Organic Chemistry International

Organic Chemistry International / 2013 / Article

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Volume 2013 |Article ID 127585 | https://doi.org/10.1155/2013/127585

Mina Mohamadi, Davood Setamdideh, Behrooz Khezri, "Regioselective and Chemoselective Reduction of ,-Unsaturated Carbonyl Compounds by /Ba as a Reducing System", Organic Chemistry International, vol. 2013, Article ID 127585, 5 pages, 2013. https://doi.org/10.1155/2013/127585

Regioselective and Chemoselective Reduction of , -Unsaturated Carbonyl Compounds by /Ba as a Reducing System

Academic Editor: Robert Salomon
Received24 Feb 2013
Revised12 Apr 2013
Accepted12 Apr 2013
Published02 May 2013

Abstract

, -unsaturated aldehydes and ketones are regioselectively reduced to the corresponding allylic alcohols with /Ba system in CH3CN. This system is also efficient for the chemoselective reduction of enals in the presence of enones at room temperature.

1. Introduction

Reduction of , -unsaturated carbonyl compounds widely has been carried out by different reducing agents. This reaction is highly solvent dependent and generally does not result in a useful regioselectivity [13]. It can follow two pathways: addition to carbonyl group (1,2-reduction) to give allylic alcohols or addition to the conjugated double bond (1,4-addition) to give saturated carbonyl compounds. To control the reducing potential and selectivity of metal hydrides specially NaBH4 (common reducing agent) for the 1,2-reduction of conjugated carbonyl compounds, numerous hydroborate agents have been developed in the following ways: (a) by the replacement of hydride(s) with bulky substituents or electron-withdrawing/releasing groups in order to discriminate between the structural and electronic environments of carbonyl groups [47]; (b) combination with Lewis acids [810] such as Luche reduction [11, 12] and mixed solvent systems [1, 2]; (c) use of transition metal hydroborates and their new modifications [13], (d) use of phosphonium tetrahydroborates [14, 15], and finally (e) immobilization on an anion exchange resin [16]. In this context and continuation of our studies for the reduction of functional groups in organic synthesis [1720], we decided to apply NaBH4/Ba(OAc)2 as new a reducing system for reduction of α,β-unsaturated carbonyl compounds. Now we wish to report an efficient method for the regioselective reduction of α,β-unsaturated aldehydes and ketones by NaBH4/Ba(OAc)2 as a new reducing system.

2. Experimental

2.1. General

All substrates and reagents were purchased from commercial sources with the best quality and used without further purification. IR and 1H NMR spectra were recorded on PerkinElmer FT-IR RXI and 300 MHz Bruker spectrometers, respectively. The products were characterized by their 1H NMR or IR spectra and comparison with authentic samples (melting or boiling points). Organic layers were dried over anhydrous sodium sulfate. All yields referred to isolated pure products. TLC was applied for the purity determination of substrates, products, and reaction monitoring over silica gel 60 aluminum sheet.

2.2. A Typical Procedure for Regioselective 1,2-Reduction of Conjugated Carbonyl Compounds with NaBH4/Ba(OAc)2 as a New Reducing System

In a round-bottomed flask (10 mL) equipped with a magnetic stirrer and a condenser, a solution of benzylideneacetone (0.146 g, 1 mmol) and Ba(OAc)2 (0.05 g, 0.2 mmol) in CH3CN (3 mL) was prepared, and NaBH4 (0.076 g, 2 mmol) was added. The resulting mixture was stirred under reflux conditions. TLC monitored the progress of the reaction (eluent; -hexan/EtOAc: 9/1). After completion of the reaction within 15 min, distilled water (5 mL) was added to the reaction mixture and it was stirred for an additional 5 min. The mixture was extracted with CH2Cl2 (3 × 8 mL) and dried over anhydrous sodium sulfate. Evaporation of the solvent afforded the pure 4-phenyl-3-buten-2-ol (0.l41 g, 95% yield, Table 2, entry 3).

3. Results and Discussions

Due to the importance of synthetic precursors of allylic alcohols, the regioselective reduction of α,β-unsaturated aldehydes and ketones seems to be a convenient and easy way to obtain these compounds. So, this achievement is synthetically very important. We first examined the reduction of cinnamaldehyde as a model compound. The reduction reaction took place with 0.5 molar amounts of NaBH4 in the presence of 0.2 molar amounts of Ba(OAc)2 in CH3CN at room temperature. The reaction was completed within 5 min with a complete regioselectivity (Table 1, entry 2). The product, cinnamyl alcohol, was obtained in high yield (Table 2, entry 1) as shown in Scheme 1.


EntrySubstrateMolar ratioaSolventTime (min)Conversionb (%)

1Cinnamaldehyde1 : 0.5 : 0.5CH3CN2100
2Cinnamaldehyde1 : 0.5 : 0.2CH3CN5100
3
Cinnamaldehyde1 : 0.25 : 0.5CH3CN60>100
4
Cinnamaldehyde1 : 0.5 : 0.2THF10100
5
Cinnamaldehyde1 : 0.5 : 0.1CH3CN10100
6
Benzylideneacetone1 : 1 : 0.5THF60>100
7
Benzylideneacetone1 : 1 : 0.5CH3CN60>100
8
Benzylideneacetone1 : 2 : 0.5CH3CN60>100
9cBenzylideneacetone1 : 2 : 0.5CH3CN15100
10cBenzylideneacetone1 : 2 : 0.2CH3CN20100

aMolar ratio as substrate: NaBH4 : Ba(OAc)2; bcompletion of the reactions was monitored by TLC (eluent; n-hexane/EtOAc: 9/1). cReaction was carried out under reflux conditions.

EntrySubstrateProductMolar ratiocTime (min)Yield (%)d

1aCinnamaldehyde3-phenyl-2-propen-1-ol1 : 0.5 : 0.2594
2aCitral3,7-dimethyl-2,6-octadien-1-ol1 : 0.5 : 0.2593
3bBenzylideneacetone4-phenyl-3-buten-2-ol1 : 2 : 0.21595
4bChalcone1,3-diphenyl-2-propen-1-ol1 : 2 : 0.21596
5bβ-ionone4-(2,6,6-trimethylcyclohex-1-enyl)-3-buten-2-ol1 : 2 : 0.21097
6b2-cyclohexenone2-cyclohexenol1 : 2 : 0.21095
7b3-methyl-2-cyclopentenone3-methyl-2-cyclopentenol1 : 2 : 0.21098

aThe reduction reaction was carried out at room temperature; bthe reduction reaction was carried out under reflux conditions. cMolar ratio as substrate: NaBH4 : Ba(OAc)2; dyields refer to isolated pure products.
127585.sch.001

This procedure was also applied for the reduction of citral to geraniol (3,7-dimethyl-2,6-octadien-1-ol) which was obtained regioselectively in 93% yield. In the next attempt, we examined the reductions of conjugated enones with the NaBH4/Ba(OAc)2 reducing system. The results showed that our procedure was also regioselective and efficient, but reduction reactions were performed by using 2 molar amounts of NaBH4 in the presence of 0.2 molar amounts of Ba(OAc)2 in CH3CN under reflux conditions (Table 1, entry 9). Regioselective 1,2-reductions of benzalacetone, benzalacetophenone, β-ionone, 2-cyclohexenone, and 3-methyl-2-cyclopentenone were achieved successfully with high to excellent yields of the corresponding allylic alcohols (Table 2, entries 3–7).

The chemoselective reduction of one functional group without affecting the other one is a well-known strategy for preparing molecules with ever-increasing complexity in organic synthesis. Since the reduction of enals and enones with NaBH4 in the presence of Ba(OAc)2 is dependent on molar ratio of NaBH4 and temperature, therefore, we thought that this system has a chemoselectivity towards reduction of enals over enones. The chemo- and regioselectivity of this procedure were demonstrated by a competitive reduction of cinnamaldehyde over benzalacetone as shown in Scheme 2.

127585.sch.002

The usefulness of this chemo- and regioselectivity of the reduction was further examined with the reduction of cinnamaldehyde in the presence of other enones (Table 3).


EntryEnoneMolar ratioaTime (min)1,2-reduction of cinnamaldehyde/enone (%)b

1Benzylideneacetone1 : 1 : 0.5 : 0.25100 : 0
2Chalcone1 : 1 : 0.5 : 0.25100 : 0
3β-ionone1 : 1 : 0.5 : 0.25100 : 0
42-cyclohexenone1 : 1 : 0.5 : 0.25100 : 0
53-methyl-2-cyclopentenone1 : 1 : 0.5 : 0.25100 : 0

aMolar ratio as substrate: cinnamaldehyde : enone : NaBH4 : Ba(OAc)2; bcompletion of the reactions was monitored by TLC (eluent; n-hexane/EtOAc: 9/1).

Since the insolubility of Ba(OAc)2 in CH3CN, the reaction takes place under heterogeneous conditions. The mechanism for the influence of Ba(OAc)2 is not clear. But, we think that with the addition of Ba(OAc)2 as Lewis acid to the reaction mixture, the carbonyl group is more susceptible to attack by the hydride ions. Therefore, the rates of reduction reactions have been accelerated.

To highlight the efficiency of our system, we compared our results with other reported reducing systems in the literature such as Ph3PMeBH4 [21, 22], NaBH3(OAc) [3], NaBH3CN [23], Li- -BuBH3 [6], (i-PrO)2TiBH4 [24], NaBH4/C [25], NaBH4/wet SiO2 [26], NaBH4/Dowex1-8x [27], and NaBH4/DOWEX(R)50WX4 [28] (Table 4). Some of the reducing systems have been used in more hydride anions versus one molar equivalent of carbonyl group. Also, it should be noted that the synthesis of some reducing agents is more costly than the NaBH4/Ba(OAc)2 system. It is clear that in most cases, the NaBH4/Ba(OAc)2 system is more efficient or comparable in the reaction times and yields of products. Therefore, the NaBH4/Ba(OAc)2 system has a greater potential for 1, 2-reduction of α,β-unsaturated carbonyl compounds.


EntryReducing systemsMolar ratio, atime (h), and yield (%)
CinnamaldehydeCitralBenzylideneacetoneChalconeβ-ionone2-cyclohexenone

1NaBH4/Ba(OAc)2(0.5)(0.08)(94)(0.5)(0.08)(93)(2)(0.25)(95)(2)(0.25)(96)(2)(0.25)(97)(2)(0.25)(95)
2Ph3PMeBH4(1)(Im)(95)(1)(3.5)(90)(1.2)(6)(90)(1)(6)(71)
3NaBH3(OAc)(1.67)(20)(70)(1.67)(20)(70)(1.67)(20)(86)(1.67)(20)(32)
4NaBH3CN(2)(90)(80)(2)(90)(77)(3)(150)(0)(2)(120)(88)
5Li-n-BuBH3(1)(2)(98)(2)(2)(99)(1)(2)(98)(1)(2)(84)
6(i-PrO)2TiBH4(1)(0.08)(90)(1)(0.08)(95)
7NaBH4/C(0.5)(Im)(92)(0.5)(0.16)(92)(2)(0.67)(96)(2)(0.4)(98)(2)(0.5)(91)
8NaBH4/wet SiO2(1)(0.016)(96)(1)(0.066)(95)(2)(0.15)(97)(2)(0.25)(98)(2)(0.25)(97)
9NaBH4/Dowex1-8x(1)(0.7)(96)(1)(1.3)(94)(1)(1.4)(98)(1)(0.7)(95)(1)(2.2)(91)(1)(0.8)(89)
10NaBH4/DOWEX(R)50WX4(1)(0.25)(97)(1)(0.33)(94)(2)(0.91)(95)(2)(1.5)(95)

aReducing agent/substrate. Im: immediately.

4. Conclusion

In this investigation, we have shown that the combination system of NaBH4/Ba(OAc)2 in CH3CN reduces a variety of α, β-unsaturated carbonyl compounds to their corresponding allylic alcohols in high to excellent yields. Reduction reactions were carried out with 0.5–2 molar equivalents of NaBH4 in the presence of 0.2 molar amounts of Ba(OAc)2. The chemoselective reduction of enals over enones was accomplished successfully with this reducing system. High efficiency of the reductions, shorter reaction times, and easy work-up procedure make it as an attractive new protocol for reduction of α,β-unsaturated carbonyl compounds, and it could be a useful addition to the present methodologies.

Acknowledgment

The authors gratefully appreciated the financial support of this work by the research council of Islamic Azad University, branch of Mahabad.

References

  1. R. S. Varma and G. W. Kabalka, “Selective reduction of a, β-unsaturated nitrocompounds with sodium borohydride in methanolic solutions: a facile route to nitroalkenes,” Synthetic Communications, vol. 15, no. 2, pp. 151–155, 1985. View at: Publisher Site | Google Scholar
  2. D. C. Sarkar, A. R. Das, and B. C. Ranu, “Use of zinc borohydride as an efficient and highly selective reducing agent. Selective reduction of ketones and conjugated aldehydes over conjugated enones,” Journal of Organic Chemistry, vol. 55, no. 22, pp. 5799–5801, 1990. View at: Google Scholar
  3. C. F. Nutaitis and J. E. Bernardo, “Regioselective 1,2-reduction of conjugated enones and enals with sodium monoacetoxyborohydride: preparation of allylic alcohols,” Journal of Organic Chemistry, vol. 54, no. 23, pp. 5629–5630, 1989. View at: Google Scholar
  4. S. Krishnamurthy and H. C. Brown, “9-borabicyclo[3.3.1]nonane as a highly selective reducing agent for the facile conversion of α,β-unsaturated aldehydes and ketones to the corresponding allylic alcohols in the presence of other functional groups,” Journal of Organic Chemistry, vol. 40, no. 12, pp. 1864–1865, 1975. View at: Google Scholar
  5. S. Krishnamurthy and H. C. Brown, “Selective reductions. 22. Facile reduction of α,β-unsaturated aldehydes and ketones with 9-borabicyclo[3.3.1]nonane. A remarkably convenient procedure for the selective conversion of conjugated aldehydes and ketones to the corresponding allylic alcohols in the presence of other functional groups,” Journal of Organic Chemistry, vol. 42, no. 7, pp. 1197–1201, 1977. View at: Google Scholar
  6. S. Kim, Y. C. Moon, and K. H. Ahn, “Lithium n-butylborohydride as a selective reducing agent for the reduction of enones, cyclic ketones, and selected carbonyl compounds,” Journal of Organic Chemistry, vol. 47, no. 17, pp. 3311–3315, 1982. View at: Google Scholar
  7. E. J. Corey, K. B. Becker, and R. K. Varma, “Efficient generation of the 15S configuration in prostaglandin synthesis. Attractive interactions in stereochemical control of carbonyl reduction,” Journal of the American Chemical Society, vol. 94, no. 24, pp. 8616–8618, 1972. View at: Google Scholar
  8. J. C. Fuller, E. L. Stangeland, C. T. Goralski, and B. Singaram, “Aminoborohydrides. 2. Regiospecific reductions of α,β-unsaturated carbonyl compounds with lithium pyrrolidinoborohydride. A facile conversion of α,β-unsaturated aldehydes and ketones to the corresponding allylic alcohols in high purity,” Tetrahedron Letters, vol. 34, no. 2, pp. 257–260, 1993. View at: Publisher Site | Google Scholar
  9. B. Ganem, “Conjugate reduction and reductive alkylation of α,β-unsaturated cyclohexenones using potassium tri-sec-butylborohydride,” Journal of Organic Chemistry, vol. 40, no. 1, pp. 146–147, 1975. View at: Google Scholar
  10. J. M. Fortunato and B. Ganem, “Lithium and potassium trialkylborohydrides. Reagents for direct reduction of α,β-unsaturated carbonyl compounds to synthetically versatile enolate anions,” Journal of Organic Chemistry, vol. 41, no. 12, pp. 2194–2200, 1976. View at: Google Scholar
  11. J. L. Luche, “Lanthanides in organic chemistry. 1. Selective 1,2 reductions of conjugated ketones,” Journal of the American Chemical Society, vol. 100, no. 7, pp. 2226–2227, 1978. View at: Google Scholar
  12. A. L. Gemal and J. L. Luche, “Lanthanoids in organic synthesis. 6. The reduction of α-enones by sodium borohydride in the presence of lanthanoid chlorides: synthetic and mechanistic aspects,” Journal of the American Chemical Society, vol. 103, no. 18, pp. 5454–5459, 1981. View at: Google Scholar
  13. H. Fujii, K. Oshima, and K. Utimoto, “A facile and selective 1,2-reduction of conjugated ketones with NaBH4 in the presence of CaCl2,” Chemistry Letters, vol. 20, no. 10, pp. 1847–1848, 1991. View at: Publisher Site | Google Scholar
  14. H. Firouzabadi, M. Adibi, and M. Ghadami, “Modified borohydride agents, bis(triphenylphosphine) (tetra-hydroborato)zinc complex [Zn(BH4)2(PPh3)2] and (triphenylphosphine) (tetrahydroborato)zinc complex [Zn(BH4)2(PPh3)]. New ligand metal borohydrides as stable, efficient, and versatile reducing agents,” Phosphorus, Sulfur and Silicon and Related Elements, vol. 142, pp. 191–220, 1998. View at: Google Scholar
  15. H. Firouzabadi, M. Adibi, and B. Zeynizadeh, “Modified borohydride agents; efficient reduction of azides with (1,4-diazabicyclo[2.2.2]octane) (tetrahydroborato)zinc complex [Zn(BH4)2(dabco)] and methyltriphenylphosphonium tetrahydroborate [MePh3P+BH4  −],” Synthetic Communications, vol. 28, no. 7, pp. 1257–1273, 1998. View at: Google Scholar
  16. A. R. Sande, M. H. Jagadale, R. B. Mane, and M. M. Salunkhe, “Borohydride reducing agent derived from anion exchange resin: selective reduction of α, β-unsaturated carbonyl compounds,” Tetrahedron Letters, vol. 25, no. 32, pp. 3501–3504, 1984. View at: Google Scholar
  17. D. Setamdideh, B. Khezri, M. Rahmatollahzadeh, and A. Aliporamjad, “Mild and efficient reduction of organic carbonyl compounds to their corresponding alcohols with Zn(BH4)2 under protic condition,” Asian Journal of Chemistry, vol. 24, no. 8, pp. 3591–3596, 2012. View at: Google Scholar
  18. D. Setamdideh and M. Rafig, “Reduction of carbonyl compounds to their corresponding alcohols by (nicotine)(tetrahydroborato)zinc complex as a new stable and efficient reducing agent,” E-Journal of Chemistry, vol. 9, no. 4, pp. 2338–2345, 2012. View at: Publisher Site | Google Scholar
  19. D. Setamdideh and M. Rahmatollahzadeh, “Efficient and convenient reduction of organic carbonyl compounds to their corresponding alcohols by Zn(BH4)2/charcoal in THF,” Journal of the Mexican Chemical Society, vol. 56, no. 3, 2012. View at: Google Scholar
  20. D. Setamdideh, B. Khezri, and M. Rahmatollahzadeh, “Zn(BH4)2/Al2O3: a new synthetic method for the efficient and convenient reduction of organic carbonyl compounds to their corresponding alcohols,” Journal of the Serbian Chemical Society, vol. 79, pp. 1–13, 2013. View at: Google Scholar
  21. H. Firouazabadi and M. Adibi, “Modified borohydride agents 1a-d, methyltriphenylphosphonium tetrahydroborate; MePh3P+BH4  − as a selective and an efficient reducing agent,” Synthetic Communications, vol. 26, no. 13, pp. 2429–2441, 1996. View at: Google Scholar
  22. H. Firouzabadi and M. Adibi, “Methyltriphenylphosphonium tetrahydroborate (MePh3PBH4). A stable, selective and versatile reducing agent,” Phosphorus, Sulfur and Silicon and Related Elements, vol. 142, pp. 125–147, 1998. View at: Google Scholar
  23. R. O. Hutchins and D. Kandasamy, “Reductions of conjugated carbonyl compounds with cyanoborohydride in acidic media,” Journal of Organic Chemistry, vol. 40, no. 17, pp. 2530–2533, 1975. View at: Google Scholar
  24. K. S. Ravikumar, S. Baskaran, and S. Chandrasekaran, “Diisopropoxytitanium(III) tetrahydroborate: a highly useful reagent for the remarkably selective 1,2-reduction of α,β-unsaturated carbonyl compounds,” Journal of Organic Chemistry, vol. 58, no. 22, pp. 5981–5982, 1993. View at: Google Scholar
  25. D. Setamdideh and B. Zeynizadeh, “Mild and convenient method for reduction of carbonyl compounds with the NaBH4/charcoal system in wet THF,” Zeitschrift für Naturforschung B, vol. 61, no. 10, pp. 1275–1281, 2006. View at: Google Scholar
  26. B. Zeynizadeh and T. Behyar, “Fast and efficient method for reduction of carbonyl compounds with NaBH4/wet SiO2 under solvent free condition,” Journal of the Brazilian Chemical Society, vol. 16, no. 6A, pp. 1200–1209, 2005. View at: Google Scholar
  27. B. Zeynizadeh and F. Shirini, “Mild and efficient reduction of α,β-unsaturated carbonyl compounds, α-diketones and acyloins with sodium borohydride/Dowex1-x8 system,” Bulletin of the Korean Chemical Society, vol. 24, no. 3, pp. 295–298, 2003. View at: Google Scholar
  28. D. Setamdideh, B. Khezri, and A. Alipouramjad, “NaBH4/DOWEX(R)50WX4: a convenient reducing system for fast and efficient reduction ofcarbonyl compounds to their corresponding alcohols,” Journal of the Chinese Chemical Society, 2013. View at: Publisher Site | Google Scholar

Copyright © 2013 Mina Mohamadi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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