Showing papers by "Leo A. Paquette published in 1995"

Total Synthesis of Crenulatan Diterpenes: Strategy and stereocontrolled construction of a bicyclic keto‐lactone building block

Abstract: The bicyclic keto lactone 26 was synthesized for the purpose of developing a viable route to marine diterpenes of the crenulatan type. Following the efficient conversion of (S)-citronellol (5) to the allylated alcohol 9a (Scheme 2), the αβ-unsaturated lactone 12 was efficiently accessed in preparation for stereocontrolled conjugate addition. The hydroxymethyl equivalent most suited to this task was (i-PrO)Me2SiCH2MgCl, which gave 13 predominantly in the presence of CuI and Me3SiCl. Once the OH group was deprotected ( 14), it proved an easy matter to implement acid-catalyzed isomerization to lactone 15, oxidation of which gave the pivotal aldehyde 16. Condensation of 16 with PhSeCH2Li led via21 to 22 (Scheme 3). Once the OH group was protected ( 22b), it proved possible to effect aldolization with crotonaldehyde ( 23). Exposure of 23 to acid gave the sub-target compound 25. Its subsequent oxidation and thermal activation resulted in sequential selenoxide elimination with Claisen rearrangement ( 26). The structural features of 26 require that a chair-like transition state be adopted during the [3.3]sigmatropic event. With the clarification of these issues, a highly serviceable and more advanced assault on the crenulatans should prove capable of being mounted.

Studies Directed Toward the Total Synthesis of Polycavernoside A. Enantioselective Synthesis of the Disaccharide Component.

Abstract: Adaptation of the Mukaiyama-Nicolaou protocol to the coupling of a monounprotected thioglycoside to a glycosyl fluoride is capable of delivering the unusual disaccharide present in the title toxin.

Through‐Bond Interaction via Cyclobutane Relay Orbitals. Evaluation of the Question of Extended Conjugation in Belted (4,5)Dihomotropones.

Abstract: The preparation of tricyclo[6.5.0.0 2.9 ]trideca-3,6,10,12-tetraen-5-one (3), its dihydro derivative 18, and the structurally related carbinol 17 has been successfully realized. In a companion synthesis of the lower homolog 4, an inability to effect the desulfonylative ring contraction either of 28 or 29 was encountered. Although introduction of the ethylene bridge could be accomplished first as in 23, the ease with which this ketal isomerized to 24 precluded its further use in the pursuit of 4. Molecular mechanics calculations showed the dienone subunit in 4 to deviate significantly from planarity. This behavior is in striking contrast to the planar minimum energy conformations computed for [4,5]dihomotropone (2) and its higher vinylog 3. An evaluation of the spectral properties of 3 reveal this ketone not to be polarized. No evidence that could be constructed to be a reflection of ground-state through-bond interaction was uncovered

Is Through-Bond Dihydroaromaticity Attainable? Preparation of (4,5) Dihomotropone, Investigation of Its Ground-State Properties, and an Attempt to Generate the Dihomotropylium Cation.

Abstract: Construction of the first dihomotropone (6) has been accomplished. The key elements of the synthesis were a regiocontrolled expansion of a [4.1.1] bicyclic α-bromo ketone and introduction of the dienone double bonds by means of the Garbisch method. The spectral properties of 6 under neutral and strongly acidic conditions are described and interpreted in terms of a lack of dihomoaromatic character. The parent bicyclo[5.1.1]nonadienyl cation is unstable and experiences ready Wagner-Meerwein rearrangement to the bicyclo[4.2.1]nonadien-7-yl cation. These features appear well suited to the ultimate evaluation of through-bond interaction in tricyclic homologues of 6 that carry perpendicular π arrays in the third ring

Total Synthesis of (+)-Grindelic Acid by Stereocontrolled Oxonium Ion Activated Pinacol Ring Expansion. Chemical Proof of the Absolute Configuration of All Grindelane Diterpenes.

Abstract: (+)-Grindelic acid, synthesized enantioselectively from the levorotatory Wieland-Miescher ketone and (−)-linalool and necessarily formulated as 1a, is shown to be antipodal to the major diterpenoid of Grindelia species.

Total Synthesis of Natural (-)-Vulgarolide. A Concise Stereocontrolled Means for Twofold Distal Oxaannulation of a Cyclooctanone Core.

Abstract: An anionic oxy-Cope rearrangement has been developed to produce enantiomerically pure keto ester 3, which was structurally modified to produce epoxy acid 2 whose ozonolysis led directly to a 1:1 mixture of (−)-vulgarolide and its anomer.

Efficient Stereocontrolled Synthesis of the ABC Subunit of Dumsin.

Abstract: The oxygenated ABC network of the potent insect antifeedant dumsin has been expediently assembled in a totally stereocontrolled manner by exploiting the acylation of a lactone carbonyl with a masked keto anion equivalent.

Total Synthesis of Crenulatan Diterpenes: Strategy and Stereocontrolled Construction of a Bicyclic Keto-Lactone Building Block.

Abstract: The bicyclic keto lactone 26 was synthesized for the purpose of developing a viable route to marine diterpenes of the crenulatan type. Following the efficient conversion of (S)-citronellol (5) to the allylated alcohol 9a (Scheme 2), the αβ-unsaturated lactone 12 was efficiently accessed in preparation for stereocontrolled conjugate addition. The hydroxymethyl equivalent most suited to this task was (i-PrO)Me2SiCH2MgCl, which gave 13 predominantly in the presence of CuI and Me3SiCl. Once the OH group was deprotected ( 14), it proved an easy matter to implement acid-catalyzed isomerization to lactone 15, oxidation of which gave the pivotal aldehyde 16. Condensation of 16 with PhSeCH2Li led via21 to 22 (Scheme 3). Once the OH group was protected ( 22b), it proved possible to effect aldolization with crotonaldehyde ( 23). Exposure of 23 to acid gave the sub-target compound 25. Its subsequent oxidation and thermal activation resulted in sequential selenoxide elimination with Claisen rearrangement ( 26). The structural features of 26 require that a chair-like transition state be adopted during the [3.3]sigmatropic event. With the clarification of these issues, a highly serviceable and more advanced assault on the crenulatans should prove capable of being mounted.

Acetylide Anions Exert Complete Control over Aldolization During the Direct Conversion of Squarate Esters into Polyquinanes.

Abstract: The sequential condensation of diisopropyl squarate with a vinyl anion and a lithium acetylide triggers a cascade of mechanistic events that eventuates in formation of highly functionalized unsaturated diquinanes.