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Karl A Scheidt

Publications and source records attributed to Karl A Scheidt.

24 records · Page 2Linked to original sources
PubMed2003

Catalytic, three-component assembly reaction for the synthesis of pyrrolidines.

[reaction: see text] Copper(I) salts catalyze the three-component assembly reaction between an alpha-diazo ester, an imine, and various alkenes and alkynes to form substituted pyrrolidines with excellent to good diastereoselectivities in high yields. The transition metal-catalyzed decomposition of the alpha-diazo compound in the presence of the imine likely generates a transient azomethine ylid that undergoes addition with various dipolarophiles in a highly convergent manner.

Journal Article↗
PubMed2003

Enantioselective indole Friedel--Crafts alkylations catalyzed by bis(oxazolinyl)pyridine-scandium(III) triflate complexes.

A highly enantioselective Friedel-Crafts alkylation of electron-rich aromatic nucleophiles catalyzed by scandium(III) triflate-pyridyl(bis)oxazoline complexes has been accomplished. The reaction involves alpha,beta-unsaturated acyl phosphonates as electrophiles and primarily substituted indoles as nucleophiles. The reactive acyl phosphonate product is converted to the corresponding ester or amide in good overall yield by adding an alcohol or amine directly to the reaction mixture.

Alkylation↗
PubMed2002

Total synthesis of (-)-bafilomycin A(1).

A highly stereoselective total synthesis of (-)-bafilomycin A(1), the naturally occurring enantiomer of this potent vacuolar ATPase inhibitor, is described. The synthesis features the highly stereoselective aldol reaction of methyl ketone 8b and aldehyde 60c and a Suzuki cross-coupling reaction of the highly functionalized advanced intermediates 12 and 39. Vinyl iodide 12 was synthesized by a 14-step sequence starting from the readily available beta-alkoxy aldehyde 14, while the vinylboronic acid component 39 was synthesized by a nine-step sequence from beta-hydroxy-alpha-methyl butyrate 44 via a sequence involving the alpha-methoxypropargylation of chiral aldehyde 49 with the alpha-methoxypropargylstannane reagent 54. Syntheses of fragments 12 and 39 also feature diastereoselective double asymmetric crotylboration reactions to set several of the critical stereocenters. The Suzuki cross-coupling of 12 and 39 provided seco ester 40, which following conversion to the seco acid underwent smooth macrolactonization to give 41. The success of the macrocyclization required that C(7)-OH be unprotected. The Mukaiyama aldol reaction between aldehyde 60c and the TMS enol ether generated from 8b provided aldol 65 with high diastereoselectivity. Finally, all silicon protecting groups were removed by treatment of the penultimate intermediate 65 with TAS-F (tris(dimethylamino)sulfonium difluorotrimethylsilicate), thereby completing the total synthesis of (-)-bafilomycin A(1).

Anti-Bacterial Agents↗
PubMed2002

Studies on the synthesis of bafilomycin A(1): stereochemical aspects of the fragment assembly aldol reaction for construction of the C(13)-C25) segment.

Highly stereoselective syntheses of aldols 8a-c corresponding to the C(13)-C(25) segment of bafilomycin A(1) were developed by routes involving fragment assembly aldol reactions of chiral aldehyde 6a and the chiral methyl ketones 7. A remote chelation effect plays a critical role in determining the stereoselectivity of the key aldol coupling of 6a and the lithium enolate of 7b. The protecting group for C(23)-OH of the chiral aldehyde fragment also influences the selectivity of the lithium enolate aldol reaction. In contrast, the aldol reaction of 6a and the chlorotitanium enolates of 7a,c were much less sensitive to the nature of the C(15)-hydroxyl protecting group. Studies of the reactions of chiral aldehydes with Takai's (gamma-methoxyallyl)chromium reagent 40 are also described. The stereoselectivity of these reactions is also highly dependent on the protecting groups and stereochemistry of the chiral aldehyde substrates.

Aldehydes↗
PubMed2002

An NMR method for assigning relative stereochemistry to beta-hydroxy ketones deriving from aldol reactions of methyl ketones.

We describe a simple 1H NMR analysis that permits the stereochemistry of beta-hydroxy ketones to be assigned by visual inspection of the ABX patterns for the alpha-methylene unit of the beta-hydroxy ketone in the 1H NMR spectra. This method has been verified by application to a wide range of beta-hydroxy ketones deriving from aldol reactions of chiral aldehydes with a variety of chiral and achiral methyl ketone enolates (see Tables 1 and 2). The stereochemistry of 54 of these compounds have been assigned by rigorous chemical methods.

Catalysis↗