Rhodium-catalyzed asymmetric phenylation of N-phosphinoylarylimines with triphenylborane

Abstract

Triphenylborane asymmetrically transfers its phenyl group to N-diphenylphosphinoylarylimines to give diarylmethylamines with high ee in high yield without imine hydrolysis under the catalysis of a chiral amidomonophosphane–rhodium(I) complex.

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Success in the chiral amidomonophosphane–rhodium-catalyzed asymmetric arylation of N-diphenylphosphinoyl (Dpp) imines with arylboroxines^1,2 relied on the use of 4 Å molecular sieves (MS 4Å) as a dehydrating agent to realize almost water-free conditions, giving the corresponding diarylmethylamines with extremely high enantioselectivity in satisfactorily high yield.^3,4 For example, the arylation of benzaldehydeN-Dpp-imine 2a with 4-methylphenyl- and 4-methoxyphenylboroxines 3b and 3c in a 5 : 1 mixture of dioxane and propanol in the presence of the 1–Rh(I) catalyst and MS 4Å at 80 °C for 12 h gave the corresponding arylated amines (S)-4b and (S)-4c with 98% ee each in 96% and 92% yields, respectively (Table 1, entries 1 and 2).⁴ Continuing scope and limitation studies, however, revealed that the reaction of less reactive 4-methyl- and 4-methoxybezaldehyde N-Dpp-imines 2b and 2c with phenylboroxine 3a gave the products (R)-4b and (R)-4c with lower 84% and 83% ee in decreased 79% and 10% yields, respectively, probably due to competitive hydrolysis of the imines (entries 3 and 4). Then, our problem solving research was focused on the survey of arylation conditions that give shorter reaction time to avoid the hydrolysis.

Table 1 Scope and limitation of asymmetric arylation of N-Dpp-arylimines^a

Entry	2	Ar^1	3	Ar^2	T (°C)	Time (h)	4	Yield (%)	ee (%)^b
a The reaction was conducted with 1.67 equiv. of (Ar^2BO)3 in the presence of 6.6 mol% of 1, and 6.0 mol% of the Rh(I) except entry 6. b The ee was determined by chiral stationary phase HPLC analysis. c See ref. 4. d Microwave irradiation. e 5 equiv. of triolborate 3d was used. f Without MS 4Å. g Racemic phenyl (4-tolyl)methanol, aldehyde adduct, was obtained in 76% yield.
1^c	2a	Ph	3b	4-MeC6H4	80	12	(S)-4b	96	98
2^c	2a	Ph	3c	4-MeOC6H4	80	12	(S)-4c	92	98
3	2b	4-MeC6H4	3a	Ph	80	1	(R)-4b	79	84
4	2c	4-MeOC6H4	3a	Ph	80	12	(R)-4c	10	83
5^d	2c	4-MeOC6H4	3a	Ph	220	0.15	(R)-4c	45	68
6^e^,^f	2b	4-MeC6H4	3d	Ph	80	20	(R)-4b	0^g	—

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Microwave irradiation of a mixture of 2c and phenylboroxine 3a at 220 °C for 10 min was apparently beneficial but not satisfactory to give (R)-4c with 68% ee in improved 45% yield (entry 5). A cyclic triolborate 3d⁵ failed to give an imine adduct (R)-4b but gave the corresponding racemic aldehyde adduct, phenyl(4-tolyl)methanol, in 76% yield (entry 6).

Finally, we found triphenylborane as a reactive phenylation reagent to give phenylated amines (R)-4b and (R)-4c with 93% ee each in 92% and 91% yields, respectively, without imine hydrolysis. Herein, we report a catalytic asymmetric phenylation of N-Dpp-arylimines 2 with triphenylborane. In contrast to the widely used boronic reagents, triarylboranes have not been utilized as an aryl source in asymmetric catalysis,⁶ although a mixture of triphenylborane and diethylzinc has been employed for in situ generation of diphenylzinc.⁷

When a mixture of 4-tolylaldehyde N-Dpp-imine 2b and triphenylborane (1.67 equiv.) was heated in propan-1-ol at 100 °C for 12 h in the presence of a catalytic amount of 1 (6.6 mol%) and acetylacetonatobis(ethylene)rhodium(I) (6.0 mol%), the phenylated product (R)-4b with 81% ee was obtained in 63% yield (Table 2, entry 1). The reaction was then performed in the presence of KF because promotion of a transmetalation process of organoboron reagents by fluoride has been described.⁸ The reactions with anhydrous KF and KF on alumina resulted in less satisfactory 39% and 44% yields, and 60% and 81% enantioselectivity, respectively (entries 2 and 3). When the reaction was conducted in the presence of KF on Celite, the reaction more smoothly proceeded to give (R)-4b with 89% ee in increased 72% yield (entry 4). A mixture of dioxane and propanol⁴ was not suitable solvent for the reaction with triphenylborane, and only a trace amount of the product was produced (entry 5). Finally, tert-butanol was found to be the choice to complete the reaction in only 1 h at 100 °C, giving (R)-4b with 93% ee in 92% yield (entry 6).

Table 2 Survey of reaction conditions^a

Entry	Solvent	KF source	Time (h)	Yield (%)	ee (%)^b
a The reaction was conducted with 1.67 equiv. of Ph3B in the presence of 2.0 equiv. of the indicated KF source, 6.6 mol% of 1, and 6.0 mol% of the Rh(I). b The ee was determined by chiral stationary phase HPLC analysis.
1	PrOH	—	12	63	81
2	PrOH	KF	6	39	60
3	PrOH	KF/Al2O3	6	44	81
4	PrOH	KF/Celite	6	72	89
5	Dioxane/PrOH (1 : 1)	KF/Celite	6	<5	—
6	t-BuOH	KF/Celite	1	92	93

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This asymmetric phenylation with triphenylborane was applicable to other N-Dpp-arylimines 2 (Table 3).§Phenylation of 3-tolylimine 2d gave the corresponding 4d with high 96% ee in high 92% yield (entry 2). Electron-deficient 4-chlorobenzaldimine 2f bearing a chlorine atom was converted to 4f with 92% ee in 91% yield (entry 4). Although the reaction of sterically demanding ortho-substituted arylimines 2e and 2g was slower, the reaction proceeded in highly enantioselective manner to give 4e and 4g with 90% ee and 93% ee in 86% and 84% yield, respectively (entries 3 and 5). It is noteworthy that the reaction of 4-methoxybenzaldimine 2c, miserable results of which were the starting point for this study (Table 1, entry 4), also successfully proceeded for 12 h to give 4c with 93% ee in 91% yield (entry 6). Polyaromatic 2-naphthaldimine 2h and heteroaromatic 2-furancarboaldimine 2i were also good substrates to give 4h and 4i with 90% and 91% ee in 94% and 86% yield, respectively (entries 7 and 8).

Table 3 Catalytic asymmetric phenylation of N-Dpp-arylimines 2 with triphenylborane^a

Entry	2	Ar	Time (h)	4	Yield (%)	ee (%)^b
a The reaction was conducted with 1.67 equiv. of Ph3B in the presence of 2.0 equiv. of KF/Celite, 6.6 mol% of 1, and 6.0 mol% of the Rh(I). b The ee was determined by chiral stationary phase HPLC analysis. c Entry 6 of Table 2 is presented for comparison.
1^c	2b	4-MeC6H4	1	4b	92	93
2	2d	3-MeC6H4	1	4d	92	96
3	2e	2-MeC6H4	10	4e	86	90
4	2f	4-ClC6H4	1	4f	91	92
5	2g	2-ClC6H4	10	4g	84	93
6	2c	4-MeOC6H4	12	4c	91	93
7	2h	2-Naphthyl	1	4h	94	90
8	2i	2-Furyl	1	4i	86	91

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In conclusion, we have developed a widely applicable chiral amidomonophosphane–rhodium-catalyzed enantioselective phenylation of aryl-N-Dpp-imines with triphenylborane. The results clearly indicate the utility of triarylborane in avoiding in situwater generation. Because a Dpp group is cleaved under milder acidic conditions than a Boc group,⁹ this reaction provides a versatile methodology to access a variety type of optically active diarylmethylamines.

This research was partially supported by a Grant- in-Aid for Young Scientist (B) to KY and YY, and a Grant-in-Aid for Scientific Research (A) to KT from the Japan Society for the Promotion of Science (JSPS).

Notes and references

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Footnotes

† Electronic supplementary information (ESI) available: Experimental details, analytical, and spectral characterization data of the products. See DOI: 10.1039/c0cy00083c

‡ Dedicated to Prof. Carmen Nájera Domingo in celebration of her 60th birthday.

§ General procedure of the catalytic asymmetric phenylation: Under argon atmosphere, a round-bottom flask was charged with Rh(acac)(C₂H₄)₂ (3.1 mg, 0.012 mmol), 1 (6.5 mg, 0.013 mmol), 2 (0.200 mmol), triphenylborane (0.334 mmol), and 50% KF on Celite (40 mg). To the flask was added t-BuOH (0.5 mL), and the mixture was stirred at 100 °C. After the indicated reaction time, the mixture was diluted with AcOEt, washed with brine, dried over Na₂SO₄, and then concentrated. The resulting residue was purified through silica gel column chromatography.

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