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 what qualifies as authorship lies with Mat Todd

The licence for this page is CC BY 3.0

(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.
• 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 need a scheme of this very general idea (nice example in the Akiyama paper here) but may go in mechanism section)

Scheme (Akiyama 2004). Enantioselective Mannich-type Coupling of Enolates and Aldimines Catalyzed by Chiral Phosphoric Acids

At the same time Terada (10.1021/ja0491533) reported similar catalysts in the enantioselective Mannich reaction for the synthesis of β-aminoketones (Scheme Terada 2004a), again noting the important influence of the 3-position of the naphthyl rings in the enantioselectivity of the reaction. The nucleophile could be changed to furan (10.1021/ja046185h) (maybe include).

Scheme (Terada 2004a). Enantioselective Mannich-type Reaction in the Synthesis of β-Aminoketones

Since these early reports, several further examples have been reported of reactions that can be catalysed by these or related structures (reference reviews of chiral bronsted acid catalysts here).(Terada 2010 Bull Chem Soc Jpn 10.1246/bcsj.20090268)

Items arising from Akiyama and Terada papers: More on early work: Akiyama (2004) says these earlier reports "claim" the use of chiral B acids: B. L. Hodous, G. C. Fu, J. Am. Chem. Soc. 2002, 124, 10006 C. Palomo, M. Oiarbide, J. M. Garcia, A. Gonzalez, A. Lecumberri, A. Linden, J. Am. Chem. Soc. 2002, 124, 10288 N. T. McDougal, S. E. Schaus, J. Am. Chem. Soc. 2003, 125, 12094 Y. Huang, A. K. Unni, A. N. Thadani, V. H. Rawal, Nature 2003, 424, 146.

Akiyama (2004) also mentions these "metal salt" versions: J. Inanaga, Y. Sugimoto, T. Hanamoto, New J. Chem. 1995, 19, 707 H. Furuno, T. Hanamoto, Y. Sugimoto, J. Inanaga, Org. Lett. 2000, 2, 49

Previous Bronsted acid example from Terada 6) Schreiner, P. R. Chem. Soc. ReV. 2003, 32, 289. (7) (a) Huang, Y.; Unni, A. K.; Thadani, A. N.; Rawal, V. H. Nature 2003, 424, 146. (b) McDougal, N. T.; Schaus, S. E. J. Am. Chem. Soc. 2003, 125, 12094. (8) Some other chiral charged Brønsted acid catalysts were reported, see: Nugent, B. M.; Yoder, R. A.; Johnston, J. N. J. Am. Chem. Soc. 2004, 126, 3418.

Jacobsen Strecker and Mannich history, from Terada (a) Sigman, M. S.; Jacobsen, E. N. J. Am. Chem. Soc. 1998, 120, 4901. (b) Vachal, P.; Jacobsen, E. N. Org. Lett. 2000, 2, 867. (c) Sigman, M. S.; Vachal, P.; Jacobsen, E. N. Angew. Chem., Int. Ed. 2000, 39, 1279. (d) Su, J. T.; Vachal, P.; Jacobsen, E. N. AdV. Synth. Catal. 2001, 343, 197. (e) Vachal, P.; Jacobsen, E. N. J. Am. Chem. Soc. 2002, 124, 10013. (f) Wenzel, A. G.; Lalonde, M. P.; Jacobsen, E. N. Synlett 2003, 1919. (10) Wenzel, A. G.; Jacobsen, E. N. J. Am. Chem. Soc. 2002, 124, 12964. (11) See also: (a) Okino, T.; Hoashi, Y.; Takemoto, Y. J. Am. Chem. Soc. 2003, 125, 12672. (b) Okino, T.; Nakamura, S.; Furukawa, T.; Takemoto, Y. Org. Lett. 2004, 6, 625.

Copper complex example from Terada: Marigo, M.; Kjærsgaard, A.; Juhl, K.; Gathergood, N.; Jørgensen, K. A. Chem.- Eur. J. 2003, 9, 2359.

(end of items arising)

List reported the first Bronsted acid-catalyzed enantioselective Pictet-Spengler reaction in 2006 (10.1021/ja057444l). Chiral, substituted phosphoric acids were shown to be effective in the PS cyclization of tryptamines with a number of aliphatic and aromatic aldehydes (Scheme List 2006). The diester functionality was found to be necessary, presumably due to promotion of a clean reaction through the Thorpe-Ingold effect (and an aldol side reaction was observed when the esters were absent). Lower yields were typically observed when the methoxy group was absent from the tryptamine aromatic ring.

Scheme (List 2006). Chiral Phosphoric Acid-catalyzed PS Cyclization of Typtamine Diesters

In 2007, Hiemstra reported the enantioselective synthesis of tetra-β-carbolines via the in situ formation of N-sulfenyliminium ions (10.1002/anie.200701808). Stabilization of the intermediate iminium by the N-tritylsulfenyl group was effective at promoting the acid-catalyzed PS reaction by substituted enantiopure binaphthyl-derived phosphoric acids. Several substitutions were assayed in the 2-position of the catalyst, with no clear trend being observed in the ee of product obtained. The N-S bond in the N-tritylsulfenyl product was found to be susceptible to homolytic cleavage, but this could be suppressed by the addition of a radical scavenger. A one-pot process was developed that allowed precipitation of the product as a salt, and this was applied to the synthesis of a variety of substituted tetra-β-carbolines with high yield and high ee. The reaction was also demonstrated on a multi-gram scale.

Question: Why does the sulfenyl help? Paper says should stabilize intermediate iminium ion and favour cyclization over competitive enamine formation) Paper gives: The use of N-sulfenyl substituents as protecting groups is known in peptide synthesis; see a) L. Zervas, D. Borovas, E. Gazis, J. Am. Chem. Soc. 1963, 85, 3660 – 3666 ; for reviews on sulfenamide chemistry, see b) F. A. Davis, U. K. Nadir, Org. Prep. Proced. Int. 1979, 11, 33–51; c)L. Craine, M. Raban, Chem. Rev. 1989, 89, 689 – 712 ; d) I. V. Koval, Russ. Chem. Rev. 1996, 65, 452 – 473.

Scheme (Hiemstra 2007). Enantioselective PS Cyclization via N-Sulfenyliminium Intermediates

An extension to this methodology was developed that allowed the synthesis of enantioenriched N-benzyl-protected versions of similar products from the relevant protected tryptamines and diverse aldehydes (10.1021/jo8010478). During optimization it was found that removal of water was essential for high enantioinduction presumably because water prevents effective association between catalyst and cyclization precursor. Several control reactions were performed under the optimized conditions that suggested this PS reaction was irreversible. The best-performing catalyst was the triphenylsilyl-substituted binaphthyl system, delivering up to 100% conversion and high ee values (78-85%). The ee obtained was sensitive to the aldehyde employed. Of the aliphatic aldehydes, no product was observed with the enolizable phenylacetaldehyde and low ee (8%) was obtained with 3-phenylpropanal. While electron-deficient aromatic aldehydes generally gave products with high ee as expected, there were exceptions that performed poorly; 3-chlorobenzaldehyde gave near-racemic product, for example.

Scheme (Hiemstra 2008). Enantioselective PS Cyclization of N-Benzyltryptamines

This methodology has been employed in the syntheses of three natural products. The PS reaction employed in the synthesis of (-)-arboricine (10.1021/ol900888e) (Scheme Hiemstra 2009) involved an aldehyde containing a dioxolane-protected ketone group, preventing an aminal formation that was observed when the ketone was used unprotected, but it is notable that this protecting group withstands the PS cyclization, and that the yield and ee of the cyclization were both dramatically improved by the use of the protecting group. The partially saturated (and slightly more sterically crowded) (R)-H8-Binol-PA catalyst was also shown to be effective. This catalyst was subsequently used for the key step in the synthesis of (+)-yohimbine (Scheme Hiemstra 2011).(10.1021/jo201657n). The natural product was to be synthesized via a Diels-Alder precursor that could itself be made using an enantioselective PS reaction. However, the aldehyde required for the PS reaction was β,γ-unsaturated and this was likely to result in the unproductive formation of an enamine from the initially-formed iminium ion. This substrate limitation necessitated use of a latent double bond, in this case a phenylselenide; this group survived the successful PS cyclization and could be eliminated to the double bond via oxidation to the selenoxide. A similar synthetic strategy was employed in the synthesis of the related corynanthe alkaloid family. (10.1002/chem.201103150)

Scheme (Hiemstra 2009). Key Enantioselective PS Reaction in the Synthesis of (-)-Arboricine

Scheme (Hiemstra 2011). Enantioselective PS Reaction in the Total Synthesis of (+)-Yohimbine

Dixon included a chiral phosphoric acid as part of a reagent cocktail effecting a cascade sequence involving a Pictet-Spengler-like cyclization (Scheme Dixon 2009).(10.1021/ja9024885) Trytamines and lactones formed ketoamides with an appended pi-nucleophile that underwent enantioselective cyclizations in the presence of chiral phosphoric acids, and it was again shown that aromatic substitution of the BINOL ring system was essential for high ee. The method could be used with more substituted lactones to effect high levels of diastereocontrol: the combination of a disubstituted enol lactone with tryptamine gave isolable intermediates, the structures of which implied that the formation of the reactive iminium ion was fast and reversible, and that final ring closure occurred with one matched catalyst/substrate pair. The mechanism of the enantiodetermining cyclization is presumed to be via a tight ion pairing between iminium ion and catalyst conjugate anion. High yields and stereoselectivities could be obtained for diverse products using this methodology, which was shown to be compatible with a one-pot cascade process that also included a gold(I)-catalyzed step to generate the initial lactone.

Scheme (Dixon 2009). Cascade Cyclizations Involving an Enantioselective PS Reaction

The method was adapted... Need to edit --> Dixon reported the synthesis of fused polycyclic heterostructures from the Pictet-Spengler-type reaction of trypamines with a number of ketoacids using triphenylsilyl substituted binapthyl derived phosphoric acids (10.1021/ol101651t). Good to excellent ee values (79-98%) were obtained in the reactions with a number of cyclohexanone (and cyclopentanone) derived γ-keto acids, acyclic γ-keto acids, and γ-keto acids with electron withdrawing groups, all of which gave the expected products. It was postulated that enantioselective attack by the indole pendant nucleophile was dependent on facial differentiation imposed by the tight ion pair between the chiral Bronsted acid conjugate base and the in situ generated N-acyliminium ion. <-- KAB doing this.

'Scheme: (Dixon 2010).

In 2011, Franz reported a comparison of catalyst systems to determine the factors responsible for efficient catalytic activity and selectivity in this Pictet–Spengler type reaction. The effect of solvent and temperature was examined for the phosphoric acid catalyzed reactions in order to improve the enantioselectivity. DCM performed the best for reaction rate and enantioselectivity

Scheme: (Franz 2011). Phosphoric acid-catalyzed spirocyclization of isatins

Interestingly, Franz showed the same (S)-enantiomer of spiroindolone was obtained for (R) and (S) catalysts despite them having the opposite configurations of axial chirality. He therefore concluded that the substituents on the binaphthyl system direct the stereoinduction for the spirocyclization. This is contrary to several other instances that have been reported previously where the 3,30-substitution on the chiral phosphoric acid catalyst has been shown to reverse the sense of enantioselection. The effect of substitution was also examined for spirocyclization, providing insight into the limitations of this methodology. Yield and enantioslectivity varied as these substitution patterns were change.

Scheme: (Franz 2011). spirocyclization mechanism

To Do:

The strengths of these chiral phosphoric acids is governed by:
Akiyama Chem Rev 2007
Terada ChemComm 2008

Reviews: a) S.J. Connon, Angew. Chem. Int. Ed. 2006, 45, 3909–3912
b) T. Akiyama, J. Itoh, K. Fuchibe, Adv. Synth. Catal. 2006, 348, 999 – 1010
c) M. S. Taylor, E. N. Jacobsen, Angew. Chem. Int. Ed. 2006, 45, 1520–1543
d) Connon, S. J. Org. Biomol. Chem. 2007, 5, 3407–3417
e) Terada Synthesis 2010, 1929-1982
f) List, Top. Curr. Chem. 2010, 291, 395-456
g) Rueping Angewandte 2011, 50, 6706-6720

Organocatalysts

Check:
Jacobsen 2007 JACS, 129, 13404
MNR done Jacobsen Org Lett 2008, 10, 745-748.

In 2004, Jacobsen reported his initial findings on the asymmetric catalysis of the acyl-Pictet-Spengler reaction using chiral thioureas. Jacobsen realised the challenge of developing an asymmetric catalytic for the Pictet-Spengler reaction due to the low reactivity of the imine substrate. Also, in previously reported racemic efforts involving Lewis acid catalysis involved highly reactive agents and high temperatures. Jacobsens general strategy for enhancing this reaction was to increase the electrophilicity of the imine/iminium intermediate by generating the corresponding N-acyliminium ions. Early screening experiments gave promising results with cyclization progressing at -30 °C in 59% ee. Individual reaction parameters were screened and it was found that the reaction enantioselectivity exhibited a strong dependence upon the structure of the acylating agent as well as the reaction solvent and temperature.

Scheme: (Jacobsen 2004). Catalytic Asymmetric Acyl-Pictet-Spengler Reactions

A pathway for the thiourea catalysed enantioselective Pictet-Spengler-Type cyclization was proposed by Jacobsen in 2007. Interestingly, key experimental observations, supported by DFT computational analyses, pointed towards an SN1-type pathway in these cyclizations, with catalysis via a previously thought unprecedented anion-binding mechanism.

An extensive screen of acidic additives revealed that either chlorotrimethylsilane or the combination of HCl and 3 Å molecular sieves afforded high levels of conversion and enantioselectivity, but that water had a deleterious effect on catalyst activity. Furthermore, a quite significant inverse correlation between conversion and reaction concentration was observed, with reactions run at lower concentrations affording substantially improved yields.

As a direct demonstration of the applicability of this new methodology, Jacobsen applied the enantioselective hydroxylactam cyclization to the total synthesis of (+)-harmicine with the cyclization proceeding in 97% ee followed by subsequent LiAlH4 reduction affording the natural product in only four steps from tryptamine.

Scheme: (Jacobsen 2007). Total Synthesis of (+)-Harmicinea

Variable temperature 1H NMR studies of reaction mixtures indicated that formal dehydration and formation of the corresponding chlorolactam is rapid and irreversible. Further, the observation of enhanced reactivity of alkylated versus reduced derivatives suggests that an SN2-type displacement of chloride is not operative in the cyclization reaction and points rather to an SN1-type mechanism. Since the enantioselectivity determining step is likely, either the addition of the indole to the N-acyliminium ion (b → c or b → d) or alkyl migration of the spiroindoline intermediate (c → d), catalyst interaction with at least one of these species is required. However, there is no viable Lewis basic site for catalyst binding to substrate in c or d.

Scheme: (Jacobsen 2007). Proposed Reaction Mechamism

Therefore, Jacobsen proposed that the thiourea catalyst promotes enantioselective cyclization by inducing dissociation of the chloride counterion and forming a chiral N-acyliminium chloride-thiourea complex. Noticeable halide counterion effects and solvent effects on enantioselectivity were also observed. Furthermore it was suggested that catalysis and enantioinduction may result from initial abstraction of a chloride anion from a in an SN1-type rate determining step (a → b) and subsequent cyclization mediated by the resulting anion-bound thiourea. This mode of catalytic generation of cationic intermediates is previously reported in well-established anion-binding properties of ureas and thioureas. Further, the possibility of high levels of enantioinduction induced through counterion interactions is well precedented in chiral phase-transfer catalysis and has recently been demonstrated in the context of asymmetric counterion-directed catalysis.

In 2007, Jacobsen published a review titled “Small-Molecule H-Bond Donors in Asymmetric Catalysis” identifying chiral hydrogen-bond donors used for enantioselective synthesis. The area regarding to the PS reaction referred to previous work reported by Jacobsen. Concluding, Jacobsen stated his surprise at both phosphoric acids and thiourea derivatives being capable of mediating enantioselective transformations of prochiral iminium and N-acyliminium ion intermediates as they exist in opposite ends of the spectrum of the pKa scale of known H-bond donor catalysts.

In 2009 Jacobsen reported asymmetric Pictet-Spengler reactions cocatalyzed by a chiral thiourea and benzoic acid. A number of optically active tetrahydro-β-carbolines were obtained in high ee.

Scheme: (Jacobsen 2009). Bronsted Acid and H-Bond Donor Co-catalysis mechanism

The catalytic cycle for this was proposed where imine protonation is induced by a thiourea catalyst via H-bonding to the conjugate base of a weak Bronsted acid additive. The highly reactive protioiminium ion then cyclizes and aromatizes to generate the desired product and Bronsted acid cocatalyst. Examples also show that this thiourea catalyst promotes highly enantioselective Pictet-Spengler reactions on electronically and structurally diverse substrates.

Scheme: (Jacobsen 2009). Thiourea and Benzoic Acid Catalyzed Pictet-Spengler Reaction

Jacobsen published further work continuing with his cocatalyzed thiourea/benzoic acid Iso-Pictet-Spengler reactions in 2011. Here he focused on the synthesis of optically pure tetrahydro-γ-carbolines. He reports a straightforward procedure for upgrading the ee of the tetrahydro-γ-carbolines products by Boc protecting the free amine. This simple step elevates the ee to greater than 99% in nearly all the examples shown and by simple crystallization or trituration. Furthermore, the use of ketone substrates was also demonstrated and shown to proceed to similar yields and ee’s

Scheme: (Jacobsen 2011). Iso-Pictet-Spengler Reaction using a ketone and upgrading ee by Boc protecting and trituration

To Do:

Iso-Pictet-Spengler (C3 of indole) Jacobsen 2011- MNR Done

Thiourea plus a proton: Jacobsen 2009 - MNR Done

Franz 2011 - MNR Done, in Bronsted Acids

Cook 1992

Mechanism

Terada (10.1021/ja0491533) mentions (wrt Bronsted acids) "1) Tetradentate structure around the phosphorus(V) atom would prevent free rotation at R of the phosphorus center by formation of a ring structure. This characteristic feature cannot be found in other possible Brønsted acids, such as carboxylic and sulfonic acids, etc. 2) Their appropriate acidity16 should catch up the imine through hydrogen bonding without loose ion-pair formation. 3) Their phosphoryl oxygen should function as a Lewis basic site, and thus a phosphoric acid could function as a bifunctional catalyst."

Interesting --> Cook et al, "Study of the Cis to Trans Isomerization of 1-Phenyl-2,3-disubstituted Tetrahydro-β-carbolines at C(1). Evidence for the Carbocation-Mediated Mechanism" DOI: 10.1021/jo8028168 - Proposes mechanism for the racemisation via retro Pictet-Spengler of enantioenriched tetrahydro-β-carbolines synthesised from tryptamines and aldehydes.

For binaphthyl-derived phosphoric acids are there any trends in the nature of the substituents vs. ee obtained? In Hiemstra 2007 no clear trend is visible in Table 1.

Limitation: avoiding β,γ-unsaturated aldehydes, which tend to tautomerise from the intermediate iminium ion to the unreactive, conjugated enamine, e.g. in Hiemstra 2011.

Both enantiomers of the BINOL phosphoric acid catalyst gave the same ee. The proposed mechanism was that both reactions reached a steady state with an achiral enamide intermediate. Also, suggested enantioselectivity arose from facial differentiation imposed by the tight ion pair between the binol phosphoric acid conjugate base and the iminium ion. Dixon 2010.

Terada Review (10.1246/bcsj.20090268): Phosphoric acids as stronger Bronsted acids than thioureas or than TADDOL (used in the Rawal Nature paper). Considered other possible acids including sulfonic (too strong), carboxylic and sulfuric (free rotation problem), and phosphoric - just right, and chiral info is closer to proton. (When deprotonated, the O minus and P=O sites interconvert, right, but this is unimportant?) Phosphoric acids not expected to form loose ion pairs. Expected to be H-bonding etc that keeps components together. Ring system employed in the BINOL derivatives makes more rigid. Good? Mechanistic proposal in Figure 4. H-bonding network, not ion pair. Developed phosphorodiamidic acid in Synlett 2006, 133. Figure 11 has mechanistic cycle that may be of interest to PZQ. Do all the enecarbamate reactions known to function have N-H's?

Solvents: toluene found to be a good solvent for a number of these reactions, e.g. 10.1021/ja9024885

Miscellaneous Other Systems/Ones not yet used for PS

Strong Bronsted acids not yet applied to PS:
Chiral N-triflyl phosphoramide Yamamoto 2006 Check: C. H. Cheon, H. Yamamoto, J. Am. Chem. Soc. 2008, 130, 9246–9247
C. H. Cheon, H. Yamamoto, Org. Lett. 2010, 12, 2476–2479
M. Rueping, W. Ieawsuwan, A. P. Antonchick, B. J. Nacht- sheim, Angew. Chem. Int. Ed. 2007, 46, 2097–2100
P. Jiao, D. Nakashima, H. Yamamoto, Angew. Chem. Int. Ed. 2008, 47, 2411–2413.
H. Xu, S. J. Zuend, M. G. Woll, Y. Tao, E. N. Jacobsen, Science 2010, 327, 986–990 (mixture).
M. Treskow, J. Neudörfl, R. Giernoth, Eur. J. Org. Chem. 2009, 3693–3697.
P. García-García, F. Lay, P. García-García, C. Rabalakos, B. List, Angew. Chem. Int. Ed. 2009, 48, 4363–4366.

TADDOL ligands: Akiyama 2005

Enzymatic examples:
Norcoclaurine synthase Tanner 2007
Strictosidine Synthase Stoeckigt 2008

References

Papers included in the review should be listed here when the description of the science is complete. The papers may be found in full at the Mendeley page)

Diastereoselective:

• Enantiospecific Formation of Trans 1,3-Disubstituted Tetrahydro-β-carbolines by the Pictet-Spengler Reaction and Conversion of Cis Diastereomers into Their Trans Counterparts by Scission of the C-1/N-2 Bond, E. D. Cox, L. K. Hamaker, J. Li, P. Yu, K. M. Czerwinski, L. Deng, D. W. Bennett and J. M. Cook, J. Org. Chem. 1997, 62, 44-61. Paper

Lewis Acid Section:

• Chiral Lewis Acid-mediated Enantioselective Pictet-Spengler Reaction of N-b-Hydroxytryptamine with Aldehydes, H. Yamada, T. Kawate, M. Matsumizu, A. Nishida, K. Yamaguchi, M. Nakagawa, J. Org. Chem. 1998, 63, 6348-6354. Paper

Brønsted Section:

• Enantioselective Mannich-Type Reaction Catalyzed by a Chiral Brønsted Acid, T. Akiyama, J. Itoh, K. Yokota and K. Fuchibe, Angew. Chem. Int. Ed. 2004, 43, 1566-1568. Paper
• Chiral Brønsted Acid-Catalyzed Direct Mannich Reactions via Electrophilic Activation, D. Uraguchi and M. Terada, J. Am. Chem. Soc. 2004, 126, 5356-5357. Paper
• Catalytic Asymmetric Pictet-Spengler Reaction, J. Seayad, A. M. Seayad and B. List, J. Am. Chem. Soc. 2006, 128, 1086-1087. Paper
• Catalytic Asymmetric Pictet-Spengler Reactions via Sulfenyliminium Ions, M. J. Wanner, R. N. S. van der Haas, K. R. de Cuba, J. H. van Maarseveen and H. Hiemstra, Angew. Chem. Int. Ed. 2007, 46, 7485-7487. Paper
• Enantioselective BINOL-phosphoric Acid Catalyzed Pictet-Spengler Reactions of N-benzyltryptamine, N. V. Sewgobind, M. J. Wanner, S. Ingemann, R. de Gelder, J. H. van Maarseveen and H. Hiemstra, J. Org. Chem. 2008, 73, 6405-6408. Paper
• Organocatalytic Enantioselective Total Synthesis of (-)-Arboricine, M. J. Wanner, R. N. A. Boots, B. Eradus, R. de Gelder, J. H. van Maarseveen and H. Hiemstra, Org. Lett. 2009, 11, 2579-2581. Paper
• Chiral Phosphoric Acids as Versatile Catalysts for Enantioselective Carbon-Carbon Bond Forming Reactions, M. Terada, Bull. Chem. Soc. Jpn. 2010, 83, 101-119. Paper
• Total Synthesis of (+)-Yohimbine via an Enantioselective Organocatalytic Pictet-Spengler Reaction, B. Herle, M. J. Wanner, J. H. van Maarseveen and H. Hiemstra, J. Org. Chem. 2011, 76, 8907-8912. Paper
• Enantioselective Syntheses of Corynanthe Alkaloids by Chiral Brønsted Acid and Palladium Catalysis, M. J. Wanner, E. Claveau, J. H. van Maarseveen and H. Hiemstra, Chem. Eur. J. 2011, 17, 13680-13683. Paper
• Enantioselective Pictet-Spengler Reactions of Isatins for the Synthesis of Spiroindolones, J. J. Badillo, A. Silva-Garcia, B. H. Shupe, J. C. Fettinger and A. K. Franz, Tetrahedron Lett. 2011, 52, 5550-5553. Paper

Organocatalysis Section:

• Highly Enantioselective Catalytic Acyl-Pictet-Spengler Reactions,Taylor, M. S.; Jacobsen, E. N. J. Am. Chem. Soc. 2004, 126 10558-10559 Paper
• Small-Molecule H-Bond Donors in Asymmetric Catalysis, Doyle, A. G.; Jacobsen, E. N. Chemical Reviews 2007, 107, 5713-5743.
• Enantioselective Pictet-Spengler-Type Cyclizations of Hydroxylactams: H-Bond Donor Catalysis by Anion Binding, Raheem, I. T.; Thiara, P. S.; Peterson, E. A.; Jacobsen, E. N. Journal of the American Chemical Society 2007, 129, 13404.
• Weak Brønsted Acid-thiourea Co-catalysis: Enantioselective, Catalytic Protio-Pictet-Spengler Reactions, R. S. Klausen and E. N. Jacobsen, Org. Lett. 2009, 11, 887-890. Paper
• Thiourea-Catalyzed Enantioselective Iso-Pictet-Spengler Reactions, Y. Lee, R. S. Klausen and E. N. Jacobsen, Org. Lett. 2011, 13, 5564. Paper

Papers we're not including, and why (arranged by date)

• Asymmetric Pictet-Spengler Reactions Employing N,N-Phthaloyl Amino Acids as Chiral Auxiliary Groups, H. Waldmann, G. Schmidt, H. Henke and M. Burkard, Angew. Chem., Int. Ed. Engl. 1995, 34, 2402-2403. Paper - Diastereoselective. Use of stoichiometric chiral auxiliaries.
• Asymmetric Control in Pictet-Spengler Reaction by Means of N-Protected Amino Acids as Chiral Auxiliary Groups, G. Schmidt, H. Waldmann, H. Henke and M. Burkard, Chem. Eur. J. 1996, 2, 1566-1571. Paper - Diastereoselective. Use of stoichiometric chiral auxiliaries.
• Enantiopure Tetrahydro-β-carbolines via Pictet−Spengler Reactions with N-Sulfinyl Tryptamines, C. Gremmen, B. Willemse, M. J. Wanner, G.-J. Koomen, Org. Lett. 2000, 2, 1955-1958. [Paper]- Use of chiral auxiliary.
• Enantiopure tetrahydroisoquinolines via N-sulfinyl Pictet–Spengler reactions, C. Gremmen, M. J. Wanner, G Koomen, G.-J. Tetrahedron Lett. 2001, 42, 8885-8888. Paper - Use of chiral auxiliary and excess acid.
• General Approach for the Synthesis of Sarpagine Indole Alkaloids. Enantiospecific Total Synthesis of (+)-Vellosimine, (+)-Normacusine B, (-)-Alkaloid Q3, (-)-Panarine, (+)-Na-Methylvellosimine, and (+)-Na-Methyl-16-epipericyclivine, J. Yu, T. Wang, X. Liu, J. Deschamps, J. Flippen-Anderson, X. Liao and J. M. Cook, J. Org. Chem. 2003, 68, 7565-7581. Paper - diastereoselective
• Organocatalytic Asymmetric Aza-Friedel-Crafts Alkylation of Furan, D. Uraguchi, K. Sorimachi and M. Terada, J. Am. Chem. Soc. 2004, 126, 11804-11805. Paper - Maybe include, but non-PS, simple extension of previous paper.
• Organocatalytic Asymmetric Direct Alkylation of α-Diazoester via C−H Bond Cleavage, D. Uraguchi, K. Sorimachi and M. Terada, J. Am. Chem. Soc. 2005, 127, 9360-9361. Paper - extension to a system too far removed from PS reaction.
• Chiral Brønsted Acid Catalyzed Enantioselective Hydrophosphonylation of Imines:  Asymmetric Synthesis of α-Amino Phosphonates, T. Akiyama, H. Morita, J. Itoh and K. Fuchibe, Org. Lett. 2005, 7, 2583–2585. Paper - simple extension to other nucleophile.
• Stereocontrolled Total Synthesis of (-)-Eudistomin C, T. Yamashita, N. Kawai, H. Tokuyama and T. Fukuyama, J. Am. Chem. Soc. 2005, 127, 15038-15039. Paper - Diastereoselective.
• An Improved Total Synthesis of (+)-Macroline and Alstonerine as Well as the Formal Total Synthesis of (-)-Talcarpine and (-)-Anhydromacrosalhine-methine, X. Liao, H. Zhou, J. Yu and J. M. Cook, J. Org. Chem. 2006, 71, 8884-8890. Paper - presumed diastereoselective, but relevant chemistry is actually in J. Org. Chem. 2000, 65, 3173.
• Total Synthesis of the Opioid Agonistic Indole Alkaloid Mitragynine and the First Total Syntheses of 9-Methoxygeissoschizol and 9-Methoxy-Nb-methylgeissoschizol, J. Ma, W. Yin, H. Zhou and J. M. Cook, Org. Lett. 2007, 9, 3491-3494. Paper - diastereoselective.
• Total Synthesis of (–)-Corynantheidine by Nickel-Catalyzed Carboxylative Cyclization of Enynes, T Mizuno, Y. Oonishi, M. Takimoto, and Y. Sato, Eur. J. Org. Chem. 2011, 2606-2609. Paper - diastereoselective PS as part of longer synthesis.