Chiral building-blocks by chemoenzymatic desymmetrization of 2-ethyl-1,3-propanediol for the preparation of biologically active natural products

Dinuclear Zinc‐Catalyzed Asymmetric Desymmetrization of Acyclic 2‐Substituted‐1,3‐Propanediols: A Powerful Entry into Chiral Building Blocks

“…[7] With our asymmetric desymmetrizations, both antipodes of the desymmetrized product are accessible in high enantioselectivities by switching the chirality of the ligand. [7] The substrate scope of these reactions extends to both 2-alkyl-and 2-aryl-1,3-propanediols. The reactions are operationally simple and the product can be obtained in excellent purities by directly loading the crude reaction mixture onto silica gel.…”

“…Furthermore, the enzymatic desymmetrization of diol 3 has proven to be problematic. [7] For our initial studies, vinyl benzoate was the electrophile of choice, as the by-product (acetaldehyde) cannot participate in the reverse reaction. Further, it has been observed that the acyl transfer that led to product racemization is slower in the benzoyl, relative to the acetyl derivatives ( Figure 2, R = Ph vs. R = CH 3 ).…”

“…[7] Although the enzymatic hydrolysis of the diacetylated product derived from diol 3 gives higher enantioselectivities (94% ee), only the (R) enantiomer can be directly accessed by this method. [7] With our asymmetric desymmetrizations, both antipodes of the desymmetrized product are accessible in high enantioselectivities by switching the chirality of the ligand. [7] The substrate scope of these reactions extends to both 2-alkyl-and 2-aryl-1,3-propanediols.…”

“…Furthermore, enzymes possess high substrate specificities and thus general methods to obtain high yields and enantioselectivities of both enantiomers of many substrates remain elusive. [2][3][4][5][6][7][8] Additionally, products obtained from enzymatic desymmetrization often contain an acetate group that can lead to product racemization by means of intramolecular acetyl migration (Scheme 2). [9] Motivated by the limited generality of enzymatic desymmetrization processes, several efforts using non-enzymatic pathways have been undertaken to desymmetrize 2-substituted-1,3-propanediols.…”

Asymmetric Synthesis of Naturally Occuring Spiroketals

“…The synthesis of talaromycins C and E is based on the synthesis of first racemic alcohol 3 RS -561 , and then diastereomeric enzymatic resolution to desired 3 S - 561 components. The attempt to make 3S -561 component by enzymatic desymmetrization of 2-ethyl-1,3-propanediol was unsuccessful, since it gives only 3 R - 561 , although different enzymes are used [ 220 ]. Synthesis of 561 is started with 1- O -benzyl-2-ethyl-3-iodopropanol ( 563 ), which is converted to its phosphonium salt 564 .…”