Ketones and related substrate classes undergo enol silane formation in the presence of trimethyls... more Ketones and related substrate classes undergo enol silane formation in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) and triethylamine, reaction conditions that also promote the in situ ionization of allyl propionates. When these two processes are performed in one pot, allylation of the ketone is observed in high yields. Aldehydes, esters, and thioesters also serve as enol silane precursors under these conditions. When unsymmetrical allyl cations are employed, regioselectivity depends upon the electronic and steric properties of the substituents.
Supporting Information I. General All air-and moisture-sensitive reactions were carried out under... more Supporting Information I. General All air-and moisture-sensitive reactions were carried out under nitrogen in a glovebox or under argon using Schlenk techniques. CH 2 Cl 2 was purified by passage through a neutral alumina column under argon. CHCl 3 and Cy 2 NMe (Aldrich) were distilled from CaH 2 prior to use. CuI (99.999%, Strem) was used as received. Ethyl propiolate (Aldrich) was distilled under vacuum.
A slight excess of silyl trifluoromethanesulfonate mediates a tandem enol silane formation-Mukaiy... more A slight excess of silyl trifluoromethanesulfonate mediates a tandem enol silane formation-Mukaiyama aldol reaction in the presence of Hunig's base. Preformation of the enol silane is unnecessary for efficient reactions, which proceed in 75-97% yield for the addition of aryl methyl ketones and acetate esters to non-enolizable aldehydes. Mechanistic data suggests that free amine is crucial for full conversion.
(Trimethylsilyl)acetonitrile reacts smoothly with dimethyl acetals in the presence of stoichiomet... more (Trimethylsilyl)acetonitrile reacts smoothly with dimethyl acetals in the presence of stoichiometric trimethylsilyl trifluoromethanesulfonate (TMSOTf) to yield β-methoxynitriles. The ideal substrates for this reaction are acetals derived from aromatic aldehydes. Elimination to the corresponding α,β-unsaturated nitriles is observed as the major product in the case of electron-rich acetals. A mechanistic hypothesis that includes isomerization of the silylnitrile to a nucleophilic N-silyl ketene imine is presented.
... David A. Evans,* Karl A. Scheidt, and C. Wade Downey. Department of Chemistry and Chemical Bi... more ... David A. Evans,* Karl A. Scheidt, and C. Wade Downey. Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138. Org. Lett. ... We wish to thank Dr.Mick Dart of Abbott Laboratories for providing a sample of racemic epibatidine. ...
Various ketones, esters, amides, and thioesters add in high yield to dimethyl acetals in the pres... more Various ketones, esters, amides, and thioesters add in high yield to dimethyl acetals in the presence of silyl trifluoromethanesulfonates and an amine base. Acetals derived from aryl, unsaturated, and aliphatic aldehydes are all effective substrates. The reaction proceeds in a single reaction flask, with no purification of the intermediate enol silane necessary.
Three asymmetric pathways to the kavalactones have been developed. The first method is chiral aux... more Three asymmetric pathways to the kavalactones have been developed. The first method is chiral auxiliary-based and utilizes aldol reactions of N-acetyl thiazolidinethiones followed by a malonate displacement/decarboxylation reaction. The second approach uses the asymmetric catalytic Mukaiyama additions of dienolate nucleophile equivalents developed by Carreira and Sato. Finally, tin-substituted intermediates, prepared by either of these routes, can serve as advanced general precursors of kavalactone derivatives via Pd(0)-catalyzed Stille couplings with aryl halides.
Journal of the American Chemical Society, Sep 1, 2000
C 2-symmetric bis(oxazoline)-Cu(II) complexes 1 catalyze the Mukaiyama Michael reaction of alkyli... more C 2-symmetric bis(oxazoline)-Cu(II) complexes 1 catalyze the Mukaiyama Michael reaction of alkylidene malonates and enolsilanes. The use of hexafluoro-2-propanol is essential to induce catalyst turnover. High enantioselectivities are exhibited by bulky alkylidene malonate-substituents using catalyst 1a. The glutarate ester products are readily decarboxylated to provide chiral 1,5-dicarbonyl synthons. Crystallographic characterization of substrate-catalyst complexes provides insight into the binding event with these catalysts and affords a rationale for the observed facial selectivities.
Abstract Trimethylsilyl trifluoromethanesulfonate (TMSOTf) and a trialkylamine base promote the c... more Abstract Trimethylsilyl trifluoromethanesulfonate (TMSOTf) and a trialkylamine base promote the conversion of acetonitrile to its silyl ketene imine in situ when acetonitrile is employed as solvent. Residual TMSOTf acts as a Lewis acid catalyst to activate acetals and nitrones in the reaction mixture, yielding β-methoxynitriles and β-(silyloxy)aminonitriles, respectively. Some reaction products undergo elimination under the reaction conditions to provide the α,β-unsaturated nitrile directly.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Supporting Information General Information. Nitroaldol reactions were carried out in screw cap vi... more Supporting Information General Information. Nitroaldol reactions were carried out in screw cap vials with magnetic stirring; no special precautions were taken to exclude water or air from the reaction vessel. Cu(OAc) 2 •H 2 O, nitromethane and ethanol (200 proof) were used as received. Aldehydes were obtained from commercial sources and were distilled, recrystallized or filtered through a plug of neutral alumina prior to use except 4-nitrobenzaldehyde, 2-nitrobenzaldehyde and 2-methoxybenzaldehyde which were used as received. Purification of reaction products was carried out by flash chromatography using EM Reagent silica gel 60 (230-400 mesh). Analytical thin layer chromatography was performed on EM Reagent 0.25 mm silica gel 60-F plates. Visualization was accomplished with UV light and either ceric ammonium nitrate or permanganate stain, followed by heating. Optical rotations were measured on a Jasco DIP-0181 digital polarimeter with a sodium lamp and are reported as follows: [α] λ T °C (c = g/100 mL, solvent). Infrared spectra were recorded on a Perkin Elmer 1600 series FT-IR spectrometer. 1 H-NMR spectra were recorded on a Varian Inova-500 (500 MHz) or on a Varian Mercury 400 (400 MHz) spectrometer and are reported in ppm using solvent as an internal standard (CDCl 3 at 7.26 ppm). Data are reported as app = apparent, s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, b = broad; integration; coupling constant(s) in Hz. Proton-decoupled 13 C-NMR spectra were recorded on a Varian Inova-500 (125 MHz) or on a Varian Mercury 400 (100 MHz) spectrometer and are reported in ppm using solvent as an internal standard (CDCl 3 at 77.0 ppm). Low-and high-resolution mass spectra were obtained on Jeol AX-505 or SX-102 spectrometers in the Harvard University Mass Spectrometry Laboratory. General Procedure: Copper acetate catalyzed direct nitroaldol reaction of nitromethane with aldehydes. Ligand 2 (19.7 mg, 0.055 mmol) and Cu(OAc) 2 •H 2 O (10.0 mg, 0.05 mmol) were added to a screw cap vial containing a stir bar. Ethanol (1.5 mL) was added and the mixture was stirred for 1 hour. To the resulting clear blue solution nitromethane (0.54 mL, 10 mmol) and aldehyde (1 mmol) were added. After stirring for the amount of time indicated the volatile components were removed under reduced pressure and the crude product purified by column chromatography. Stereochemical Assignments: The absolute configurations of compounds 3a, 3f, 3g, 3j, 3k, 3l, 3m and 3o were assigned by comparison of their optical rotations with literature values. 1-3 The absolute configuration of compound 3c was assigned by Mosher ester analysis 4 of the derived N-Boc aminoalcohol. These assignments showed the reaction to be stereochemically homogeneous, giving products of (R) configuration. The absolute configurations of the remaining examples 3b, 3d, 3e, 3h, 3i and 3n were assigned by analogy.
European Journal of Organic Chemistry, Jul 19, 2013
Ketones, amides, and thioesters form enol silanes and add to Nphenylnitrones in one pot in the pr... more Ketones, amides, and thioesters form enol silanes and add to Nphenylnitrones in one pot in the presence of trimethylsilyl trifluoromethanesulfonate and trialkylamine. The reaction is general to a range of silyl trifluoromethanesulfonates and Nphenylnitrones. The β-(silyloxy)amino carbonyl products are stable to chromatography and can be isolated in 63-99% yield.
Supporting Information General Information. Aldol reactions were carried out nitrogen atmosphere ... more Supporting Information General Information. Aldol reactions were carried out nitrogen atmosphere with a septum cap and magnetic stirring; no special precautions were taken to exclude water from the reaction vessel. Toluene and CH 2 Cl 2 were purified by passage through a bed of activated alumina. 1 MeOH was distilled from Mg(OMe) 2. All other reaction solvents were used as received. Benzaldehyde, 2-naphthaldehyde, TESOTf, imidazole, Me(OMe)NH 2 Cl, and AgOTf were used as received from Aldrich Chemical Co. Other aldehydes were distilled from suitable desiccants. NiCl 2 was used as received from Alfa/Aesar Chemical Co. 2,6-Lutidine was distilled from CaH 2 prior to use. TMSOTf was distilled prior to use. Reagents were purified prior to use unless otherwise stated following the guidelines of Perrin and Armarego. 2 Purification of reaction products was carried out by flash chromatography using EM Reagent silica gel 60 (230-400 mesh). Analytical thin layer chromatography was performed on EM Reagent 0.25 mm silica gel 60-F plates. Visualization was accomplished with UV light and ceric ammonium nitrate stain, followed by heating. Optical rotations were measured on a Jasco DIP-0181 digital polarimeter with a sodium lamp and are reported as follows: [α] λ T °C (c = g/100 mL, solvent). Infrared spectra were recorded on a Perkin Elmer 1600 series FT-IR spectrometer. 1 H-NMR spectra were recorded on a Varian Inova-500 (500 MHz) spectrometer and are reported in ppm using solvent as an internal standard (CDCl 3 at 7.26 ppm). Data are reported as (ap = apparent, s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, b = broad; coupling constant(s) in Hz; integration. Proton-decoupled 13 C-NMR spectra were recorded on a Varian Mercury 400 (100 MHz) spectrometer and are reported in ppm using solvent as an internal standard (CDCl 3 at 77.0 ppm). Low-and highresolution mass spectra were obtained on Jeol AX-505 or SX-102 spectrometers in the Harvard University Mass Spectrometry Laboratory. General Procedure: Nickel-catalyzed direct aldol reaction of N-propionylthiazolidinethione with aldehydes To a 10-mL round-bottom flask in a glove box was added Ni(OTf) 2 (t-BuBox) (0.10 mmol, 0.1 equiv). The flask was fitted with a septum cap and removed to ambient atmosphere. The nickel complex was dissolved in 50 µL CH2Cl2 and 200 µL toluene. After cooling to-78 °C, 2,6-lutidine (3.33 mmol, 3.33 equiv), Npropionylthiazolidinethione (1.0 mmol, 1 equiv), aldehyde (1.2 mmol, 1.2 equiv), and TMSOTf (1.25 mmol, 1.25 equiv) were added sequentially. The yellow reaction mixture was stirred 12-36 h until complete by TLC, then filtered directly through a plug of silica gel (5.0 cm x 5.0 cm) and eluted with Et 2 O. The eluent was concentrated in vacuo and dissolved in THF (10 mL) and treated with 1.0 N HCl (2 mL). After stirring 1 h, the mixture was diluted with Et 2 O (20 mL) and water (20 mL). The layers were separated and the organic layer was extracted sequentially with saturated NaHCO 3 (20 mL) and brine (20 mL). The organic layer was dried over Na 2 SO 4 for 1 h, then filtered through a cotton plug and concentrated in vacuo. A sample was subjected to HPLC analysis to determine enantio-and diastereoselectivity. Flash chromatography (10-20% EtOAc/hexanes) afforded the pure major diastereomer, except where otherwise noted.
The desired acetals, important substrates in organic chemistry, are available via a two-step sequ... more The desired acetals, important substrates in organic chemistry, are available via a two-step sequence. Both aromatic and aliphatic aldehydes are suitable reactants. In the case of substrate (VIIId), addition of dichloromethane is necessary in the etherification step due to insolubility of the hemiaminal intermediate. With the furyl derivative (VIIIf), the reaction time with MeOH is 24h. If alcohols other than MeOH are used, the acid catalyst has to be changed to Sc(O-Tf) 3 in order to get higher yields.-(HALLI,
Ketones and related substrate classes undergo enol silane formation in the presence of trimethyls... more Ketones and related substrate classes undergo enol silane formation in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) and triethylamine, reaction conditions that also promote the in situ ionization of allyl propionates. When these two processes are performed in one pot, allylation of the ketone is observed in high yields. Aldehydes, esters, and thioesters also serve as enol silane precursors under these conditions. When unsymmetrical allyl cations are employed, regioselectivity depends upon the electronic and steric properties of the substituents.
Supporting Information I. General All air-and moisture-sensitive reactions were carried out under... more Supporting Information I. General All air-and moisture-sensitive reactions were carried out under nitrogen in a glovebox or under argon using Schlenk techniques. CH 2 Cl 2 was purified by passage through a neutral alumina column under argon. CHCl 3 and Cy 2 NMe (Aldrich) were distilled from CaH 2 prior to use. CuI (99.999%, Strem) was used as received. Ethyl propiolate (Aldrich) was distilled under vacuum.
A slight excess of silyl trifluoromethanesulfonate mediates a tandem enol silane formation-Mukaiy... more A slight excess of silyl trifluoromethanesulfonate mediates a tandem enol silane formation-Mukaiyama aldol reaction in the presence of Hunig's base. Preformation of the enol silane is unnecessary for efficient reactions, which proceed in 75-97% yield for the addition of aryl methyl ketones and acetate esters to non-enolizable aldehydes. Mechanistic data suggests that free amine is crucial for full conversion.
(Trimethylsilyl)acetonitrile reacts smoothly with dimethyl acetals in the presence of stoichiomet... more (Trimethylsilyl)acetonitrile reacts smoothly with dimethyl acetals in the presence of stoichiometric trimethylsilyl trifluoromethanesulfonate (TMSOTf) to yield β-methoxynitriles. The ideal substrates for this reaction are acetals derived from aromatic aldehydes. Elimination to the corresponding α,β-unsaturated nitriles is observed as the major product in the case of electron-rich acetals. A mechanistic hypothesis that includes isomerization of the silylnitrile to a nucleophilic N-silyl ketene imine is presented.
... David A. Evans,* Karl A. Scheidt, and C. Wade Downey. Department of Chemistry and Chemical Bi... more ... David A. Evans,* Karl A. Scheidt, and C. Wade Downey. Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138. Org. Lett. ... We wish to thank Dr.Mick Dart of Abbott Laboratories for providing a sample of racemic epibatidine. ...
Various ketones, esters, amides, and thioesters add in high yield to dimethyl acetals in the pres... more Various ketones, esters, amides, and thioesters add in high yield to dimethyl acetals in the presence of silyl trifluoromethanesulfonates and an amine base. Acetals derived from aryl, unsaturated, and aliphatic aldehydes are all effective substrates. The reaction proceeds in a single reaction flask, with no purification of the intermediate enol silane necessary.
Three asymmetric pathways to the kavalactones have been developed. The first method is chiral aux... more Three asymmetric pathways to the kavalactones have been developed. The first method is chiral auxiliary-based and utilizes aldol reactions of N-acetyl thiazolidinethiones followed by a malonate displacement/decarboxylation reaction. The second approach uses the asymmetric catalytic Mukaiyama additions of dienolate nucleophile equivalents developed by Carreira and Sato. Finally, tin-substituted intermediates, prepared by either of these routes, can serve as advanced general precursors of kavalactone derivatives via Pd(0)-catalyzed Stille couplings with aryl halides.
Journal of the American Chemical Society, Sep 1, 2000
C 2-symmetric bis(oxazoline)-Cu(II) complexes 1 catalyze the Mukaiyama Michael reaction of alkyli... more C 2-symmetric bis(oxazoline)-Cu(II) complexes 1 catalyze the Mukaiyama Michael reaction of alkylidene malonates and enolsilanes. The use of hexafluoro-2-propanol is essential to induce catalyst turnover. High enantioselectivities are exhibited by bulky alkylidene malonate-substituents using catalyst 1a. The glutarate ester products are readily decarboxylated to provide chiral 1,5-dicarbonyl synthons. Crystallographic characterization of substrate-catalyst complexes provides insight into the binding event with these catalysts and affords a rationale for the observed facial selectivities.
Abstract Trimethylsilyl trifluoromethanesulfonate (TMSOTf) and a trialkylamine base promote the c... more Abstract Trimethylsilyl trifluoromethanesulfonate (TMSOTf) and a trialkylamine base promote the conversion of acetonitrile to its silyl ketene imine in situ when acetonitrile is employed as solvent. Residual TMSOTf acts as a Lewis acid catalyst to activate acetals and nitrones in the reaction mixture, yielding β-methoxynitriles and β-(silyloxy)aminonitriles, respectively. Some reaction products undergo elimination under the reaction conditions to provide the α,β-unsaturated nitrile directly.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Supporting Information General Information. Nitroaldol reactions were carried out in screw cap vi... more Supporting Information General Information. Nitroaldol reactions were carried out in screw cap vials with magnetic stirring; no special precautions were taken to exclude water or air from the reaction vessel. Cu(OAc) 2 •H 2 O, nitromethane and ethanol (200 proof) were used as received. Aldehydes were obtained from commercial sources and were distilled, recrystallized or filtered through a plug of neutral alumina prior to use except 4-nitrobenzaldehyde, 2-nitrobenzaldehyde and 2-methoxybenzaldehyde which were used as received. Purification of reaction products was carried out by flash chromatography using EM Reagent silica gel 60 (230-400 mesh). Analytical thin layer chromatography was performed on EM Reagent 0.25 mm silica gel 60-F plates. Visualization was accomplished with UV light and either ceric ammonium nitrate or permanganate stain, followed by heating. Optical rotations were measured on a Jasco DIP-0181 digital polarimeter with a sodium lamp and are reported as follows: [α] λ T °C (c = g/100 mL, solvent). Infrared spectra were recorded on a Perkin Elmer 1600 series FT-IR spectrometer. 1 H-NMR spectra were recorded on a Varian Inova-500 (500 MHz) or on a Varian Mercury 400 (400 MHz) spectrometer and are reported in ppm using solvent as an internal standard (CDCl 3 at 7.26 ppm). Data are reported as app = apparent, s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, b = broad; integration; coupling constant(s) in Hz. Proton-decoupled 13 C-NMR spectra were recorded on a Varian Inova-500 (125 MHz) or on a Varian Mercury 400 (100 MHz) spectrometer and are reported in ppm using solvent as an internal standard (CDCl 3 at 77.0 ppm). Low-and high-resolution mass spectra were obtained on Jeol AX-505 or SX-102 spectrometers in the Harvard University Mass Spectrometry Laboratory. General Procedure: Copper acetate catalyzed direct nitroaldol reaction of nitromethane with aldehydes. Ligand 2 (19.7 mg, 0.055 mmol) and Cu(OAc) 2 •H 2 O (10.0 mg, 0.05 mmol) were added to a screw cap vial containing a stir bar. Ethanol (1.5 mL) was added and the mixture was stirred for 1 hour. To the resulting clear blue solution nitromethane (0.54 mL, 10 mmol) and aldehyde (1 mmol) were added. After stirring for the amount of time indicated the volatile components were removed under reduced pressure and the crude product purified by column chromatography. Stereochemical Assignments: The absolute configurations of compounds 3a, 3f, 3g, 3j, 3k, 3l, 3m and 3o were assigned by comparison of their optical rotations with literature values. 1-3 The absolute configuration of compound 3c was assigned by Mosher ester analysis 4 of the derived N-Boc aminoalcohol. These assignments showed the reaction to be stereochemically homogeneous, giving products of (R) configuration. The absolute configurations of the remaining examples 3b, 3d, 3e, 3h, 3i and 3n were assigned by analogy.
European Journal of Organic Chemistry, Jul 19, 2013
Ketones, amides, and thioesters form enol silanes and add to Nphenylnitrones in one pot in the pr... more Ketones, amides, and thioesters form enol silanes and add to Nphenylnitrones in one pot in the presence of trimethylsilyl trifluoromethanesulfonate and trialkylamine. The reaction is general to a range of silyl trifluoromethanesulfonates and Nphenylnitrones. The β-(silyloxy)amino carbonyl products are stable to chromatography and can be isolated in 63-99% yield.
Supporting Information General Information. Aldol reactions were carried out nitrogen atmosphere ... more Supporting Information General Information. Aldol reactions were carried out nitrogen atmosphere with a septum cap and magnetic stirring; no special precautions were taken to exclude water from the reaction vessel. Toluene and CH 2 Cl 2 were purified by passage through a bed of activated alumina. 1 MeOH was distilled from Mg(OMe) 2. All other reaction solvents were used as received. Benzaldehyde, 2-naphthaldehyde, TESOTf, imidazole, Me(OMe)NH 2 Cl, and AgOTf were used as received from Aldrich Chemical Co. Other aldehydes were distilled from suitable desiccants. NiCl 2 was used as received from Alfa/Aesar Chemical Co. 2,6-Lutidine was distilled from CaH 2 prior to use. TMSOTf was distilled prior to use. Reagents were purified prior to use unless otherwise stated following the guidelines of Perrin and Armarego. 2 Purification of reaction products was carried out by flash chromatography using EM Reagent silica gel 60 (230-400 mesh). Analytical thin layer chromatography was performed on EM Reagent 0.25 mm silica gel 60-F plates. Visualization was accomplished with UV light and ceric ammonium nitrate stain, followed by heating. Optical rotations were measured on a Jasco DIP-0181 digital polarimeter with a sodium lamp and are reported as follows: [α] λ T °C (c = g/100 mL, solvent). Infrared spectra were recorded on a Perkin Elmer 1600 series FT-IR spectrometer. 1 H-NMR spectra were recorded on a Varian Inova-500 (500 MHz) spectrometer and are reported in ppm using solvent as an internal standard (CDCl 3 at 7.26 ppm). Data are reported as (ap = apparent, s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, b = broad; coupling constant(s) in Hz; integration. Proton-decoupled 13 C-NMR spectra were recorded on a Varian Mercury 400 (100 MHz) spectrometer and are reported in ppm using solvent as an internal standard (CDCl 3 at 77.0 ppm). Low-and highresolution mass spectra were obtained on Jeol AX-505 or SX-102 spectrometers in the Harvard University Mass Spectrometry Laboratory. General Procedure: Nickel-catalyzed direct aldol reaction of N-propionylthiazolidinethione with aldehydes To a 10-mL round-bottom flask in a glove box was added Ni(OTf) 2 (t-BuBox) (0.10 mmol, 0.1 equiv). The flask was fitted with a septum cap and removed to ambient atmosphere. The nickel complex was dissolved in 50 µL CH2Cl2 and 200 µL toluene. After cooling to-78 °C, 2,6-lutidine (3.33 mmol, 3.33 equiv), Npropionylthiazolidinethione (1.0 mmol, 1 equiv), aldehyde (1.2 mmol, 1.2 equiv), and TMSOTf (1.25 mmol, 1.25 equiv) were added sequentially. The yellow reaction mixture was stirred 12-36 h until complete by TLC, then filtered directly through a plug of silica gel (5.0 cm x 5.0 cm) and eluted with Et 2 O. The eluent was concentrated in vacuo and dissolved in THF (10 mL) and treated with 1.0 N HCl (2 mL). After stirring 1 h, the mixture was diluted with Et 2 O (20 mL) and water (20 mL). The layers were separated and the organic layer was extracted sequentially with saturated NaHCO 3 (20 mL) and brine (20 mL). The organic layer was dried over Na 2 SO 4 for 1 h, then filtered through a cotton plug and concentrated in vacuo. A sample was subjected to HPLC analysis to determine enantio-and diastereoselectivity. Flash chromatography (10-20% EtOAc/hexanes) afforded the pure major diastereomer, except where otherwise noted.
The desired acetals, important substrates in organic chemistry, are available via a two-step sequ... more The desired acetals, important substrates in organic chemistry, are available via a two-step sequence. Both aromatic and aliphatic aldehydes are suitable reactants. In the case of substrate (VIIId), addition of dichloromethane is necessary in the etherification step due to insolubility of the hemiaminal intermediate. With the furyl derivative (VIIIf), the reaction time with MeOH is 24h. If alcohols other than MeOH are used, the acid catalyst has to be changed to Sc(O-Tf) 3 in order to get higher yields.-(HALLI,
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