From Carbamoyl Enol Ether To Stereodefined Enolates: A New Route To Quaternary Stereocenters

Elvira Haimov, Organic chemistry, Technion, Haifa, Israel
Alexander Shterenberg, Technion, Haifa, Israel
Camille Oger, Organic chemistry, Technion, Haifa, Israel
Polina Smirnov, Organic chemistry, Technion, Haifa, Israel
Timothy F. Jamison, Department of Chemistry, Massachusetts Institute of Technology, Cambridge, USA
Ilan Marek, Organic chemistry, Technion, Haifa, Israel

Polypropionate motifs, consisting of alternating stereogenic centers, are found in many natural products having a wide range of biological activities.[1] The Preparation of such molecules has attracted a great deal of interest among synthetic chemists due to the challenging assembly of these stereocenters.[2]

We are proposing an alternative approach where heterosubstituted alkynes serves as starting material for the creation of four to five contiguous stereogenic centers in a single-pot operation as described in the following Scheme.

Complex molecules with two, three, four and five stereocenters were successfully prepared in good yield and good to excellent diastereomeric ratios using the proposed reactions[3]. Moreover, molecules with all carbon quaternary stereocenter where successively synthesized with good yields and excellent diastereoselectivity. The scope of our methodology is being extensively expanded by changing the nature of the first and second electrophiles.

[1] S. Omura, editor Macrolide Antibiotic Chemistry, Biology and Practice. vol. 2. Academic Press; New York:2002.

[2] N. Z. Burns,  P. S. Baran, R. W. Hoffmann, Angew. Chem. Int. Ed. 2009, 48, 2854-2867.

3 Convergent and Flexible Approach to Stereodefined Polyhydroxylated Fragments. E. Haimov, A. Shterenberg, T. F. Jamisonand I. Marek. Submitted.

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