Letter pubs.acs.org/OrgLett
Nickel-Mediated Asymmetric Allylic Alkylation between Nitroallylic Acetates and Acyl Imidazoles Jie Wang,† Pengxin Wang,† Linqing Wang, Dan Li, Kezhou Wang, Yuan Wang, Haiyong Zhu, Dongxu Yang,* and Rui Wang* Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China S Supporting Information *
ABSTRACT: A nickel-mediated asymmetric allylic alkylation reaction between imidazole-modified ketones and nitroallylic acetates is presented. This reaction is catalyzed by a simple chiral diamine-nickel catalyst under mild conditions and leads to a series of novel enantioenriched α-allylic adducts in moderate to good yields with excellent enantioselectivities. Furthermore, transformation of the allylic adducts could smoothly lead to chiral γ-nitroesters containing three continuous stereocenters in good yields.
T
Scheme 1. Nitroallylic Acetates in Asymmetric Allylic Alkylation Reactions
he development of efficient methods to build continuous stereogenic centers with high stereochemical control is of great importance in synthetic organic chemistry. The asymmetric allylic alkylation (AAA) reaction represents a well-established and important tool for organic chemistry since its discovery in the early 1970 s,1,2 which allows easy access to a diverse type of chiral allylic intermediates. Since the pioneering works by Tsuji and Trost on allylic alkylation reactions, a series of preactivated allylic substrates, including allylic halids, esters, and other structural analogues, have been exploited to react with either soft or hard nucleophiles to build carbon−carbon or carbon−heteroatom chemical bonds effeciently.3−5 And by the use of dual activation strategy, often with the assistance of an acid cocatalyst, allylic alcohols are also able to undergo the asymmetric allylic alkylation reactions under mild conditions.6 On the other hand, the asymmetric allylic substitution reactions utilizing Morita−Baylis−Hillman (MBH) adducts as an electrophilic allylation reaction partner also emerged as a powerful strategy in AAA reactions; various nucleophiles including oxygen, nitrogen, carbon, and phosphorus species have been successfully employed to construct diversiform chemical bonds under Lewis base or metal catalysis (Scheme 1, eq 1).7,8 Although these aforementioned strategies have been well established for asymmetric allylic alkylation reactions, new methods for building different chiral allylic intermediates are still in high demand. Recently, nitroallylic acetates have been utilized as an important synthon for asymmetric cyclization reactions. These types of cyclic structures could be easily accessed with continuous stereocenters on desired five- or six-membered rings (Scheme 1, eq 2).9 However, surprisingly, the application of nitroallylic acetates in asymmetric allylic alkylation reactions has not been successfully developed, which could build different chiral allylic intermediates (Scheme 1, eq 3). So here we report a simple nickel-mediated asymmetric allylic reaction between © 2017 American Chemical Society
nitroallylic acetates and imidazole-modified ketones10 under mild conditions. Our initial studies began by evaluation of the Ni(II) catalyst in the asymmetric allylic reaction between (E)-nitroallylic acetate 2a and imidazole-modified ketone 1a. As the results illustrated in Table 1, simple diamine-Ni(II) catalysts11 could lead to the desired chiral allylic adduct 3a with high ee values but moderate yields. The introduction of different additives in the reaction dramatically affected the results of the model reaction, and we identified basic Al2O3 would give a slightly higher yield. Carrying out the reaction at 10 °C on 0.3 mmol scale resulted in a better yield with an excellent ee value (Table 1, entry 11). Received: July 23, 2017 Published: September 1, 2017 4826
DOI: 10.1021/acs.orglett.7b02264 Org. Lett. 2017, 19, 4826−4829
Letter
Organic Letters
groups were all tolerated in the current nickel-mediated asymmetric allylic reaction, leading to the corresponding chiral alkylation adducts in moderate yields with high enantioselectivities. Condensed aromatic rings were also tested and gave similar results. And it should be noted that substrates with larger groups attached at the ortho-position of the phenyl ring were not compatible in the current asymmetric allylic reaction (Table 2, entry 3). Next the reactivity of different imidazole-modified ketones was investigated. As the results illustrated in Scheme 2, ketones
Table 1. Optimization of the Nickel-Catalyzed Asymmetric Allylic Alkylation Reactiona
Scheme 2. Reactivity of Different Imidazole-Modified Ketones entry
L
additives
yield (%)b
ee (%)c
1 2 3d 4 5 6 7e 8e 9e 10e 11e,f
L1 L1 L1 L1 L1 L1 L1 L2 L3 L4 L1
− Et3N Et3N DIPEA PhMeNH Al2O3 Al2O3 Al2O3 Al2O3 Al2O3 Al2O3
48 56 34 12 34 56 64 40 52 39 68
90 54 83 65 90 86 97 95 96 95 97
with N-phenyl imidazole were highly reactive substrates in the nickel-mediated allylic alkylation reaction (3l vs 3m), which might be due to the fact that N-phenyl imidazole modified ketones more easily form an enolate in the presence of catalysts. And it was also observed that α-aryl ketones were more reactive than α-alkyl ketones (3m vs 3n). Moreover, the employment of ketones with N-methyl imidazole would lead to relatively lower enantioselectivities in the current asymmetric alkylation reaction (3n vs 3o). Then, further substrate scope investigation was carried out (Scheme 3). Different types of α-alkyl- or α-aryl-substituted ketones were screened under the reaction conditions and led to the desired highly enantioselective α-allylic adducts in moderate to good yields with excellent ee values, and β-alkyl-substituted nitroallylic acetates were also tested, leading to the desired alkylation adducts in good yields and enantioselectivities. It is notable that the ketone without substitutions at the α-position is not compatible in the allylic reaction. Also, the substrates with bulky substituents are not good reactive partners for nitroallylic acetates. The absolute configuration of the enantioenriched allylic products was determined by the X-ray crystallographic analysis of 3t (Scheme 4). Furthermore, some α-heteroatom-substituted ketones were applied in the current nickel-mediated asymmetric allylic alkylation reactions (Scheme 5). The reactions could proceed under mild conditions and led to the corresponding chiral alkylation adducts in moderate to good yields. Finally, some transformations were performed as illustrated in Scheme 6. The double bond of nitroalkenes could be smoothly reduced by simple treatment with NaBH4, and the corresponding ester 7 was then obtained by utilization of the mature method to preactivate the imidazole group, followed by the esterification process employing corresponding alcohols. In summary, a diamine-nickel catalyzed asymmetric allylic alkylation reaction between imidazole-modified ketones and nitroallylic acetates is developed. The reaction was performed under mild conditions and led to a series of enantioenriched α-
a
Reactions were performed with ketone (1a, 0.10 mmol), nitroallylic acetate (2a, 0.12 mmol) in THF (1.0 mL) in the presence of LNi(OAc)2 (20 mol %). bIsolated yields. cThe ee value of 3a was analyzed by chiral stationary phase HPLC. dThe reaction were carried out in DCM. eThe reaction was carried out at 10 °C. fThe reaction was carried out on 0.3 mmol scale using 10 mol % L-Ni(OAc)2 catalyst.
With optimized conditions in hand, we first investigated the substrate scope with respect to different nitroallylic acetates. The results are shown in Table 2. Nitroallylic acetates with different electron-donating or electron-withdrawing substituted Table 2. Substrate Scope of the Nickel-Mediated Asymmetric Allylic Alkylation Reactiona
entry
3, R
drb
yield (%)c
ee (%)d
1 2 3 4 5 6 7 8 9 10
3a, Ph 3b, m-Me-Ph 3c, o-Me-Ph 3d, o-F-Ph 3e, p-Cl-Ph 3f, p-Br-Ph 3g, m-OMe-Ph 3h, p-OMe-Ph 3i, 2-naphthyl 3j, 2-furyl
>20:1 >20:1 − >20:1 >20:1 20:1 >20:1 >20:1 14:1 5.6:1
68 64
