the acrylate carbonyl oxygen in the endo s-cis transition structures. Ab initio methods reproduce well the experimentally observed trends in both endo/exo and diastereofacial selectivity. Density functional calculations in the gas phase correctly reproduce the observed trends in diastereofacial selectivity but single-point MP2 calculations are necessary to reproduce the experimental trend in endo/exo selectivity.     

Additivity of ring distortions in halogen-substituted aromatics: a gas-phase electron diffraction and computational study

The gas-phase structures of 1,2,3-trifluorobenzene, 1,3,5-trifluorobenzene, 2,6-difluoropyridine, and 2,6-dichloropyridine have been determined using electron diffraction and computational methods. The accuracy afforded by modern experimental methods has allowed subtle trends to be identified in the geometrical parameters of the rings. Comparisons have also been made between experimental and theoretical structures. Although the effects of multiple fluorine substituents on a benzene ring are shown to be more or less additive, distortions caused by replacement of a ring carbon atom by nitrogen and by halogen substituents are not.     

The clerodane ring system: investigating the viability of a direct Diels-Alder approach

A direct synthetic approach to the spiro-γ-lactone clerodane ring system has been investigated. This work builds on that of Jung and highlights the inherent difficulties associated with the otherwise obvious Diels-Alder approach.     

CC Triple-bond stabilization in three-membered ring compounds: Boriryne,dilithiumcyclopropyne and berylliryne

Ab initio calculations have been performed on the title compounds. At 3-21G, boriryne is not a minimum on the potential energy hypersurface. The 3-21G optimized minimum of dilithiumcyclopropyne corresponds to dilithiumcyclopropenylidene with a planar tetracoordinated carbon atom and CC bond lengths intermediate between single and double bonds. Berylliryne is calculated to be a stable molecule, being the global minimum at the C₂ Be energy hypersurface at MP2/6-31G*//6-31G* with a CC bond length of 1.258 Å.     

Experimental determination of the absolute enantioselectivity of an antibody-catalyzed Diels-Alder reaction and theoretical explorations of the origins of stereoselectivity

The exo and endo Diels-Alder adducts of p-methoxycarbonylbenzyl trans-1,3-butadiene-1-carbamate and N,N-dimethylacrylamide have been synthesized, and the absolute configurations of resolved enantiomers have been determined. On the basis of this information, the absolute enantioselectivities of the Diels-Alder reaction catalyzed by antibodies 13G5 and 4D5 as well as other catalytic antibodies elicited in the same immunizations have been established. The effects of different arrangements of catalytic residues on the structure and energetics of the possible Diels-Alder transition states were modeled quantum mechanically at the B3LYP/6-311++G**//B3LYP/6-31+G** level of theory. Flexible docking of these enantiomeric transition states in the antibody active site followed by molecular dynamics on the resulting complexes provided a prediction of the transition-state binding modes and an explanation of the origin of the observed enantioselectivity of antibody 13G5.     

Type 2 intramolecular N-acylnitroso Diels-Alder reaction: scope and application to the synthesis of medium ring lactams

Heteroatom variants of the type 2 intramolecular Diels-Alder reaction provide an efficient method for the preparation of bridged bicyclic heterocycles. The type 2 variant of the intramolecular N-acylnitroso Diels-Alder reaction is an effective method for the synthesis of bridged bicyclic oxazinolactams. Structural studies of the cycloadducts have allowed for quantification of the deformations of the bridgehead functionalities and provided a strategy for the stereoselective synthesis of substituted seven- and eight-membered ring lactams. Diastereoselective cycloadditions followed by cleavage of the oxazine ring afford azepin-2-ones or azocin-2-ones.     

Theoretical investigation on the GaCl3-catalyzed ring-closing metathesis reaction of N-2,3-butadienyl-2-propynyl-1-amine: three-membered ring versus four-membered ring mechanism

The gallium chloride (GaCl(3))-catalyzed ring-closing metathesis reaction mechanism of N-2,3-butadienyl-2-propynyl-1-amine has been studied at the Becke three-parameter hybrid functional combined with Lee-Yang-Parr correlation functional (B3LYP)/6-31G(d), B3LYP/6-31+G(d,p), B3LYP/6-311++G(d,p)//B3LYP/ 6-31G(d) and the second-order M?ller-Plesset perturbation (MP2)/6-311++G(d,p)//B3LYP/6-31+G(d,p) levels. It was found that the final metathesis product can be yielded via a three-membered or four-membered ring mechanism. The three-membered ring pathway is favorable due to its low energy barrier at the rate determining step. The whole reaction is stepwise and strongly exothermic.     

Stoichiometric hydrosilylation of nitriles with hydrido(hydrosilylene)tungsten complexes: formation of W-Si-N three-membered ring complexes and their unique thermal behaviors

Reactions of hydrido(hydrosilylene)tungsten complexes, Cp'(CO)2(H)W=Si(H)[C(SiMe3)3], with nitriles (MeCN, tBuCN) at 60 degrees C gave hydrosilylation products, Cp'(CO)2W[kappa2(N,Si)-Si(H)(N=CHR'){C(SiMe3)3}] (R' = Me, tBu), with a novel W-Si-N three-membered ring structure. The product of the hydrosilylation of tBuCN underwent reversible rearrangement at 70 degrees C to a silylene complex, Cp'(CO)2(H)W=Si(N=CHtBu)[C(SiMe3)3], which was a major component in equilibrium. A reaction mechanism for the hydrosilylation involving coordination of nitriles to the silylene ligand and subsequent migration of the hydrido ligand to the nitrile carbon was proposed.     

The Diels-Alder reaction of C60 and cyclopentadiene in mesoporous silica as a reaction medium

As a new organic reaction medium, a periodic mesoporous inorganic material was found to function as a "solid solvent" in a Diels-Alder reaction of C(60) with cyclopentadiene. This finding was supported by a concentration effect and a kinetic study of the reaction.     

Predicting reactivity and stereoselectivity in the Nazarov reaction: a combined computational and experimental study

The Nazarov reaction of pentadienyl cations generated by protonation of either dienones or alkoxytrienes has been examined in detail both experimentally and by DFT calculations. In particular, calculations at the B3LYP/6‐311G** level of theory accurately predicted, and accounted for, the outcome of the Brønsted acid catalyzed electrocyclization of 4π‐electron systems in which one of the double bonds involved in the process was embedded in N‐ and S‐heterocyclic rings. Calculations showed that both heteroatoms are capable of accelerating the ring closure by stabilizing the partial positive charge which develops at C‐6 (C‐2) in the transition state, with S‐heterocyclic derivatives being more reactive than the corresponding N‐containing compounds. In general, pentadienyl cations generated by protonation of alkoxytrienes were expected to react faster than those obtained by protonation of the corresponding dienones, as the latter were stabilized by a hydrogen bond. The presence of a substituent on the heterocyclic ring significantly affects the stereoselectivity (torquoselectivity) only in the case of the N‐heterocyclic derivatives, in which a 2‐alkyl group is axially oriented, providing the cis‐2,5‐disubstituted isomer only. Instead, with substituted S‐heterocyclic compounds, the anticipated torquoselectivity was very low and, in fact, a 3:1 diastereomeric mixture between the trans and cis products was experimentally found after ring closure. For this study, the synthesis of the appropriate N‐ and S‐containing dienones and alkoxytrienes was realized to evaluate the predictivity power of the DFT computations, which was very good in all of the cases examined, both in terms of reactivity and stereoselectivity. The consistency observed between computational and experimental results, therefore, shows the usefulness of DFT calculations at the B3LYP/6‐311G** level of theory as a robust instrument for the prediction of reactivity and stereoselectivity in the Nazarov electrocyclic reaction.     

Origins of stereoselectivity in the Diels-Alder addition of chiral hydroxyalkyl vinyl ketones to cyclopentadiene: a quantitative computational study

Modest basis set level MP2/6-31G(d,p) calculations on the Diels-Alder addition of S-1-alkyl-1-hydroxy-but-3-en-2-ones (1-hydroxy-1-alkyl methyl vinyl ketones) to cyclopentadiene correctly reproduce the trends in known experimental endo/exo and diastereoface selectivity. B3LYP theoretical results at the same or significantly higher basis set level, on the other hand, do not satisfactorily model observed endo/exo selectivities and are thus unsuitable for quantitative studies. The same is valid also with regard to subtle effects originating from, for example, conformational distributions of reactants. The latter shortcomings are not alleviated by the fact that observed diastereoface selectivities are well-reproduced by DFT calculations. Quantitative computational studies of large cycloaddition systems would require higher basis sets and better account for electron correlation than MP2, such as, for example, CCSD. Presently, however, with 30 or more non-hydrogen atoms, these computations are hardly feasible. We present quantitatively correct stereochemical predictions using a hybrid layered ONIOM computational approach, including the chiral carbon atom and the intramolecular hydrogen bond into a higher level, MP2/6-311G(d,p) or CCSD/6-311G(d,p), layer. Significant computational economy is achieved by taking account of surrounding bulky (alkyl) residues at 6-31G(d) in a low HF theoretical level layer. We conclude that theoretical calculations based on explicit correlated MO treatment of the reaction site are sufficiently reliable for the prediction of both endo/exo and diastereoface selectivity of Diels-Alder addition reactions. This is in line with the understanding of endo/exo selectivity originating from dynamic electron correlation effects of interacting pi fragments and diastereofacial selectivity originating from steric interactions of fragments outside of the Diels-Alder reaction site.