Showing papers by "Leo A. Paquette published in 1998"
TL;DR: The unprotected 2 and 3-hydroxycyclohexanones 1−8 were prepared by methods that skirted as much as possible their proclivity for α-ketol rearrangement as discussed by the authors.
Abstract: The unprotected 2- and 3-hydroxycyclohexanones 1−8 were prepared by methods that skirted as much as possible their proclivity for α-ketol rearrangement (where the possibility for such isomerization...
43 citations
TL;DR: In this article, the stereochemistry of the coupling reactions of oxygen-substituted bromides 8−10 with isobutyraldehyde, benzaldehyde, and cyclohexanecarboxaldehyde in water is described.
Abstract: The stereochemistry of the coupling reactions of oxygen-substituted bromides 8−10 with isobutyraldehyde, benzaldehyde, and cyclohexanecarboxaldehyde in water is described. The examples involving the O-silylated derivatives 8 exhibit moderate anti stereoselectivity. In contrast, rather high (most often in excess of 80:20) syn diastereofacial bias is observed when hydroxy bromides 10 are involved. Consequently, stereocontrolled 1,4-asymmetric induction under aqueous conditions can be realized in either direction on demand. These results are considered to reflect the fact that the siloxy systems enter into C−C bond formation via conventional Felkin−Anh transition state arrangements. The crossover observed for the unprotected analogues is believed to be a consequence of the preferred adoption of chelated transition states, these interactions likely being fundamental to aqueous organometallic chemistry.
38 citations
TL;DR: The double 1,2-addition of alkenyl, cycloalkenyl, and alkynyllithium reagents to squarate esters constitutes a very expedient method for rapidly increasing structural complexity with formation of polycyclic end products.
34 citations
TL;DR: A systematic investigation of the stereoselectivity associated with coupling reactions involving the allylindium reagent and 6-substituted 2-hydroxy-1-tetralones is presented, finding stereoinduction to be in line with the normal predilection of 2-cyclohexenones for axial attack.
Abstract: A systematic investigation of the stereoselectivity associated with coupling reactions involving the allylindium reagent and 6-substituted 2-hydroxy-1-tetralones is presented. In each instance, the allylations were carried out in water, 50% aqueous THF, and dry THF. The extent of 1,2-induction was found to be highest in THF−H2O (1:1) and to favor the trans diol isomer. Somewhat lower levels of stereochemical bias in the same direction were observed in pure water. However, further erosion of this trend was noted for those reactions performed in THF, such that a modest crossover in product distribution became apparent in certain examples. On the basis of competition experiments, both reaction trajectories give evidence of proceeding via chelated intermediates. The extent of stereoinduction was found to be in line with the normal predilection of 2-cyclohexenones for axial attack, which is the process believed to be beset with minimal torsional effects. The substituents situated para to the ketone carbonyl do...
26 citations
TL;DR: In this paper, a complete dissection of a squarate cascade when a stereogenic center attached to an amino substituent effects 1,5-asymmetric induction prior to β-elimination of the entire fragment is presented.
Abstract: Both the sigmatropic and electrocyclic rearrangement pathways that can arise when a pair of alkenyl anions are added to a squarate ester have high stereochemical demands. The distinction is nontrivial. When cis addition occurs initially, the stereoinduction that materializes at this point is fully transmitted into the product(s). The more commonly observed trans addition exhibits fleeting stereochemical consequences because of rapid equilibration of the octatetraenyl intermediates. In this instance, product distribution is governed by the relative rates of conrotatory cyclization at this advanced stage. Herein reported is a complete dissection of a squarate cascade when a stereogenic center attached to an amino substituent effects 1,5-asymmetric induction prior to β-elimination of the entire fragment. Deuterium labeling permits a direct measure of the contrasting kinetic imbalances associated with the two possible modes of alkenyl anion addition. Furthermore, quantitative analysis of the partitioning expe...
20 citations
TL;DR: In this article, the tandem addition of an alkenyllithium reagent and a 2-lithioally-lamine to squarate esters has been systematically examined, and the effect of the sequencing of this twofold addition has been investigated.
Abstract: The tandem addition of an alkenyllithium reagent and a 2-lithioallylamine to squarate esters has been systematically examined. The effect of the sequencing of this twofold addition has been investigated. The extent to which the amino group is eliminated was found to be dependent on the structural features of the companion nucleophile. Also assessed was the comparative ease with which the amino and methoxy groups experience competitive β-elimination from the highly reactive, medium-ring dianionic intermediates. Attempts were made to curtail the level of competing 1,4-addition, and success was achieved by increasing the effective size of the O-alkyl groups in the squarate ester. The highly stereocontrolled transformations described represent a notably direct means for producing highly fused polycyclic compounds. Mechanistic considerations surrounding these reactions, which are characterized by an impressive enhancement of molecular scaffolding, are discussed.
18 citations
TL;DR: A program directed toward a total synthesis of polycavernoside A is described, and the strategic incorporation of the trienyl sector was accomplished, although no attempt was made to control the diastereoselectivity of the process.
Abstract: A program directed toward a total synthesis of polycavernoside A is described. The synthesis of five building blocks is detailed. The first of two electrophilic units, the lactone 3, was prepared in four steps from the known enantiomerically pure oxirane 15. Pyranyl aldehyde 5 was elaborated in turn from l-malic acid via 10. While the route to 30 involved 3 as a starting material, dithiane 2 was obtained in a straightforward manner from 10 as well. The merging of the chiral sectors could not be accomplished by way of the lithiated dithianyl anions, presumably as a consequence of their heightened basicity. The strategic incorporation of the trienyl sector was accomplished, although no attempt was made to control the diastereoselectivity of the process.
18 citations
TL;DR: The stereodifferentiation attending the coupling of geometrically stable allylindium reagents to a 2,3-azetidinedione has been assessed and found to operate at a synthetically useful level in most cases.
Abstract: The stereodifferentiation attending the coupling of geometrically stable allylindium reagents to a 2,3-azetidinedione has been assessed and found to operate at a synthetically useful level in most cases, The synthetic potential of organoindium reagents, as generated in the presence of water, is now recognized to be highly utilitarian on several fronts.2 Recent developments include an awareness that this class of organometallics is capable of engaging in chelation control,3 is amenable to stereodifferentiation in setting multiple contiguous stereogenic centers,4 and is entirely reliable in situations involving long-range asymmetric induction.5 The attractive safety and environmental benefits of these transformations have prompted a study in this laboratory of the diastereoselectivity with which the important heterocyclic building block N-benzyl-2,3azetidinedione (1)6 reacts with variously substituted allylic bromides.' At issue is whether the prochiral keto carbonyl group in 1 can respond stereochemically in a manner paralleling that exhibited by aldehydes. Stirring a suspension of indium powder with 1 and methyl (2)-2-bromomethyl-2-butenoate (2a)E in THF and water (1 :1) at 20 \"C for 5 h resulted in complete consumption of the reactants and afforded 3a and 4a with a significant bias in the syn direction. When 2bs was brought
17 citations
TL;DR: In this paper, the intramolecular indium-promoted cyclization of 4'-substituted (Z)- and (E)-7-bromo-5-heptenophenones has been examined in aqueous tetrahydrofuran.
Abstract: The intramolecular indium-promoted cyclization of 4‘-substituted (Z)- and (E)-7-bromo-5-heptenophenones has been examined in aqueous tetrahydrofuran. In every instance, ring closure occurred to deliver the syn-2-vinylcyclopentanol exclusively. The corresponding allylsilanes have been prepared as well, and the course of their fluoride ion-induced cyclization was also studied. In these systems, a kinetic bias for formation of the anti-2-vinylcyclopentanol is observed, although not with the same exclusivity. Accordingly, complementarity in product diastereoselectivity can be realized in purposeful fashion. The data acquired in this investigation suggest that the indium-catalyzed reactions involve intramolecularly coordinated transition states where development of a cis 5/6-bicyclic framework is most energetically feasible. In contrast, the silanes appear to utilize open-chain antiperiplanar transition states. While the latter are not particularly sensitive to double-bond geometry, they are responsive to ster...
15 citations
TL;DR: In this article, a complete dissection of a squarate cascade when a stereogenic center attached to an amino substituent effects 1,5-asymmetric induction prior to β-elimination of the entire fragment is presented.
Abstract: Both the sigmatropic and electrocyclic rearrangement pathways that can arise when a pair of alkenyl anions are added to a squarate ester have high stereochemical demands. The distinction is nontrivial. When cis addition occurs initially, the stereoinduction that materializes at this point is fully transmitted into the product(s). The more commonly observed trans addition exhibits fleeting stereochemical consequences because of rapid equilibration of the octatetraenyl intermediates. In this instance, product distribution is governed by the relative rates of conrotatory cyclization at this advanced stage. Herein reported is a complete dissection of a squarate cascade when a stereogenic center attached to an amino substituent effects 1,5-asymmetric induction prior to β-elimination of the entire fragment. Deuterium labeling permits a direct measure of the contrasting kinetic imbalances associated with the two possible modes of alkenyl anion addition. Furthermore, quantitative analysis of the partitioning expe...
6 citations
TL;DR: Homoallylic alcohols have been prepared from alkenes by direct reaction of the ozonide with an allylic bromide in the presence of zinc as mentioned in this paper, where the zinc is added to the mixture.
TL;DR: In this paper, the exo carbinol 3 and endo CARBINOL 7 can be easily transformed into the relatively complex end products 6 and 11, respectively, upon appropriate exposure to basic conditions.
TL;DR: The de novo acquisition of taxusin and taxol has been fueled in large part by the enchanted structural features of these molecules and the much heralded antitumor efficacy of 2, particularly in patients beset with refractory ovarian, breast, and lung cancers.
Abstract: Our involvement with the de novo acquisition of taxusin (1) and taxol (2) has been fueled in large part by the enchanting structural features of these molecules and the much heralded antitumor efficacy of 2, particularly in patients beset with refractory ovarian, breast, and lung cancers.1 In combination with the unusual mode of action of 2, which exhibits a remarkable capacity for stabilizing microtubule assembly and deterring cell division,2 the intrinsically exciting promise shown by taxol for benefiting human health has commanded unrivaled attention.
TL;DR: The double 1,2-addition of alkenyl, cycloalkenyl, and alkynyllithium reagents to squarate esters constitutes a very expedient method for rapidly increasing structural complexity with formation of polycyclic end products as mentioned in this paper.
Abstract: The double 1,2-addition of alkenyl, cycloalkenyl, and alkynyllithium reagents to squarate esters constitutes a very expedient method for rapidly increasing structural complexity with formation of polycyclic end products. The simple one-pot process is amenable to regioselective operation, stereochemical control, self-immolative chirality transfer, 1,5-asymmetric induction, and chemical modulation.
TL;DR: In this article, the exo carbinol 3 and endo CARBINOL 7 can be easily transformed into the relatively complex end products 6 and 11, respectively, upon appropriate exposure to basic conditions.
Abstract: The exo carbinol 3 and endo carbinol 7 can be expeditiously transformed into the relatively complex end products 6 and 11, respectively, upon appropriate exposure to basic conditions.
TL;DR: In this article, the tandem addition of an alkenyllithium reagent and a 2-lithioally-lamine to squarate esters has been systematically examined, and the effect of the sequencing of this twofold addition has been investigated.
Abstract: The tandem addition of an alkenyllithium reagent and a 2-lithioallylamine to squarate esters has been systematically examined. The effect of the sequencing of this twofold addition has been investigated. The extent to which the amino group is eliminated was found to be dependent on the structural features of the companion nucleophile. Also assessed was the comparative ease with which the amino and methoxy groups experience competitive β-elimination from the highly reactive, medium-ring dianionic intermediates. Attempts were made to curtail the level of competing 1,4-addition, and success was achieved by increasing the effective size of the O-alkyl groups in the squarate ester. The highly stereocontrolled transformations described represent a notably direct means for producing highly fused polycyclic compounds. Mechanistic considerations surrounding these reactions, which are characterized by an impressive enhancement of molecular scaffolding, are discussed.
TL;DR: In this article, the stereochemistry of the coupling reactions of oxygen-substituted bromides 8−10 with isobutyraldehyde, benzaldehyde, and cyclohexanecarboxaldehyde in water is described.
Abstract: The stereochemistry of the coupling reactions of oxygen-substituted bromides 8−10 with isobutyraldehyde, benzaldehyde, and cyclohexanecarboxaldehyde in water is described. The examples involving the O-silylated derivatives 8 exhibit moderate anti stereoselectivity. In contrast, rather high (most often in excess of 80:20) syn diastereofacial bias is observed when hydroxy bromides 10 are involved. Consequently, stereocontrolled 1,4-asymmetric induction under aqueous conditions can be realized in either direction on demand. These results are considered to reflect the fact that the siloxy systems enter into C−C bond formation via conventional Felkin−Anh transition state arrangements. The crossover observed for the unprotected analogues is believed to be a consequence of the preferred adoption of chelated transition states, these interactions likely being fundamental to aqueous organometallic chemistry.
TL;DR: The first pathway consists of α -phenylthiomethylation and subsequent desulfurization with Raney nickel, and the second sequence proceeds via the 1,2-addition of ethylmagnesium bromide followed by dihydroxylation, ring cleavage with lead tetraacetate, and basepromoted cyclization as mentioned in this paper.
Abstract: Bicyclo[5.3.1]undec-10-en-9-one ( 3 ) has been converted via two routes into the 10-methyl homolog 11 . The first pathway consists of α -phenylthiomethylation and subsequent desulfurization with Raney nickel. The second sequence proceeds via the 1,2-addition of ethylmagnesium bromide followed by dihydroxylation, ring cleavage with lead tetraacetate, and basepromoted cyclization.
TL;DR: In this article, a sesquiterpene (-)-salsolene oxide (1) was synthesized in enantioselective fashion from (R)-(-)-carvone.
Abstract: The architecturally unprecedented sesquiterpene (-)-salsolene oxide (1) has been synthesized in enantioselective fashion from (R)-(-)-carvone. Generation of the phenylthio-substituted vinyl ketene 4 is followed by intramolecular cyclization to the functionalized cyclobutanone 9. Vinyllithium addition to this intermediate proceeds in that stereocontrolled fashion which enables oxy-Cope rearrangement to operate readily under conditions of kinetic control. After hydride reduction, the desulfurization of 16 proceeds with inversion of bridgehead olefin geometry to deliver 17. This access route to the thermodynamically more stable geometric arrangement permits direct entry to 1. Attention is called specifically to the critical 3-fold function played by a phenylthio group introduced at the outset.
TL;DR: Homoallylic alcohols have been prepared from alkenes by direct reaction of the ozonide with an allylic bromide in the presence of zinc as discussed by the authors, where the zinc is added to the mixture.
Abstract: Homoallylic alcohols have been prepared from alkenes by direct reaction of the ozonide with an allylic bromide in the presence of zinc.
TL;DR: The unprotected 2 and 3-hydroxycyclohexanones 1−8 were prepared by methods that skirted as much as possible their proclivity for α-ketol rearrangement as mentioned in this paper.
Abstract: The unprotected 2- and 3-hydroxycyclohexanones 1−8 were prepared by methods that skirted as much as possible their proclivity for α-ketol rearrangement (where the possibility for such isomerization...