Endo Approach Research Articles

A Stereospecific Transannular Diels-Alder Approach to the [6.6.7] Tricyclic Skeleton Related to Aphidicolin and Scopadulan Natural Products

Model trans-cis-cis (TCC) macrocyclic triene 7 was synthesized using a convergent approach. Upon heating at 200°C, a 1,5-hydrogen-shift on the diene moiety was found to compete with the transannular Diels-Alder (TADA) reaction, thus leading to a mixture of tricyclic products. However, the diene rearrangement could be avoided by using boron trifluoride-diethyl ether complex as catalyst at reduced temperature (60°C). The exclusive formation of the trans-syn-cis [6.6.7] (TSC) tricyclic product 8 through an endo approach was observed. This result demonstrates the feasibility of a TADA strategy for synthesizing the title compounds and analogs.

Asymmetric intermolecular Diels-Alder reactions of enantiopure sulfinyl-homo- and -hetero-dienes: Preliminary results.

Reaction of (E)-(+)-(R)-2- p-tolylsulfinyl-1,3-pentadiene 1 with maleimide afforded 3 as a single, enantiomerically pure adduct under very mild conditions. 3 resulted from exclusive endo approach by a completely diastereofacialselective route. On the other hand, heterodiene (+)-(S)-3- p-tolylsulfinyl-3-buten-2-one 2 smoothly reacted with sensitive 2-methylenetetrahydrofuran yielding 1:1 diastereomeric dioxaspiroadducts 4a and 4b, readily separated by liquid chromatography.

The endo approach

The world can only be described from within. To understand the situation qualitatively, it is necessary to go to another level of description (model-universe approach). Each observer possesses his own interface. It depends on the momentary assignment conditions. The different interfaces (observer-relative worlds) are distorted, nonconstant, and nonintertransformable. An objective reality of ”subjective“ type exist. An empirical approach towards its unmasking appears possible.

Single and double asymmetric induction in the cycloaddition of chiral nitrones to achiral and chiral vinylphosphine oxides

The asymmetric 1,3-dipolar cycloadditions of the chiral α,β-dialkoxynitrones(4S)-(Z)-N-(2,2-dimethyl-1,3-diorolan-4-yl)methylenebenzylamineN-oxide 3 and (4S,SS)-(Z)-N-(2,2,5-trimethyl-1,3-dioxolan-4yl) methylene-benzylarnine N-oxide 4a to diphenylvinylphosphine oxide 2 give, besides complex mixtures of all the possible regio- diastereoisonters, one majorisorner, 5a and 8a respectively, consisting of 65% of the total isomeric amount. This comnpoundshavebeen assigned the erythro C(3)-C(4') configuralions derivingfrom the most reactive conformation A or B through an endo transition state. The cyclo addition of the same nitrones with racemic and enantiometrically pure (−)-S-methylphertylviaylphosphine aide ( 1 ) allowed the study of the double asymmetric induction. The selectivity towards the erythro compounds increases remarkably to ca. 40:1 for the endo approach, indicating that (2S)-nitrones 3 or 4a and (S)-phosphineoxide 1 constilute a matched pair of reactants. The synthesized phosphinylisoxazolidines can be conveniently transformed into selectively protected C-phosphinyl-aminotriols. An illustrative example of the synthesis of the novel filly and selectively protected 1 phosphinyl- seco-daunosamine 22 is reported.

Zur Stereoselektivität der intramolekularen Diels‐Alder‐Reaktion von 1,7,9‐Decatrien‐3‐onen zu Octalonderivaten

Stereoselectivity of Intramolecular Diels-Alder Reactions of 1,7,Q-Decatrien-3-ones to Octalone Derivatives 2-Alkenyl-substituted 2-siloxycyclopropanes 1 and 2 serve as protected enone equivalents and are converted into key building blocks 5–8 in excellent yields. After desilylation and ring cleavage these compounds provide 1,7,9-decatrien-3-ones 9–12, which undergo smooth intramolecular Diels-Alder reaction at room temperature or approximately 100°C. The resulting octalone derivatives 13–16 are formed with exclusive or preferred cis connection of the rings. The relative configurations of the cycloadducts are secured by equilibration experiments and NMR spectroscopy (selective proton decouplings). For 11 → 15 and 12 → 16 the cis selectivitiy can remarkably be enhanced by trifluoroacetic acid catalysis. This high noninduced diastereoselectivity is caused by the endo approach of the reactive molecular sites, whereas the configuration of the third stereogenic centre (C-2) is determined by the folding of the linking carbon chain. Preference of a boat conformation with equatorial ester group endo-Beq may be assumed and appears to be general for intramolecular cycloadditions of such trienones. This effect as well as the influence of further substituents at the diene or dienophile portion on stereoselectivity and the reactions of other model compounds are discussed.

The Stereochemistry of Styrene-Maleic Anhydride Copolymers:13C-NMR Study and Pvcilo and Indo/1 Calculations

Abstract The stereochemistry of alternating copolymers of styrene (ST) with maleic anhydride (MA) was examined by 13C-NMR spectroscopy, and the stabilization energies and the most stable geometries of complexes and adducts between ST and MA were calculated by the PVCILO program and by INDO/1. The methine and carbonyl carbon atoms of the MA portion and the quaternary carbon atom of the ST portion reveal different stereochemistries due to various polymerization conditions, suggesting that the donor-acceptor complex may participate in the co-polymerization. The complex postulated according to the Diels-Alder geometry was more stable than that according to [2+2] cycloaddition geometry. It is believed that the stabilization energy is so great that the copolymerization occurs spontaneously via forming a donor-acceptor complex and adducts. The geometries of 1:1 adducts formed by endo and exo approaches in the Diels-Alder geometry mode were also calculated.

Transformed steroids. 115. Stability of nitrogen invertomers in steroido[16?,17?-d]-N-methoxyisoxazolidine series

1. The regiospecific 1,3-dipolar cycloaddition of Z- and E-nitronic esters to steroidal Δ16-olefins gives both of the possible diastereomers, which arise as the result of the exo and endo approach of the dipole. 2. In each pair of diastereomers one is unstable and undergoes transformation to the stable isomer of another pair. 3. The transformation of unstable stereoisomers to stable isomers represents inversion of the isoxazoline nitrogen atom, accompanied by conformational reorganization of the ciscoupled convertolike (five-membered) carbo- and heterocycles.

Photoénolisation—VIII: Stéréospécificitéet régiospécificitéde la réaction de diels-alder avec les photodiénols issus de la benzyl-2 et de l'éthyl-2 benz

Photoenols derived from 2-benzyl- and 2-ethylbenzophenone have been trapped by maleic anhydride, methyl fumarate and phenyl fumarate. Stereochemical determinations of the single adduct obtained in each case in high yield have shown unequivocally that the Diels-Alder addition proceeds from the ( E,E)-dienol by an endo approach, an interaction between the dienol hydroxylic group and one of the dienophile carbonyl group being strongly determinant. These results do not eliminate the possibility that an unreactive ( Z,E)-dienol be formed during the photochemical step.

Azafulvenes 8. Cycloaddition Reaction of 8-Azaheptafulvene to Sulfene

Abstract Peri- and stereoselective cycloadducts were obtained from the reactions of 8-aryl-8-azaheptafulvenes with some sulfenes. 8-Aryl-8-azaheptafulvenes reacted with phenylsulfene to give cis [8+2] cycloadducts as the sole products which would have resulted either from the endo approach or via the endo intermediate of the two reagents. On the other hand, with benzoylsulfene trans [8+2] cycloadducts were isolated. The formation of the latter products was rationalized by considering epimerization of the initially formed cis adducts. The cis [8+2] cycloadducts to vinylsulfene did not give the trans isomers but the hydrogen migrated derivatives under the influence of bases. The mechanism of the above reactions is also discussed.

Stereoselektivität und Reaktivität bei der 1,3‐dipolaren Cycloaddition chiraler N‐(Alkoxyalkyl)nitrone

Stereoselectivity and Reactivity in the 1,3‐Dipolar Cycloaddition of Chiral N‐(Alkoxyalkyl)nitronesThe stereoselectivity in the reaction of hydroxy‐oxime 1 with acetaldehyde and methyl methacrylate yielding the diastereomeric isoxazolidine‐ribosides 9–12 was determined to be 93%. The predominant adducts 9 and 10 were cleaved to the diastereomeric isoxazolidines 19 and 20, respectively, which upon oxidation gave the same optically active 2‐isoxazoline 21, thus demonstrating the participation in the cycloaddition of both (E/Z)‐isomeric nitrones 13 and 14. Based upon comparison of the optical rotations, the isoxazolidines 7, 8, 19 and 20 and the 2‐isoxazolines 21 and 22 possess the same chirality, found to be R by correlating 7 with (+)‐(S)‐citramalic acid. ‐ Since the hydroxy‐oximes 1 and 36 showed the same stereo‐selectivity in the reaction with formaldehyde and methyl methacrylate, the trityl group of 1 does not influence the stereoselectivity in the cycloaddition. The hydroxyoxime 38 led in the same type of reaction to the isoxazolidines 7, 8, 19 and 20 possessing (S)‐chirality, the stereoselectivity (79–95%) being similar to the one observed with 1 (67–95%). The explanation of this stereoselectivity is based upon a stereoelectronic effect in the transition state of the cycloadditions (kinetic anomeric effect). As predicted, the N‐(alkoxyalkyl)nitrones showed enhanced reactivity in the cycloaddition with unactivated olefins (leading to 47, 48, 50 and 51). The importance of exo vs. endo approach of the dipolarophile was evidenced by reacting 1 with formaldehyde and methyl acrylate giving predominantly 57 with (5S)‐configuration. ‐ Use of the hydroxy‐oxime 65 allows synthesis of optically active isoxazolidines with regeneration of the starting hydroxy‐oxime.