DuPhos

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DuPhos配体

DuPhos是一种用于不对称合成中的不对称配体。DuPhos之名称取自其研发公司(DuP,杜邦公司)和化合物的种类:膦杂环(Phos)。这种二膦配体首先由化学家M.J. Burk于1991年发现, [1][2] 并首次在不对称氢化反应中,成功地将特定的烯基酰氨酯还原为氨基酸前体:

Hydrogenation DupHos Burk 1993

同期发现其他有机磷不对称配体有诸如:DIPAMPBINOLChiraphos,而后期发现了一批新的配体被证明比前者更具活性。

描述[编辑]

DuPhos配体由两个2,5-烷基取代膦杂环(THF的磷类似物)通过1,2-苯桥连而成。这里的烷基可以是:甲基乙基丙基异丙基。DuPhos的类似物,双(二甲基膦)乙烷或BPE配体[3][4] 相当于苯基桥被1,2-乙基所替代之产物。该两种化合物都可通过相应的手性二醇化合物,转化为环状硫酸盐,继而与双锂二苯基膦反应制备获得。DuPhos配体中,磷原子属于富电子原子团,使形成的金属络合物具有强活性。磷原子还引入了一种假-手性,使对映体选择性不受整个分子的化学构象影响。[5] DuPhos的另一种早期应用,是通过还原胺化反应合成非天然手性氨基酸[6] 如先通过二苯甲酮苯甲酰氯合成的得到亚胺,而后在DuPhos催化下发生不对称氢化反应,最后脱去苯甲酰保护基得到非天然手性氨基酸产物:[7]

Reductive Amination DuPhos Burk 1994

在早期的过渡金属催化反应中,是常用的催化剂,直到在1995年才引入了催化剂,[8] 实例是氢化还原β-酮酯的羰基,合成手性的β-羟基酯:

Hydrogenation ketoester DuPhos Genet 1994

应用[编辑]

DuPhos的一个不对称合成实例为催化“脱氢华法林”氢化为华法林的反应:[9]

Warfarin synthesis

Duphos还可用于合成色氨酸的衍生物。[10]

BozPhos配体[编辑]

使用硼烷二甲硫醚作为保护基,在过氧化氢条件下单氧化(R,R)-Me-Duphos即得到BozPhos。[11][12] 该配体可用于铜-催化的二有机锌试剂对N-二苯基次磷酰亚胺的不对称加成反应。

参考文献[编辑]

  1. ^ Burk, Mark J. C2-symmetric bis(phospholanes) and their use in highly enantioselective hydrogenation reactions. Journal of the American Chemical Society (American Chemical Society (ACS)). 1991, 113 (22): 8518–8519. ISSN 0002-7863. doi:10.1021/ja00022a047. 
  2. ^ Burk, Mark J.; Feaster, John E.; Nugent, William A.; Harlow, Richard L. Preparation and use of C2-symmetric bis(phospholanes): production of .alpha.-amino acid derivatives via highly enantioselective hydrogenation reactions. Journal of the American Chemical Society (American Chemical Society (ACS)). 1993, 115 (22): 10125–10138. ISSN 0002-7863. doi:10.1021/ja00075a031. 
  3. ^ Burk, Mark J.; Feaster, John E.; Harlow, Richard L. New electron-rich chiral phosphines for asymmetric catalysis. Organometallics (American Chemical Society (ACS)). 1990, 9 (10): 2653–2655. ISSN 0276-7333. doi:10.1021/om00160a010. 
  4. ^ Burk, Mark J.; Feaster, John E.; Harlow, Richard L. New chiral phospholanes; Synthesis, characterization, and use in asymmetric hydrogenation reactions. Tetrahedron: Asymmetry (Elsevier BV). 1991, 2 (7): 569–592. ISSN 0957-4166. doi:10.1016/s0957-4166(00)86109-1. 
  5. ^ Crépy, Karen V. L.; Imamoto, Tsuneo. Recent Developments in Catalytic Asymmetric Hydrogenation Employing P-Chirogenic Diphosphine Ligands. Advanced Synthesis & Catalysis (Wiley-Blackwell). 2003, 345 (12): 79–101. ISSN 1615-4150. doi:10.1002/adsc.200390031. 
  6. ^ Burk, Mark J.; Feaster, John E. Enantioselective hydrogenation of the C:N group: a catalytic asymmetric reductive amination procedure. Journal of the American Chemical Society (American Chemical Society (ACS)). 1992, 114 (15): 6266–6267. ISSN 0002-7863. doi:10.1021/ja00041a067. 
  7. ^ Burk, Mark J.; Martinez, Jose P.; Feaster, John E.; Cosford, Nick. Catalytic asymmetric reductive amination of ketones via highly enantioselective hydrogenation of the CN double bond. Tetrahedron (Elsevier BV). 1994, 50 (15): 4399–4428. ISSN 0040-4020. doi:10.1016/s0040-4020(01)89375-3. 
  8. ^ Genêt, J.P.; Ratovelomanana-Vidal, V.; Caño de Andrade, M.C.; Pfister, X.; Guerreiro, P.; Lenoir, J.Y. Practical asymmetric hydrogenation of β-keto esters at atmospheric pressure using chiral Ru (II) catalysts. Tetrahedron Letters (Elsevier BV). 1995, 36 (27): 4801–4804. ISSN 0040-4039. doi:10.1016/0040-4039(95)00873-b. 
  9. ^ Robinson, Andrea; Li, Hui-Yin; Feaster, John. The first practical asymmetric synthesis of R and S-Warfarin. Tetrahedron Letters (Elsevier BV). 1996, 37 (46): 8321–8324. ISSN 0040-4039. doi:10.1016/0040-4039(96)01796-0. 
  10. ^ Hoerrner, R. Scott; Askin, David; Volante, R.P.; Reider, Paul J. A highly enantioselective asymmetric hydrogenation route to β-(2R,3S)-methyltryptophan. Tetrahedron Letters (Elsevier BV). 1998, 39 (21): 3455–3458. ISSN 0040-4039. doi:10.1016/s0040-4039(98)00604-2. 
  11. ^ Alexandre Côté, Jean-Nicolas Desrosiers, Alessandro A. Boezio, and André B. Charette (2006). "Preparation of enantiomerically pure (R,R)-BozPhos". Org. Synth. 83: 1. 
  12. ^ Jean-Nicolas Desrosiers, Alexandre Côté, Alessandro A. Boezio, and André B. Charette (2006). "Preparation of enantiomerically enriched (1S)-1-Phenylpropan-1-amine hydrochloride by a catalytic addition of diorganozinc reagents to imines". Org. Synth. 83: 5.