Cp*Rh(III)-catalyzed electrophilic amination of arylboronic acids with azo compounds for synthesis of arylhydrazides

Abstract

A [Cp*Rh(III)]-catalyzed electrophilic amination of arylboronic acids with diethyl azodicarboxylate (DEAD) was developed, and arylhydrazides were produced in excellent yields and selectivity. The analogous amination with the arylazocarboxylates afforded the corresponding N,N-diarylhydrazides. The electrophilic amination of arylboronic acids with azocarboxylates proceeds readily under mild conditions with excellent functional group tolerance. Up to 99% yields were obtained. Preliminary mechanistic studies revealed that prior formation of an arylrhodium(III) intermediate for the azo coupling reaction can be ruled out.

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Transition metal-catalyzed electrophilic (umpolung) aminations are attractive approaches for arylamine synthesis under mild conditions.¹ Characterized by weak N–X (X = leaving group) σ-bonds, haloamines and hydroxyamine derivatives have been extensively investigated for electrophilic amination with organolithium and -magnesium reagents.² Dialkyl azodicarboxylates are conceptually different classes of electrophilic amination reagents. Unlike the halo/hydroxyamine-type reagents, the azodicarboxylates react with carbanionic nucleophiles via N–N π-bond cleavage. While dialkyl azodicarboxylates are known to react with stoichiometric organometallic reagents for C–N bond coupling reactions,³ examples involving transition metal catalysis are sparse in the literature (Scheme 1). About a decade ago, Carreira and coworkers reported a Co- and Mn-catalyzed alkene hydrohydrazination using di-tert-butyl azodicarboxylate and triphenylsilane as reagents.^3e–g Recently, Chatani and coworkers reported a Cu-catalyzed hydroarylation of azodicarboxylates.^3h Muniz and coworkers reported a Pd-catalyzed coupling of arylboronic acids with diethyl azodicarboxylate (DEAD). A palladadiaziridine complex was structurally characterized and was shown to mediate the C–N bond coupling reaction.^3i,j

Scheme 1 Recent examples of transition metal-catalyzed electrophilic amination with azo reagents.

Owing to an interest in developing transition metal catalyzed C–H bond aminations under mild conditions,⁴ we previously accomplished regioselective Pd-/Rh-catalyzed ortho-selective arene C–H amination with tosyloxycarbamates and N-chloroamines.^4k–o The catalytic arene C–H amination should proceed by coupling of reactive arylpalladium(II) and -rhodium(III) complexes with the amination reagents. By virtue of the weak N–N π-bond, we envisioned that dialkyl azodicarboxylates would be effective coupling partners with arylmetal complexes for C–N bond formation. Here we describe [Cp*Rh(III)]-catalyzed (Cp* = 1,2,3,4,5-pentamethyl-cyclopentadienyl) cross coupling of arylboronic acids with azo compounds for the synthesis of arylhydrazides.

When phenylboronic acid (1a; 0.3 mmol) was treated with DEAD (0.2 mmol) and [Cp*Rh(OAc)₂] (5 mol%) in THF at 80 °C under an N₂ atmosphere for 4 h, phenylhydrazide (2a) was obtained in 85% yield (Table 1, entry 1). In this work, we found that employing phenylboronic acid pinacol ester and potassium phenyltrifluoroborate alone did not bring about effective C–N coupling reactions (entries 2 and 3). The boron reagents were fully recovered with substantial decomposition of the DEAD. Interestingly, when potassium phenyltrifluoroborate was employed together with B(OH)₃ as additives and DMF as the solvent, 2a was formed in 70% yield (entry 4).

Table 1 Reaction optimization^a

Entry	Aryl boron reagent	Catalyst	Solvent	T (°C)	Yield^b (%)
a Conditions: aryl boron reagent (0.3 mmol), DEAD (0.2 mmol), catalyst (5 mol%), solvent (1 mL), 4 h in an N2 atmosphere. b Isolated yield. c n.d. = not detected. d B(OH)3 (0.3 mmol) was added. e [Cp*Rh(OAc)2] (2 mol%) was used. f Di-tert-butyl azodicarboxylate (0.2 mmol) was used instead.
1	PhB(OH)2 (1a)	[Cp*Rh(OAc)2]	THF	80	85
2	PhB(pin)	[Cp*Rh(OAc)2]	THF	80	n.d.^c
3	KPhBF3	[Cp*Rh(OAc)2]	THF	80	n.d.^c
4^d	KPhBF3	[Cp*Rh(OAc)2]	THF	80	70
5	1a	[Cp*RhCl2]2	THF	80	10
6	1a	[Rh(COD)Cl]2	THF	80	11
7	1a	[Rh(COD)(OH)]2	THF	80	n.d.^c
8	1a	[Cp*IrCl2]2	THF	80	n.d.^c
9	1a	[Cp*Rh(OAc)2]	^tBuOH	80	64
10	1a	[Cp*Rh(OAc)2]	MeCN	80	3
11	1a	[Cp*Rh(OAc)2]	Dioxane	80	50
12	1a	[Cp*Rh(OAc)2]	DCE	80	31
13^e	1a	[Cp*Rh(OAc)2]	DMF	40	99
14^f	1a	[Cp*Rh(OAc)2]	THF	80	42

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Other rhodium catalysts such as [Cp*RhCl₂]₂ are less effective catalysts (entry 5). According to the literature, rhodium(I) diene complexes such as [Rh(COD)X]₂ (X = Cl, OH) are known to catalyze arylation of enones with arylboron reagents.⁵ However, these Rh(I)–diene complexes were found to be ineffective catalysts for the reaction of 1a with DEAD (entries 6 and 7). In this work, the related [Cp*IrCl₂]₂ complex exhibited negligible catalytic activities under our reaction conditions (entry 8).

Other solvents such as ^tBuOH, MeCN, dioxane and DCE gave inferior results compared to THF (entries 9–12). After several trials, we found that DMF gave the best result with 2a being formed in a nearly quantitative yield.⁶ Upon further refinement of several experimental parameters, an optimized reaction protocol was established: [Cp*Rh(OAc)₂] (2 mol%), 1a (0.3 mmol), DEAD (0.2 mmol) in DMF at 40 °C (entry 13). It is noteworthy that the azo coupling reaction is sensitive to the ester substituents on the azocarboxylates. For instance, the amination of 1a with di-tert-butyl azodicarboxylate produced the corresponding arylhydrazides in only 42% yield (entry 14). The coupling with azobenzene was unsuccessful, and no C–N coupled products were obtained.⁶

With DEAD as the model substrate, the scope of the arylboronic acids was examined (Scheme 2). The reactions of arylboronic acids containing electron-donating and -withdrawing groups (e.g. OMe, Me and Br) afforded the corresponding hydrazides (2a–2d) in excellent yields. Other functionalized arylboronic acids bearing TMS, CHO, C(O)Me, CO₂Et, NHC(O)Me and SO₂Me were converted to 2e–2j in 83–98% yields. Fruitful results were achieved for the analogous amidation of 6-methoxy-1-naphthyl, 3-chloro and 3,5-bis(trifluoromethyl)phenylboronic acids with 2k–2m being formed in excellent yields. Likewise, effective transformations of styrylboronic acid and heteroaromatic boronic acids were also achieved to give the corresponding products (2n–2q) in good to moderate yields.

Scheme 2 Scope of the arylation of DEAD. Yields of isolated products are given. General reaction conditions: 1 (0.3 mmol), DEAD (0.2 mmol), [Cp*Rh(OAc)₂] (2 mol%), DMF (1 mL), 40 °C for 4 h in an N₂ atmosphere. ^aThe reaction was performed at 80 °C.

Diarylamines are prevalent scaffolds found in many natural products, pharmaceuticals and functional materials.⁷ The Pd- and Cu-catalyzed arylation of anilines with haloarenes are widely employed for diarylamine synthesis.⁸ Yet, examples of diarylamine synthesis via electrophilic amination are sparse.⁹ Lei and coworkers reported the synthesis of diarylamines by Cu-catalyzed arylation of N-chloroanilides with arylboronic acids.^9e Recently, Chang and coworkers reported a reaction of aryl azides with aryliridium(III) complexes for diarylamine synthesis.^9f–h In this work, we developed the catalytic arylation of arylazocarboxylates for the synthesis of N,N-diarylhydrazides.

The arylazocarboxylate was prepared by reacting arylhydrazine with ethyl chloroformate, followed by NBS oxidation. When phenylazocarboxylate (3a) was treated with 4-methoxyphenylboronic acid (1b) and [Cp*Rh(OAc)₂] (2 mol%) in DMF at 40 °C under an N₂ atmosphere, N,N-diarylhydrazides (4aa) was isolated as a single regioisomer in 81% yield (Scheme 3). The molecular structure of 4aa has been established by single-crystal X-ray crystallography. Arylboronic acids containing electron-donating and -withdrawing substituents were well tolerated (see results for 4ba–4da). Similarly, amidation of 6-methoxy-1-naphthyl, 3,4-(methylenedioxy) and 3,5-ditrifluorophenylboronic acids furnished 4ea–4ga in excellent yields.

Scheme 3 Scope of the arylation of arylazocarboxylate. Yields of isolated products are given. General reaction conditions: 1 (0.3 mmol), 3 (0.2 mmol), [Cp*Rh(OAc)₂] (2 mol%), DMF (1 mL), 40 °C for 4 h in an N₂ atmosphere. ^aThe reaction was performed at 80 °C.

With 4-methoxyphenylboronic acid as the arylating reagent, the reactions of some substituted arylazocarboxylates were examined. Effective C–N coupling was observed in all cases, and the diarylhydrazides (4ab–4ae) were formed in 78–93% yields.

Arylrhodium(III) complexes are known to mediate catalytic C–N bond coupling reactions.^4m,10 To examine the involvement of the arylrhodium(III) complexes, we prepared the well-defined [Cp*Rh(Ph)(Br)(PPh₃)] complex 5a (71% yield) by reacting [Cp*RhCl₂(PPh₃)] with PhMgBr.¹¹ The analogous [Cp*Rh(Ph)(Cl) (PPh₃)] complex 5b (83% yield) was also prepared by employing phenylboronic acid as the aryl source (Scheme 4).¹² The molecular structures of 5a and 5b have been confirmed by single-crystal X-ray crystallography.⁶

Scheme 4 Synthesis of [Cp*Rh(Ph)(X)(PPh₃)].

In this work, when [Cp*Rh(Ph)(Br)(PPh₃)] (5a) (10 mol%) was treated with AgSbF₆ (10 mol%) and phenylazocarboxylate (0.5 mmol) in DMF at 40 °C for 4 h, no N,N-diphenylhydrazide was formed. Notably, [Cp*Rh(Ph)₂(PPh₃)] was isolated in 30% yield, and 18% of the starting [Cp*Rh(Ph)(Br)(PPh₃)] was recovered (Scheme 5). Notwithstanding, [Cp*RhCl₂(PPh₃)] was found to be an effective catalyst for the arylation reaction. For example, reacting [Cp*RhCl₂(PPh₃)] (5 mol%) with 4-methoxyphenylboronic acid (1b) and phenylazocarboxylate (3a) in DMF at 40 °C afforded 4aa in 99% yield. Based on the above findings, direct coupling of arylrhodium(III) with the azo reagent may not be a productive step for the arylation reaction.

Scheme 5 Investigation of the stoichiometric reaction of arylrhodium(III) complexes with phenylazocarboxylate.

Previously, Muniz and coworkers reported the Pd-catalyzed arylation of DEAD by arylboronic acids, and palladadiaziridine complexes have been characterized as the key intermediate. However, the attempt to characterize well-defined rhodalladiaziridine complexes was unsuccessful. The preparation and characterization of some reactive metalladiaziridine complexes are currently in progress, and the results will be reported separately.

Conclusions

In conclusion, we developed a [Cp*Rh(III)]-catalyzed electrophilic amination of arylboronic acids by employing azo reagents. Effective coupling of DEAD and the aryl azocarboxylates with arylboronic acids afforded mono- and diarylhydrazides in good yields under mild conditions.

Acknowledgements

We thank the Hong Kong Research Grants Council (PolyU5032/13P, C5023/14G) for financial support.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available. CCDC 1455768–1455771. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6ob00719h

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