Practical Asymmetric Synthesis of (S)-MA20565, a Wide-Spectrum Agricultural Fungicide

Abstract

A practical asymmetric synthesis of a wide-spectrum agricultural fungicide, (S)-MA20565 (1), is described. The convergent synthesis was achieved starting from commercially available 3-(trifluoromethyl)aniline (7) in 44% overall yield through five steps and 2-bromobenzaldehyde (9) in 48% overall yield through four steps, respectively. (S)-O-[1-(3-Trifluoromethylphenyl)ethyl]hydroxylamine (2), a key intermediate of 1, was prepared via ruthenium(II)-catalyzed asymmetric transfer hydrogenation of 1-(3-trifluoromethylphenyl)ethanone (6) followed by chlorination using methanesulfonyl chloride and oxyamination using potassium acetohydroxamate with high level of stereocontrol.

The asymmetric synthesis of (R,R)‐formoterol via transfer hydrogenation with polyethylene glycol bound Rh catalyst in PEG2000 and water

“…The yield increased to 37% with 62% ee at a lower HCOOH/ NEt 3 ratio (1:1). 12 On the other hand, when sodium formate in water was selected as the hydrogen donor, Ru-and Rh-catalysts gave 86% ee and 92% ee, respectively, with good yield (entry 4,5). Under the same condition, the yield and enantioselectivity were slightly improved using Ru-and Rh-(S,S)-PEGBsDPEN as catalysts (entry 6, 7).…”

Application of Copper(II)–Dipyridylphosphine Catalyst in the Asymmetric Hydrosilylation of Simple Ketones in Air

“…For example, in the presence of 1 mol % each of CuF 2 and (S)-1 a, the hydrosilylation of 3,5-bis(trifluoromethyl)acetophenone proceeded in air at À40 8C to afford 7 a, which is the key building block for aprepitant, an NK-1 receptor antagonist, [14] in 92 % ee. Likewise, attractive intermediates 7 b [15] and 7 c [16] were also obtained in 90 % and 94 % ee, respectively. Interestingly, the hydrosilylation of cyclohexyl phenyl ketone exhibited an enantiomeric induction of the opposite sense to give (R)-7 e in 88 % ee.…”

Further ‘tethered’ Ru(II) catalysts for asymmetric transfer hydrogenation (ATH) of ketones; the use of a benzylic linker and a cyclohexyldiamine ligand

“…Again this reflects the lower level of transition state organization when an aryl ring is absent from the ketone substrate. In addition to several of the same acetophenone derivatives as were used with 4, we examined ketone 23, since its reduction product is an intermediate in the synthesis of the Merck drug aprepitant [8], and 24, a building block of the agricultural fungicide MA-20565 [9]. Whilst both were fully converted to alcohols, 24 was reduced in good ee (but lower than that of similar ketones) ketone 23 was reduced in rather poor yield.…”