DuPhos

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：DIPAMP、BINOL和Chiraphos，而后期发现了一批新的配体被证明比前者更具活性。

描述

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、丙基或异丙基。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] 如先通过二苯甲酮和苯甲酰氯合成的腙得到亚胺，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，铑是常用的催化剂，直到在1995年才引入了钌催化剂，[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

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

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

  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.