Todd:Catalytic, Asymmetric Pictet-Spengler Reaction

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The Catalytic, Asymmetric Pictet-Spengler Reaction

Katrina A. Badiola, School of Chemistry, The University of Sydney, NSW 2006, Australia
Murray N. Robertson, School of Chemistry, The University of Sydney, NSW 2006, Australia
Matthew H. Todd, School of Chemistry, The University of Sydney, NSW 2006, Australia

Additional authors - add alphabetically if you contribute something substantial (e.g., the summary of a paper with a scheme). Final arbitration on authorship (as opposed to acknowledgement) lies with Mat Todd

(This article is intended as a stand-alone review. It also acts as background to the open science project to find a catalytic, asymmetric route to praziquantel. The review is open source, meaning anyone can add and edit. When it is deemed to be up to date, comprehensive, error-free and well-written, it will be submitted for publication to a peer-reviewed open access journal, but editing can continue here after that point. This page is currently active - when this changes <= these words will be changed (and you can see when the last edit of this page was made at the bottom). References for this page may be found in full at the Mendeley page). If you want to get in touch to ask questions please do not use email. You can use the talk page (tab above), or directly insert a question on this page (below) with your initials, or discuss via Google+ pages: Mat, (please add other public places where you can be contacted if you contribute as an author).

Important note on simultaneous edits: If you are intending to work for some time on editing the page, we'd recommend writing text elsewhere then pasting it in here, since there is a small but non-zero chance that you might simultaneously edit the same section as someone else, resulting in the chance of the loss of some information.

Schemes: Use Wiley/Angewandte settings for the .cdx files and add below as 300 dpi .png files.

Introduction

Other reviews of the area, to be distinguished from this one:

• Current Organic Synthesis 2010 - ordered from interlibrary loan.
• [Angew 2011]

Importance of the structural motifs constructed with the reaction:

• Brown, R. T. In Indoles; Saxton, J. E., Ed.; Wiley- Interscience: New York, 1983; Part 4 (The Monoterpenoid Indole Alkaloids)
• Bentley, K. W. Nat. Prod. Rep. 2004, 21, 395-424 and references therein
• W. Jiang, J. Guan, M. J. Macielag, S. Zhang, Y. Qiu, P. Kraft, S.

Bhattacharjee, T. M. John, D. Haynes-Johnson, S. Lundeen, Z. Sui, J. Med. Chem. 2005, 48, 2126 – 2133

Carbolines:

• Kawasaki, T.; Higuchi, K. Nat. Prod. Rep. 2005, 22, 761–793
• Yu, J.; Wang, T.; Liu, X.; Deschamps, J.; Anderson, J. F.; Liao, X.; Cook, J. M. J. Org. Chem. 2003, 68, 7565–7581
• Liao, X.; Zhou, H.; Yu, J.; Cook, J. M. J. Org. Chem. 2006, 71, 8884–8890
• Ma, J.; Yin, W.; Zhou, H.; Cook, J. M. Org. Lett. 2007, 9, 3491–3494
• Herraiz, T. J. Chromatogr. A 2000, 881, 483–499
• Herraiz, T.; Galisteo, J.; Chamorro, C. J. Agric. Food Chem. 2003, 51, 2168–2173.

Racemic/Achiral

To Do:

• Pictet, A.; Spengler, T. Ber. Dtsch. Chem. Ges. 1911, 44, 2030-2036.
• Tatsui, G. J. Pharm. Soc. Jpn. 1928, 48, 92 (may be 453-459).
• Cox, E. D.; Cook, J. M. Chem. Rev. 1995, 95, 1797- 1842 (especially their tryptophan ester strategy)
• Chrzanowska, M.; Rozwadowska, M. D. Chem. Rev. 2004, 104, 3341-3370.
• Nature: Naoi, M.; Maruyama, W.; Nagy, G. M. Neurotoxicology 2004, 25, 193- 204

Diastereoselective

Early diastereoselective, to reference: Ungemach, F.; DiPierro, M.; Weber, R.; Cook, J. M. J. Org. Chem. 1981, 46, 164.

Study to reference: Cox, E. D.; Hamaker, L. K.; Li, J.; Yu, P.; Czerwinski, K. M.; Deng, L.; Bennett, D. W.; Cook, J. M. J. Org. Chem. 1997, 62, 44-61 [Paper].

To Do:

• Czarnocki, Z.; MacLean, D. B.; Szarek, W. A. Can. J. Chem. 1986, 64, 2205-2210. <-- KAB doing this next.
• Czarnocki, Z.; Suh, D.; MacLean, D. B.; Hultin, P. G.; Szarek, W. A. Can. J. Chem. 1992, 70, 1555-1561.
• Czarnocki, Z.; Mieckzkowsi, J. B.; Kiegiel, J.; Arazn ́y, Z. Tetrahyedron: Asymmetry 1995, 6, 2899-2902.
• Tsuji, R.; Nakagawa, M.; Nishida, A. Tetrahedron: Asymmetry 2003, 14, 177- 180.

Enantioselective

Lewis Acids

Nakagawa reported the first example of a reagent-controlled enantioselective Pictet-Spengler reaction in 1998. He used a chiral Lewis acid to promote the enantioselective cyclization of nitrones to give optically active Nb-hydroxytetrahydro-β-carbolines. Treatment of nitrone with (-)-Ipc2BCl in DCM at -78 °C gave e desired product in 94% yield with 83% ee. Replacing the chlorine atom of the Ipc2BCl in an attempt to alter the Lewis acidity of the boron did not improve yield or ee. The reaction should proceed via an iminium ion intermediate, in which the boron of Ipc2BCl is coordinated to the oxygen of the nitrone. The stereochemical outcome can be explained by assuming a transition state involving the nucleophilic attack of indole to the C=N double bond from the less hindered side.

Scheme: (Nakagawa 1998). Pictet-Spengler Reaction of nitrones with Diisopinocampheylchloroboranes

To Do:

• Non-catalytic borane: Yamada, H.; Kawate, T.; Matsumizu, M.; Nishida, A.; Yamaguchi, K.; Nakagawa, M. J. Org. Chem. 1998, 63, 6348-6354 - Done MNR
• Hino, T.; Nakagawa, M. Heterocycles 1998, 49, 499-531.
• Leighton Angew 2009

Bronsted Acids

(Note - consider a diagram section at start which includes the structures of all the BINOL-derived catalysts so we don't have to include in the individual schemes). i.e. we draw them at start and then number them then just include the numbers in the schemes.

Chiral Brønsted acids have been shown to be effective in the catalytic, asymmetric PS reaction, and this builds on earlier work demonstrating the ability of such compounds to catalyze the reaction between nucleophiles and iminium ions.

Akiyama (10.1002/anie.200353240) reported chiral phosphoric acids prepared from BINOL in the enantioselective Mannich-type coupling of silyl enolates with aldimines (Scheme Akiyama 2004). High yields and enantio- (as well as, in appropriate cases, diastereo-) selectivities were observed with a variety of substituted aldimines and enolates. Limitations to the methodology were that an ortho hydroxy group was required on the N-aryl ring of the aldimine, and that aldimines derived from aliphatic aldehydes did not participate effectively. The catalyst was typically used at a loading of 10 mol%. The structure of the catalyst itself may be thought of as a chiral proton, i.e., a proton surrounded by a chiral structure, particularly given the aromatic rings of the BINOL and the 3-substituents are not coplanar. However, the mechanism was proposed to operate via an ion pair of phosphate and iminium ion. The bond-forming event would naturally disrupt such an ion pair, ensuring catalytic turnover. (ultimately ne