Steven D. Burke

Intramolecular phosphine-directed hydroformylation: application to the total synthesis of (+)-phyllanthocin

Abstract The temporary incorporation of a coordinating phosphine residue [ m -(Ph 2 P)C 6 H 4 CO] into the tetracyclic phyllanthocin precursor 1a directed the [(COD)RhOAc] 2 -catalyzed hydroformylation of 1d largely to the desired C(3) position. This “intramolecular hydroformylation” strategy substantially improves a key transformation in the total synthesis of (+)-phyllanthocin.

Synthesis of a C(22)a˚C(34) halichondrin precursor via a double dioxanone-to-dihydropyran rearrangement

An enantioselective synthesis of the C(22)a˚C(34) halichondrin segment1 in nine steps from mesocyclopenten-1,4-diol (5) is described. Asymmetric bis(epoxidation) of meso bis(allylic alcohol)8 and two concurrent [3,3] sigmatropic rearrangements of bis(dioxanone)2 are featured.

An enolate claisen route to c-pyranosides : Development and application to an ionophore synthon

Abstract A new method for the stereoselective synthesis of dihydropyrans of various substitution patterns is described, involving the Ireland ester enolate Claisen rearrangements of 6-alkenyl-1,4-dioxan-2-ones. The method has been applied to an enantioselective synthesis of the “left-wing” tetrahydropyran portion 2 of the ionophore antibiotic indanomycin ( 1 ). The synthetic sequence employed for the production of 2 proceeded in greater than 29% overall yield in 12 steps from the allylic alcohol 26 , thus underscoring the utility of the heterocycle synthesis described.

A Citric Acid-Derived Ligand for Modular Functionalization of Metal Oxide Surfaces via “Click” Chemistry

Citric acid is a widely used surface-modifying ligand for growth and processing of a variety of nanoparticles; however, the inability to easily prepare derivatives of this molecule has restricted the development of versatile chemistries for nanoparticle surface functionalization. Here, we report the design and synthesis of a citric acid derivative bearing an alkyne group and demonstrate that this molecule provides the ability to achieve stable, multidentate carboxylate binding to metal oxide nanoparticles, while also enabling subsequent multistep chemistry via the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The broad utility of this strategy for the modular functionalization of metal oxide surfaces was demonstrated by its application in the CuAAC modification of ZnO, Fe(2)O(3), TiO(2), and WO(3) nanoparticles.

Synthesis of (+)-didemniserinolipid B: application of a 2-allyl-4-fluorophenyl auxiliary for relay ring-closing metathesis.

The synthesis of didemniserinolipid B utilizing a ketalization/ring-closing metathesis (K/RCM) strategy is described. In the course of this work, a novel 2-allyl-4-fluorophenyl auxiliary for relay ring-closing metathesis (RRCM) was developed, which increased the yield of the RCM. The resulting 6,8-dioxabicyclo[3.2.1]octene core was selectively functionalized by complimentary dihydroxylation and epoxidation routes to install the C10 axial alcohol. This bicyclic ketal core was further functionalized by etherification and an alkene cross metathesis with an unsaturated alpha-phenylselenyl ester en route to completing the total synthesis.

2,3-Disubstituted tetrahydrofuran synthesis via radical and anionic cyclization

Abstract Cyclization of the radicals derived from Cbond homolysis as well as via 1,5-hydrogen atom transfer afforded tetrahydrofurans in high yield. An alternative anionic cyclization method provided the anti diastereomer preferentially.

An expeditious synthesis of the C(1)-C(14) subunit of halichondrin B

Abstract The synthesis of the C(1)-C(14) segment 1 of halichondrin B was achieved efficiently. Featured are the pinacol rearrangement of α-hydroxymesylate 9 , the intramolecular Michael addition of 11 , and the one-pot multistep conversion of 13 to 1 .

Stereocontrolled one-pot conversions of α-alkoxy esters to syn- and anti-1,2-diol derivatives

Abstract Complementary one-pot methods for the sequential addition of carbon and hydride nucleophiles to α-alkoxy esters leading to syn or anti mono-protected vicinal glycol derivatives are described.

The ester enolate claisen rearrangement. Total synthesis of (±)-ethisolide

Abstract A total synthesis of the mold metabolite ethisolide (1a) is described, wherein a glycolate ester enolate Claisen rearrangement and an acid-induced intramolecular bis-transesterification are key steps.

The dioxanone-to-dihydropyran Claisen rearrangement. Synthesis of C(7)-C(13) fragments of erythronolides A and B

Abstract Iterative applications of the dioxanone-to-dihydropyran Claisen rearrangement have resulted in the efficient conversion of ( S )-(−)-ethyl lactate to the erythronolide A and B C(7)C(13) subunits 19 , 23 , and 27 via the common synthetic intermediates 13 and 22 .