PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
Synlett. Author manuscript; available in PMC 2010 December 29.
Published in final edited form as:
Synlett. 2010 February; 2010(3): 419–422.
doi:  10.1055/s-0029-1218555
PMCID: PMC3011227
NIHMSID: NIHMS216824

Gold(I)-Catalyzed Intermolecular Hydroamination of Allenes with Arylamines

Abstract

A mixture of (3)AuCl [3 = P(t-Bu)2o-biphenyl] and AgOTf catalyzes the intermolecular hydroamination of monosubstituted and 1,1- and 1,3-disubstituted allenes with primary and secondary arylamines.

Keywords: Allylations, allenes, amines, homogenous catalysis, regioselectivity

The transition metal-catalyzed addition of the N–H bond of an amine across the C=C bond of an allene represents an attractive, atom economical approach to the synthesis of allylic amines.1 Although a number of general and efficient methods have been developed for the intramolecular hydroamination of allenes,2,3 effective methods for the intermolecular hydroamination of allenes, particularly those that utilize alkyl- or arylamines, remain scarce.412 Zirconium4 and titanium5 complexes catalyze the intermolecular hydroamination of allenes with amines to form imines via addition of nitrogen to the central carbon atom of the allene. Palladium(II) complexes catalyze the intermolecular hydroamination of allenes with arylamines to form allylic amines, but these methods are of limited scope.6,7 More recently, Yamamoto has described gold(III)-8 and gold(I)-catalyzed9 methods for the intermolecular hydroamination of allenes with arylamines and morpholine, respectively although efficient hydroamination was restricted to mono-substituted and 1,3-disubstituted allenes. Bertrand has reported the hydroamination of allenes with ammonia catalyzed by a cationic gold(I) cyclic (alkyl)(amino)carbene (CAAC) complex under forcing conditions (≥155 °C).10

We have recently reported the regio- and diastereoselective intermolecular hydroamination of allenes with carbamates catalyzed by a gold(I) N-heterocyclic carbene (NHC) complex that displayed excellent scope with respect to the allene.11 We therefore considered that gold(I) NHC complexes might also catalyze the intermolecular hydroamination of allenes with arylamines with improved substrate scope relative to extant protocols. During the course of these studies, Bertrand and coworkers reported the intermolecular hydroamination of allenes with arylamines catalyzed by a gold(I) CAAC complex.12 Although this procedure extended the scope of allene hydroamination to include 1,1-disubstituted allenes, neither the requisite gold CAAC catalyst, nor the ligand from which it is derived are commercially avialable.13 Here we report an operationally simple method for the intermolecular hydroamination of monosubstituted and 1,1- and 1,3-disubstituted allenes with primary and N-alkyl anilines catalyzed by a commercially available gold(I) complex under mild conditions.

The catalyst system optimized for the intermolecular hydroamination of allenes with carbamates proved only modestly effective for the intermolecular hydroamination of allenes with arylamines. As an example, treatment of aniline with 3-methyl-1,2-butadiene (1; 2 equiv) and a catalytic 1:1 mixture (IPr)AuCl [IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidine] and AgOTf in toluene at room temperature for 24 h led to 10% conversion to form N-prenylaniline (2a) as the exclusive product (Table 1, entry 1). Substitution of the sterically hindered o-biphenyl phosphine ligand P(t-Bu)2o-biphenyl (3) for IPr and dioxane for toluene increased the conversion under these conditions to 35% (Table 1, entry 3). Raising the temperature to 45 °C led to complete consumption of aniline after 12 h to form a 4.1:1 mixture of 2a and N,N-diprenylaniline (2b) (Table 1, entry 4). Aniline derivatives 2a and 2b were isolated in 73 and 17% yield, respectively, from the corresponding preparative-scale reaction of 1 with aniline (Table 2, entry 1). Control experiments ruled out silver- and acid-catalyzed pathways for the hydroamination of 1 with aniline (Table 1, entries 5–7).

Table 1
Gold(I)-Catalyzed Hydroamination of 3-Methyl-1,2-butadiene (1) (0.8 M) with Aniline (0.4 M) as a Function of Ligand and Reaction Conditions.
Table 2
Intermolecular Hydroamination of 1 (0.8 M) with Arylamines (0.4 M) Catalyzed by a Mixture of (3)AuCl (5 mol %) and AgOTf (5 mol %) in Dioxane at 45 °C.

In addition to aniline, a number of primary arylamines reacted with 1 (2 equiv) to form the corresponding N-prenylaniline derivatives in good to excellent yield with exclusive formation of the regioisomer resulting from attack of aniline at the less substituted allene terminus (Table 2, entries 2–11).14 p-Nitro- and p-bromoaniline were highly active nucleophiles that reacted with 1 (2 equiv) at 45 °C for 12 h to form mixtures of the corresponding N-prenyl- and N,N-diprenylaniline derivatives (Table 2, entries 6 and 7). However, increasing the 1:aniline ratio to 3:1 led to exclusive formation of the N,N-diprenylanilines in excellent yield as single regioisomers (Table 2, entries 8 and 9). o-Substituted anilines proved highly selective nucleophiles for the gold(I)-catalyzed hydroamination of 1, leading to formation of the N-prenylanilines in good to excellent yield without formation of the corresponding N,N-diprenylanilines (Table 2, entries 2–4, 10, 11). N-Methylanilines were also effective nucleophiles for the gold(I)-catalyzed hydroamination of 1, forming the corresponding N-methyl-N-prenyl anilines in good yield as single regioisomers (Table 2, entries 12 and 13). Dialkylamines, however, were not effective nucleophiles for the hydroamination of allenes under these conditions.

In addition to 3-methyl-1,2-butadiene (1), monosubstituted, functionalized 1,1-disubstituted, and 1,3-disubstituted allenes also underwent gold(I)-catalyzed intermolecular hydroamination with arylamines in good yield with good regio- and diastereoselectivity (Table 3). As an example of the hydroamination of a monosubstituted allene, reaction of m-bromoaniline with 1-cyclohexyl-1,2-propadiene at 45 °C for 24 h led to isolation of N-(3-cyclohexyl-2-propenyl) aniline 4 in 91% as a 5.2:1 mixture of E:Z isomers (Table 3, entry 1). As an example of the hydroamination of a 1,3-disubstituted allene, reaction of m-bromoaniline with 1-phenyl-1,2-butadiene at 45 °C for 24 h led to isolation of the N-(1-methyl-3-phenyl-2-propenyl) aniline 5 in 86% as a >25:1 mixture of E:Z isomers resulting from addition of the nucleophile to the methyl substituted allene terminus (Table 3, entry 4). As an example of the hydroamination of a functionalized 1,1-disubstituted allene, reaction of m-bromoaniline with ethyl 3-hexyl-3,4-pentadienoate formed N-allylic aniline 6 in 93% isolated yield as a 4.4:1 mixture of Z:E isomers (Table 3, entry 5).

Table 3
Intermolecular Hydroamination of Monosubstituted, 1,3-Disubstituted, and Functionalized 1,1-Disubstituted Allenes with m-Bromoaniline Catalyzed by a Mixture of (3)AuCl (5 mol %) and AgOTf (5 mol %) in Dioxane at 45 °C.

Stereochemical analysis of the gold(I)-catalyzed intra-molecular hydroamination of N-γ-allenyl carbamates3 and the intermolecular hydroalkoxylation of allenes with alcohols15 supported mechanisms involving outer-sphere attack of the nucleophile on a gold π-allene complex. Largely on the basis of these precedents, we proposed an outer-sphere mechanism for the gold(I)-catalyzed intermolecular hydroamination of allenes with carbamates.11 Conversely, Yamamoto8 and Bertrand12,13 have proposed inner-sphere pathways for the gold-catalyzed intermolecular hydroamination of allenes with aryl amines and ammonia. Therefore, we have considered both outer-sphere and inner-sphere mechanisms for the gold(I)-catalyzed intermolecular hydroamination of allenes with arylamines. In the former pathway, endoergonic displacement of aniline from I via the 16-electron, three-coordinate intermediate II would form gold(I) π-allene complex III. Outer-sphere attack of the aniline on III would then form the gold σ-alkenyl ammonium complex IV. Deprotonation of IV with free aniline followed by protonolysis of the Au–C bond of V would then release the N-prenyl aniline with regeneration of I. Alternatively, β-migratory insertion of the coordinated allene into the Au–N bond of II would likewise generate IV (Scheme 1).

Scheme 1
Potential mechanisms for the gold(I)-catalyzed hydroamination of 1 with aniline.

In summary, we have developed an effective Au(I)-catalyzed protocol for the intermolecular hydroamination of allenes with arylamines to form N-allyl aniline derivatives with excellent regioselectivity and good diastereoselectivity. We continue to work toward the elucidation of the mechanism of gold(I)-catalyzed allene hydroamination and toward the development of effective methods for the catalytic hydroamination of allenes with alkyl amines.

Supplementary Material

Acknowledgments

Acknowledgment is made to the NIH (GM-080422) for support of this research.

Footnotes

References and Notes

1. For recent reviews of catalytic hydroamination see: (a) Müller TE, Hultzsch KC, Yus M, Foubelo F, Tada M. Chem Rev. 2008;108:3795. [PubMed] (b) Widenhoefer RA, Han X. Eur J Org Chem. 2006:4555. (c) Pohlki F, Doye S. Chem Soc Rev. 2003;32:104. [PubMed] (d) Hong S, Marks TJ. Acc Chem Res. 2004;37:673. [PubMed]
2. For recent examples of the intramolecular hydroamination of allenes see: (a) Volz F, Krause N. Org Biomol Chem. 2007;5:1519. [PubMed] (b) Morita N, Krause N. Eur J Org Chem. 2006:4634. (c) Morita N, Krause N. Org Lett. 2004;6:4121. [PubMed] (d) Hoover JM, Petersen JR, Pikul JH, Johnson AR. Organometallics. 2004;23:4614. (e) Zhang Z, Bender CF, Widenhoefer RA. Org Lett. 2007;9:2887. [PubMed] (f) LaLonde RL, Sherry BD, Kang EJ, Toste FD. J Am Chem Soc. 2007;129:2452. [PubMed] (g) Lee PH, Kim H, Lee K, Kim M, Noh K, Kim H, Seomoon D. Angew Chem Int Ed. 2005;44:1840. [PubMed] (h) Patil NT, Lutete LM, Nishina N, Yamamoto Y. Tetrahedron Lett. 2006;47:4749. (i) Zhang Z, Bender CF, Widenhoefer RA. J Am Chem Soc. 2007;129:14148. [PubMed]
3. Zhang Z, Liu C, Kinder RE, Han X, Qian H, Widenhoefer RA. J Am Chem Soc. 2006;128:9066. [PubMed]
4. Walsh PJ, Baranger AM, Bergman RG. J Am Chem Soc. 1992;114:1708.
5. (a) Johnson JS, Bergman RG. J Am Chem Soc. 2001;123:2923. [PubMed] (b) Ayinla RO, Schafer LL. Inorg Chim Acta. 2006;359:3097.
6. Al-Masum M, Meguro M, Yamamoto Y. Tetrahedron Lett. 1997;38:6071.
7. Besson L, Gore J, Cazes B. Tetrahedron Lett. 1995;36:3857.
8. Nishina N, Yamamoto Y. Angew Chem Int Ed. 2006;45:3314. [PubMed]
9. Nishina N, Yamamoto Y. Synlett. 2007:1767.
10. Lavallo V, Frey GD, Donnadieu B, Soleilhavoup M, Bertrand G. Angew Chem Int Ed. 2008;47:5224. [PMC free article] [PubMed]
11. Kinder RE, Zhang Z, Widenhoefer RA. Org Lett. 2008;10:3157. [PMC free article] [PubMed]
12. Zeng X, Soleilhavoup M, Bertrand G. Org Lett. 2009;11:3166. [PMC free article] [PubMed]
13. (a) Lavallo V, Frey GD, Kousar S, Donnadieu B, Bertrand G. Proc Natl Acad Sci USA. 2007;104:13569. [PubMed] (b) Frey GD, Dewhurst RD, Kousar S, Donnadieu B, Bertrand G. J Organomet Chem. 2008;693:1674. [PubMed]
14. Experimental Procedure and Spectroscopic Data for the Gold(I)-Catalyzed Hydroamination of 1 with o-Bromoaniline (Table 2, entry 2). Dioxane (0.50 mL) was added to a mixture of o-bromoaniline (39 mg, 0.23 mmol), (3)AuCl (6.2 mg, 1.1 × 10−2 mmol), and AgOTf (2.8 mg, 1.1 × 10−2 mmol) and the resulting suspension was stirred for 10 min at room temperature. 3-Methyl-1,2-butadiene (1; 29 mg, 0.43 mmol) was added via syringe and the resulting mixture was stirred at 45 °C for 24 h. Column chromatography of the reaction mixture (SiO2; hexanes–EtOAc = 15:1) gave N-(3-methyl-2-butenyl)-o-bromoaniline (48 mg, 87%) as a pale yellow oil. 1H NMR (CDCl3, 400 MHz): δ 7.41 (dd, J = 1.5, 8.5 Hz, 1 H), 7.17 (dd, J = 1.5, 7.8 Hz, 1 H), 6.62 (dd, J = 1.0, 8.3 Hz, 1 H), 6.55 (dt, J = 1.5, 7.5 Hz, 1 H), 5.31–5.35 (m, 1 H), 4.23 (br s, 1 H), 3.72 (d, J = 6.8, Hz, 2 H), 1.76 (d, J = 1.0 Hz, 3 H), 1.72 (s, 3 H). 13C{1H} NMR (CDCl3, 100 MHz): δ 145.1, 136.1, 132.3, 128.4, 121.1, 117.5, 111.4, 109.7 41.9, 25.7, 18.1. HRMS calcd (found) for C11H14BrN (M+): 39.0310 (239.0313).
15. Zhang Z, Widenhoefer RA. Org Lett. 2008;10:2079. [PubMed]