Enantioselective Construction of Arrays of Stereogenic Centers
Single enantiomer synthesis is of increasing importance in pharmaceutical
production. It is essential that practical and scalable procedures be developed
for controlling the absolute configuration of new stereogenic centers as they
are formed. In the previous column, recent advances
for the preparation of single stereogenic centers were covered. The construction
of more extended arrays of stereogenic centers, which is also is important, is
Enantioselective aldol reactions also can be used to create arrays of stereogenic centers. Two elegant α-amino anion approaches have recently been published. Fujie Tanaka and Carlos F. Barbas III of the Scripps Institute, La Jolla, have shown (Org. Lett. 2004, 6, 3541. ) that L-proline catalyzes the addition of the aldehyde 6 to other aldehydes with high enantio- and diastereocontrol. Keiji Maruoka of Kyoto University has developed (J. Am. Chem. Soc. 2004, 126, 9685. ) a chiral phase transfer catalyst that mediates the addition of the ester 9 to aldehydes, again with high enantio- and diastereocontrol.
Michael addition can also be used to establish arrays of stereogenic centers. Hiyoshuzi Kotsuki of Kochi University has shown (J. Am. Chem. Soc. 2004, 126, 9558. ) that the chiral DMAP derivative 13 mediates the addition of cyclic ketones such as 11 to nitrostyrene 12 with high enantio- and diastereocontrol. Acyclic aldehydes also add with high stereocontrol. Li Deng of Brandeis University has developed (Angew. Chem. Int. Ed. 2005, 44, 105. ) a quinine-based catalyst 16 that directs the addition of 12 to a single face of the cyclic β-ketoester 15, establishing adjacent ternary and quaternary centers. For the conversion of the nitro group to a nitrile without epimerization, see Angew. Chem. Int. Ed. 2005, 44, 612, ).
The construction of more extended arrays is also possible. Justin Du Bois of Stanford University has reported (Angew. Chem. Int. Ed. 2004, 43, 4349. ) diastereoselective remote functionalization using C-H insertion of a sulfamate such as 18 to give the oxathiazinane 19, which on reaction with an allyl silane gives the alkylated product 20 with high diastereocontrol. Note that the oxygen of 20 is activated as a leaving group.