Chemoenzymatic synthesis of chiral isoxazole derivatives

Enantioselective Synthesis of Both Enantiomers of Various Propargylic Alcohols by Use of Two Oxidoreductases

“…The best results so far with regard to the enantioselective reduction of 3a have been obtained with TBADH [ee ϭ 86%; (S)]. [13] Several multistep procedures have been developed to overcome this problem. [11,14] As expected, enzymatic reduction of 3a with recLBADH and CPCR only produced unsatisfactory results, of 60% and 49% ee, respectively ( Table 2).…”

Studies of a Diazo Cyclopropanation Strategy for the Total Synthesis of (−)‐Lundurine A

“…Our failed attempts to prepare β‐ketone ester 47 a or ketone 47 b from 14 a and 14 b forced us to synthesize the alternative β‐ketone cyanide 53 as a precursor for preparing a β‐ketone α‐diazocyanide functional group ( 54 ), which has been used for Rh‐catalyzed cyclopropanation by Prof. Reisman’s group in recent years 16. As shown in Scheme , β‐ketone cyanide 53 was prepared from 14 b through three steps of cyclization ( 14 b to 51 ),17 oxidization ( 51 to 52 ), and cleavage of the NO bond ( 52 to 53 ). Diazo functionalization of 53 with p ‐ABSA and Et 3 N afforded β‐ketone α‐diazocyanide 54 in 88 % yield.…”

Efficient Synthesis of Enantioenriched Isoxazoles by Chirality Transfer in Gold‐Catalyzed Cyclization/Methylene‐Group Transfer Followed by Carbonyl Ene Reaction

“…[6] In particular, the effective synthesis of isoxazoles having a chiral side chain under mild conditions is beneficial for pharmaceutical science. [7] Recently, we demonstrated that the gold-catalyzed skeletal rearrangement of O-propargylic formaldoxime 1 afforded 4-methylenated isoxazoline 2, and a subsequent aromatization-driven ene reaction of 2 with various enophiles afforded good yields of isoxazoles 3 having a highly functionalized substituent at the 4-position. [8,9] Accordingly, we envisioned that isoxazoles having a chiral side chain could be efficiently synthesized from enantioenriched O-propargylic oximes by transferring the chiral information of the propargylic position through gold catalysis [10,11] and an ene reaction, [12] as the stereogenic center at the propargyl position is readily accessible by utilizing Shibasaki's asymmetric alkynylation of aldehydes (Scheme 1b).…”