Theoretical study of the facial selectivity in Diels-Alder reactions of 4,4-disubstituted cyclohexadienones

Silvero, Guadalupe; Lucero, Melissa J.; Winterfeldt, E.; Houk, K. N.

doi:10.1016/s0040-4020(98)00384-6

Cited by 22 publications

(12 citation statements)

References 14 publications

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“…The endoselectivity of these Diels-Alder reactions and the preference for the oxygen or fluorine substituents to be placed in the inside position of the Diels-Alder adducts are most important for the observed chiral discrimination. According to quantum-mechanical calculations the endo-selectivity and the preference of the heteroatoms in the inside position arises from the high steric interactions between the bulky substituents such as methyl, and the π-system and hydrogen atoms of the cyclopentadiene moiety [47].…”

Section: ____________________________________________________________mentioning

confidence: 99%

The Effect of Pressure on Organic Reactions

Klärner¹,

Wurche²

2000

J. prakt. Chem.

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The utility of high pressure for the understanding of chemical reactions and its application in organic synthesis is shown for cycloadditions (inter‐ and intramolecular Diels‐Alder reactions, 1,3‐dipolar and [2+2] cycloadditions), cheletropic reactions and pericyclic rearrangements (Cope and Claisen rearrangements and electrocyclizations). The origin of the effect of pressure on chemical reactions is discussed. Especially, the change in the packing coefficient during cyclization of chains and the effect of electrostriction on reactions, in which charged species are generated, contribute substantially to a volume contraction leading to a powerful pressure‐induced acceleration of such reactions. Finally, the effect of pressure on free‐radical reactions (homolytic bond dissociations and quinone oxidations) is described.

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Section: ____________________________________________________________mentioning

confidence: 99%

The Effect of Pressure on Organic Reactions

Klärner¹,

Wurche²

2000

J. prakt. Chem.

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“…12 However, this does not account for the apparent reversal of regioselectivity observed for the Lewis acid-catalysed cycloaddition of acrolein to the dienyl acetate 1, where the head-to-head adduct 10 is the major product. Transition state calculations 13 are one way in which this, and the aforementioned results, can be fully interpreted.…”

Section: Methodsmentioning

confidence: 92%

“…The addition of Lewis acid to a reaction of a monosubstituted dienophile leads to apparent reversal of the latter expression of regioselectivity. 13 C NMR spectra were recorded on the same instruments at 50 MHz or 100 MHz, using TMS as an internal standard. 3-Methoxy-8a-estra-1,3,5(10),14,16-pentaen-17-yl acetate (1) was prepared as described.…”

Section: Methodsmentioning

confidence: 99%

Diels-Alder Cycloadditions of 3-Methoxy-8α-estra-1,3,5(10),14,16-pentaen-17-yl Acetate: Unexpected Trends in Regioselectivity

Bull¹,

Koning²

2000

Synthesis

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In contrast to Diels-Alder reactions of 3-methoxyestra-1,3,5(10),14,16-pentaen-17-yl acetate, in which 14,17-bridged cycloadducts are formed with high head-to-head b-face selectivity, product distributions for similar reactions of 3-methoxy-8a-estra-1,3,5(10),14,16-pentaen-17-yl acetate display sensitivity to the nature and reactivity of the dienophile, with a trend favouring regioreversal during b-face cycloaddition. Results are interpreted in terms of competing stereoelectronic and steric influences.As part of a programme directed towards the synthesis of skeletally modified 14,17-bridged estradiol analogues, we have recently described the Diels-Alder reaction of phenyl vinyl sulfone (PVS) with 3-methoxy-8a-estra-1,3,5(10),14,16-pentaen-17-yl acetate (1). The reaction proceeds with poor regio-and stereoselectivity to give a complex mixture of cycloadducts (Scheme 1), 2 in contrast to the efficient and highly stereoselective cycloaddition of PVS with 3-methoxyestra-1,3,5(10),14,16-pentaen-17-yl acetate. 3 The latter reaction proceeds in accordance with frontier molecular orbital (FMO) expectations and the well-established preference for b-face entry of conventional dienophiles to this and related 14,16-dienyl systems in the natural steroid series. 4 The principle has been elegantly utilised in both kinetic resolution and desymmetrisation reactions of cycloadducts derived from structurally related chiral diene templates to give, after retro-DielsAlder reaction, optically pure products. 5 While a number of skeletal variations of such templates have been examined, 4,5 and various other cycloaddition-mediated approaches to ring D modified estradiol analogues have been developed, 6 the influence of C-8 configurational inversion exemplified by the steroidal dienyl acetate 1, has not hitherto been described.The reduction in b-face stereoselectivity during the reaction of the 8a-isomer 1 is not surprising, in view of the change in the steric environment of the 14,16-dienyl moiety accompanying C-8 inversion. However, the additional manifestation of regioreversal during cycloaddition suggests that the skeletal change may also influence the FMO status of the diene. Accordingly, cycloadditions of dienyl acetate 1 were performed with a variety of dienophiles, in order to seek evidence of a trend in reactivity and selectivity, and as a prerequisite for determining the scope for synthesis of ring D modified analogues of 8a-estradiol.Cycloaddition of the dienyl acetate 1 with methyl propiolate (benzene, 100°C, 72 h) gave one isolable product (66%), formulated as the 14a,17a-etheno-16-carboxylate 2 (Scheme 2). The structure of cycloadduct 2 was confirmed by NOE difference spectroscopy. Upon irradiation of the 13b-methyl signal (d = 1.25), that of 15-H (d = 7.5; 1%) was enhanced, confirming that a b-face reaction had occurred, whereas the regiochemistry was supported by enhancements of the 8a-H (d = 2.4; 3%) and 7-H 2 (d = 1.7-1.8; 6%) signals upon irradiation of the 15-H signal (d = 7.5).Experimental confirmation of the regioche...

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“…[59][60][61][62][63] Transition structures prefer a staggered orientation around the forming bonds. For nitrile oxide cycloadditions, this leads to three possible positions for a substituent: inside, outside, or anti relative to the forming bonds of the cycloaddition transition structure (Scheme 2).…”

Section: Stereoselectivities Of Transition Structuresmentioning

confidence: 99%

“…However, in both cases, large alkyl groups prefer the anti position, 59,66,67 but steric interactions from Z-alkenes have been found to alter the conformational preference of electronegative substituents. 61 Considering these effects, seven transition structures were calculated for the first cycloaddition (TS1) ( Figure S1). (1) and nitrile oxide (2) yields the cycloadduct (3) and afterwards the 2:1 cycloadduct (4).…”

Section: Stereoselectivities Of Transition Structuresmentioning

confidence: 99%

The 1,3-Dipolar Cycloaddition of Nitrile Oxide to Vinylacetic Acid: Computational Study of Transition States Selectivity, Solvent Effects, and Bicyclo Formation

Toldo¹,

Merlo²,

Gonçalves³

2016

Journal of the Brazilian Chemical Society

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The 1,3-dipolar cycloaddition reaction is a powerful tool for the cycloaddition of nitrile oxides to olefins, and this reaction is of considerable interest to obtain isoxazolines. Density functional theory (DFT) was used to study the 1,3-dipolar cycloaddition reaction mechanism that initially occurs between benzonitrile oxide and vinylacetic acid to yield a bicyclo, from successive cycloadditions. PBE1PBE, B3LYP and CAM-B3LYP functionals were used together with 6-311+G(2d,p) basis set. CCSD(T)/6-311+G(2d,p) calculations were done to compare the DFT energy barriers. The solvent effects were included using polarizable continuum model (PCM), with three different solvents. In the first cycloaddition, only the 3,5-regioisomer is expected. In the gas phase, the β face attack, that originates the trans-bicyclo, is slightly favored, but the cis-bicyclo is considerably more stable. However, the α face attack was favored with solvent effects. The PBE1PBE functional gives the closest activation energies and reaction energies to CCSD(T). The inclusion of solvent effects changes the preferential rotamer in each cycloaddition.

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Theoretical study of the facial selectivity in Diels-Alder reactions of 4,4-disubstituted cyclohexadienones

Cited by 22 publications

References 14 publications

The Effect of Pressure on Organic Reactions

The Effect of Pressure on Organic Reactions

Diels-Alder Cycloadditions of 3-Methoxy-8α-estra-1,3,5(10),14,16-pentaen-17-yl Acetate: Unexpected Trends in Regioselectivity

The 1,3-Dipolar Cycloaddition of Nitrile Oxide to Vinylacetic Acid: Computational Study of Transition States Selectivity, Solvent Effects, and Bicyclo Formation

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