Latest Information:


02/25/2013 - Dr. Tiffany Piou has joined our group as a post-doctoral fellow from the EPFL where she worked for Jieping Zhu.


01/24/2013 - Congratulations to Dr. Philip Wheeler for successfully defending his Ph. D. thesis. Philip has accepted a position a Sigma Aldrich in Milwaukee, Wisconsin.


01/03/2013 - Our group welcomes are new graduate students Phil Goldplatt and Fei Zhao.

RECENT PUBLICATIONS

Enantioselective Synthesis of the Tricyclic Core of FR901483 Featuring a Rhodium-Catalyzed [2+2+2] Cycloaddition

Stéphane Perreault; Tomislav Rovis

SYNTHESIS 45, 719-728 (2013)


An efficient approach to the tricyclic framework of FR901483 is described. The sequence features a [3,3]-sigmatropic rearrangement of a cyanate to an isocyanate, followed by its subsequent asymmetric rhodium-catalyzed [2+2+2] cycloaddition with a terminal alkyne for the synthesis of the indolizidine core. The aza-tricyclic core is completed using an intramolecular benzoin reaction to close the last ring of the natural product. Through a model study of the key cycloaddition, we evaluated the impact of different substituents on the tether of the alkenyl isocyanate.


Perfluorinated Taddol phosphoramidite as an L,Z-ligand on Rh(I) and Co(−I): evidence for bidentate coordination via metal–C6F5 interaction

Derek M. Dalton; Anthony K. Rappé; Tomislav Rovis

CHEMICAL SCIENCE 4, ADVANCED ARTICLE



Perfluorinated Taddol-based phosphoramidite, CKphos, is a highly selective ligand for formation of vinylogous amide cycloadducts in the Rh(I) catalyzed [2 + 2 + 2] cycloaddition of alkenyl isocyanates and alkynes. CKphos overrides substrate bias of product selectivity in the cycloaddition, providing indolizidinones in excellent yields and enantioselectivities. The excellent selectivities are attributed to a shortened Rh–P bond and coordination of one C6F5 to rhodium via a Z-type interaction, making the phosphoramidite a bidentate L,Z-ligand on rhodium. Evidence for the shortened Rh–P and C6F5 coordination is provided by X-ray, NMR and DFT computational analyses. Additionally, an anionic cobalt complex with CKphos was synthesized and two Co–C6F5 interactions are seen. The Rh(C2H4)Cl·CKphos catalyst in the [2 + 2 + 2] cycloaddition of alkenyl isocyanates and alkynes represents a rare example of metal–C6F5 Z-type interaction affecting selectivity in transition metal catalysis.



A photoisomerization-coupled asymmetric Stetter reaction: application to the total synthesis of three diastereomers of (−)-cephalimysin A

Stephen P. Lathrop; Tomislav Rovis

CHEMICAL SCIENCE 4, 1668-1673 (2013)



The total synthesis of 8-epi, 8,9-epi, and 9-epi-(−)-cephalimysin A is described. Our catalytic enantioselective synthesis takes advantage of a novel tandem photoisomerization/Stetter reaction. The approach provides rapid access to the desired spirofuranone lactam core in good yield and excellent enantioselectivity. A late stage oxidation strategy allows for flexible access to three of the four diastereomers of cephalimysin A. Access to the epimers provides further support for the correction of the initially proposed relative stereochemistry of cephalimysin A.



Asymmetric NHC-catalyzed synthesis of α-fluoroamides from readily accessible α-fluoroenals

Philip Wheeler; Harit U. Vora; Tomislav Rovis

CHEMICAL SCIENCE 4, 1674-1679 (2013)



The scope of the NHC-redox amidation has been expanded to include a variety of α,β-unsaturated aldehydes, including α-fluoro α,β-unsaturated aldehydes which give rise to enantioenriched α-fluoroamides in good to excellent yield and enantioselectivity (up to 97% ee). Enantioenriched amines may be elaborated to either diastereomer of the product in high diastereoselectivity (up to 99:1). Functionalization of the amide products to amines and fluorohydrins is also demonstrated with retention of enantioenrichment at the fluorine stereocenter.