Note pubs.acs.org/Organometallics
Efficient Iridium-Thioether-Dithiolate Catalyst for β-Alkylation of Alcohols and Selective Imine Formation via N-Alkylation Reactions Chang Xu,† Lai Yoong Goh,‡ and Sumod A. Pullarkat*,† †
Division of Chemistry & Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637616 ‡ ICP, UTAR Global Research Network, Universiti Tunku Abdul Rahman, 46200 Petaling Jaya, Selangor, Malaysia ABSTRACT: An Ir-thioether-dithiolate complex, [Cp*Ir(η 3tpdt)] (Cp* = η 5-C5Me5, tpdt = S(CH2CH2S−)2), is evaluated for its catalytic potential in the β-alkylation of secondary alcohols and the N-alkylation of amines with alcohols. The β-alkylation reaction proceeded efficiently under low catalyst loading and in the absence of any sacrificial hydrogen additive with only water being formed as the coproduct. The same complex also proved to be efficient in the synthesis of imines via the N-alkylation reaction. The predominant formation of imines, rather than amines, in this reaction is a deviation from the product selectivity usually observed in similar N-alkylation reactions involving organometallic catalysts.
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hydrogenation of the resulting enone to yield the coupled alcohol (Scheme 2).6
INTRODUCTION
Transition metal complexes incorporating thiolato ligands have attracted continuing interest by virtue of their potential applications as models for biological systems and as catalysts in various processes.1 In particular, [Cp*IrCl2]2 and its derivatives have attracted much attention in their role as effective catalysts for a variety of transformations, such as hydrogenation, C−C bond formation, allylic substitution, cycloaddition, and other reactions.2 In ongoing investigations on the reactions of μ-dichloro complexes [(η 3:η 3-C10H16)RuCl2]23 and [Cp*RuCl2]24 with thioether-thiolato ligands [XC(S)S]2 (X = NR2, OR (R = alkyl)), we had isolated the complex [Cp*Ir(η 3-tpdt)] (1), in 81% yield (Scheme 1).5
Scheme 2
Several transition metal complexes have been reported to catalyze this reaction. These range from the readily available [Cp*IrCl2]26 and [RuCl2(DMSO)4]7 to the extremely active Ru and Ir complexes containing N-heterocyclic carbenes (NHCs),8 phosphines (e.g., RuCl2(PPh3)39), and terpyridine ligands10 (e.g., [(terpy)Ru(PPh3)Cl2],10a [(terpy)IrCl3]10a). Of particular interest to us is a comparison of the catalytic activity of 1 with its precursor complex [Cp*IrCl2]2 in β-alkylation of secondary alcohols with primary alcohols, bearing in mind that the tpdt ligand is a S-bearing moiety. Initially, 1 mol % of catalyst was evaluated for the β-alkylation reaction between 1-phenylethanol and phenylmethanol in the presence of 1 equiv of NaOtBu (Table 1, entry 1), and 1,3diphenylpropan-1-ol (3a) was found to be the major product, in admixture with 1,3-diphenylpropan-1-one (4a). The results obtained under optimization conditions are summarized in Table 1. Entry 8 gives the result of Fujita’s reaction using [Cp*IrCl2]2 as catalyst.6
Scheme 1
In this paper, we report the effective role of 1 as a catalyst in the β-alkylation reaction of secondary alcohols with primary alcohols and in the N-alkylation reaction of amines with various alcohols.
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RESULTS AND DISCUSSION
a. β-Alkylation Reaction of Secondary Alcohols with Primary Alcohols. Alkylation of secondary alcohols with primary alcohols is an important tandem multistep reaction that typically involves dehydrogenation of the alcohols to aldehyde or ketone, aldol coupling, loss of water, and subsequent © 2011 American Chemical Society
Received: September 21, 2011 Published: November 15, 2011 6499
dx.doi.org/10.1021/om200883e | Organometallics 2011, 30, 6499−6502
Organometallics
Note
Table 1. β-Alkylation of R1-Phenylethanol (1a) with Phenylmethanol (2a) under Various Conditions
a
product (%) entry
catalyst (mol %)
R
base (mol %)
conversion
1 2 3 4 5 6 7d 8e
1 (1.0) 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) [Cp*IrCl2]2 (1.0)
H H H H 4-OMe 4-Cl H H
NaOtBu (100) NaOtBu (100) NaOtBu (50) NaOH (100) NaOtBu (100) NaOtBu (100) NaOtBu (100) NaOtBu (100)
97 96 93 87 88 98 99
b
yield 92 90 68 80 82 85 88 75
c
3a
4a
95 93 94 75 81 95 77
5 7 6 25 19 5 23
a
The reaction was carried out with secondary alcohol (1 mmol), primary alcohol (1 mmol), catalyst 1, and base in toluene (0.3 mL) at 110 °C for 17 h. Conversions (based on the secondary alcohol) are determined by the consumption of alcohol. cYields of 3a (based on the secondary alcohol, 1a) were determined by 1H NMR spectroscopy using 1,3,5-trimethoxybenzene as an internal standard. dThe reaction was allowed to proceed for 48 h. e Reported value.6 b
The complex [Cp*IrCl2]2 as catalyst under the same conditions gave 1-phenylhexan-1-ol (3a) in 75% yield, a yield surpassed by the use of 1 (92%) (Table 1, entry 1). More significantly, we observed that the desired product 3a could be achieved in comparably good yield under the same reaction conditions but with a significantly reduced catalyst loading (0.1 mol % vs 1.0 mol %) (entry 2). As far as we are aware, this catalyst loading is lower than any reported for the β-alkylation of 1a with 2a in the literature. It was also noted that when the amount of base was decreased to 50%, the yields were substantially reduced but the selectivity observed for the coupling products (3a vs 4a) did not show any noticeable change for 1 (entry 2 vs entry 3). Replacement of the base NaOtBu with NaOH did not affect the catalytic potential (entry 2 vs entry 4), while Na2CO3 gave no product yields when employed as an alternative base. The presence of substituents on the secondary alcohol (entry 5 and entry 6) did not produce any drastic reduction in either yield or selectivity. As observed in previous reports,8a,b a longer reaction time did not improve yields since it led to the dehydrogenation of the coupled alcohol product to form the corresponding ketone (entry 2 vs entry 7). We also used complex 1 to catalyze the β-alkylation of aliphatic secondary alcohols with primary alcohols or arylalkyl secondary alcohols with aliphatic primary alcohols (Table 2). It is seen that β-alkylation of isopropyl alcohol with n-pentyl alcohol and n-hexyl alcohol gave coupled products in yields of 41% and 50%, respectively (entries 1 and 2). These yields, albeit moderate, are encouraging when compared to reported yields of the reactions of aliphatic secondary alcohols with aliphatic primary alcohols.9 β-Alkylation of isopropyl alcohol with benzyl alcohol gave coupled product in 67% yield (entry 3). Entries 4 and 5 give the results of β-alkylation of 1-phenylethanol with n-pentyl and n-hexyl alcohol, giving products in high to moderate yields. However, isopropyl alcohol with 1-phenyl-1propanol does not undergo alkylation. The mechanism proposed for [Cp*IrCl2]2 as catalyst in β-alkylation involves a multiple-step tandem process involving oxidation of alcohols to aldehyde and ketone, generation of a hydrido iridium species, base-mediated cross aldol condensation, and successive transfer hydrogenation of CC and CO
Table 2. β-Alkylation of Aliphatic Secondary Alcohol with Primary Alcohols and Arylalkyl Secondary Alcohol with Aliphatic Primary Alcoholsa
a
The reaction was carried out with secondary alcohol (1 mmol), primary alcohol (1 mmol), catalyst 1 (0.1 mol %), and NaOtBu (100 mol %) in toluene (0.3 mL) at 110 °C for 17 h. bYields (based on the secondary alcohol) were determined by 1H NMR spectroscopy using 1,3,5-trimethoxybenzene as an internal standard.
bonds, yielding the final product.6 We investigated these individual steps in our protocol using the same methodology adopted by Fujita et al. The analysis of the results obtained after performing the catalytic oxidation of 1-phenylethanol to acetophenone using acetone as hydrogen acceptor (
