Showing papers by "Leo A. Paquette published in 1992"

Synthesis and molecular structure of belted spirocyclic tetrahydrofurans, a new class of preorganized hosts for cations

Abstract: The preparation and binding properties of spirocyclic tetrahydrofurans 7-11 are described. The condensition of cyclopentanone with 5-lithio-2,3-dihydrofuran (12) provided an alcohol which readily rearranged to ketone 14 under acidic condition. »Capping« of the carbonyl group in 14 so as to generate a second spiro tetrahydrofuran subunit gave rise to 7 and 8. Starting with cyclobutanone, 2-fold ring expansion involving 12 provided the key reaction leading to 22 and 23, which were »capped« as before

Relevance of oxyanion stereochemistry to chirality transfer in anionic oxy-cope rearrangements

Abstract: Geometrically and optically pure (3R,5E)- and (3R,5Z)-1,5-heptadien-3-ols undergo anionic oxy-Cope rearrangement under the exclusice control of oxyanion orientation with a 58-64% preference for equatorial oxygen. Six semicyclic dienols have also been synthesized where the preferred oxyanion-driven sigmatropic rearrangement pathway is obligatorily pitted against π-facial biases offered by 4-tert-butylcyclohexenyl, norbornenyl, and camphenyl rings. These rearrangements therefore offer especially stringent tests of those factors that control the level and direction of chirality transfer. The data show the oxyanion to disfavor becoming involved in 1,3-diaxial relationships

Asymmetric functionalization of conformationally distinctive Cs-symmetric cis-[n.3.1] bicyclic ketones. Definition of the absolute course of enantio- and diastereodifferentiation

Abstract: The four C s -symmetric cis[n.3.1] bicyclic ketones where n=3,5,7, and 9 were acetalized with (R,R)-2,4-pentanediol, and the resulting derivatives were cleaved with triisobutylaluminum (TRIBAL). The first three examples, all of which have their polymethylene chain rigidly fixed in a diaxial orientation, undergo ring opening with very high diastereoselectivity. In the fourth case (n=9), the chain is sufficiently long to be attached in a diequatorial manner

Stereocontrolled Access to the Most Highly Condensed Pentalenolactone Antibiotic. from Cycloheptatriene to Pentalenolactone P Methyl Ester

Abstract: The first total synthesis of the title compound has been accomplished. Besides the immediate establishment of the trans cyclopropane-lactone relationship by an appropriate Diels-Alder reaction, other notable transformations include a regioselective chain-lengthening, oxadi-π-methane rearrangement, lactone ring construction by an intramolecular Michael reaction-oxidation sequence, and use of monomeric formaldehyde to introduce the final carbon atom. The chemistry outlined defines a strategy that is highly stereocontrolled and completely tolerant of a sterically congested cyclopropane ring that is carried through to the target from the very first step

An Enantioselective Approach to the Taxanes: Direct access to functionalized cis‐tricyclo[9.3.1.03,8]pentadecanes via α‐hydroxy ketone and Wagner‐Meerwein rearrangements

Abstract: The feasibility of the titled reactions for the rapid, enantioselective synthesis of cis-tricyclo[9.3.1.03,8]pentadecane precursors to taxusin and taxol has been examined. The catalysts most well suited to inducing the appropriate 1,2-shifts have been identified. To a great extent, the rearrangement products are formed as a direct consequence of appropriate structural features (kinetic phenomenon) and strain minimization (thermodynamic driving force). Complementary MM2 calculations of the global minimum in each series provided indications that were completely in line with the experimental observations. Sophisticated NMR studies and X-ray crystallographic determinations were coordinated to remove any ambiguity of product structure and solid-state conformation.

Setting the Bridgehead Oxidation Level in trans‐Tricyclo[9.3.1.03,8]pentadecanes as a Prelude to the Dual Synthesis of Taxol and Taxusin

Abstract: The key elements associated with the synthetic elaboration of functionalized trans-tricyclo-[9.3.1.03,8]pentadecanes carrying either a bridgehead H or OH substituent are detailed. Starting with 12, a ketone available in two steps from (R)-2-oxo-7,7-dimethyl-l-vinylbicyclo[2.2.1]heptane, it proved possible to introduce trans-B/C ring juncture configuration as in 16 in five steps. This advanced intermediate constitutes the point of bifurcation. The pathway to taxusin precursor 23 was attained by stereospecific osmylation, reduction, and pinacol-like 1,2-Wagner-Meerwein rearrangement within acetoxy mesylate 22c. Still more abbreviated is the route to 32, which again takes advantage of the osmylation step but proceeds, forward without reduction of the rear carbonyl group. Once hydroxy diketone 31 is produced, equilibration in the presence of (t-BuO)3Al results in complete conversion to 32. The many stereoselective transformations developed in the course of this study, in combination with the several thermodynamic questions that have been clarified, are expected to be highly serviceable as more advanced thrusts toward taxusin and taxol are mounted.

Ring expansion by tandem double Tebbe–Claisen technology

Abstract: 2-Cyclohexenone rings that form part of a larger structural assembly are amenable to peracid oxidation with formation of an epoxy lactone. These intermediates are readily transformed under acidic, basic, or neutral conditions to ring-contracted aldehydo lactones, which are then subjected to condensation with a slight excess of Tebbe reagent. These conditions result in methylenation of carbonyl groups and set the stage for operation of a Claisen rearrangement. When the latter is catalyzed by Tribal, the sigmatropic process occurs at room temperature. With systems typified by 17 and 24, the isomerization is complete within 15 min. The presence of a proximate angular methyl group as in 9b, 29, and 37 exerts a retarding kinetic effect. In such examples, a period of 6 h is required to achieve completion. Swern oxidation completes the conversion to the 4-cyclooctenones, where the two carbons stemming from the Tebbe reagent are inserted between the original carbonyl and α-olefinic carbons. The overall process is...

Electrostatic modulation of hydroxyl group ionization in acidic media. Evidence for the competitive operation of intramolecular SN2 reactions

Abstract: The acid-catalyzed cyclodehydration of the cis and trans isomers of 2-substituted 1-(3-hydroxypropyl)cyclohexanols results in the formation of spirocyclic tetrahydrofurans. The stereochemical course of these reactions is highly varied, ranging from a dominant preference for retention when R=OCH 3 to modestly favored inversion when R=CH 3 . Experiments with 18 O-labeled diols show that in the methoxyl series most of the isotope is retained irrespective of relative stereochemistry. On the other hand, the pair of phenyl-substituted isomers responds by losing approximately 50% of the label

Multifaceted consequences of holding two [8]annulene rings face-to-face. Synthesis, structural characteristics, and reduction behavior of [22](1,5)cyclooctatetraenophane

Abstract: The doubly-decked [8]annulene 11 has been prepared in 13 steps from octahydro 3a,9a-propenocyclopentacycloocten-2,11-dione. The scheme takes advantage of the annulating capacity of the Cook-Weiss reaction and the ability of semibullvalenes to undergo thermal isomerization to cyclooctatetraenes. Bis(semibullvalene) is both conformationally dynamic and subject to very rapid Cope rearrangement. The energetics of inversion within its interconnective cyclooctane ring have been elucidated by variable-temperature 1 H NMR spectroscopy

Multifaceted Consequences of Holding Two (8)Annulene Rings Face-to- Face. Synthesis, Structural Characteristics, and Reduction Behavior of (22)(1,5)Cyclooctatetraenophane.

Abstract: The doubly-decked [8]annulene 11 has been prepared in 13 steps from octahydro 3a,9a-propenocyclopentacycloocten-2,11-dione. The scheme takes advantage of the annulating capacity of the Cook-Weiss reaction and the ability of semibullvalenes to undergo thermal isomerization to cyclooctatetraenes. Bis(semibullvalene) is both conformationally dynamic and subject to very rapid Cope rearrangement. The energetics of inversion within its interconnective cyclooctane ring have been elucidated by variable-temperature 1 H NMR spectroscopy

Sequential Annulation in Molecular Construction. A Short, Stereocontrolled Synthesis of (.+‐.)‐Hirsutene.

Abstract: A total synthesis of (±)-hirsutene has been achieved in 9 steps and in 14% overall yield via a twofold cycloadditive scheme that utilizes 4,4-dimethylcyclopentene, 1-(trimethylsilyloxy)butadiene, and ethylene as the three key building blocks.

Structure of 9‐Nitro‐(4)peristylane‐1,5‐dione

Abstract: Decahydro-1,6:3,4-dimethano-3a-nitrocyclobuta [1,2:3,4]dicyclopentene-2,5-dione (II), C12-H11NO4, Mr = 233.2, monoclinic, P2(1)/n, a = 13.378 (7), b = 6.614 (1), c = 23.040 (15) A, beta = 92.53 (5) degrees, V = 2036.6 (4) A3, Z = 8, D chi = 1.521 g cm-3, Cu K alpha, lambda = 1.54178 A, mu = 9.3 cm-1, F(000) = 1312, T = 293 K, final R = 0.047, wR = 0.075 for 3075 reflections with I greater than 3 sigma(I). There are no unusually short intermolecular distances. A comparison of the molecular densities and packing coefficients of (I) [4]peristylane-1,5-dione with (II), indicates that the change in crystal density from (I) (1.415 g cm-3) to (II) (1.521 g cm-3) is the sole result of an increase in molecular density with NO2 substitution. The packing coefficients for (I) and (II) are identical.

Synthesis and Molecular Structure of Belted Spirocyclic Tetrahydrofurans, a New Class of Preorganized Hosts for Cations.

Abstract: The preparation and binding properties of spirocyclic tetrahydrofurans 7-11 are described. The condensition of cyclopentanone with 5-lithio-2,3-dihydrofuran (12) provided an alcohol which readily rearranged to ketone 14 under acidic condition. »Capping« of the carbonyl group in 14 so as to generate a second spiro tetrahydrofuran subunit gave rise to 7 and 8. Starting with cyclobutanone, 2-fold ring expansion involving 12 provided the key reaction leading to 22 and 23, which were »capped« as before

Intramolecularly Competitive Anionic Oxy-Cope Rearrangements.

Abstract: Two examples of the title reaction are described. While the kinetically preferred pathway for 2 utilizes the vinyl substituent, that for 16 skirts this option completely. To a great extent, these biases are a function of the structural features inherent to these alochols.

The Dodecahedryl Anion.

Abstract: The feasibility of generating the anion of dodecahedrane by direct metalation, by reductive lithiation with aromatic radical anions, and by transmetalation with alkyllithiums has been examined.

Electrophilic Chemistry of Dodecahedrane. Direct Entry to Epoxydodecahedrane and the First Tethered Derivative.

Abstract: (Phenylseleno)dodecahedrane is shown to be a useful precursor of dodecahedrene (not isolated) and epoxydodecahedrane. The conjoining of two dodecahedryl units in a para relationship on a benzene ring has also been realized.

Relevance of Oxyanion Stereochemistry to Chirality Transfer in Anionic Oxy‐Cope Rearrangements.

Abstract: Geometrically and optically pure (3R,5E)- and (3R,5Z)-1,5-heptadien-3-ols undergo anionic oxy-Cope rearrangement under the exclusice control of oxyanion orientation with a 58-64% preference for equatorial oxygen. Six semicyclic dienols have also been synthesized where the preferred oxyanion-driven sigmatropic rearrangement pathway is obligatorily pitted against π-facial biases offered by 4-tert-butylcyclohexenyl, norbornenyl, and camphenyl rings. These rearrangements therefore offer especially stringent tests of those factors that control the level and direction of chirality transfer. The data show the oxyanion to disfavor becoming involved in 1,3-diaxial relationships