Next Article in Journal
Polyamine Metabolites Profiling for Characterization of Lung and Liver Cancer Using an LC-Tandem MS Method with Multiple Statistical Data Mining Strategies: Discovering Potential Cancer Biomarkers in Human Plasma and Urine
Next Article in Special Issue
Recent Advances in Dynamic Kinetic Resolution by Chiral Bifunctional (Thio)urea- and Squaramide-Based Organocatalysts
Previous Article in Journal
Pd@[nBu4][Br] as a Simple Catalytic System for N-Alkylation Reactions with Alcohols
Previous Article in Special Issue
Organocatalyzed Intramolecular Carbonyl-Ene Reactions
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Molecules
Volume 21
Issue 8
10.3390/molecules21081030
molecules-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

TBD- or PS-TBD-Catalyzed One-Pot Synthesis of Cyanohydrin Carbonates and Cyanohydrin Acetates from Carbonyl Compounds

by
Satoru Matsukawa
*,
Junya Kimura
and
Miki Yoshioka
Department of Science Education, Faculty of Education, Ibaraki University, Ibaraki 310-8512, Japan
*
Author to whom correspondence should be addressed.
Molecules 2016, 21(8), 1030; https://doi.org/10.3390/molecules21081030
Submission received: 30 June 2016 / Revised: 27 July 2016 / Accepted: 3 August 2016 / Published: 10 August 2016
(This article belongs to the Collection Recent Advances in Organocatalysis)
Browse Figures
Versions Notes

Abstract

:
Cyanation reactions of carbonyl compounds with methyl cyanoformate or acetyl cyanide catalyzed by 5 mol % of 1,5,7-triazabicyclo[4,4,0]dec-5-ene (TBD) were examined. Using methyl cyanoformate, the corresponding cyanohydrin carbonates were readily obtained in high yield for aromatic and aliphatic aldehydes and ketones. Similar results were obtained when acetyl cyanide was used as the cyanide source. The polymer-supported catalyst, PS-TBD, also acted as a good catalyst for this reaction. PS-TBD was easily recovered and reused with minimal activity loss.

Graphical Abstract

1. Introduction

The addition of cyanide to carbonyl compounds is among the most fundamental carbon–carbon bond formation reactions in modern organic chemistry [1,2,3,4,5,6]. The resultant cyanohydrins are easily converted into important synthetic intermediates including α-hydroxyl-carbonyl compounds and β-amino alcohols. Multiple cyanation methods have been examined, and trimethylsilyl cyanide has most commonly been used as the source of the cyanide anion [7,8]. While hundreds of examples have been reported to this day, the inherent instability of trimethylsilyl cyanohydrins sometimes limits the applications of this reaction. Therefore, alternative synthetic procedures for the preparation of stable O-protected cyanohydrins instead of trimethylsilyl cyanohydrin have been developed. Cyanohydrin carbonates and cyanohydrin acylates are configurationally stable and less prone to hydrolysis than cyanohydrin trimethylsilyl ethers. Therefore, one-pot synthesis of cyanohydrin carbonates and acylated cyanation using cyanoformates and cyanoacylates have recently been developed. Several catalytic reactions have been recently studied. To date, reactions using tributyltin cyanide [9], K2CO3 [10], tertiary amines [11,12], DABCO (1,4-diazabicyclo[2.2.2]octane) [13,14], dimethyl sulfoxide [15], TTMPP (tris(2,4,6-trimethoxyphenyl)phsphine) [16], DMAP (N,N-dimethyl-4-aminopyridine) [17], and N-heterocyclic carbenes [18] as catalysts or activators have been reported. Asymmetric catalytic reactions have also been reported using cinchona alkaloids [19,20,21,22,23,24,25], Y complexes [26,27,28], Al complexes [29,30], Ti complexes [31,32,33,34,35,36,37,38,39,40], and V complexes [41]. To further extend the scope of this versatile synthetic reaction, we have now examined the use of 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) as a Lewis base catalyst.
It is well-known that TBD is a strong Lewis base owing to its distorted bicyclic guanidine structure [42,43]. Employing this property, multiple unique reactions have been reported using TBD as an organobase catalyst including Henry reactions [44], Wittig and Horner-Wadsworth-Emmons reactions [45], Michael reactions [46,47], intramolecular aldol reactions [48,49], ring-opening polymerization [50,51], aminolysis of esters [52,53], conjugate addition to activated alkenes [54], synthesis of pyrazolines [55], and others [56,57]. Although TBD usually behaves as a base, it also contains an acidic N–H group; therefore, TBD may act as a bifunctional acid-base catalyst [58,59,60]. Recently, we have reported the trifluoromethylation of aldehydes [61] and the ring-opening reactions of aziridines [62,63] catalyzed using TBD as an organocatalyst. Here, we report that TBD acts as an effective organobase catalyst for the cyanation of carbonyl compounds using methyl cyanoformate or acetyl cyanide as cyanide source.

2. Results and Discussion

Initially, the cyanomethoxycarbonylation reaction of p-anisaldehyde using methyl cyanoformate was examined in the presence of 5 mol % of TBD in THF at room temperature. The desired product was obtained in 90% yield after 2 h (Table 1, entry 1). The product was obtained in a lower yield when DMF (N,N-dimethylformamide), toluene or ClCH2CH2Cl was used as the solvent. An approximately comparable yield was observed when CH3CN was used (Table 1, entry 2). The yield was decreased when 1 mol % of TBD was used (Table 1, entry 6). To clarify the scope of this reaction, the cyanation of several aldehydes was examined in the presence of 5 mol % of TBD. In the case of aromatic aldehydes, the yield was influenced by the substituents on the aromatic ring. With aromatic aldehydes bearing an electron-withdrawing group, it was necessary to change the order of reagent addition to obtain the desired product in good yield. Using other aromatic aldehydes, the products were obtained in good to high yields. trans-Cinnamaldehyde was subjected to our reaction conditions, and the 1,2-addition product was obtained in 85% yield. Although slightly longer reaction times were required, aliphatic aldehydes also produced similar high yields.
Ketones were also examined using the 10 mol % of TBD (Table 2). In the case of aliphatic ketones, good results were obtained for both acyclic and cyclic ketones. The reaction proceeded more smoothly than the reported example [17]. Only 1,2-addition products were observed for unsaturated ketones. On the other hand, for aromatic ketones, only a small amount of the desired product was obtained at room temperature even after 24 h. When the reactions were performed at elevated temperature (50 °C), a variety of aromatic ketones were converted to their corresponding cyanohydrin carbonates in moderate to good yields. In this reaction, novel cyanohydrin carbonates (4c, 4g) could be obtained. In addition, 4d and 4e were obtained for the first time as products of this one-pot method. Unfortunately, in the reaction of 4-methoxyacetophenone, no product was found under these conditions.
Acetyl cyanide was also examined in the TBD-catalyzed reaction (Table 3). The acylated cyanohydrin products were readily obtained in high yields in a similar manner for aromatic aldehydes. Although the bond between the acetyl and cyanide groups is stronger in acetyl cyanide than in methyl cyanoformate, the reactivity did not decrease. In the case of 4-nitrobenzaldehyde, the starting material was rapidly consumed; however, the product yield was not good. In this case, it is likely that attack at the NO2 group occurred. Longer reaction times were needed in the reaction of aromatic aldehydes bearing electron-donating groups on the aromatic ring. This trend has been similarly reported in a recent related report [18]. The aliphatic, heterocyclic, and α,β-unsaturated aldehydes also reacted to give the corresponding products in similarly high yields.
Furthermore, we applied a polymer-supported TBD, PS-TBD [64,65,66,67] to this reaction (Table 4). Polymer-supported catalysts have attracted significant attention in recent decades because of their inherent advantages in synthetic chemistry, e.g., the simplification of reaction procedures including the easy recovery of the catalyst using filtration, application to automated systems, and recycling of the catalyst [68,69,70,71,72,73]. Thus, we examined the cyanomethoxycarbonylation reaction of p-anisaldehydes in the presence of 10 mol % of PS-TBD [63,74,75,76,77,78,79]. The reaction proceeded smoothly and the desired product was obtained in 95% yield after 3 h at room temperature. A variety of aldehydes reacted well with methyl cyanoformate to give cyanohydrin carbonates. Aromatic aldehydes with either electron-donating or electron-withdrawing groups afforded the corresponding products in high yields. Aliphatic aldehydes also worked well. In the reaction with aldehyde, the catalytic reactivity of PS-TBD seems to be slightly lower than TBD. Ketones were also examined; however, the reaction was very slow. Then, the reaction was performed at elevated temperature. The desired product was obtained at moderate to yield in 4 h at 50 °C. In addition, the recovery and reuse of PS-TBD for the reaction of p-anisaldehyde with methyl cyanoformate was also examined. After the reaction was completed, ethyl acetate was added to the reaction mixture and the catalyst was recovered by filtration. The recovered catalyst was washed, dried and then reused. The catalyst was reused, maintaining its catalytic activity after three times.
A possible mechanism for the TBD-catalyzed cyanation is illustrated in Scheme 1. First, the nitrogen atom of TBD activates the cyanoformates or cyanoacylates to form [N⁺C(O)R]CN⁻ intermediate A. Next, the CN⁻ anion immediately reacts with the carbonyl compounds to give the alkoxide anion of the cyanohydrin B. Finally, the alkoxide anion is carbonylated or acylated to give the O-protected cyanohydrin with the regeneration of TBD. In this reaction, acidic N–H group of TBD may activate the carbonyl group (C).

3. Experimental Section

3.1. General

IR spectra were recorded on a JUSCO FT/IR-430 spectrometer (JASCO Corporation, Tokyo, Japan). 1H-NMR spectra were determined for solutions in CDCl3 with Me4Si as internal standard (CDCl3: 7.24 ppm, Me4Si: 0.00 ppm) on a Bruker Avance III instrument (Bruker Corporation, Billerica, MA, USA). 13C-NMR spectra were determined for solutions in CDCl3 with Me4Si as internal standard (CDCl3: 77.00 ppm, Me4Si: 0.00 ppm) on a Bruker Avance III instrument (Bruker Corporation). HRMS data were measured on a JEOL JMS-700 mass spectrometer (JEOL Ltd., Tokyo, Japan).
All reactions were performed under an argon atmosphere using oven-dried glassware. Flash column chromatography was performed using silica gel Wakogel C-200 (Wako Chemical, Osaka, Japan). Dehydrate DMF, THF, toluene and CH3CN were purchased from Kanto Kagaku (Tokyo, Japan) as the “anhydrous” and stored over 4A molecular sieves under Ar. Other commercially available reagent was used as received without further purification.

3.2. Method

3.2.1. General Procedure for TBD-Catalyzed Cyanation Reactions of Carbonyl Compounds with Methyl Cyanoformate

TBD was dried in vacuo before use. To a solution of TBD (0.05 mmol) in CH3CN (1 mL) was added carbonyl compound (1.0 mmol) and methyl cyanoformate (1.25 mmol) at room temperature. After the reaction was complete (as determined by TLC), the reaction mixture was quenched with water. The resultant mixture was extracted with EtOAc (3 × 10 mL). The combined organic layers were washed with water and brine and dried with Na2SO4. After the filtration, the residue was concentrated in vacuo. The crude product was purified by column chromatography on silica gel (EtOAc:hexane = 1:5 → 1:3) to give the corresponding product.

3.2.2. General Procedure for TBD-Catalyzed Cyanation Reactions of Aldehydes with Acetyl Cyanide

TBD was dried in vacuo before use. To a solution of TBD (0.10 mmol) in CH3CN (1 mL) was added aldehyde (1.0 mmol) and acetyl cyanide (1.5 mmol) at room temperature. After the reaction was complete (as determined by TLC), the reaction mixture was quenched with water. The resultant mixture was extracted with EtOAc (3 × 10 mL). The combined organic layers were washed with water and brine and dried with Na2SO4. After the filtration, the residue was concentrated in vacuo. The crude product was purified by column chromatography on silica gel (EtOAc:hexane = 1:10 → 1:5) to give the corresponding product.

3.2.3. General Procedure for PS-TBD Catalyzed Cyanation Reactions of Carbonyl Compounds with Methyl Cyanoformate

PS-TBD was dried in vacuo before use. To a solution of PS-TBD (0.10 mmol) in CH3CN (1 mL) was added carbonyl compound (1.0 mmol) and methyl cyanoformate (1.25 mmol) at room temperature. After the reaction was complete (as determined by TLC), EtOAc (10 mL) was added to the mixture and PS-TBD was separated by filtration. The filtrate was washed with water and brine and dried with Na2SO4. After the filtration, the residue was concentrated in vacuo. The crude product was purified by column chromatography on silica gel (EtOAc:hexane = 1:5 → 1:3) to give the corresponding product. The recovered catalyst is reusable after washing (acetone and water) and drying in vacuo.

3.3. General Characterization of the Products

Cyano(4-methoxyphenyl)methyl methyl carbonate (2a) [11]: IR (neat): 2245, 1761 cm⁻1; 1H-NMR (500 MHz, CDCl3): δ 3.80 (s, 3H), 3.82, (s, 3H), 6.18 (s, 1H), 6.92 (d, J = 8.8 Hz, 2H), 7.44 (d, J = 8.8 Hz, 2H); 13C-NMR (125 MHz, CDCl3): δ 55.5, 55.7, 66.4, 114.6, 115.9, 123.2, 129.8, 154.1, 161.4. The corresponding spectra are shown in Supplementary Materials.
Cyano(phenyl)methyl methyl carbonate (2b) [11]: IR (neat): 2249, 1760 cm⁻1; 1H-NMR (500 MHz, CDCl3): δ 3.77 (s, 3H), 6.18 (s, 1H), 7.35–7.46 (m, 5H); 13C-NMR (125 MHz, CDCl3): δ 55.9, 66.6, 115.7, 127.9, 129.3, 130.7, 131.1, 154.1.
Cyano(4-chlorophenyl)methyl methyl carbonate (2c) [11]: IR (neat): 2250, 1758 cm⁻1; 2347, 1762 cm⁻1; 1H-NMR (500 MHz, CDCl3): δ 3.84 (s, 3H), 6.21 (s, 1H), 7.40 (d, J = 8.6 Hz, 2H), 7.46 (d, J = 8.6 Hz, 2H); 13C-NMR (125 MHz, CDCl3): δ 56.0, 65.8, 115.3, 129.2, 129.3, 129.6, 136.9, 153.9.
Cyano(4-nitrophenyl)methyl methyl carbonate (2d) [16]: IR (neat): 2251, 1760 cm⁻1; 1H-NMR (500 MHz, CDCl3): δ 2.20 (s, 3H), 6.49 (s, 1H), 7.71 (d, J = 8.7 Hz, 2H), 8.30 (d, J = 8.7 Hz, 2H); 13C-NMR (125 MHz, CDCl3): 20.3, 61.6, 115.1, 124.4, 128.7, 138.1, 149.0, 168.6.
Cyano(naphthalen-1-yl)methyl methyl carbonate (2e) [15]: IR (neat): 2247, 1768 cm⁻1; 1H-NMR (500 MHz, CDCl3): δ 3.77 (s, 3H), 6.18 (s, 1H), 7.51–7.58 (m, 3H), 7.80–7.96 (m, 4H); 13C-NMR (125 MHz, CDCl3): δ 56.0, 65.3, 115.8, 122.6, 125.0, 126.4, 127.7, 129.1, 129.2, 130.0, 131.8, 133.9, 154.2.
Cyano(naphthalen-2-yl)methyl methyl carbonate (2f) [15]: IR (neat): 2254, 1757 cm⁻1; 1H-NMR (500 MHz, CDCl3): δ 3.85 (s, 3H), 6.42 (s, 1H), 7.51–7.56 (m, 3H), 7.84–7.96 (m, 4H); 13C-NMR (125 MHz, CDCl3): δ 55.9, 66.8, 115.8, 124.1, 127.1, 127.7, 127.9, 128.1, 128.4, 128.5, 129.5, 132.8, 134.0, 154.2.
Cyano-3-phenylpropen-2-yl methyl carbonate (2g) [15]: IR (neat): 2260, 1759 cm−1; 1H-NMR (500 MHz, CDCl3): δ 3.86 (s, 3H), 5.88(dd, J = 1.1, 6.8 Hz, 1H), 6.20(dd, J = 6.8, 15.8 Hz, 1H), 6.98 (d, J = 15.8 Hz, 1H), 7.33–7.38 (m, 3H), 7.40–7.46 (m, 2H); 13C-NMR (125 MHz, CDCl3): δ 55.9, 65.2, 114.9, 117.6, 127.2, 128.2, 129.5, 134.2, 138.4, 154.0.
Cyano-3-phenylpropyl methyl carbonate (2h) [15]: IR (neat): 2240, 1760 cm⁻1; 1H-NMR (500 MHz, CDCl3): δ 2.22–2.30 (m, 2H), 2.85 (t, J = 7.8 Hz, 2H), 3.86 (s, 3H), 5.13 (t, J = 7.8 Hz, 2H), 7.18–7.21 (m, 3H), 7.29–7.33 (m, 2H); 13C-NMR (125 MHz, CDCl3): δ 30.4, 33.8, 55.8, 64.0, 116.2, 126.7, 128.2, 128.4, 128.7, 129.0, 138.7, 154.0.
Cyano(cyclohexyl)methyl methyl carbonate (2i) [15]: IR (neat): 2247, 1758 cm⁻1; 1H-NMR (500 MHz, CDCl3): δ 1.06–1.25 (m, 5H), 1.65 (d, J = 12.7 Hz, 1H), 1.89 (m, 6H), 3.79 (s, 3H), 4.98 (d, J = 6.0 Hz, 1H) 3.80 (s, 3H), 6.28 (s, 1H), 6.37 (dd, J = 1.9, 3.4 Hz, 1H), 6.66 (d, J = 3.4 Hz, 1H), 7.45 (m, 1H); 13C-NMR (125 MHz, CDCl3): δ 25.2, 27.7, 27.9, 40.1, 55.7, 69.5, 115.7, 154.3.
Cyano(1-octyl)methyl methyl carbonate (2j) [16]: IR (neat): 2249, 1760 cm⁻1; 1H-NMR (500 MHz, CDCl3): δ 0.81 (m, 3H), 1.19–1.21 (m, 12H), 1.87 (dd, J = 6.8, 15.8 Hz, 2H), 3.79 (s, 3H), 5.13 (t, J = 6.8 Hz, 1H); 13C-NMR (125 MHz, CDCl3): δ 14.0, 22.6, 24.4, 28.8, 29.2, 29.5, 31.7, 32.3, 55.7, 64.9, 116.5, 154.3.
Cyano(furan-2-yl)methyl methyl carbonate (2k) [11]: IR (neat): 2247, 1768 cm⁻1; 1H-NMR (500 MHz, CDCl3): δ 3.80 (s, 3H), 6.28 (s, 1H), 6.37 (dd, J = 1.9, 3.4 Hz, 1H), 6.66 (d, J = 3.4 Hz, 1H), 7.45 (m, 1H); 13C-NMR (125 MHz, CDCl3): δ 56.0, 59.3, 111.2, 113.2, 143.5, 145.4, 153.9.
1-Cyano-1-methyl-3-phenylpropyl methyl carbonate (4a) [11]: IR (neat): 2250, 1760 cm⁻1; 1H-NMR (500 MHz, CDCl3): δ 1.82 (s, 3H), 2.17–2.34 (m, 2H), 2.82–2.90 (m, 2H), 3.83 (s, 3H), 7.16–7.24 (m, 3H), 7.26–7.31 (m, 2H); 13C-NMR (125 MHz, CDCl3): δ 24.5, 30.2, 41.6, 55.3, 74.0, 118.2, 126.5, 128.4, 128.7, 139.7, 153.2.
1-Cyano-1-ethylhexyl methyl carbonate (4b) [16]: IR (neat): 2250, 1759 cm⁻1; 1H-NMR (500 MHz, CDCl3): δ 0.85 (t, J = 6.9 Hz, 3H), 1.03 (t, J = 7.5 Hz, 3H), 1.24–1.33 (m, 4H), 1.35–1.54 (m, 2H), 1.88–2.10 (m, 4H), 3.78 (s, 3H); 13C-NMR (125 MHz, CDCl3): δ 7.9, 13.8, 22.3, 23.2, 29.8, 31.3, 36.0, 55.1, 78.5, 117.8, 153.2.
1-Cyanocyclohexyl methyl carbonate (4c): colorless oil; IR (neat): 2250, 1760 cm⁻1; 1H-NMR ( 500 MHz, CDCl3 ) : δ 1.15–1.35 (m, 1H), 1.53–1.64 (m, 3H), 1.70–1.77 (m, 2H), 1.80–1.85 (m, 2H), 2.26–2.28 (m, 2H), 3.79 (s, 3H); 13C-NMR (125 MHz, CDCl3): δ 22.0, 24.3, 35.0, 55.1, 75.0, 118.2, 153.0; HRMS (FAB): m/z: calcd for C9H14NO3: 184.0973; found: 184.0991 [M + H]+.
1-cyanocyclohex-2-en-1-yl methyl carbonate (4d) [80]: IR (neat): 2245, 1753 cm⁻1; 1H-NMR (500 MHz, CDCl3 ): δ 1.68–72 (m, 2H), 1.97–1.99 (m, 2H), 2.40 (t, J = 6.6 Hz, 2H), 3.81 (s, 3H), 5.98 (d, J = 10 Hz, 1H), 6.99 (ddd, J = 7.1, 7.1, 4.1 Hz, 1H); 13C-NMR (125 MHz, CDCl3 ): δ 20.9, 22.7, 24.3, 51.9, 74.4, 112.5, 116.9, 129.8, 152.9.
1-Cyano-1-methyl-3-phenylprope-2-yl methyl carbonate (4e) [81]: IR (neat): 2250, 1760 cm⁻1; 1H-NMR (500 MHz, CDCl3) : δ 1.84 (s, 3H), 3.72 (s, 3H), 6.10 (d, J = 16.0 Hz, 1H), 6.95 (d, J = 16.0 Hz, 1H), 7.29–7.30 (m, 3H), 7.43–7.44 (m, 2H); 13C-NMR (125 MHz, CDCl3 ): δ 14.2, 21.1, 55.4, 60.4, 73.8, 117.3, 124.0, 128.8, 130.5, 134.4, 152.9.
1-Cyano-1-phenylethyl methyl carbonate (4f) [11]: IR (neat) 2250, 1752 cm⁻1; 1H-NMR (500 MHz, CDCl3): δ 2.01 (s, 3H), 3.77 (s, 3H), 7.37–7.46 (m, 3H), 7.53–7.55 (m, 2H); 13C-NMR (125 MHz, CDCl3): δ 29.9, 55.4, 75.7, 117.9, 124.5, 129.1, 129.5, 137.6, 152.9.
1-Cyano-1-phenylpropyl methyl carbonate (4g): pale yellow oil; IR (neat) 2249, 1758 cm⁻1; 1H-NMR (500 MHz, CDCl3): δ 1.03 (t, J = 7.4 Hz, 3H), 2.05–2.12 (m, 1H), 2.27–2.34 (m, 1H), 3.74 (s, 3H), 7.36–7.42 (m, 5H); 13C-NMR (125 MHz, CDCl3): δ 8.5, 36.0, 55.4, 65.6, 80.4, 117.0, 124.8, 129.0. HRMS (FAB): m/z: calcd for C9H14NO3: 220. 0968; found: 220. 0979 [M + H]+.
1-Cyano-1-(4-chlorophenyl)ethyl methyl carbonate (4h) [11]: IR (neat) 2250, 1760 cm⁻1; 1H-NMR (500 MHz, CDCl3): δ 1.99 (s, 3H), 3.76 (s, 3H), 7.38 (d, J = 8.7 Hz, 2H), 7.48 (d, J = 8.7 Hz, 2H); 13C-NMR (125 MHz, CDCl3): δ 29.7, 55.5, 66.0, 75.1, 117.5, 126.1, 129.3, 135.6, 136.1, 152.8.
1-Cyano-1-(4-nitrophenyl)ethyl methyl carbonate (4i) [11]: IR (neat) 2251, 1749 cm⁻1; 1H-NMR (500 MHz, CDCl3): δ 2.00 (s, 3H), 3.76 (s, 3H), 7.70 (d, J = 8.9 Hz, 2H), 8.06 (d, J = 8.9 Hz, 2H); 13C-NMR (125 MHz, CDCl3): δ 29.7, 55.8, 65.8, 74.8, 117.0, 123.8, 124.4, 125.7, 152.8.
Cyano(phenyl)methyl methyl acetate (5a) [14]: IR (neat) 2250, 1742 cm⁻1; 1H-NMR (500 MHz, CDCl3): δ 2.17 (s, 3H), 6.39 (s, 1H), 7.44 (m, 3H), 7.51 (d, J = 11.1 Hz, 2H); 13C-NMR (125 MHz, CDCl3): δ 20.4, 62.8, 116.1, 127.9, 129.2, 130.4, 131.7, 168.9.
Cyano(4-chlorophenyl)methyl methyl acetate (5b) [18]: IR (neat) 2245, 1756 cm⁻1; 1H-NMR (500 MHz, CDCl3): δ 2.15 (s, 3H), 6.36 (s, 1H), 7.41 (d, J = 8.7 Hz, 2H), 7.45 (d, J = 8.7 Hz, 2H); 13C-NMR (125 MHz, CDCl3): δ 20.4, 62.1, 115.7, 129.3, 129.5, 130.2, 136.6, 168.8.
Cyano(4-methylphenyl)methyl methyl acetate (5c) [18]: IR (neat) 2250, 1753 cm⁻1; 1H-NMR (500 MHz, CDCl3): δ 2.13 (s, 3H), 2.37 (s, 3H), 6.35 (s, 1H), 7.23 (d, J = 8.0 Hz, 2H), 7.39 (d, J = 8.0 Hz, 2H); 13C-NMR (125 MHz, CDCl3): δ 20.5, 21.3, 62.7, 116.2, 127.9, 128.8, 129.9, 140.7, 169.0.
Cyano(4-methoxyphenyl)methyl methyl acetate (5d) [18]: IR (neat) 2249, 1747 cm⁻1; 1H-NMR (500 MHz, CDCl3): δ 2.12 (s, 3H), 3.81 (s, 3H), 6.34 (s, 1H), 6.93 (d, J = 8.8 Hz, 2H), 7.43 (d, J = 8.8 Hz, 2H); 13C-NMR (125 MHz, CDCl3): δ 20.5, 55.4, 62.6, 114.5, 116.3, 123.8, 129.6, 161.1, 169.0.
Cyano(4-nitrophenyl)methyl methyl acetate (5e) [82]: IR (neat): 2251, 1760 cm⁻1; 1H-NMR (500 MHz, CDCl3): δ 2.20 (s, 3H), 6.49 (s, 1H), 7.71 (d, J = 8.7 Hz, 2H), 8.30 (d, J = 8.7 Hz, 2H); 13C-NMR (125 MHz, CDCl3): δ 20.3, 61.6, 115.1, 124.4, 128.7, 138.1, 149.0, 168.6.
Cyano(naphthalen-1-yl)methyl methyl acetate (5f) [18]: IR (neat) 2249, 1755 cm⁻1; 1H-NMR (500 MHz, CDCl3): δ 2.17 (s, 3H), 7.02 (s,1H), 7.50 (dd, J = 7.1, 8.1 Hz, 1H), 7.54 (t, J = 8.1 Hz, 1H), 7.60 (t, J = 6.2 Hz, 1H), 7.71 (d, J = 6.2 Hz, 1H), 7.86 (d, J = 7.1 Hz, 1H), 7.94 (d, J = 9.9 Hz, 1H), 7.98 (d, J = 8.6 Hz, 1H); 13C-NMR (125 MHz, CDCl3): δ 20.4, 61.3 116.1 122.5, 125.0, 126.6, 126.9, 127.6, 129.1, 130.0, 131.5, 133.9, 169.0.
Cyano(naphthalen-1-yl)methyl methyl acetate (5g) [82]: IR (neat) 2250, 1753 cm⁻1; 1H-NMR (500 MHz, CDCl3): δ 2.17 (s, 3H), 6.57 (s, 1H), 7.53–7.57 (m, 3H), 7.87 (t, J = 9.3 Hz, 2H), 7.91 (d, J = 8.6Hz, 1H), 8.00 (d, J = 1.3 Hz, 1H); 13C-NMR (125 MHz, CDCl3): δ 20.6, 63.1, 116.2, 124.3, 127.1, 127.6, 127.1, 127.6, 127.9, 128.1, 128.4, 129.5, 132.9, 133.9, 169.0.
Cyano-3-phenylpropen-2-yl methyl acetate (5h) [32]: IR (neat) 2251, 1751 cm⁻1; 1H-NMR (500 MHz, CDCl3): δ 2.15 (s, 3H), 6.00 (d, J = 6.7 Hz, 1H), 6.18 (dd, J = 6.7, 15.8 Hz, 1H), 6.95 (d, J = 15.8 Hz, 1H), 7.31–7.37 (m, 3H), 7.41 (d, J = 7.9 Hz, 2H); 13C-NMR (125 MHz, CDCl3): δ 20.3, 61.4, 115.4, 118.2, 127.0, 128.7, 129.3, 134.3, 137.7, 168.8.
Cyano-3-phenylpropeyl methyl acetate (5i) [18]: IR (neat) 2248, 1755 cm⁻1; 1H-NMR (500 MHz, CDCl3): δ 2.11 (s, 3H), 2.22 (dd, J = 7.6, 15.0 Hz, 2H), 2.82 (t, J = 7.6 Hz, 2H), 5.25 (t, J = 6.8 Hz, 1H), 7.17 (d, J = 7.2 Hz, 2H), 7.23 (d, J = 8.1 Hz, 1H), 7.30 (t, J = 7.2 Hz, 2H); 13C-NMR (125 MHz, CDCl3): δ 20.3, 30.7, 33.7, 60.5, 116.7, 126.7, 128.3, 128.7, 139.0, 169.1.
Cyano(cyclohexyl)methyl methyl acetate (5j) [18]: IR (neat) 2248, 1755 cm⁻1; 1H-NMR (500 MHz, CDCl3): δ 1.07–1.21 (m, 4H), 1.21–1.30 (m, 2H), 1.66–1.69 (m, 1H), 1.73–1.80 (m, 3H), 1.84–1.92 (m, 1H), 2.13 (s, 3H), 5.15 (d, J = 6.6 Hz, 1H); 13C-NMR (125 MHz, CDCl3): δ 20.3, 25.3, 25.7, 28.1, 40.0, 65.6, 116.2, 169.2.
Cyano(1-octyl)methyl methyl acetate (5k) [83]: IR (neat) 2218, 1756 cm⁻1; 1H-NMR (500 MHz, CDCl3): δ 0.83 (t, J = 7.0 Hz, 3H), 1.15–1.33 (m, 14H), 1.57 (quin, J = 6.8 Hz, 2H), 1.99 (s, 3H), 4.00 (t, J = 6.8 Hz, 2H); 13C-NMR (125 MHz, CDCl3): δ 14.0, 20.9, 22.6, 25.8, 28.5, 29.2, 29.4, 31.8, 64.6, 117.6, 171.1.
Cyano(furan-2-yl)methyl methyl acetate (5l) [82]: IR (neat) 2248, 1753 cm⁻1; 1H-NMR (500 MHz, CDCl3): δ 2.14 (s, 3H), 6.42 (dd, J = 1.9, 3.4 Hz, 1H), 6.45 (s, 1H), 6.66 (d, J = 3.4 Hz, 1H), 7.49 (dd, J = 0.8, 1.9 Hz, 1H); 13C-NMR (125 MHz, CDCl3): δ 20.3, 55.7, 111.0, 112.6, 114.1, 144.1, 145.0, 168.7.

4. Conclusions

In conclusion, we have demonstrated the TBD-catalyzed cyanation reaction of carbonyl compounds using methyl cyanoformate or acetyl cyanide as cyanide sources. A broad range of aldehydes and ketones reacted to produce O-protected cyanohydrins in the presence of 5–10 mol % of TBD. Furthermore, a polymer-supported catalyst, PS-TBD, also acted as a good catalyst for this reaction. PS-TBD was easily recovered and reused with minimal loss of activity. These reactions provide a simple and convenient method for synthesis of highly functionalized α-hydroxyl-carbonyl compounds and β-amino alcohols.

Supplementary Materials

Supplementary materials can be accessed at: https://www.mdpi.com/1420-3049/21/8/1030/s1.

Author Contributions

S.M. conceived the ideas, analyzed the data, and wrote the paper; J.K and M.Y. performed the experiments and analyzed the data; and all authors read and approved the final manuscript.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. North, M. Catalytic, asymmetric cyanohydrin formation. Synlett 1993, 1993, 807–820. [Google Scholar] [CrossRef]
  2. Gregory, J.H. Cyanohydrins in nature and the laboratory: Biology, preparations, and synthetic applications. Chem. Rev. 1999, 99, 3649–3682. [Google Scholar] [CrossRef] [PubMed]
  3. North, M. Synthesis and applications of non-racemic cyanohydrins. Tetrahedron Asymmetry 2003, 14, 147–176. [Google Scholar] [CrossRef]
  4. Brunel, J.M.; Holmes, I.P. Chemically catalyzed asymmetric cyanohydrin syntheses. Angew. Chem. Int. Ed. 2004, 43, 2752–2778. [Google Scholar] [CrossRef] [PubMed]
  5. Chen, F.X.; Feng, X. Synthesis of racemic tertiary cyanohydrins. Synett 2005, 2005, 892–899. [Google Scholar] [CrossRef]
  6. Khan, N.H.; Kureshy, R.I.; Abdi, S.H.R.; Agrawal, S.; Jasra, R. Metal catalyzed asymmetric cyanation reactions. Coord. Chem. Rev. 2008, 252, 593–623. [Google Scholar] [CrossRef]
  7. Evans, D.A.; Truesdale, L.K. Carbonyl insertion reactions of silicon pseudohalides: Catalysis. Tetrahedron Lett. 1973, 14, 4929–4932. [Google Scholar] [CrossRef]
  8. Evans, D.A.; Carroll, G.L.; Truesdale, L.K. Synthetic applications of trimethylsilyl cyanide. An efficient synthesis of aminomethyl alcohols. J. Org. Chem. 1974, 39, 914–917. [Google Scholar] [CrossRef]
  9. Scholl, M.; Lim, C.K.; Fu, G.C. Convenient and efficient conversion of aldehydes to acylated cyanohydrins using tributyltin cyanide as a catalyst. J. Org. Chem. 1995, 60, 6229–6231. [Google Scholar] [CrossRef]
  10. Okimoto, M.; Chiba, T. A Convenient and Improved Method for the Preparation of Cyanohydrin Esters from Acyl Cyanides and Aldehydes. Synthesis 1996, 1996, 1188–1190. [Google Scholar] [CrossRef]
  11. Baeza, A.; Najera, C.; Retamosa, M.G.; Sansano, J.M. Solvent-free synthesis of cyanohydrin derivatives catalysed by triethylamine. Synthesis 2005, 2005, 2787–2797. [Google Scholar]
  12. Poirier, D.; Berthiaume, D.; Boivi, R.P. Unexpected formation of O-methoxycarbonyl cyanohydrin showing potential as a protective group of ketones. Synlett 1999, 1999e, 1423–1425. [Google Scholar] [CrossRef]
  13. Deardorff, D.R.; Taniguchi, C.M.; Tafti, S.A.; Kim, H.Y.; Choi, S.Y.; Downey, K.J.; Nguyen, T.V. A two-Step procedure for the conversion of α,β-Unsaturated aldehydes into γ-Azido-α,β-unsaturated nitriles. J. Org. Chem. 2001, 66, 7191–7194. [Google Scholar] [CrossRef] [PubMed]
  14. Hoffmann, H.M.R.; Ismail, Z.M.; Hollweg, R.; Zein, A.R. DABCO-mediated synthesis and biological activity of cyanohydrin esters. Bull. Chem. Soc. Jpn. 1990, 63, 1807–1810. [Google Scholar] [CrossRef]
  15. Iwanami, K.; Hinakubo, Y.; Oriyama, T. Catalyst-free DMSO-promoted synthesis of cyanohydrin carbonates from aldehydes. Tetrahedron Lett. 2005, 46, 5881–5883. [Google Scholar] [CrossRef]
  16. Matsukawa, S.; Sekine, I.; Iitsuka, A. Tris(2,4,6-trimethoxyphenyl) phosphine (TTMPP): Efficient Catalysts for the Cyanosilylation and Cyanocarbonation of Aldehydes and Ketones. Molecules 2009, 14, 3353–3359. [Google Scholar] [CrossRef] [PubMed]
  17. Aoki, S.; Kotani, S.; Sugiura, M.; Nakajima, M. DMAP-catalyzed cyanation of aldehydes and ketones with ethyl cyanoformate. Tetrahedron Lett. 2010, 51, 3547–3549. [Google Scholar] [CrossRef]
  18. Zhang, J.; Du, G.; Xu, Y.; He, L.; Dai, B. N-heterocyclic carbene catalyzed cyanation reaction of carbonyl compounds with ethyl cyanoformate and acetyl cyanide. Tetrahedron Lett. 2011, 52, 7153–7156. [Google Scholar] [CrossRef]
  19. Tian, S.K.; Deng, L. A Highly enantioselective chiral Lewis base-catalyzed asymmetric cyanation of ketones. J. Am. Chem. Soc. 2001, 123, 6195–6196. [Google Scholar] [CrossRef] [PubMed]
  20. Tian, S.K.; Deng, L. Enantioselective cyanocarbonation of ketones with chiral base. Tetrahedron 2006, 62, 11320–11330. [Google Scholar] [CrossRef]
  21. Chinchilla, R.; Nájera, C.; Ortega, F.J. Enantioselective cyanoformylation of aldehydes using a recyclable dimeric cinchonidine ammonium salt as an organocatalyst. Tetrahedron Asymmetry 2008, 19, 265–268. [Google Scholar] [CrossRef]
  22. Li, F.; Widyan, K.; Wingstrand, E.; Moberg, C. Chiral Lewis base catalyzed enantioselective acetylcyanation of α-oxo esters. Eur. J. Org. Chem. 2009, 2009, 3917–3922. [Google Scholar] [CrossRef]
  23. Wang, J.; Wang, W.; Li, W.; Hu, X.; Shen, K.; Tan, C.; Liu, X.; Feng, X. Asymmetric Cyanation of Aldehydes, Ketones, Aldimines, and Ketimines Catalyzed by a Versatile Catalyst Generated from Cinchona Alkaloid, Achiral Substituted 2,2′-Biphenol and Tetraisopropyl Titanate. Chem. Eur. J. 2009, 15, 11642–11659. [Google Scholar] [CrossRef] [PubMed]
  24. Ogura, Y.; Akakura, M.; Sakakura, A.; Ishihara, K. Enantioselective cyanoethoxycarbonylation of Isatins promoted by a Lewis base-Brønsted acid cooperative catalyst. Angew. Chem. Int. Ed. 2013, 52, 8299–8303. [Google Scholar] [CrossRef] [PubMed]
  25. Ishihara, K.; Ogura, Y. Enantioselective Cyano-Alkoxycarbonylation of α-Oxoesters Promoted by Brønsted Acid-Lewis Base Cooperative Catalysts. Org. Lett. 2015, 17, 6070–6073. [Google Scholar] [CrossRef] [PubMed]
  26. Tian, J.; Yamagiwa, N.; Matsunaga, S.; Shibasaki, M. An asymmetric cyanation reaction and sequential asymmetric cyanation-nitroaldol reaction using a [YLi3{tris(binaphthoxide)}] single catalyst component: catalyst tuning with achiral additives. Angew. Chem. Int. Ed. 2002, 41, 3636–3638. [Google Scholar] [CrossRef]
  27. Tian, J.; Yamagiwa, N.; Matsunaga, S.; Shibasaki, M. Efficient two-step conversion of α,β-unsaturated aldehydes to optically active γ-oxy-α,β-unsaturated nitriles and its application to the total synthesis of (+)-Patulolide C. Org. Lett. 2003, 5, 3021–3024. [Google Scholar] [CrossRef] [PubMed]
  28. Yamagiwa, N.; Tian, J.; Matsunaga, S.; Shibasaki, M. Catalytic asymmetric cyano-ethoxycarbonylation reaction of aldehydes using a YLi3Tris (binaphthoxide) (YLB) complex:  Mechanism and roles of achiral additives. J. Am. Chem. Soc. 2005, 127, 3413–3422. [Google Scholar] [CrossRef] [PubMed]
  29. Casas, J.; Baeza, A.; Sansano, J.M.; Nájera, C.; Saá, J.M. Enantioselective cyanoformylation of aldehydes mediated by BINOLAM-AlCl as a monometallic bifunctional catalys. Tetrahedron Asymmetry 2003, 14, 197–200. [Google Scholar] [CrossRef]
  30. Baeza, A.; Casas, J.; Nájera, C.; Sansano, J.M.; Saá, J.M. Enantioselective synthesis of O-methoxycarbonyl cyanohydrins: Chiral building blocks generated by bifunctional catalysis with BINOLAM-AlCl. Eur. J. Org. Chem. 2006, 2006e, 1949–1958. [Google Scholar] [CrossRef]
  31. Belokon’, Y.N.; Blacker, A.J.; Clutterbuck, L.A.; North, M. Catalytic, asymmetric synthesis of cyanohydrin ethyl carbonates. Org. Lett. 2003, 5, 4505–4507. [Google Scholar] [CrossRef] [PubMed]
  32. Lundgren, S.; Wingstrand, E.; Penhoat, M.; Moberg, C. Dual Lewis Acid-Lewis Base activation in enantioselective cyanation of aldehydes using acetyl cyanide and cyanoformate as cyanide sources. J. Am. Chem. Soc. 2005, 127, 11592–11593. [Google Scholar] [CrossRef] [PubMed]
  33. Li, Q.; Chang, L.; Liu, X.; Feng, X. Catalytic asymmetric cyano-ethoxycarbonylation reaction of aldehydes using a novel C2-symmetric chiral N, N′-dioxide Titanium complex. Synlett 2006, 1675–1678. [Google Scholar] [CrossRef]
  34. Gou, S.; Chen, X.; Xiong, Y.; Feng, X. Highly Enantioselective cyanation of aldehydes catalyzed by a multicomponent Titanium complex. J. Org. Chem. 2006, 71, 5732–5736. [Google Scholar] [CrossRef] [PubMed]
  35. Chen, S.K.; Peng, D.; Zhou, H.; Wang, L.W.; Chen, F.X.; Feng, X.M. Highly enantioselective cyanoformylation of aldehydes catalyzed by a mononuclear Salen-Ti(OiPr)4 complex produced in situ. Eur. J. Org. Chem. 2007, 2007, 639–644. [Google Scholar] [CrossRef]
  36. Gou, S.; Liu, X.; Zhou, X.; Feng, X. Asymmetric cyano-ethoxycarbonylation of aldehydes catalyzed by self-assembled titanium catalyst. Tetrahedron 2007, 63, 7935–7941. [Google Scholar] [CrossRef]
  37. Lundgren, S.; Wingstrand, E.; Moberg, C. Lewis Acid-Lewis Base-Catalysed Enantioselective Addition of a-Ketonitriles to Aldehydes. Adv. Synth. Catal. 2007, 349, 364–372. [Google Scholar] [CrossRef]
  38. Belokon’, Y.N.; Clegg, W.; Harrington, R.W.; Ishibashi, E.; Nomura, H.; North, M. Enantioselective and diastereoselective syntheses of cyanohydrin carbonates. Tetrahedron 2007, 63, 9724–9740. [Google Scholar] [CrossRef]
  39. Wingstrand, E.; Laurell, A.; Fransson, L.; Hult, K.; Moberg, C. Minor Enantiomer Recycling: Metal Catalyst, Organocatalyst and Biocatalyst Working in Concert. Chem. Eur. J. 2009, 14, 12107–12113. [Google Scholar] [CrossRef] [PubMed]
  40. Ji, N.; Yao, L.; He, W.; Li, Y. Bifunctional Schiff base/Ti (IV) catalysts for enantioselective cyanoformylation of aldehydes with ethyl cyanoformate. Appl. Organomet. Chem. 2013, 27, 209–213. [Google Scholar] [CrossRef]
  41. Khan, N.U.H.; Agrawal, S.; Kureshy, R.I.; Abdi, S.H.R.; Pathak, K.; Bajaj, H.C. Enantioselective cyanoformylation of aldehydes catalyzed with solid base mediated chiral V (V) salen complexes. Chirality 2010, 22, 153–158. [Google Scholar] [CrossRef] [PubMed]
  42. Schroeder, G.; Łeska, B.; Jarczewski, A.; Nowak-Wydra, B.; Brzezinski, B. FTIR, NMR and kinetic studies of proton transfer reactions from nitro-substituted diarylmethanes to N-bases with guanidine character. J. Mol. Struct. 1995, 344, 77–88. [Google Scholar] [CrossRef]
  43. Coles, M.P. Bicyclic-guanidines, -guanidinates and -guanidinium salts: Wide ranging applications from a simple family of molecules. Chem. Commun. 2009, 2009, 3659–3676. [Google Scholar] [CrossRef] [PubMed]
  44. Simoni, D.; Rondanin, R.; Morini, M.; Baruchello, R.; Invidata, F.P. 1,5,7-Triazabicyclo [4.4.0] dec-1-ene (TBD), 7-methyl-TBD (MTBD) and the polymer-supported TBD (P-TBD): Three efficient catalysts for the nitroaldol (Henry) reaction and for the addition of dialkyl phosphites to unsaturated systems. Tetrahedron Lett. 2000, 41, 1607–1610. [Google Scholar] [CrossRef]
  45. Simoni, D.; Rossi, M.; Rondanin, R.; Mazzali, A.; Baruchello, R.; Malagutti, C.; Roberti, M.; Invidata, F.P. Strong bicyclic guanidine base-promoted Wittig and Horner-Wadsworth-Emmons reactions. Org. Lett. 2000, 2, 3765–3768. [Google Scholar] [CrossRef] [PubMed]
  46. Ye, W.; Xu, J.; Tan, C.T.; Tan, C.H. 1,5,7-Triazabicyclo [4.4.0]dec-5-ene (TBD) catalyzed Michael reactions. Tetrahedron Lett. 2005, 46, 6875–6878. [Google Scholar] [CrossRef]
  47. Deredas, D.; Huben, K.; Maniukiewicz, W.; Krawczyk, H. Highly syn-diastereoselective Michael addition of enolizable ketones to 3-(diethoxyphosphoryl)coumarin. Tetrahedron 2014, 70, 8925–8929. [Google Scholar] [CrossRef]
  48. Ghobril, C.; Sabot, C.; Mioskowski, C.; Baati, R. TBD-Catalyzed Direct 5- and 6-enolexo Aldolization of Ketoaldehydes. Eur. J. Org. Chem. 2008, 2008, 4104–4108. [Google Scholar] [CrossRef]
  49. Lanari, D.; Rosati, O.; Curini, M. A solvent-free protocol for the synthesis of 3-formyl-2H-chromenes via domino oxa Michael/aldol reaction. Tetrahedron Lett. 2014, 55, 1752–1755. [Google Scholar] [CrossRef]
  50. Pratt, R.C.; Lohmeijer, B.G.G.; Long, D.A.; Waymouth, R.A.; Hedric, J.A. Triazabicyclodecene: A simple bifunctional organocatalyst for acyl transfer and ring-opening polymerization of cyclic esters. J. Am. Chem. Soc. 2006, 129, 4556–4557. [Google Scholar] [CrossRef] [PubMed]
  51. Simón, L.; Goodman, J.M. The Mechanism of TBD-catalyzed ring-opening polymerization of cyclic esters. J. Org. Chem. 2007, 72, 9656–9662. [Google Scholar] [CrossRef] [PubMed]
  52. Sabot, C.; Kumar, K.A.; Meunier, S.; Mioskowski, C. A convenient aminolysis of esters catalyzed by 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) under solvent-free conditions. Tetrahedron Lett. 2007, 48, 3863–3866. [Google Scholar] [CrossRef]
  53. Sabot, C.; Kumar, K.A.; Antheaume, C.; Mioskowski, C. Triazabicyclodecene: An Effective Isotope Exchange Catalyst in CDCl3. J. Org. Chem. 2007, 72, 5001–5004. [Google Scholar] [CrossRef] [PubMed]
  54. Jiang, Z.; Zhang, Y.; Ye, W.; Tan, C.H. P-C Bond formation via direct and three–component conjugate addition catalyzed by 1,5,7-triazabicyclo [4.4.0]dec-5-ene (TBD). Tetrahedron Lett. 2007, 48, 51–54. [Google Scholar] [CrossRef]
  55. Mahe, O.; Frath, D.; Dez, I.; Marsais, F.; Levacher, V.; Briere, J.F. TBD-organocatalysed synthesis of pyrazolines. Org. Biomol. Chem. 2009, 7, 3648–3651. [Google Scholar] [CrossRef] [PubMed]
  56. Saliu, F.; Rindone, B. Organocatalyzed synthesis of ureas from amines and ethylene carbonate. Tetrahedron Lett. 2010, 51, 6301–6304. [Google Scholar] [CrossRef]
  57. Poladura, B.; Martínez-Castañeda, Á.; Rodríguez-Solla, H.; Concellón, C.; del Amo, V. TBD-catalyzed α-sulfenylation of cyclic ketones: Desymmetrization of 4-substituted cyclohexanone. Tetrahedron 2012, 68, 6438–6446. [Google Scholar] [CrossRef]
  58. Kiesewetter, M.K.; Scholten, M.; Kirn, N.; Weber, R.L.; Hedrick, J.L.; Waymouth, R.M. Cyclic guanidine organic catalysts: What is magic about triazabicyclodecene? J. Org. Chem. 2009, 74, 9490–9496. [Google Scholar] [CrossRef] [PubMed]
  59. Hammar, P.; Ghobril, C.; Antheaume, C.; Wagner, A.; Baati, R.; Himo, F. Theoretical Mechanistic Study of the TBD-Catalyzed Intramolecular aldol reaction of ketoaldehydes. J. Org. Chem. 2010, 75, 4728–4736. [Google Scholar] [CrossRef] [PubMed]
  60. Fu, X.; Tan, C.H. Mechanistic considerations of guanidine-catalyzed reactions. Chem. Commun. 2011, 47, 8210–8222. [Google Scholar] [CrossRef] [PubMed]
  61. Matsukawa, S.; Harada, T.; Takahashi, H. TBD-catalyzed ring opening of aziridines with silylated nucleophiles. Synth. Commun. 2013, 43, 406–414. [Google Scholar] [CrossRef]
  62. Matsukawa, S.; Takahashi, H.; Takahashi, S. TBD-catalyzed trifluoromethylation of carbonyl compounds with (trifluoromethyl)trimethylsilane. Synth Commun. 2013, 43, 1523–1529. [Google Scholar] [CrossRef]
  63. Matsukawa, S.; Mouri, Y. A mild and regioselective ring-opening of aziridines with acid anhydride using TBD or PS-TBD as a catalyst. Molecules 2015, 20, 18482–18495. [Google Scholar] [CrossRef] [PubMed]
  64. Tomoi, M.; Kato, Y.; Kakiuchi, H. Polymer-supported bases, 2. Polystyrene-supported 1,8-diazabicyclo[5.4.0]undec-7-ene as reagent in organic syntheses. Makromol. Chem. 1984, 185, 2117–2124. [Google Scholar] [CrossRef]
  65. Iijima, K.; Fukuda, W.; Tomoi, M. Polymer-supported bases. XI. Esterification and alkylation in the presence of polymer-supported bicyclic amidine or guanidine moieties. J. Macromol. Sci. A Pure Appl. Chem. 1992, 29, 249–261. [Google Scholar] [CrossRef]
  66. Xu, W.; Mohan, R.; Morrissey, M.M. Polymer supported bases in combinatorial chemistry: Synthesis of aryl ethers from phenols and alkyl halides and aryl halides. Tetrahedron. Lett. 1997, 38, 7337–7340. [Google Scholar] [CrossRef]
  67. Boisnard, S.; Chastanet, J.; Zhu, J. A high throughput synthesis of aryl triflate and aryl nonaflate promoted by a polymer supported base (PTBD). Tetrahedron Lett. 1999, 40, 7469–7472. [Google Scholar] [CrossRef]
  68. McNamara, C.A.; Dixon, M.J.; Bradley, M. Recoverable catalysts and reagents using recyclable polystyrene-based supports. Chem. Rev. 2002, 102, 3275–3300. [Google Scholar] [CrossRef] [PubMed]
  69. Benaglia, M.; Puglisi, A.; Cozzi, F. Polymer-supported organic catalysts. Chem. Rev. 2003, 103, 3401–3429. [Google Scholar] [CrossRef] [PubMed]
  70. Cozzi, F. Immobilization of organic catalysts: When, why, and how. Adv. Synth. Catal. 2006, 348, 1367–1390. [Google Scholar] [CrossRef]
  71. Ikegami, S.; Hamamoto, H. Novel recycling system for organic synthesis via designer polymer-gel catalysts. Chem. Rev. 2009, 109, 583–593. [Google Scholar] [CrossRef] [PubMed]
  72. Lu, J.; Toy, P.H. Organic polymer supports for synthesis and for reagent and catalyst immobilization. Chem. Rev. 2009, 109, 815–838. [Google Scholar] [CrossRef] [PubMed]
  73. Kristensen, T.E.; Hansen, T. Polymer-supported chiral organocatalysts: Synthetic strategies for the road towards affordable polymeric immobilization. Eur. J. Org. Chem. 2010, 17, 3179–3204. [Google Scholar] [CrossRef]
  74. Fringuelli, F.; Pizzo, F.; Vittoriani, C.; Vaccaro, L. Polystyryl-supported TBD as an efficient and reusable catalyst under solvent-free conditions. Chem. Commun. 2004, 2004, 2756–2757. [Google Scholar] [CrossRef] [PubMed]
  75. Fringuelli, F.; Pizzo, F.; Vittoriani, C.; Vaccaro, L. Polystyrene-supported 1,5,7-triazabicyclo[4.4.0]dec-5-ene as an efficient and reusable catalyst for the thiolysis of 1,2-epoxides under solvent-free conditions. Eur. J. Org. Chem. 2006, 2006, 1231–1236. [Google Scholar] [CrossRef]
  76. Lanari, D.; Balini, R.; Palmieri, A.; Pizzo, F.; Vaccaro, L. Diastereoselective three-step route to o-(6-nitrocyclohex-3-en-1-yl) phenol and tetrahydro-6H-benzo[c]chromen-6-ol derivatives from salicylaldehydes. Eur. J. Org. Chem. 2011, 2011, 2874–2884. [Google Scholar] [CrossRef]
  77. Matsukawa, S.; Fujikawa, S. Polystyrene-supported TBD as an efficient and reusable organocatalyst for cyanosilylation of aldehydes, ketones, and imines. Tetrahedron Lett. 2012, 53, 1075–1077. [Google Scholar] [CrossRef]
  78. Matsukawa, S.; Harada, T.; Yasuda, S. Polystyrene-supported TBD catalyzed ring-opening of N-tosylaziridines with silylated nucleophiles. Org. Biomol. Chem. 2012, 10, 4886–4890. [Google Scholar] [CrossRef] [PubMed]
  79. Matsukawa, S.; Tsukamoto, K.; Harada, T.; Yasuda, S. An efficient method for opening N-tosyl aziridines with silylated nucleophiles using polystyrene-supported TBD as a reusable organocatalyst. Synthesis 2013, 45, 2959–2965. [Google Scholar] [CrossRef]
  80. Berthiaume, D.; Poirier, D. O-Methoxycarbonyl Cyanohydrin as a New Protective Group for Carbonyls. Tetrahedron 2000, 56, 5995–6003. [Google Scholar] [CrossRef]
  81. Hünig, S.; Reichelt, H. Trimethylsilylcyanid als umpolungsreagens, XI. Über den ambidenten charakter substituierter allyl-anionen. Chem. Ber. 1986, 119, 1772–1800. [Google Scholar] [CrossRef]
  82. Kadam, S.T.; Kim, S.S. One-pot three components synthesis of O-acetylcyanohydrins with TMSCN, acetic anhydride and carbonyl compounds under solvent-free condition. Tetrahedron 2009, 65, 6330–6334. [Google Scholar] [CrossRef]
  83. Quin, Y.C.; Liu, L.; Pu, L. On-step synthesis of a bifunctional BINOL ligand for the highly enantioselective cyanation of aliphatic aldehydes. Org. Lett. 2005, 7, 2381–2383. [Google Scholar] [CrossRef] [PubMed]
  • Sample Availability: Samples of the compounds 2a–2j, 4a–4i, 5a–5l are available from the authors.
Molecules 21 01030 sch001 550
Scheme 1. Proposed mechanism. [N⁺C(O)R]CN⁻ intermediate A; alkoxide anion of the cyanohydrin B and alternative transition state C.
Scheme 1. Proposed mechanism. [N⁺C(O)R]CN⁻ intermediate A; alkoxide anion of the cyanohydrin B and alternative transition state C.
Molecules 21 01030 sch001
Table
Table 1. TBD (1,5,7-triazabicyclo[4,4,0]dec-5-ene) catalyzed cyanation of aldehydes with methyl cyanoformate.
Table 1. TBD (1,5,7-triazabicyclo[4,4,0]dec-5-ene) catalyzed cyanation of aldehydes with methyl cyanoformate.
Molecules 21 01030 i001
EntryAldehyde(1)ProductSolventTimeYield (%) a
1 Molecules 21 01030 i0022aCH3CN2 h90
2 THF2 h81
3 ClCH2CH2Cl3 h65
4 DMF3 h60
5 toluene12 h35
6 b CH3CN12 h68
7 Molecules 21 01030 i0032bCH3CN12 h89
8 Molecules 21 01030 i0042c 4 h92
9 c Molecules 21 01030 i0052d 0.5 h70
10 Molecules 21 01030 i0062e 4 h96
11 Molecules 21 01030 i0072f 4 h90
12 Molecules 21 01030 i0082g 2 h85
13 Molecules 21 01030 i0092h 4 h75
14 Molecules 21 01030 i0102i 4 h96
15 Molecules 21 01030 i0112j 4 h89
16 Molecules 21 01030 i0122k 4 h88
a Isolated yield; b 1 mol % of TBD was used; c Aldehyde was added after addition of methyl cyanoformate.
Table
Table 2. TBD catalyzed cyanation of ketones with methyl cyanoformate.
Table 2. TBD catalyzed cyanation of ketones with methyl cyanoformate.
Molecules 21 01030 i013
EntryKetone(3)ProductTimeYield (%) a
1 Molecules 21 01030 i0144a4 h85
2 Molecules 21 01030 i0154b1 h90
3 Molecules 21 01030 i0164c1 h86
4 Molecules 21 01030 i0174d1 h70
5 b Molecules 21 01030 i0184e24 h33
6 b Molecules 21 01030 i0194f24 h31
7 b Molecules 21 01030 i0204g24 h75
8 Molecules 21 01030 i0214h6 h55
9 b Molecules 21 01030 i0224i24 h38
10 Molecules 21 01030 i0234j24 h0
a Isolated yield; b at 50 °C.
Table
Table 3. TBD catalyzed cyanation of aldehydes with acetyl cyanide.
Table 3. TBD catalyzed cyanation of aldehydes with acetyl cyanide.
Molecules 21 01030 i024
EntryAldehyde(1)ProductTimeYield (%) a
1 Molecules 21 01030 i0255a3 h80
2 Molecules 21 01030 i0265b6 h91
3 Molecules 21 01030 i0275c24 h94
4 Molecules 21 01030 i0285d48 h67
5 Molecules 21 01030 i0295e0.5 h40
6 Molecules 21 01030 i0305f3 h90
7 Molecules 21 01030 i0315g3 h90
8 Molecules 21 01030 i0325h3 h92
9 Molecules 21 01030 i0335i6 h70
10 Molecules 21 01030 i0345j6 h88
11 Molecules 21 01030 i0355k6 h85
12 Molecules 21 01030 i0365l6 h80
a Isolated yield.
Table
Table 4. PS (polymer-supported)-TBD catalyzed cyanation of carbonyl compounds with methyl cyanoformate.
Table 4. PS (polymer-supported)-TBD catalyzed cyanation of carbonyl compounds with methyl cyanoformate.
Molecules 21 01030 i037
EntryCarbonyl CompoundsProductTimeYield (%) a
1 Molecules 21 01030 i0382a2 h90
2 b 2a2 h88
3 c 2a2 h92
4 d 2a2 h88
5 Molecules 21 01030 i0392b12 h73
6 Molecules 21 01030 i0402c16 h86
7 Molecules 21 01030 i0412d4 h94
8 Molecules 21 01030 i0422e4 h98
9 Molecules 21 01030 i0432h4 h90
10 Molecules 21 01030 i0442k2 h78
11 Molecules 21 01030 i0452i2 h82
12 Molecules 21 01030 i0464a24 h24
13 e 4a12 h75
14 e Molecules 21 01030 i0474b24 h70
15 e Molecules 21 01030 i0484c18 h76
a Isolated yield; b 2nd run; c 3rd run; d 4th run; e at 50 °C.

Share and Cite

MDPI and ACS Style

Matsukawa, S.; Kimura, J.; Yoshioka, M. TBD- or PS-TBD-Catalyzed One-Pot Synthesis of Cyanohydrin Carbonates and Cyanohydrin Acetates from Carbonyl Compounds. Molecules 2016, 21, 1030. https://doi.org/10.3390/molecules21081030

AMA Style

Matsukawa S, Kimura J, Yoshioka M. TBD- or PS-TBD-Catalyzed One-Pot Synthesis of Cyanohydrin Carbonates and Cyanohydrin Acetates from Carbonyl Compounds. Molecules. 2016; 21(8):1030. https://doi.org/10.3390/molecules21081030

Chicago/Turabian Style

Matsukawa, Satoru, Junya Kimura, and Miki Yoshioka. 2016. "TBD- or PS-TBD-Catalyzed One-Pot Synthesis of Cyanohydrin Carbonates and Cyanohydrin Acetates from Carbonyl Compounds" Molecules 21, no. 8: 1030. https://doi.org/10.3390/molecules21081030

Article Metrics

Back to TopTop