Diastereoselective Imino-Aldol Condensation of Chiral 3-(p-Tolylsulfinyl)-2-furaldimine and Ester Enolates.

Abstract

The biological importance of b-lactams as antibiotics has stimulated the development of efficient procedures for the preparation of this class of compounds. Of the synthetic routes to b-lactams that have been reported, Lewis acid-promoted [1][2][3] and catalyzed [4][5][6][7][8][9][10][11] condensations of imines with silyl ketene acetals and imino-aldol condensations with ester enolates are powerful methods which involve the efficient construction of stereogenic centers of the b-lactam moiety.12-14) Chiral versions of these condensations have also been devised by the use of imines with a chiral auxiliary, [1][2][3][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] chiral ester enolate derivatives, [30][31][32][33][34][35][36] and chiral Lewis acids. [37][38][39][40][41] In the course of our studies on remote asymmetric induction using chiral sulfoxides, we previously reported the lanthanoid triflate-catalyzed Mukaiyama aldol reaction of sulfinyl aldehyde 1 with silyl ketene acetals.42) Highly remote stereocontrol of 1 in this reaction led us to examine an enantioselective route to b-lactams by diastereoselective condensation of an aldimine 2 derived from 1 with silyl ketene acetals as well as enolates. We would like to report the details of this condensation using the sulfinyl furaldimine 2. 43)Initial experiments were performed with a typical silyl ketene acetal 3a in the presence of a lanthanoid triflate, which is found to be effective for the aldol condensation of the aldehyde 1. 42) In fact, the reaction using Yb(OTf) 3 proceeded smoothly; diastereoisomeric b-amino esters 4a and 6a were produced in a ratio of 1 : 1 (Table 1, entry 1).44) The use of other lanthanoid triflates did not improve the diastereoselectivity. The relative stereochemistry of the two products 4a and 6a was not determined at this stage; however, the configuration at the C(3) position was later determined (vide infra). We then turned our attention to using an ester enolate

Novel and Recent Synthesis and Applications of β-Lactams

“…The condensation of chiral furaldimines with lithium esther enolates has been reported as an efficient route to chiral furyl b-lactams [138]. The (4R)-b-lactam was formed with high diastereoselectivity.…”

Development of Catalytic Enantioselective Mannich Reactions Using Esters

“…The asymmetric Mannich reaction of simple esters with imines is one of the most important methods to synthesize optically active β-amino esters directly without any redox process; such compounds are found in many natural products and drug structures. Although catalytic enantioselective Mannich reactions of functionalized amides have been developed recently, − catalytic enantioselective Mannich reactions of simple esters such as alkyl acetates are still difficult and have not yet been achieved, and stoichiometric amounts of strong bases and chiral auxiliaries have always been employed for asymmetric Mannich reactions of the esters. − However, the simple esters are stable, readily available, and often employed as solvents in organic synthesis; therefore, they are promising pronucleophiles for the reactions. Our group has been focusing on developing strong Brønsted base-catalyzed reactions and has realized catalytic enantioselective 1,4-addition reactions of weakly acidic carbon pronucleophiles including simple amides and esters. − The key to the success was designing strongly basic reaction intermediatestermed the “product base.” − Recently, we reported catalytic enantioselective Mannich reactions of simple amides by using a potassium salt of chiral bisoxazoline (Box) as a chiral ligand .…”