Azaenolates of 2-Chloromethyl-4-methoxymethyl-5-phenyl-2-oxazoline − A Highly Diastereo- and Enantioselective Synthesis of Oxazolinyloxiranes

Abstract

The oxazoline‐derived titanium azaenolate 6 couples highly stereoselectively with aldehydes affording highly optically pure oxazolinyloxiranes 7. The epoxide 7a has been deblocked to form the optically pure formyl oxirane 9. In contrast, the corresponding boron azaenolates 2 and 3 couple with very poor or no stereoselectivity. Lithium, aluminum and tin azaenolates have also been shortly studied.

Oxazolinyloxiranyllithium-Mediated Stereoselective Synthesis of α-Epoxy-β-amino Acids

“…The ( S , S ) absolute configuration of the major diastereomer of oxazolinyloxirane (−)- 1e (dr 98/2) was deduced by combining the results of a 2D-NOESY Phase-Sensitive experiment and calculations (see Supporting Information) and was in agreement with what reported for other optically active oxazolinyloxiranes prepared as just described for (−)- 1e (see ref ).…”

“…We reasoned it could be done using a chiral oxazolinyloxirane as the starting material. Enantiomeric oxazolinyloxiranes (+)- and (−)- 1e 12 (Schemes and ) were prepared starting from the chiral 2-chloromethyl-2-oxazolines (+)- and (−)- 9 by lithiation followed by lithium−titanium transmetalation as similarly reported . Then, the oxazolinyloxirane ( S , S )-(−)- 1e (dr 98/2, ee > 99%, [α] D −79) was lithiated and reacted with 3a to give the optically active (3 R ,4 R ,7 S ,11 S ) - ( + ) - 4i as a single diastereoisomer in a very good yield (75%) (Scheme ).…”

Theoretical Study on the Structural Properties of Various Solvated Metalated 3-Halo-1-azaallylic Anions

“…In general, 3-halo-1-azaallylic anions 5 are mostly synthesized using lithium diisopropylamide (LDA) as a base for the deprotonation of the starting imines 4 . However, to influence the structural, coordination, and reactivity properties of 1-azaallylic anions − and to increase the stereoselectivity in organic reactions with these species and related enolates, such as additions across aldehydes − or imines, , it can be of considerable benefit to introduce another metal counterion to the anion (as shown above for the zincated 3-chloro-1-azaallylic anion). ,, The addition of a salt of the desired counterion to the lithiated anions will result in the transmetalation of the starting 3-halo-1-azaallylic anions. In this part, the driving force for the transmetalation reaction will be discussed.…”

Expedient routes to 4,4-dialkyl- 5-methylene-1,3-oxazolines

“…Recent investigations [1][2][3][4][5][6][7][8][9][10][11] have shown that 1,3-oxazolines (4,5-dihydro-oxazoles or 2-oxazolines)…”