Pt 催化水合中 Pt-PR2OH 基团攻击配位腈形成非对映选择性和可逆金属环,Organometallics

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Pt 催化水合中 Pt-PR2OH 基团攻击配位腈形成非对映选择性和可逆金属环
Organometallics ( IF 2.5 ) Pub Date : 2024-01-23 , DOI: 10.1021/acs.organomet.3c00483
Jorge A. Garduño ₁ , Andrew J. Sasser ₁ , Hannah J. Sexton ₁ , Russell P. Hughes ₁ , David S. Glueck ₁ , Arnold L. Rheingold ₂

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通过催化不对称水合反应动力学拆分外消旋腈 CH(Et)(CN)(环-N(CH ₂ ) ₃ C(O)–) 形成酰胺 CH(Et)(C(O)NH ₂ )(环-N(CH ₂ ) ₃ C(O)–)（左乙拉西坦，Keppra）是一种工业生物催化过程。为了开发使用手性金属配合物作为催化剂前体的类似程序，我们研究了各个步骤的机理和选择性。用 AgOTf 和仲膦氧化物 (SPO)处理 Pt(diphos)Cl ₂得到含有手性二磷₍ ( R , R )-FerroLANE 衍生物或 ( S , S )-Et-FerroTANE) 或手性 SPO 互变异构体 (( R )-DMB-SPOPine)。第二当量的 AgOTf 产生双离子 [Pt(diphos)(PR' ₂ OH)][OTf] ₂ ( 9–12和14 )，具有 Fe-Pt 相互作用，或 [Pt(( S , S )-Et-FerroTANE )(PMe ₂ OH)(OTf)][OTf] ( 13 )。Pt 配合物9和11 – 14在温和条件下催化 Keppra 腈水合为酰胺，并增加了较小 FerroLANE 取代基的活性。以水作为限制试剂和过量的外消旋腈，在催化腈水合的动力学拆分中没有观察到对映选择性。[Pt( R , R )-Me-FerroLANE)(PMe ₂ OH)][OTf] ₂ ( 9 ) 与对映体富集或外消旋 Keppra 腈反应，导致非对映选择性和可逆金属环形成，得到 [Pt(( R , R )-Me-FerroLANE)(PMe ₂ OC(R*)=NH][OTf] ₂ ( 15 , R* = CH(Et)(环-N(CH ₂ ) ₃ C(O)–))。类似过程发生在10 – 11和13 – 14与rac -Keppra 腈，或与9和rac -PhCH(R)(CN) (R = Me, Et, i -Pr, Cy) 或与外消旋环-Ph ₂ CCH时₂ CH(CN) 生成金属环16–24 . 金属环15通过攻击 PMe _{2 O 基团与水反应，经}^{18 个}O 标记研究证明，通过中间亚胺醇复合物 [Pt(( R , R )-Me-FerroLANE)(PMe ₂ OH)(NH)产生 Keppra 酰胺＝C(R*)(OH))][OTf] ₂ ( 25 )。

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Diastereoselective and Reversible Metallacycle Formation by Attack of a Pt-PR2OH Group on a Coordinated Nitrile in Pt-Catalyzed Hydration

Kinetic resolution of the racemic nitrile CH(Et)(CN)(cyclo-N(CH₂)₃C(O)–) by catalytic asymmetric hydration to form the amide CH(Et)(C(O)NH₂)(cyclo-N(CH₂)₃C(O)–) (Levetiracetam, Keppra) is an industrial biocatalytic process. To develop analogous procedures using chiral metal complexes as catalyst precursors, we investigated the mechanism and selectivity of the individual steps. Treatment of Pt(diphos)Cl₂ with AgOTf and secondary phosphine oxides (SPOs) gave the cations [Pt(diphos)(PR'₂OH)(Cl)][OTf] 1–6 containing either a chiral diphos ((R,R)-FerroLANE derivatives or (S,S)-Et-FerroTANE) or a chiral SPO tautomer ((R)-DMB-SPOPine). A second equiv of AgOTf yielded dicationic [Pt(diphos)(PR'₂OH)][OTf]₂ (9–12 and 14), with Fe–Pt interactions, or [Pt((S,S)-Et-FerroTANE)(PMe₂OH)(OTf)][OTf] (13). Pt complexes 9 and 11–14 catalyzed hydration of the Keppra nitrile to the amide under mild conditions, with increased activity for smaller FerroLANE substituents. With water as the limiting reagent and an excess of racemic nitrile, no enantioselectivity in kinetic resolution by catalytic nitrile hydration was observed. Reaction of [Pt(R,R)-Me-FerroLANE)(PMe₂OH)][OTf]₂ (9) with enantiomerically enriched or racemic Keppra nitrile resulted in diastereoselective and reversible metallacycle formation to give [Pt((R,R)-Me-FerroLANE)(PMe₂OC(R*)═NH][OTf]₂ (15, R* = CH(Et)(cyclo-N(CH₂)₃C(O)–)). Similar processes occurred with dications 10–11 and 13–14 with rac-Keppra nitrile, or with 9 and rac-PhCH(R)(CN) (R = Me, Et, i-Pr, Cy) or with racemic cyclo-Ph₂CCH₂CH(CN) to generate metallacycles 16–24. Metallacycle 15 reacted with water by attack at the PMe₂O group, demonstrated by ¹⁸O-labeling studies, to yield the Keppra amide via an intermediate iminol complex [Pt((R,R)-Me-FerroLANE)(PMe₂OH)(NH═C(R*)(OH))][OTf]₂ (25).

更新日期：2024-01-23

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