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Facile Synthetic Methods for Diverse N-Arylphenylalanine Derivatives via Transformations of Aryne Intermediates and Cross-Coupling Reactions

2021, Vol.94, No.7

1823-1832

Open Access

Facile Synthetic Methods for Diverse N-Arylphenylalanine Derivatives via Transformations of Aryne Intermediates and Cross-Coupling Reactions

Tsuneyuki Kobayashi ,¹Takamitsu Hosoya ,¹ and Suguru Yoshida ^*¹^,²

¹Laboratory of Chemical Bioscience, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU), 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan
²Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science, 6-3-1 Niijuku, Katsushika-ku, Tokyo 125-8585, Japan

https://doi.org/10.1246/bcsj.20210149

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Abstract

Section:

Synthesis of diverse N-arylphenylalanine derivatives through sequential transformations of N-arylphenylalanine ester-type platforms is disclosed. The highly functionalized platforms were prepared by an oxidative cross-coupling reaction leaving aryne generating moieties and halogeno groups intact. Great transformability of N-arylphenylalanine ester-type platforms by aryne reactions and cross-coupling reactions allowed us to prepare analogs of bioactive compounds.

1. Introduction

Section:

A wide variety of functionalized amino acids have served as bioactive compounds such as pharmaceuticals, and also as building blocks particularly for peptide synthesis. Particularly, N-arylphenylalanine substructures are found in various bioactive compounds including VLA-4 antagonist 1 and PPARγ agonist 2 (Figure 1).¹

Figure 1. Biologically active N-arylphenylalanines.

In general, N-arylphenylalanines have been synthesized by N-arylation of amino acids including the classical Ullmann and the Buchwald–Hartwig cross-coupling reactions.²^,³ Various conditions for the N-arylation of phenylalanine derivatives 4, 7, and 10 have been found using a range of coupling partners 3, 6, and 9 (Figure 2).^2d^,^3a^,^3b However, available N-arylphenylalanines by the cross-coupling reactions of amino acids are limited due to the low nucleophilicity of the amino group and the presence of reactive functional groups. In addition, introducing transformable functional groups like bromo or iodo groups is a challenging issue. Also, it is difficult to realize direct substituent introductions into phenylalanine in terms of regioselectivity and functional group tolerance.

Figure 2. Reported synthesis of N-arylphenylalanines by N-arylation of phenylalanine derivatives.

Alternative methods to prepare functionalized phenylalanine derivatives have been developed (Figure 3). For instance, the synthesis of a range of N-arylphenylalanines was accomplished by benzylation of a Schiff base under basic conditions followed by a functional group transformation to amine 15 and subsequent palladium-catalyzed N-arylation (Figure 3A).⁴ Rhodium-catalyzed conjugate addition of arylboronic acids to α-aminoacrylic acid ester 17 also enabled the preparation of a variety of functionalized phenylalanines (Figure 3B).⁵ Since synthesizable functionalized phenylalanine derivatives are limited by conventional methods, a novel method to synthesize highly functionalized N-arylphenylalanines is sought.

Figure 3. Reported synthesis of N-arylphenylalanines. (A) Schiff base approach. (B) Conjugate addition approach.

We recently communicated an efficient method to synthesize various N-arylphenylalanines through N-arylphenylalanine ester-type intermediates by aryne reactions and cross-coupling reactions.⁶ Here, we disclose full details of the facile method for preparing diverse N-arylphenylalanine ester-type intermediates containing an aryne generating moiety and a halogeno group via oxidative cross-coupling reaction (Scheme 1). Also, the synthesis of a wide variety of N-arylphenylalanine esters through aryne generation and cross-coupling reactions were accomplished.

Scheme 1. Our idea of oxidative cross-coupling approach.

Aryne reactions such as addition and cycloaddition reactions lead to a wide range of highly functionalized arenes involving diverse fused benzenes.⁷^,⁸ Additionally, cross-coupling reactions using a bromo or iodo group significantly expand synthesizable arenes.⁹ Thus, we designed N-arylphenylalanine ester-type platforms 21 having significant transformable groups, an aryne generating moiety and a halogeno group (Scheme 1). Although the synthesis of highly functionalized N-arylphenylalanines 21 and their selective transformations are challenging issues, we envisioned that N-arylphenylalanine ester-type platforms will serve in the facile preparation of a great diversity of N-arylphenylalanine derivatives 22–24 by various transformations via aryne intermediates, cross-coupling reactions, and further transformations.

This study was started from examinations to prepare N-arylphenylalanine ester-type platforms. It is not easy to synthesize N-arylphenylalanine ester-type platforms 21 without damaging highly reactive functional groups such as halogen, triflate, silyl, and ester moieties. Only a limited number of syntheses have been reported in which a silyl group or triflate is introduced onto the benzene ring of the phenylalanine skeleton by triflylation after protecting the amino group, or C–H silylation (Figures 4A and 4B).^1b^,¹⁰ Thus, one challenging issue for the synthesis of platforms 21 is how to construct an aryne generating moiety such as a benzene ring bearing a silyl and a triflyloxy group in the N-arylphenylalanine scaffold.

Figure 4. (A) Triflylation of 25. (B) C–H silylation of 28. (C) Cross-coupling reactions of 30.

Although a few successful cross-coupling reactions leaving an o-silylaryl triflate moiety untouched have been reported so far, it is not easy to realize cross-couplings avoiding the reaction of silyl and triflyloxy groups. For instance, Raminelli and coworkers achieved the synthesis of 6-phenyl-2-(trimethylsilyl)phenyl triflate (31) by Suzuki–Miyaura cross-coupling of 6-iodo-2-(trimethylsilyl)phenyl triflate (30) having an o-silylaryl triflate moiety at the iodo group (Figure 4C, lower), where the undesired side-reactions such as cross-coupling at the triflyloxy group also took place depending on the reaction conditions (Figure 4C, upper and middle).¹¹ With these results in mind, we at first examined the reactivity of o-silylaryl triflate moiety in cross-coupling reactions.

2. Results and Discussion

Section:

2.1 Synthesis of N-Arylphenylalanine Ester-Type Platforms.

Our attempts using 6-iodo-2-(trimethylsilyl)phenyl triflate (30) to check the functional group tolerance under conditions for Chan–Lam–Evans or Stille cross-coupling reactions showed that the transition-metal catalyzed transformations of iodinated o-silylaryl triflates are difficult, in which corresponding products were not detected (Scheme 2). In order to carry out the cross-coupling reaction keeping the aryne generating site unreacted, we then focused on oxidative cross-coupling reactions¹² using organoborons preinstalled with an o-silylaryl triflate moiety for the synthesis of α-amino acid derivatives without damaging silyl and triflyloxy groups.

Scheme 2. Attempts for coupling reactions of 30.

We succeeded in the synthesis of a variety of benzylboronic acid derivatives 20 bearing o-silylaryl triflate moiety by Ni-catalyzed reductive arylation¹³ of bromomethylboronic acid pinacol ester (36) from brominated o-silylaryl triflates 35, which we previously prepared through iridium-catalyzed C–H borylation¹⁴ (Figure 5). Indeed, various benzylboronic acid esters 20a–20e with methoxy, methyl, morpholino, triflyloxy, and benzyloxy groups were successfully synthesized from aryl bromide 35 and 36 in the presence of zinc powder and a catalytic amount of nickel(II) bromide diglyme complex and 4,4′-di-tert-butyl-2,2′-dipyridyl (dtbpy) leaving the o-silylaryl triflate moiety untouched. Of note, we accomplished a gram-scale synthesis of borylmethyl-substituted o-silylaryl triflate 20a.

Figure 5. Synthesis of various benzylboronic acid esters 20 bearing an aryne generation moiety. DMPU = N,N′-dimethylpropyleneurea. ^a2.0 equiv of 36, 40 mol % of NiBr₂/diglyme, and 40 mol % of dtbpy were used.

Next, we examined oxidative cross-coupling of benzylboronic acid esters 20a with ethyl (4-bromophenyl)glycinate (19a), according to previous reports on the reactions between organoborons and N-arylglycine esters (Table 1).^12c After extensively screening the Lewis acids for the oxidative coupling, we found that copper(II) triflate-mediated C–C bond formation proceeded smoothly to afford the desired N-arylphenylalanine ester 21a in good yield (Entry 8), where the addition of triphenylphosphine slightly decreased the yield of 21a (Entry 7). Efficient synthesis of N-arylphenylalanine ester 21a was achieved under the Lewis acidic conditions without damaging bromo, triflate, silyl, or ester moiety, although labile o-silylaryl triflate moiety can be damaged by desilylprotonation.^14a Scandium triflate or silver triflate also facilitated the oxidative coupling of 20a with 19a in the presence of triphenylphosphine furnishing N-arylphenylalanine derivative 21a in moderate yields, while the coupling product 21a was obtained in low yields when using magnesium bromide, boron trifluoride, iron(II) sulfate, or aluminum trichloride.

Table 1. Optimization of the reaction conditions.

entry	catalyst	ligand	yield (%)^a
1	Sc(OTf)₃	PPh₃	64^b
2	MgBr₂·OEt₂	PPh₃	16
3	BF₃·THF	PPh₃	23
4	FeSO₄	PPh₃	5
5	AlCl₃	PPh₃	3
6	AgOTf	PPh₃	52
7	Cu(OTf)₂	PPh₃	74
8	Cu(OTf)₂	—	89^b

Reaction conditions: 19a (0.1 mmol), 20a (0.2 mmol), catalyst (10 mol %), ligand (10 mol %), Ag₂CO₃ (2.0 equiv), 1,2-dichloroethane (0.1 M), 80 °C, 13 h. ^aYields based on ¹H NMR analysis. ^bIsolated yields.

We then paid attention to the scope of N-substituted phenylalanine esters 19b–19j in the copper-catalyzed oxidative coupling using benzylboronic acid ester 20a (Table 2). The optimized reaction conditions were applicable to the synthesis of various N-arylphenylalanine esters 21b–21e having a wide range of electron-withdrawing groups such as iodo, chloro, fluoro, and trifluoromethoxy groups (Entries 1–4). Ethyl (3-bromophenyl)glycinate (19f) smoothly reacted with benzylboronic acid derivative 20a to afford N-arylphenylalanine-type platform 21f in moderate yield (Entry 5). The copper-catalyzed coupling of methyl (4-bromophenyl)glycinate (19g) with benzylboronic acid ester 20a also proceeded to provide methyl ester 21g in moderate yield (Entry 6). In contrast, the oxidative coupling products were not obtained from tert-butyl ester 19h, N-Boc-protected glycine ester 19i and ethyl N-(4-bromophenyl)-N-methylglycinate (19j) (Entries 7–9). These results clearly showed that substituents at the amino group significantly affected the reactivity in the oxidative cross-coupling reaction.

Table 2. Oxidative cross-coupling of N-arylglycine esters 19b–19j and benzylboronic acid ester 20a.

^aIsolated yields.

We succeeded in the oxidative cross-coupling reaction of ethyl (4-bromophenyl)glycinate (19a) with a range of benzylboronic acid derivatives 20b–20e affording the corresponding N-arylphenylalanine esters 21k–21n (Table 3). Indeed, treatment of 5-methyl-3-(triflyloxy)-4-(trimethylsilyl)benzylboronic acid pinacol ester (20b) with glycine derivative 19a in the presence of silver carbonate and a catalytic amount of copper(II) triflate in dichloroethane at 80 °C furnished N-arylphenylalanine ester 21k in good yield leaving a variety of functional groups intact (Entry 1). The synthesis of N-arylphenylalanine-type platforms 21l and 21m bearing morpholino and triflyloxy groups, respectively, was achieved without damaging these reactive functional groups albeit in low yields (Entries 2 and 3). Benzyloxy-substituted N-arylphenylalanine ester 21n was also prepared under the oxidative conditions keeping a wide range of functional groups unreacted (Entry 4).

Table 3. Scope of benzylboronic acid pinacol esters 20b–20e.

^aIsolated yields.

The borylmethylation of bromo-substituted o-silylaryl triflates and following oxidative cross-coupling with N-arylglycine esters enabled the synthesis of sterically congested N-arylphenylalanine 39 (Scheme 3). Indeed, benzylboron 38 possessing an o-silylaryl triflate moiety was synthesized by the nickel-catalyzed borylmethylation leaving silyl and triflyloxy groups untouched. Subsequent oxidative coupling of benzylboron 38 with ethyl N-(4-bromophenyl)glycinate (19a) took place smoothly at the bulky benzylic position to provide N-arylphenylalanine platform 39 in moderate yield.

Scheme 3. Synthesis of N-arylphenylalanine 39. ^a2.0 equiv of 38 was used.

Preparation of benzylboronic acid ester 40 bearing o-iodoaryl triflate moiety was accomplished by desilyliodination¹⁵ using 1,3-diiodo-5,5-dimethylhydantoin (DIH) and aluminum trichloride without damaging boryl, methoxy, and triflyloxy groups (Scheme 4). We achieved the oxidative cross-coupling of benzylboronic acid ester 40 with glycine derivative 19a catalyzed by copper(II) triflate to afford N-arylphenylalanine ester 41 keeping the iodo group remained.

Scheme 4. Synthesis of N-arylphenylalanine 41 bearing o-iodoaryl triflate moiety. ^a2.0 equiv of 40 was used.

2.2 Transformations of N-Arylphenylalanine Ester-Type Platforms.

We then turned our attention to selective transformations of N-arylphenylalanine-type platforms. It has been reported that aryne reactions with amino acid derivatives easily proceed owing to the significant electrophilicity of aryne intermediates (Figure 6). For example, Larock and coworkers observed N-arylation of amino acid 43 with benzyne at ambient temperature (Figure 6A).^16a In 2008, Stoltz and coworkers reported that indoline 46 was obtained through a benzyne reaction by the treatment of a mixture of ethyl α-(N-Boc-amino)acrylate (45) and o-silylphenyl triflate 42 with tetrabutylammonium difluorotriphenylsilicate (TBAT) (Figure 6B).^16b Considering the possibility that the N-arylphenylalanine ester moiety reacts with aryne intermediates generated in situ, we decided to examine the detailed scope of aryne reactions using N-arylphenylalanine-type platform. Furthermore, selective cross-couplings keeping o-silylaryl triflate moiety unreacted were also examined.

Figure 6. Selective aryne reaction with amino acid derivatives. (A) Larock’s study. (B) Stoltz’s study.

With N-arylphenylalanine esters 21a bearing o-silylaryl triflate and halogen moieties in hand, we then envisioned that addition reaction of morpholine (48a) to an aryne intermediate generated from 21a can be realized by the activation of the o-silylaryl triflate moiety with a fluoride anion source (Table 4). As a result, the treatment of a mixture of N-arylphenylalanine ester 21a and morpholine (48a) with cesium fluoride afforded the desired adduct 47a leaving bromo, amino, and ester moieties untouched, where side-products through N-arylation of the amino group were not obtained (Entry 1). This addition reaction via aryne generation from N-arylphenylalanine ester platform 21a on a 1 mmol scale proceeded uneventfully, showing good scalability. Not only the addition reaction of morpholine (48a) but also [2+3] cycloaddition with benzyl azide (49) and Diels–Alder reaction with 2-methoxyfuran (50) followed by ring-opening proceeded smoothly to afford N-arylphenylalanine esters 47b and 47c, in which regioisomers were not obtained (Entries 2 and 3). These results clearly show that a variety of N-arylphenylalanine esters having fused structures can be easily prepared by the aryne reactions. Furthermore, a wide range of amines possessing various functional groups such as alkyne, N-Boc-amine, and t-butyl ester also participated in the addition reaction onto the aryne intermediate generated from 21a to afford N-arylphenylalanine ester 47d–47f having various transformable functional groups (Entries 4–6).

Table 4. Scope of arynophiles with 21a.

^aIsolated yields. ^bYield for the reaction conducted at 1.0 mmol scale is shown in parentheses.

A range of N-arylphenylalanine ester-type platforms were applicable to the aryne reactions (Table 5). For instance, the addition reaction of morpholine (48a) with an aryne intermediate generated from 21b took place smoothly to provide adduct 47g in good yield without damaging the iodo group (Entry 1). We also succeeded in the selective cycloaddition of azide 49 with the aryne intermediates from 21b and 21l to furnish cycloadducts 47h and 47i in moderate yields (Entries 2 and 3).

Table 5. Aryne reactions of platforms 21b and 21l.

^aIsolated yields.

In N-arylation, which is a general method for synthesizing N-arylphenylalanines, there had been a problem that the optical purity can decrease due to the racemization during the cross-coupling reactions under basic conditions.¹⁷ Thus, we then examined the optical purity of adducts synthesized from enantiopure N-arylphenylalanine esters (+)-21a and (−)-21a to check the possibility of epimerization in the aryne reaction (Scheme 5). First, we successfully separated both enantiomers (+)-21a and (−)-21a by HPLC equipped with a chiral column. Then, each enantiomer (+)-21a and (−)-21a was treated with cesium fluoride in the presence of morpholine (48a). As a result, it was confirmed that the corresponding adducts (+)-47a and (−)-47a were obtained from (+)-21a and (−)-21a, respectively, without loss of the enantiopurity. These results obviously indicated that enantiopure N-arylphenylalanine esters (+)-21a and (−)-21a are significant chiral building blocks for synthesizing diverse optically active N-arylphenylalanine derivatives.

Scheme 5. Aryne reaction using enantiopure platforms (+)-21a and (−)-21a.

Subsequently, we performed cross-coupling reactions of N-arylphenylalanine esters after the aryne reactions at the remaining halogeno groups (Table 6). When a mixture of bromide 47a and arylboronic acid 51a was boiled in the presence of a palladium precatalyst and potassium carbonate, cross-coupling product 22a was successfully prepared in high yield without damaging the phenylalanine moiety (Entry 1). Bromide 47b having a benzotriazole ring also reacted with arylboronic acid 51b to afford highly functionalized N-arylphenylalanine derivative 22b (Entry 2). Introduction of heterocyclic benzofuran ring to iodide 47g was achieved efficiently providing N-arylphenylalanine ester 22c in high yield (Entry 3). Furthermore, we succeeded in the cross-coupling of bromide 47i bearing benzotriazole and morpholine rings (Entry 4). These results indicated that the Suzuki–Miyaura cross-coupling reaction of N-arylphenylalanine esters 47 enabled a facile synthesis of diverse multi-substituted N-arylphenylalanine esters.

Table 6. Synthesis of arylated N-arylphenylalanine esters 22 by Suzuki–Miyaura cross-coupling of 47.

^aIsolated yields. ^b2.0 equiv of 51c was used.

We accomplished the Sonogashira cross-coupling of N-arylphenylalanine derivatives 47 bearing an iodo group (Table 7). Indeed, treatment of N-arylphenylalanine ester 47g with triisopropylsilylacetylene (52a) in the presence of palladium catalyst, copper iodide, and triethylamine provided alkynylated N-arylphenylalanine ester 22e in good yield leaving amino, ethoxycarbonyl, morpholino, methoxy, and silyl groups untouched (Entry 1). Alkynylation of iodide 47h possessing a benzotriazole moiety with phenylacetylene (52b) also took place smoothly to afford N-arylphenylalanine ester 22f in moderate yield (Entry 2). Furthermore, cyanation of iodide 47g was realized using potassium ferrocyanide catalyzed by palladium–XPhos (Scheme 6).¹⁸ Thus, we achieved modular synthesis of various multisubstituted N-arylphenylalanines by aryne generation and cross-coupling reactions.

Scheme 6. Palladium-catalyzed cyanation reaction of 47g.

Table 7. Synthesis of alkynylated N-arylphenylalanine esters 22e and 22f by Sonogashira cross-coupling of 47.

^aIsolated yields.

We then conducted selective palladium-catalyzed couplings of N-arylphenylalanine-type platform 21b (Scheme 7). As a result, Suzuki–Miyaura cross-coupling of iodide 21b with 4-methoxyphenylboronic acid (51a) smoothly took place to afford N-arylphenylalanine ester 53a in high yield leaving o-silylaryl triflate moiety intact. Sonogashira cross-coupling of iodide 21b was also accomplished without damaging silyl or triflyloxy groups, providing N-arylphenylalanine ester 53b in good yield. Further aryne reactions of o-silylaryl triflates 53a and 53b allowed us to synthesize highly functionalized N-arylphenylalanine esters 22a and 22h. These results indicate that a wide variety of N-arylphenylalanines can be easily synthesized from readily available modules by various transformations since the order of cross-couplings and aryne reactions is changeable.

Scheme 7. Synthesis of 22a and 22h by cross-couplings followed by aryne reactions.

2.3 Syntheses of Analogs of Bioactive Compounds from N-Arylphenylalanine Ester-Type Platforms.

A range of transformations of N-arylphenylalanine ester-type platforms were showcased toward synthesizing analogs of bioactive compounds. For example, N-arylphenylalanine ester-type platform 21a was successfully hydrolyzed to afford the corresponding carboxylic acid 54 without affecting functional groups such as amino, bromo, silyl, and triflyloxy groups despite the basic conditions which can trigger the aryne generation (Scheme 8). Then, protease inhibitor analog 56 was prepared easily by condensation of carboxylic acid 54 with glycine derivative 55 facilitated by 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU) and Hünig’s base.¹⁹^,²⁰ Thus, a wide range of peptides will be synthesized from N-arylphenylalanine-type platform 54 by condensation, aryne reactions, and cross-couplings.

Scheme 8. Synthesis of dipeptide 56.

We succeeded in the preparation of an analog of α-adrenergic antagonist intermediate by an intramolecular aryne reaction of sterically congested N-arylphenylalanine ester 39 (Scheme 9).²¹ Indeed, aryne generation from N-arylphenylalanine ester 39 followed by intramolecular hydroamination proceeded smoothly to form the indoline scaffold efficiently.

Scheme 9. Synthesis of indoline 57 via intramolecular aryne reaction of N-arylphenylalanine ester 39.

Since the nitrogen atom of N-arylphenylalanine derivatives shows good nucleophilicity, further derivatizations allowed us to prepare a wide variety of analogs of bioactive compounds. For instance, we achieved the synthesis of diketopiperazine 23a having a transformable bromo group through acylation with acyl chloride 58 in the presence of zinc powder and subsequent deprotective cyclization (Scheme 10). The diketopiperazine synthesis from N-arylphenylalanine ester-type platforms 21 via aryne reactions, construction of diketopiperazine scaffold, and further cross-coupling reactions would allowed us to synthesize diverse PPI inhibitor analogs.²²

Scheme 10. Synthesis of diketopiperazine 23a.

The synthesis of an analog of Kong’s proprietary compounds showing flaviviridae virus polymerase inhibitory activity was accomplished by transformations from N-arylphenylalanine ester 22c (Scheme 11).²³ First, acylation of N-arylphenylalanine ester 22c with acyl chloride 60 mediated by zinc powder took place smoothly to afford amide 61. Then, the hydrolysis of the ester moiety of 61 was achieved by treatment with aqueous sodium hydroxide without damaging the amide moiety and aromatic rings. Since a wide range of analogs can be synthesized only by changing modules in aryne reactions, cross-couplings, and acylation, this synthetic method is of significance serving in pharmaceutical sciences.

Scheme 11. Synthesis of flaviviridae viral polymerase inhibitor analog 24a.

3. Conclusion

Section:

In conclusion, we have developed N-arylphenylalanine ester-type platforms by oxidative cross-coupling reaction leaving aryne generating moieties and halogeno groups intact. Great transformability of N-arylphenylalanine ester-type platforms realized a facile synthesis of diverse N-arylphenylalanine esters by aryne reactions and cross-coupling reactions. Preparing analogs of bioactive compounds was achieved by further derivatizations of N-arylphenylalanine derivatives. Since a wide variety of N-arylphenylalanine derivatives can be synthesized from easily available modules in a convergent manner, this synthetic approach through aryne reactions, cross-couplings, and further transformations at the amino acid moiety will serve in drug discovery by the construction of a vast N-arylphenylalanine derivative library.

The authors thank Dr. Yuki Sakata at Tokyo Medical and Dental University for HRMS analyses. This work was supported by JSPS KAKENHI Grant Numbers JP19K05451 (C; S.Y.); the Naito Foundation (S.Y.); the Japan Agency for Medical Research and Development (AMED) under Grant Number JP20am0101098 (Platform Project for Supporting Drug Discovery and Life Science Research, BINDS); and the Cooperative Research Project of Research Center for Biomedical Engineering.

Supporting Information

Typical procedures and spectroscopic data of products are described. This material is available on https://doi.org/10.1246/bcsj.20210149

Suguru Yoshida

Suguru Yoshida received his Ph.D. from Kyoto University in 2009 under the supervision of Prof. Koichiro Oshima. From 2009 to 2010, he joined the group of Prof. Katsuhiko Tomooka at Kyushu University and that of Prof. Marcus Tius at the University of Hawaii as a postdoctoral fellow. In 2010, he became Assistant Professor at Tokyo Medical and Dental University working with Prof. Takamitsu Hosoya and was promoted to Associate Professor in 2015. He moved to Tokyo University of Science in 2021 as Associate Professor. He received the CSJ Award for Young Chemists (2017) and the Commendation for Science and Technology by MEXT (2019).

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2021, Vol.94, No.7

Facile Synthetic Methods for Diverse N-Arylphenylalanine Derivatives via Transformations of Aryne Intermediates and Cross-Coupling Reactions

Abstract

2.1 Synthesis of N-Arylphenylalanine Ester-Type Platforms.

2.2 Transformations of N-Arylphenylalanine Ester-Type Platforms.

2.3 Syntheses of Analogs of Bioactive Compounds from N-Arylphenylalanine Ester-Type Platforms.

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