English

• 1.   Introduction

  α-Acyloxyacetates and cyanomethyl esters are found as the core structure of numerous natural products and are also useful synthetic building blocks.^[1] Despite their interesting biological activities, synthetic methodologies for construction of these compounds under mild conditions are limited, especially for cyanomethyl esters derivatives. Prevalent synthesis involves the reaction of acids with α-hydroxy or α-halogeno carbonyls, ^[2] carboxylic acids with diazocarbonyl compounds or halogeno-acetonitrile, ^[3] activated carboxylates with cyanide, ^[4] and the Passerini reaction.^[5] In general, these approaches required harsh conditions, such as relatively high temperature, long reaction times, a large excess of carboxylic acid or the toxic cyanide. Although, metal catalysis for α-acyloxy carbonyls esters formation has also reported, these reactions required protection/deprotection steps or relative instable diazo compounds.^[6]

  N-Heterocyclic carbenes (NHCs) have received great attention in recent years and have been widely used as versatile ligands in translation-metal catalysis, ^[7] and organo-catalysts.^[8] Besides the classic umpolung reaction, ^[9] NHCs were also employed in CO₂ fixation reactions, ^[10] cycloadditions, ^[11] redox reactions, ^{[9g, 12]} and in combination with photoredox catalysts, ^[13] cascade catalysis, ^[14] or cooperative catalysis.^[15] Recently, NHC combining with an external oxidant was uncovered for the easy construction of carbon-heteroatom bonds, such as C—O bond (esterification), ^[16] C—N bond (amidation), ^[17] and lactone-ring- formation reactions.^[18])

  For example, Gois, ^[19] Deng, ^[20] Xu, ^[21] and Anand^[22] reported NHCs-catalyzed esterification reactions of aromatic aldehydes and boronic acids, benzyl bromides, alkyl halides, or propargyl bromide, respectively. Very recently, Chi et al.^[23] reported a NHC-catalyzed single-electron- transfer (SET) reactions of enals that introduces a hydroxyl group to the β-carbon of enals. By the same group, in 2015, they also demonstrated the use of a NHC catalyst to catalyze the breaking of C—C single bonds for preparation of lactams.^[24] However, previous research mainly focused on the oxidative esterification of aldehydes with benzyl bromide, alkyl halides, and propargyl bromide to synthesize the corresponding esters. Herein, we report a straightforward and mild method to prepare α-acyloxyacetates and cyanomethyl esters via NHC-catalyzed oxidative esterification of aldehydes with ethyl bromoacetate or bromoacetonitrile.

  2.   Results and discussion

  We started our investigation with the reaction of ethyl bromoacetate and benzaldehyde. Unfortunately, the combination of NHC precursor (A) with cesium carbonate (Cs₂CO₃) in dry THF or CH₂Cl₂ afforded product 3aa with very poor yield (Table 1, Entries 1 and 2). Next, a variety of NHC precursors (B~F) were examined for this transformation under the same reaction conditions (Entries 3~7). Only B could afford the product with 65% yield (Entry 3). When we increased the amount of cesium carbonate to 2.0 equiv., the desired product significantly improved the yield to 86% (Entry 8). It is found that the load of catalyst and amount of base have greatly influenced the reaction yield. Decreasing the amount of catalyst and base, all led to reduction of the product yield (Entries 3, 9~11). The reaction yield was decreased to 32% when the catalyst loading was lowered to 10 mol% (Entry 11). Moreover, the effects of solvent on the reaction were also evaluated (Entries 12~15). Finally, base screening showed that cesium carbonate was the best for this process (Entries 8, 16~18).

  Table 1

  

  Table 1.  Optimization of reaction conditions^a

  下载: 导出CSV

  Entry	NHC precursor(mol%)	Base(equiv.)	Solvent	Yield/%
  1	A(20)	Cs2CO3(1.5)	THF	35
  2	A(20)	Cs2CO3(1.5)	CH2Cl2	23
  3	B(20)	Cs2CO3(1.5.)	THF	65
  4	C(20)	Cs2CO3(1.5)	THF	20
  5	D(20)	Cs2CO3(1.5)	THF	15
  6	E(20)	Cs2CO3(1.5)	THF	12
  7	F(20)	Cs2CO3(1.5)	THF	10
  8	B(20)	Cs2CO3(2.0)	THF	86
  9	B(20)	Cs2CO3(1.0)	THF	36
  10	B(15)	Cs2CO3(2.0)	THF	50
  11	B(10)	Cs2CO3(2.0)	THF	32
  12	B(20)	Cs2CO3(2.0)	CH2Cl2	48
  13	B(20)	Cs2CO3(2.0)	CHCl3	30
  14	B(20)	Cs2CO3(2.0)	Dioxane	8
  15	B(20)	Cs2CO3(2.0)	DCE	66
  16	B(20)	Et3N(2.0)	THF	33
  17	B(20)	DBU(2.0)	THF	27
  18	B(20)	(i-Pr)2NEt(2.0)	THF	38
  a Reaction conditions:1a(0.2 mmol), 2a(0.24 mmol), NHC precursor(n mol%), base(0.2 mmol~0.4 mmol), solvent(2 mL), r.t. and 8 h.b Isolated yields.

  With the optimized conditions in hand (Table 1, Entry 8), the scope and limitations of this protocol to aromatic aldehydes were examined. The results are summarized in Scheme 1. The results showed that, in general, the reactions took place efficiently in high yields (up to 96%) and functional group tolerance.

  It is found that the nature of the electronic properties of the substituents and position on the aromatic aldehydes have a limited effect on the reaction. Substituents on para-position including halogen (3ab and 3ac), electron- donating (3ad, 3ae and 3af) and electron-withdrawing substituents (3ag, 3ah and 3ai) on the aromatic aldehydes all could give corresponding acyloxy carbonyls esters in moderate yield. Especially, the yield of the product is nearly quantified when 4-(trifluoromethyl)benzaldehyde was chosen to the reaction (3ag, 96%). Besides, 3-fluorobenzaldehyde could give the desired esters in good yields (3aj, 74%), 3-bromo-, 3-methoxy- and 3-(trifluoro- methyl)-benzaldehyde also afforded the desired products 3ak~3am in high yields. Moreover, 2-halogen (F, Cl and Br) and 2-methylbenzaldehyde also delivered the desired esters with acceptable yield (3an~3aq, 60%~92%). The reaction could proceed smoothly even though Michael receptor or phenylethynyl was introduced into the ortho-positon of aldehydes (3ar and 3as).^{[18c, 18e]} Furthermore, 2-naphthaldehyde (3at) and heteroatom containing alde-hydes (3au, 3av and 3aw) also responded well for the esters.

  Interestingly, when bromoacetonitrile was used instead of ethyl bromoacetate, the reaction could also proceed well and the desired product cyanomethyl esters were obtained in good yield (58%~88%). Substituents at different positions, such as para-methoxy (3bb), para-phenyl (3bc), para-bromo (3bd), or meta-bromo (3be) and ortho-fluoro (3bf), the desired products were still obtained without loss in reaction efficiency. 2-Naphthaldehyde with bromo- acetonitrile could also yield the product 3bg in 77% yield in the standard reactions.

  A plausible mechanistic pathway is proposed to illustrate the oxidative esterification process (Table 1). As shown in Table 2, Breslow intermediate Ⅰ generating from N-heterocyclic carben catalyst and aromatic aldehyde could react with oxygen to form the peroxide anion Ⅱ. Then acid Ⅲ, which was yielded from the reaction of peroxide Ⅱ and a second molecule of aromatic aldehyde after NHC departure, reacts with substrate 2 to provide the desired products 3 in the presence of base.^[21]

  Table 2

  

  Table 2.  Substrates scope^a

  下载: 导出CSV

  Scheme 2

  

  Scheme 2.  Proposed machanistic pathway for NHC-catalyzed oxidative esterification

  下载: 全尺寸图片 幻灯片

  3.   Conclusions

  In conclusion, we have developed a NHC-catalyzed oxidative esterification reaction of aldehydes and ethyl bromoactate to give the corresponding 2-ethoxy-2-oxoethy- benzoates in excellent yields up to 96% under air atmosphere. By this means, a variety of α-acyloxyacetates and cyanomethyl esters were obtained mildly and efficiently. It is worth noting that this process could also tolerate ortho-functionalized aromatic aldehydes. Further study on its practical application is still ongoing in our lab.

  4.   Experimental

  4.1   General procedure of products 3

  The substrate 1 (0.5 mmol) was added to a suspension of B (0.1 mmol) and Cs₂CO₃ (1.0 mmol) in THF (5 mL) at room temperature (18~25 ℃) and the mixture was stirred for 10 min. The substrate 2 (0.6 mmol) was added to the reaction mixture in a dropwise manner and the resulting suspension was stirred until most of 1 had been consumed (monitored by TLC). The yield was determined by isolation of the product using flash chromatography.

  4.2   Characteristic data for compounds 3aa~3bg

  2-Ethoxy-2-oxoethyl benzoate (3aa): 89 mg, pale yellow oil, 86% yield. ¹H NMR (400 MHz, CDCl₃) δ: 8.10 (d, J＝7.6 Hz, 2H), 7.57 (t, J＝7.4 Hz, 1H), 7.44 (t, J＝7.7 Hz, 2H), 4.84 (s, 2H), 4.24 (q, J＝7.1 Hz, 2H), 1.28 (t, J＝7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 167.8, 165.9, 133.4, 129.9, 129.2, 128.4, 61.4, 61.2, 14.1; HRMS (EI) calcd for C₁₁H₁₂O₄: 208.0736, found 208.0738.

  2-Ethoxy-2-oxoethyl 4-chlorobenzoate (3ab): 109 mg, pale yellow oil, 90% yield. ¹H NMR (400 MHz, CDCl₃) δ: 8.03 (d, J＝8.5 Hz, 2H), 7.43 (d, J＝8.4 Hz, 2H), 4.84 (s, 2H), 4.26 (q, J＝7.1 Hz, 2H), 1.30 (t, J＝7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl3) δ: 167.6, 165.1, 139.9, 131.3, 128.8, 127.7, 61.5, 61.3, 14.1; HRMS (EI) calcd for C₁₁H₁₁ClO₄: 242.0346, found 242.0348.

  2-Ethoxy-2-oxoethyl 4-bromobenzoate (3ac): 126 mg, pale yellow oil, 88% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.95 (d, J＝8.3 Hz, 2H), 7.60 (d, J＝8.3 Hz, 2H), 4.84 (s, 2H), 4.26 (q, J＝7.1 Hz, 2H), 1.29 (t, J＝7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl3) δ: 167.6, 165.2, 131.8, 131.4, 128.6, 128.1, 61.5, 61.3, 14.1; HRMS (EI) calcd for C₁₁H₁₁BrO₄: 285.9841, found 285.9846.

  2-Ethoxy-2-oxoethyl 4-methoxybenzoate (3ad): 81 mg, pale yellow oil, 68% yield. ¹H NMR (400 MHz, CDCl₃) δ: 8.05 (d, J＝8.8 Hz, 2H), 6.93 (d, J＝8.8 Hz, H), 4.81 (s, 2H), 4.25 (q, J＝7.1 Hz, 2H), 3.86 (s, 3H), 1.29 (t, J＝7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 168.1, 165.7, 163.7, 132.0, 121.5, 113.7, 61.4, 61.0, 55.5, 14.1; HRMS (EI) calcd for C₁₂H₁₄O₅: 238.0841, found 238.0842.

  2-Ethoxy-2-oxoethyl 4-methylbenzoate (3ae): 80 mg, pale yellow oil, 72% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.98 (d, J＝8.0 Hz, 2H), 7.24 (d, J＝7.9 Hz, 2H), 4.82 (s, 2H), 4.24 (q, J＝7.1 Hz, 2H), 2.40 (s, 3H), 1.28 (t, J＝7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 167.9, 165.9, 144.2, 129.9, 129.2, 126.5, 61.4, 61.1, 21.7, 14.1; HRMS (EI) calcd for C₁₂H₁₄O₄: 222.0892, found 222.0894.

  2-Ethoxy-2-oxoethyl [1, 1'-biphenyl]-4-carboxylate (3af): 131 mg, pale yellow solid, 92% yield. ¹H NMR (400 MHz, CDCl₃) δ: 8.15 (d, J＝8.1 Hz, 2H), 7.65 (d, J＝8.1 Hz, 2H), 7.60 (d, J＝7.5 Hz, 2H), 7.44 (t, J＝7.4 Hz, 2H), 7.41~7.34 (m, 1H), 4.85 (s, 2H), 4.25 (q, J＝7.1 Hz, 2H), 1.28 (t, J＝7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 167.8, 165.8, 146.1, 139.9, 130.5, 128.9, 128.3, 128.0, 127.3, 127.1, 61.5, 61.2, 14.2; HRMS (EI) calcd for C₁₇H₁₆O₄: 284.1049, found 284.1048.

  2-Ethoxy-2-oxoethyl 4-(trifluoromethyl)benzoate (3ag): 133 mg, pale yellow oil, 96% yield. ¹H NMR (400 MHz, CDCl₃) δ: 8.22 (d, J＝8.2 Hz, 2H), 7.73 (d, J＝8.2 Hz, 2H), 4.88 (s, 2H), 4.27 (q, J＝7.1 Hz, 2H), 1.30 (t, J＝7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 167.4, 164.8, 134.8 (q, J＝32.7 Hz), 132.5, 130.3, 125.5 (q, J＝3.7 Hz), 123.6 (q, J＝272.8 Hz), 61.6, 61.5, 14.1; HRMS (EI) calcd for C₁₂H₁₁F₃O₄: 276.0609, found 276.0610.

  2-Ethoxy-2-oxoethyl methyl terephthalate (3ah): 85 mg, pale yellow solid, 75% yield. ¹H NMR (400 MHz, CDCl₃) δ: 8.14 (q, J＝8.3 Hz, 2H), 4.87 (s, 2H), 4.27 (q, J＝7.1 Hz, 2H), 3.95 (s, 3H), 1.31 (t, J＝7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 167.5, 166.2, 165.2, 134.3, 132.9, 129.9, 129.6, 61.6, 61.4, 52.5, 14.1; HRMS (EI) calcd for C₁₃H₁₄O₆: 266.0790, found 266.0792.

  2-Ethoxy-2-oxoethyl 4-nitrobenzoate (3ai): 83 mg, pale yellow oil, 66% yield. ¹H NMR (400 MHz, CDCl₃) δ: 8.30 (q, J＝9.0 Hz, 4H), 4.90 (s, 2H), 4.28 (q, J＝7.1 Hz, 2H), 1.31 (t, J＝7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 167.2, 164.1, 150.8, 134.6, 131.1, 123.6, 61.8, 61.7, 14.1; HRMS (EI) calcd for C₁₁H₁₁NO₆: 253.0586, found 253.0587.

  2-Ethoxy-2-oxoethyl 3-fluorobenzoate (3aj): 84 mg, pale yellow oil, 74% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.90 (d, J＝7.7 Hz, 1H), 7.78 (d, J＝9.2 Hz, 1H), 7.44 (dd, J＝13.6, 7.9 Hz, 1H), 7.34~7.25 (m, 1H), 4.85 (s, 2H), 4.26 (q, J＝7.1 Hz, 2H), 1.30 (t, J＝7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 167.5, 164.8 (d, J＝3.1 Hz), 162.5 (d, J＝247.3 Hz), 131.3 (d, J＝7.6 Hz), 130.1 (d, J＝7.8 Hz), 125.7 (d, J＝3.1 Hz), 120.5 (d, J＝21.3 Hz), 116.8 (d, J＝23.2 Hz), 61.6, 61.4, 14.1; HRMS (EI) calcd for C₁₁H₁₁FO₄: 226.0641, found 226.0640.

  2-Ethoxy-2-oxoethyl 3-bromobenzoate (3ak): 122 mg, pale yellow oil, 85% yield. ¹H NMR (400 MHz, CDCl₃) δ: 8.23 (s, 1H), 8.03 (d, J＝7.8 Hz, 1H), 7.71 (d, J＝8.0 Hz, 1H), 7.34 (t, J＝7.9 Hz, 1H), 4.85 (s, 2H), 4.26 (q, J＝7.1 Hz, 2H), 1.30 (t, J＝7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 167.5, 164.7, 136.4, 132.9, 131.1, 130.1, 128.5, 122.5, 77.4, 77.1, 76.8, 61.6, 61.4, 14.1; HRMS (EI) calcd for C₁₁H₁₁BrO₄: 285.9841, found 285.9839.

  2-Ethoxy-2-oxoethyl 3-methoxybenzoate (3al): 91 mg, pale yellow oil, 76% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.70 (d, J＝7.7 Hz, 1H), 7.60 (s, 1H), 7.36 (t, J＝8.0 Hz, 1H), 7.13 (dd, J＝8.3, 2.5 Hz, 1H), 4.84 (s, 2H), 4.26 (q, J＝7.1 Hz, 2H), 3.85 (s, 3H), 1.29 (t, J＝7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 167.8, 165.8, 159.6, 130.5, 129.5, 122.3, 120.0, 114.2, 61.4, 61.3, 55.4, 14.1; HRMS (EI) calcd for C₁₂H₁₄O₅: 238.0841, found 238.0842.

  2-Ethoxy-2-oxoethyl 3-(trifluoromethyl)benzoate (3am): 127 mg, pale yellow oil, 92% yield. ¹H NMR (400 MHz, CDCl₃) δ: 8.28 (s, 1H), 8.20 (d, J＝7.8 Hz, 1H), 7.76 (d, J＝7.8 Hz, 1H), 7.53 (t, J＝7.8 Hz, 1H), 4.80 (s, 2H), 4.19 (q, J＝7.1 Hz, 2H), 1.22 (t, J＝7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 167.5, 164.7, 133.1 (d, J＝0.8 Hz), 131.1 (q, J＝33.0 Hz), 130.1, 129.9 (q, J＝3.6 Hz), 129.2, 126.8 (q, J＝3.8 Hz), 123.6 (q, J＝272.4 Hz), 61.6, 61.5, 14.1; HRMS (EI) calcd for C₁₂H₁₁F₃O₄: 276.0609, found 276.0608.

  2-Ethoxy-2-oxoethyl 2-fluorobenzoate (3an): 77 mg, pale yellow oil, 68% yield. ¹H NMR (400 MHz, CDCl₃) δ: 8.01 (t, J＝7.4 Hz, 1H), 7.56 (dd, J＝13.3, 7.0 Hz, 1H), 7.28~7.12 (m, 2H), 4.86 (s, 2H), 4.26 (q, J＝7.1 Hz, 2H), 1.30 (t, J＝7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 167.6, 163.6 (d, J＝3.7 Hz), 162.2 (d, J＝261.1 Hz), 135.0 (d, J＝9.1 Hz), 132.3, 124.0 (d, J＝4.0 Hz), 117.7 (d, J＝9.5 Hz), 117.1 (d, J＝22.1 Hz), 61.5, 61.3, 14.1; HRMS (EI) calcd for C₁₁H₁₁FO₄: 226.0641, found 226.0642.

  2-Ethoxy-2-oxoethyl 2-chlorobenzoate (3ao): 107 mg, pale yellow oil, 88% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.96 (d, J＝7.8 Hz, 1H), 7.51~7.42 (m, 2H), 7.34 (t, J＝7.3 Hz, 1H), 4.86 (s, 2H), 4.27 (q, J＝7.1 Hz, 2H), 1.31 (t, J＝7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 167.5, 164.7, 134.1, 133.1, 131.8, 131.2, 128.9, 126.6, 61.6, 61.4, 14.1; HRMS (EI) calcd for C₁₁H₁₁ClO₄: 242.0346, found 242.0347.

  2-Ethoxy-2-oxoethyl 2-bromobenzoate (3ap): 132 mg, pale yellow oil, 92% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.93 (dd, J＝7.2, 2.0 Hz, 1H), 7.67 (dd, J＝8.5, 7.0 Hz, 1H), 7.42~7.32 (m, 2H), 4.85 (s, 2H), 4.26 (q, J＝7.1 Hz, 2H), 1.30 (t, J＝7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 167.5, 165.2, 134.5, 133.1, 131.8, 130.9, 127.2, 122.1, 61.6, 61.4, 14.1; HRMS (EI) calcd for C₁₁H₁₁BrO₄: 285.9841, found 285.9845.

  2-Ethoxy-2-oxoethyl 2-methylbenzoate (3aq): 67 mg, pale yellow oil, 60% yield. ¹H NMR (400 MHz, CDCl₃) δ: 8.00 (d, J＝8.2 Hz, 1H), 7.43 (t, J＝7.5 Hz, 1H), 7.26 (t, J＝6.1 Hz, 2H), 4.82 (s, 2H), 4.26 (q, J＝7.1 Hz, 2H), 2.62 (s, 3H), 1.30 (t, J＝7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 167.9, 166.8, 140.6, 132.4, 131.7, 130.9, 128.7, 125.8, 61.4, 61.0, 21.6, 14.1; HRMS (EI) calcd for C₁₂H₁₄O₄: 222.0892, found 222.0893.

  (E)-2-Ethoxy-2-oxoethyl 2-(3-methoxy-3-oxoprop-1- en-1-yl)benzoate (3ar): 133 mg, pale yellow oil, 91% yield. ¹H NMR (400 MHz, CDCl₃) δ: 8.46 (d, J＝15.9 Hz, 1H), 8.06 (d, J＝7.8 Hz, 1H), 7.64~7.52 (m, 2H), 7.46 (t, J＝7.5 Hz, 1H), 6.33 (d, J＝15.9 Hz, 1H), 4.86 (s, 2H), 4.27 (q, J＝7.1 Hz, 2H), 3.80 (s, 3H), 1.30 (t, J＝7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 167.6, 166.9, 165.9, 143.6, 136.7, 132.8, 131.1, 129.5, 128.9, 127.9, 120.9, 61.6, 61.4, 51.7, 14.1; HRMS (EI) calcd for C₁₅H₁₆O₆: 292.0947, found 292.0948.

  2-Ethoxy-2-oxoethyl 2-(phenylethynyl)benzoate (3as)131 mg, yellow oil, 85% yield. ¹H NMR (400 MHz, CDCl₃) δ: 8.06 (d, J＝7.9 Hz, 1H), 7.65 (d, J＝7.7 Hz, 1H), 7.59~7.54 (m, 2H), 7.50 (t, J＝7.6 Hz, 1H), 7.38 (t, J＝7.7 Hz, 1H), 7.33 (m, 3H), 4.87 (s, 2H), 4.23 (q, J＝7.1 Hz, 2H), 1.27 (t, J＝6.9 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 167.8, 165.3, 134.1, 132.2, 131.8, 130.9, 130.8, 128.6, 128.4, 127.9, 124.2, 123.3, 94.7, 88.0, 61.5, 61.3, 14.1; HRMS (EI) calcd for C₁₉H₁₆O₄: 308.1049, found 308.1048.

  2-Ethoxy-2-oxoethyl 2-naphthoate (3at): 105 mg, pale yellow oil, 81% yield. ¹H NMR (400 MHz, CDCl₃) δ: 8.68 (s, 1H), 8.10 (d, J＝8.6 Hz, 1H), 7.93 (t, J＝8.5 Hz, 1H), 7.91~7.83 (m, 2H), 7.56 (dt, J＝14.8, 7.1 Hz, 2H), 4.91 (s, 2H), 4.27 (q, J＝7.1 Hz, 2H), 1.30 (t, J＝7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 167.9, 166.1, 135.8, 132.4, 131.7, 129.55, 128.5, 128.3, 127.8, 126.8, 126.4, 125.3, 61.5, 61.3, 14.2; HRMS (EI) calcd for C₁₂H₁₁F₃O₄: 285.0892, found 285.0893.

  2-Ethoxy-2-oxoethyl furan-2-carboxylate (3au): 59 mg, pale yellow oil, 60% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.62 (dd, J＝1.7, 0.8 Hz, 1H), 7.29 (dd, J＝3.5, 0.7 Hz, 1H), 6.55 (dd, J＝3.5, 1.7 Hz, 1H), 4.82 (s, 2H), 4.26 (q, J＝7.1 Hz, 2H), 1.30 (t, J＝7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 167.5, 157.8, 146.9, 143.7, 119.1, 112.0, 61.6, 60.9, 14.1; HRMS (EI) calcd for C₉H₁₀O₅: 198.0528, found 198.0529.

  2-Ethoxy-2-oxoethyl picolinate (3av): 79 mg, pale yellow oil, 76% yield. ¹H NMR (400 MHz, CDCl₃) δ: 8.79 (d, J＝4.6 Hz, 1H), 8.20 (d, J＝7.8 Hz, 1H), 7.89 (dd, J＝7.6, 6.9 Hz, 1H), 7.53 (dd, J＝6.9, 5.4 Hz, 1H), 4.94 (s, 2H), 4.27 (q, J＝7.1 Hz, 2H), 1.30 (t, J＝7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 167.3, 164.5, 149.9, 147.1, 137.1, 127.3, 125.5, 61.7, 61.5, 14.1; HRMS (EI) calcd for C₁₀H₁₁NO₄: 209.0688, found 209.0691.

  2-Ethoxy-2-oxoethyl thiophene-3-carboxylate (3aw) 91 mg, pale yellow oil, 85% yield. ¹H NMR (400 MHz, CDCl₃) δ: 8.21 (d, J＝1.7 Hz, 1H), 7.57 (d, J＝5.0 Hz, 1H), 7.33 (dd, J＝4.5, 3.3 Hz, 1H), 4.80 (s, 2H), 4.25 (q, J＝7.1 Hz, 2H), 1.29 (t, J＝7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 167.8, 161.9, 133.7, 132.4, 128.0, 126.2, 61.5, 60.9, 14.1; HRMS (EI) calcd for C₉H₁₀O₄S: 214.0300, found 214.0301.

  Cyanomethyl benzoate (3ba): 65 mg, pale yellow oil, 81% yield. ¹H NMR (400 MHz, CDCl₃) δ: 8.06 (d, J＝7.9 Hz, 2H), 7.64 (t, J＝7.4 Hz, 1H), 7.49 (t, J＝7.7 Hz, 2H), 4.97 (s, 2H). ¹³C NMR (100 MHz, CDCl₃) δ: 165.0, 134.2, 130.0, 128.7, 127.9, 114.5, 48.9; HRMS (EI) calcd for C₉H₇NO₂: 161.0477, found 161.0480.

  Cyanomethyl 4-methoxybenzoate (3bb): 55 mg, pale yellow oil, 58% yield. ¹H NMR (400 MHz, CDCl₃) δ: 8.01 (d, J＝8.7 Hz, 2H), 6.95 (d, J＝8.6 Hz, 2H), 4.94 (s, 2H), 3.88 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 164.6, 164.3, 132.2, 120.1, 114.7, 114.0, 55.6, 48.6; HRMS (EI) calcd for C₁₀H₉NO₃: 191.0582, found 191.0581.

  Cyanomethyl [1, 1'-biphenyl]-4-carboxylate (3bc): 102 mg, pale yellow oil, 86% yield. ¹H NMR (400 MHz, CDCl₃) δ: 8.10 (d, J＝8.1 Hz, 2H), 7.68 (d, J＝8.1 Hz, 2H), 7.61 (d, J＝7.7 Hz, 2H), 7.47 (t, J＝7.4 Hz, 2H), 7.44~7.38 (m, 1H), 4.96 (s, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 164.9, 146.9, 139.6, 130.6, 129.1, 128.5, 127.3, 127.3, 126.6, 114.6, 48.9; HRMS (EI) calcd for C₁₅H₁₂- NO₂: 237.0790, found 237.0789.

  Cyanomethyl 4-bromobenzoate (3bd): 106 mg, white solid, 88% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.91 (d, J＝8.3 Hz, 2H), 7.63 (d, J＝8.3 Hz, 2H), 4.97 (s, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 164.3, 132.1, 131.5, 129.6, 126.8, 114.3, 49.0; HRMS (EI) calcd for C₉H₆BrNO₂: 238.9582, found 238.9583.

  Cyanomethyl 3-bromobenzoate (3be): 111 mg, pale yellow oil, 65% yield. ¹H NMR (400 MHz, CDCl₃) δ: 8.20 (s, 1H), 8.00 (d, J＝7.8 Hz, 1H), 7.77 (d, J＝8.0 Hz, 1H), 7.38 (t, J＝7.9 Hz, 1H), 4.98 (s, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 163.7, 137.1, 132.9, 130.3, 129.7, 128.6, 122.8, 114.2, 49.1; HRMS (EI) calcd for C₉H₆BrNO₂: 238.9582, found 238.9585.

  Cyanomethyl 2-fluorobenzoate (3bf): 54 mg, pale yellow oil, 60% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.99 (t, J＝7.5 Hz, 1H), 7.62 (dd, J＝13.0, 7.3 Hz, 1H), 7.27 (t, J＝7.6 Hz, 1H), 7.23~7.16 (m, 1H), 4.98 (s, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 162.7 (d, J＝3.9 Hz), 162.3 (d, J＝262.5 Hz), 135.9 (d, J＝9.2 Hz), 132.4, 124.3 (d, J＝4.0 Hz), 117.3 (d, J＝22.0 Hz), 116.4 (d, J＝9.4 Hz), 114.2, 48.9; HRMS (EI) calcd for C₉H₆FNO₂: 179.0383, found 179.0384.

  Cyanomethyl 2-naphthoate (3bg): 81 mg, white solid, 77% yield. ¹H NMR (400 MHz, CDCl₃) δ: 8.61 (s, 1H), 8.01 (d, J＝8.6 Hz, 1H), 7.94 (d, J＝8.1 Hz, 1H), 7.89 (d, J＝3.8 Hz, 1H), 7.87 (d, J＝3.1 Hz, 1H), 7.62 (t, J＝7.5 Hz, 1H), 7.56 (t, J＝7.5 Hz, 1H), 5.01 (s, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 165.1, 135.9, 132.3, 132.1, 129.5, 129.0, 128.6, 127.9, 127.1, 125.0, 124.9, 114.6, 49.0; HRMS (EI) calcd for C₁₃H₉NO₂: 211.0633, found 211.0634.

  Supporting Information ¹H NMR, ¹³C NMR, HRMS spectra of 3aa~3bg. The Supporting Information is available free of charge via the Internet at http://sioc-journal.cn/

• 1. [1]

     (a) Barratt, B. J.; Easton, C. J.; Henry, D. J.; Li, I. H.; Radom, L.; Simpson, J. S. J. Am. Chem. Soc. 2004, 126, 13306.
     (b) Sarabia, F.; Chammaa, S.; Ruiz, A. S.; Ortiz, L. M.; Herrera, F. L. Curr. Med. Chem. 2004, 11, 1309.
     (c) Hamada, Y.; Shioiri, T. Chem. Rev. 2005, 2009, 2009, 5390.
     (d) Wang, H.-W.; Liu, Z.-C.; Chen, C.-H.; Lim, T.-S.; Fann, W.; Chao, C.-G.; Yu, J.-Y.; Lee, S.-L.; Chen, C.-H.; Huang, S.-L.; Luh, T.-Y. Chem.-Eur. J. 2009, 15, 5719.
     (e) White, J. D.; Jeffrey, S. C. Tetrahedron 2009, 65, 6642.
     (f) Nahrwold, M.; Bogner, T.; Eissler, S.; Verma, S.; Sewald, N. Org. Lett. 2010, 12, 1064.

  2. [2]

     (a) Drä ger, G.; Kiss, C.; Kunz, U.; Kirschning, A. Org. Biomol. Chem. 2007, 5, 3657.
     (b) Allais, F.; Martinet, S.; Ducrot, P.-H. Synthesis 2009, 3571.
     (c) Franz, N.; Menin, L.; Klok, H. A. Eur. J. Org. Chem. 2009, 2009, 5390.
     (d) Wang, H.-W.; Liu, Z.-C.; Chen, C.-H.; Lim, T.-S.; Fann, W.; Chao, C.-G.; Yu, J.-Y.; Lee, S.-L.; Chen, C.-H.; Huang, S.-L.; Luh, T.-Y. Chem.-Eur. J. 2009, 15, 5719.
     (e) White, J. D.; Jeffrey, S. C. Tetrahedron 2009, 65, 6642.
     (f) Nahrwold, M.; Bogner, T.; Eissler, S.; Verma, S.; Sewald, N. Org. Lett. 2010, 12, 1064.

  3. [3]

     (a) Dumitrescu, L.; Azzouzi-Zriba, K.; Bonnet-Delpon, D.; Crousse, B. Org. Lett. 2011, 13, 692.
     (b) Setzer, P.; Forcher, G.; Boeda, F.; Pearson-Long, M. S. M.; Bertus, P. Eur. J. Org. Chem. 2014, 2014, 171.

  4. [4]

     Katritzky, A. R.; Abdel-Fattah, A. A. A.; Idzik, K. R.; El-Gendy, B. E.-D. M.; Soloducho, J. Tetrahedron 2007, 63, 6477. doi: 10.1016/j.tet.2007.04.021

  5. [5]

     (a) Berłożecki, S.; Szymanski, W.; Ostaszewski, R. Tetrahedron 2008, 64, 9780.
     (b) Gulevich, A. V.; Shpilevaya, I. V.; Nenajdenko, V. G. Eur. J. Org. Chem. 2009, 2009, 3801.

  6. [6]

     (a) Shinada, T.; Kawakami, T.; Sakai, H.; Takada, I.; Ohfune, Y. Tetrahedron Lett. 1998, 39, 3757.
     (b) Bertelsen, S.; Nielsen, M.; Bachmann, S.; Jørgensen, K. A. Synthesis 2005, 2234.
     (c) Vorob'eva, D. V.; Titanyuk, I. D.; Beletskaya, I. P.; Osipov, S. N. Mendeleev. Commun. 2005, 15, 222.
     (d) Wang, Z.; Bi, X.; Liang, Y.; Liao, P.; Dong, D. Chem. Commun. 2014, 50, 3976.

  7. [7]

     (a) Kantchev, E. A. B.; O'Brien, C. J.; Organ, M. G. Angew. Chem. 2007, 119, 2824.
     (b) Wuertz, S.; Glorius, F. Acc. Chem. Res. 2008, 41, 1523.
     (c) Chass, G. A.; O'Brien, C. J.; Hadei, N.; Kantchev, E. A. B.; Mu, W. H.; Fang, D. C.; Hopkinson, A. C.; Csizmadia, I. G.; Organ, M. G. Chem.-Eur. J. 2009, 15, 4281.
     (d) Díez-González, S.; Marion, N.; Nolan, S. P. Chem. Rev. 2009, 109, 3612.
     (e) Visbal, R.; Gimeno, M. C. Chem. Soc. Rev. 2014, 43, 3551.
     (f) Chirik, P. J. Acc. Chem. Res. 2015, 48, 1687.

  8. [8]

     (a) Enders, D.; Niemeier, O.; Henseler, A. Chem. Rev. 2007, 107, 5606.
     (b) Flanigan, D. M.; Romanov-Michailidis, F.; White, N. A.; Rovis, T. Chem. Rev. 2015, 115, 9307.
     (c) Wang, M. H.; Scheidt, K. A. Angew. Chem., Int. Ed. 2016, 55, 14912.
     (d) Janssen-Müller, D.; Schlepphorst, C.; Glorius, F. Chem. Soc. Rev. 2017, 46, 4845.
     (e) Chen, X.-Y.; Liu, Q.; Chauhan, P.; Enders, D. Angew. Chem., Int. Ed. 2018, 57, 3862.

  9. [9]

     (a) Enders, D.; Balensiefer, T. Acc. Chem. Res. 2004, 37, 534.
     (b) Zeitler, K. Angew. Chem., Int. Ed. 2005, 44, 7506.
     (c) Marion, N.; Díez-González, S.; Nolan, S. P. Angew. Chem., Int. Ed. 2007, 46, 2988.
     (d) Nair, V.; Vellalath, S.; Babu, B. P. Chem. Soc. Rev. 2008, 37, 2691.
     (e) Arduengo Ⅲ, A. J.; Iconaru, L. I. Dalton. Trans. 2009, 6903.
     (f) Biju, A. T.; Kuhl, N.; Glorius, F. Acc. Chem. Res. 2011, 44, 1182.
     (g) Nair, V.; Menon, R. S.; Biju, A. T.; Sinu, C.; Paul, R. R.; Jose, A.; Sreekumar, V. Chem. Soc. Rev. 2011, 40, 5336.
     (h) Rong, Z.-Q.; Zhang, W.; Yang, G.-Q.; You, S.-L. Curr. Org. Chem. 2011, 15, 3077.
     (i) Bugaut, X.; Glorius, F. Chem. Soc. Rev. 2012, 41, 3511.
     (j) Cohen, D. T.; Scheidt, K. A. Chem. Sci. 2012, 3, 53.
     (k) Grossmann, A.; Enders, D. Angew. Chem., Int. Ed. 2012, 51, 314.
     (l) De Sarkar, S.; Biswas, A.; Samanta, R. C.; Studer, A. Chem.-Eur. J. 2013, 19, 4664.
     (m) Ryan, S. J.; Candish, L.; Lupton, D. W. Chem. Soc. Rev. 2013, 42, 4906.
     (n) Mahatthananchai, J.; Bode, J. W. Acc. Chem. Res. 2014, 47, 696.

  10. [10]

      (a) Kayaki, Y.; Yamamoto, M.; Ikariya, T. Angew. Chem., Int. Ed. 2009, 48, 4194.
      (b) Yamashita, K.; Hase, S.; Kayaki, Y.; Ikariya, T. Org. Lett. 2015, 17, 2334.

  11. [11]

      (a) He, M.; Struble, J. R.; Bode, J. W. J. Am. Chem. Soc. 2006, 128, 8418.
      (b) He, M.; Uc, G. J.; Bode, J. W. J. Am. Chem. Soc. 2006, 128, 15088.
      (c) Ryan, S. J.; Candish, L.; Lupton, D. W. J. Am. Chem. Soc. 2011, 133, 4694.
      (d) Allen, S. E.; Mahatthananchai, J.; Bode, J. W.; Kozlowski, M. C. J. Am. Chem. Soc. 2012, 134, 12098.
      (e) Ryan, S. J.; Stasch, A.; Paddon-Row, M. N.; Lupton, D. W. J. Org. Chem. 2012, 77, 1113.
      (f) Wang, M.; Huang, Z.; Xu, J.; Chi, Y. R. J. Am. Chem. Soc. 2014, 136, 1214.
      (g) Zhu, T.; Zheng, P.; Mou, C.; Yang, S.; Song, B.-A.; Chi, Y. R. Nat. Commun. 2014, 5.
      (h) Xu, J.; Hu, S.; Lu, Y.; Dong, Y.; Tang, W.; Lu, T.; Du, D. Adv. Synth. Catal. 2015, 357, 923.

  12. [12]

      (a) Reynolds, N. T.; Read de Alaniz, J.; Rovis, T. J. Am. Chem. Soc. 2004, 126, 9518.
      (b) Chan, A.; Scheidt, K. A. Org. Lett. 2005, 7, 905.
      (c) Sohn, S. S.; Bode, J. W. Angew. Chem. 2006, 118, 6167.
      (d) Bode, J. W.; Sohn, S. S. J. Am. Chem. Soc. 2007, 129, 13798.
      (e) Li, G.-Q.; Li, Y.; Dai, L.-X.; You, S.-L. Org. Lett. 2007, 9, 3519.
      (f) Kaeobamrung, J.; Mahatthananchai, J.; Zheng, P.; Bode, J. W. J. Am. Chem. Soc. 2010, 132, 8810.

  13. [13]

      DiRocco, D. A.; Rovis, T. J. Am. Chem. Soc. 2012, 134, 8094. doi: 10.1021/ja3030164

  14. [14]

      (a) Candish, L.; Lupton, D. W. Chem. Sci. 2012, 3, 380.
      (b) Wu, Z.; Wang, X.; Li, F.; Wu, J.; Wang, J. Org. Lett. 2015, 17, 3588.

  15. [15]

      (a) Cardinal-David, B.; Raup, D. E.; Scheidt, K. A. J. Am. Chem. Soc. 2010, 132, 5345.
      (b) Raup, D. E.; Cardinal-David, B.; Holte, D.; Scheidt, K. A. Nat. Chem. 2010, 2, 766.
      (c) Zhao, X.; DiRocco, D. A.; Rovis, T. J. Am. Chem. Soc. 2011, 133, 12466.
      (d) Cohen, D. T.; Scheidt, K. A. Chem. Sci. 2012, 3, 53.
      (e) Dugal-Tessier, J.; O'Bryan, E. A.; Schroeder, T. B.; Cohen, D. T.; Scheidt, K. A. Angew. Chem., Int. Ed. 2012, 51, 4963.
      (f) Zhang, Y.; Lu, Y.; Tang, W.; Lu, T.; Du, D. Org. Biomol. Chem. 2014, 12, 3009.
      (g) Lin, Y.; Yang, L.; Deng, Y.; Zhong, G. Chem. Commun. 2015, 51, 8330.
      (h) Xu, J.; Chen, X.; Wang, M.; Zheng, P.; Song, B.-A.; Chi, Y. R. Angew. Chem. 2015, 127, 5250.

  16. [16]

      (a) Maki, B. E.; Scheidt, K. A. Org. Lett. 2008, 10, 4331.
      (b) De Sarkar, S.; Grimme, S.; Studer, A. J. Am. Chem. Soc. 2010, 132, 1190.
      (c) Maji, B.; Vedachalan, S.; Ge, X.; Cai, S.; Liu, X. W. J. Org. Chem. 2011, 76, 3016.
      (d) Delany, E. G.; Fagan, C. L.; Gundala, S.; Mari, A.; Broja, T.; Zeitler, K.; Connon, S. J. Chem. Commun. 2013, 49, 6510.
      (e) Berry, M. T.; Castrejon, D.; Hein, J. E. Org. Lett. 2014, 16, 3676.
      (f) Samanta, R. C.; Studer, A. Org. Chem. Front. 2014, 1, 936.

  17. [17]

      Knappke, C. E. I.; Imami, A.; Jacobivon Wangelin, A. ChemCatChem 2012, 4, 937. doi: 10.1002/cctc.201200133

  18. [18]

      (a) De Sarkar, S.; Studer, A. Angew. Chem., Int. Ed. 2010, 49, 9266.
      (b) Rose, C. A.; Zeitler, K. Org. Lett. 2010, 12, 4552.
      (c) Park, J. H.; Bhilare, S. V.; Youn, S. W. Org. Lett. 2011, 13, 2228.
      (d) Sun, Z.-X.; Cheng, Y. Org. Biomol. Chem. 2012, 10, 4088.
      (e) Youn, S. W.; Song, H. S.; Park, J. H. Org. Biomol. Chem. 2014, 12, 2388.
      (f) Youn, S. W.; Song, H. S.; Park, J. H. Org. Lett. 2014, 16, 1028.

  19. [19]

      Rosa, J. N.; Reddy, R. S.; Candeias, N. R.; Cal, P. M.; Gois, P. M. Org. Lett. 2010, 12, 2686. doi: 10.1021/ol100302e

  20. [20]

      Li, Y.; Du, W.; Deng, W.-P. Tetrahedron 2012, 68, 3611. doi: 10.1016/j.tet.2012.02.079

  21. [21]

      Xin, Y.-C.; Shi, S.-H.; Xie, D.-D.; Hui, X.-P.; Xu, P.-F. Eur. J. Org. Chem. 2011, 2011, 6527. doi: 10.1002/ejoc.v2011.32

  22. [22]

      Ramanjaneyulu, B. T.; Reddy, V.; Arde, P.; Mahesh, S.; Anand, R. V. Chem.-Asian J. 2013, 8, 1489. doi: 10.1002/asia.v8.7

  23. [23]

      Zhang, Y.; Du, Y.; Huang, Z.; Xu, J.; Wu, X.; Wang, Y.; Wang, M.; Yang, S.; Webster, R. D.; Chi, Y. R. J. Am. Chem. Soc. 2015, 137, 2416. doi: 10.1021/ja511371a

  24. [24]

      Li, B.-S.; Wang, Y.; Jin, Z.; Zheng, P.; Ganguly, R.; Chi, Y. R. Nat. Commun. 2015, 6, 6207. doi: 10.1038/ncomms7207

• 

  Scheme 2  Proposed machanistic pathway for NHC-catalyzed oxidative esterification

  下载: 全尺寸图片 幻灯片

  Table 1.  Optimization of reaction conditions^a

  Entry	NHC precursor(mol%)	Base(equiv.)	Solvent	Yield/%
  1	A(20)	Cs2CO3(1.5)	THF	35
  2	A(20)	Cs2CO3(1.5)	CH2Cl2	23
  3	B(20)	Cs2CO3(1.5.)	THF	65
  4	C(20)	Cs2CO3(1.5)	THF	20
  5	D(20)	Cs2CO3(1.5)	THF	15
  6	E(20)	Cs2CO3(1.5)	THF	12
  7	F(20)	Cs2CO3(1.5)	THF	10
  8	B(20)	Cs2CO3(2.0)	THF	86
  9	B(20)	Cs2CO3(1.0)	THF	36
  10	B(15)	Cs2CO3(2.0)	THF	50
  11	B(10)	Cs2CO3(2.0)	THF	32
  12	B(20)	Cs2CO3(2.0)	CH2Cl2	48
  13	B(20)	Cs2CO3(2.0)	CHCl3	30
  14	B(20)	Cs2CO3(2.0)	Dioxane	8
  15	B(20)	Cs2CO3(2.0)	DCE	66
  16	B(20)	Et3N(2.0)	THF	33
  17	B(20)	DBU(2.0)	THF	27
  18	B(20)	(i-Pr)2NEt(2.0)	THF	38
  a Reaction conditions:1a(0.2 mmol), 2a(0.24 mmol), NHC precursor(n mol%), base(0.2 mmol~0.4 mmol), solvent(2 mL), r.t. and 8 h.b Isolated yields.

  下载: 导出CSV

  Table 2.  Substrates scope^a

  下载: 导出CSV
•