C2gc00006g 1372.1375 ++

Cite this: Green Chem., 2012, 14, 1372 Selective reduction of aldehydes and ketones to alcohols with ammoniaborane in neat water† Lei Shi, Yingying Liu, Qingfeng Liu, Bin Wei and Guisheng Zhang* Received 4th January 2012, Accepted 20th February 2012DOI: 10.1039/c2gc00006g Chemoselective reduction of various carbonyl compounds to alcohols with ammonia borane (AB), anontoxic, environmentally benign, and easily handled reagent, in neat water was achieved in quantitativeconversions and high isolated yields. Interestingly, α- and β-keto esters were selectively reduced tocorresponding hydroxyl esters by AB, while diols were obtained when sodium borohydride was used as areducing agent. The procedure is also compatible with the presence of a variety of base-labile protectinggroups, such as tosyl, acetyl, benzoyl, ester groups, and acid-labile protecting groups such as trityl andTBDMS groups, and others, such as the unsaturated double bond, nitro and cyano groups. Finally, a kiloscale reaction of methyl benzoylformate with AB was conducted in water and gave methyl mandelate in94% yield.
thermal and hydrolytic stability. AB is not only a nontoxic,environmentally benign, and stable material that can be safely The reduction of carbonyl compounds to alcohols is one of the transported without hydrogen loss, but also equally important for most widely used and fundamental reactions in organic chem- various applications in synthetic organic chemistry.17 Recently istry.1 Catalytic hydrogenation,2 transition metal catalyzed S. G. Shore et al. and P. V. Ramachandran et al. have reported hydrogenation,3 biocatalytic reductions with bakers' yeast large-scale methods for the preparation of AB,18 which make it reductase4 and chemical reductions by LiAlH4, nickel–aluminum very readily available. Reactions in aqueous media have attracted alloy,5 tri-n-butyltin hydride,6 sodium formate,7 alkyl phos- much attention in synthetic organic chemistry, because water is phines,8 poly(methylhydrosiloxane),9 or borane reagents such as one of the most abundant, cheap, and environmentally friendly zinc borohydride, 10 NaBH4,11 NaBH3CN,12 BH3-THF,13 and solvents.19 Since AB is water-soluble, nontoxic and environmen- amine boranes14 have been utilized to accomplish the reduction tally benign, it is a good combination to conduct green organic Published on 16 March 2012. Downloaded by ZHENG ZHOU UNIVERSITY on 16/01/2015 02:49:50. of the carbonyl group. However, the reductive activity and selec- reactions in water using AB as a reductant. Although the use of tivity of catalytic hydrogenation greatly depend on the catalysts AB for the reduction of carbonyls was reported three decades and conditions used. Biocatalytic reductions usually require a ago,14b,c to the best of our knowledge, its application in neat specific temperature, pH value and reductase. The use of water for reduction of various carbonyl compounds has not been NaBH3CN may result in the contamination of products with reported. Thus, we report herein a detailed investigation on the toxic materials.15 The traditional methods for the reduction of a reduction of carbonyl compounds using AB as a green reductant carbonyl group often involve long reaction times,7 harsh con- in neat water (Scheme 1).
ditions (under nitrogen; in acid or alkaline condition5), toxic sol-vents (such as toluene,6 benzene,14a ether,14b THF) andcomplicated operation. NaBH4 is the most common reductant in Results and discussion the chemical conversion due to its relatively cheap cost, ease ofhandling, and possibility of being used in aqueous alcohol The reduction of various carbonyl compounds with AB to alco- hols in neat water was shown in Scheme 1. In a typical reaction Ammonia borane (AB), the simplest amine borane, has protocol, AB (0.5 mmol) was added to the solution of carbonyl recently received a lot of attention as one of the promising compound (0.5 mmol) in neat water (2 mL), and the reaction materials for alternate energy.16 AB is a solid with remarkable mixture was stirred at room temperature until the completion of Key Laboratory of Green Chemical Media and Reactions, Ministry ofEducation, College of Chemistry and Environmental Science, HenanNormal University, Xinxiang 453007, China. E-mail: [email protected];Tel: +86 373 3325250†Electronic supplementary information (ESI) available. See DOI:10.1039/c2gc00006g Reduction of carbonyl compounds with AB in neat water.
1372 Green Chem., 2012, 14, 1372–1375 This journal is The Royal Society of Chemistry 2012 Reduction of aldehydes and ketones to alcohols with AB in a All reactions were carried out with AB (0.5 mmol), aldehyde or ketone(0.5 mmol) in H2O (2 mL) at room temperature, unless otherwise indicated. b Isolated yields. c Reactions were conducted at 50 °C.
d Reactions were conducted at 80 °C.
the reaction. Aldehydes and ketones were reduced rapidly inquantitative conversions and excellent isolated yields (82–97%) (Tables 1 and 2). The procedure is perfectly compatible with thepresence of a variety of base-labile protecting groups, such astosyl, acetyl, benzoyl, ester groups, and acid-labile protecting groups such as trityl and TBDMS groups. Unsaturated doublebond, nitro and cyano groups also remain intact in the process.
As shown in Table 1, aliphatic aldehyde (entry 1), Published on 16 March 2012. Downloaded by ZHENG ZHOU UNIVERSITY on 16/01/2015 02:49:50. rated aldehyde (entry 2), heterocyclic aldehydes (entries 3–5),benzaldehyde (entry 6), and aromatic aldehydes with electron donating groups (EDG) or electron withdrawing groups (EWG) (entries 7–17) were reduced to alcohols 2a–q in excellent yieldsat rt in 1 h. Diverse substituents on the aryl, whether EDG or EWG, did not show significant effect on the yield. It is note-worthy that the heterocyclic aldehyde 1e, a nucleoside analogue, was reduced with AB in 10 min in 91% yield (entry 5) and nodeacetylated product was obtained, while the use of NaBH4 gave10% deacetylated product. Reductions of ketones also underwent smoothly and gave corresponding secondary alcohols in excel-lent yields, but required longer time. The slow reaction rate andlower reactivity of ketones are due to their steric hindrance and poor water-solubility (entries 18–31). The solubility is importantto the reaction rate. The reductions of substrates 1t–w, which are poorly soluble in water, needed over 10 h at rt, while highertemperatures improved the solubility and thus, accelerated the reaction (entries 20–29).
α-Hydroxyl or β-hydroxyl esters are important synthetic inter- mediates which are commonly prepared by reducing correspond-ing keto esters.20 Reduction of ketoesters to diols was observedwith most chemical reductants, such as LiAlH4 and NaBH4. Forexample, aromatic and aliphatic keto esters were reduced to diols This journal is The Royal Society of Chemistry 2012 Green Chem., 2012, 14, 1372–1375 1373 Reduction of keto-esters with AB or NaBH4 in neat watera Time/product/yield (%)b 10 min/2A,3A/22,39c a All reactions were carried out with AB (0.5 mmol), aldehyde or ketone (0.5 mmol) in H2O (2 mL) at room temperature, unless otherwise indicated.
b Isolated yields. c Recovered 20% methyl mandelate.
in methanol by NaBH4,11b and the diol was also obtained when substrates including aliphatic, aromatic, α,β-unsaturated, and using ethanol and water as solvent, whereas hydroxyl ester was heterocyclic aldehydes, and keto esters to give excellent yields in the major product when using THF as solvent.11b To further neat water. It is noteworthy that AB showed better selectivity evaluate the generality and selectivity of our procedure using AB than NaBH4 in the reduction of α- and β-keto esters to hydroxyl as a green reductant, the reactions of aromatic keto esters (1A– esters in water. The procedure is also compatible with the pres- E) and aliphatic keto ester 1F with AB were conducted in water ence of a variety of base-labile protecting groups, such as tosyl, (Table 2). As shown in Table 2, these keto esters were selectively acetyl, benzoyl, ester groups, and acid-labile protecting groups Published on 16 March 2012. Downloaded by ZHENG ZHOU UNIVERSITY on 16/01/2015 02:49:50. reduced to corresponding hydroxyl esters 2A–F in isolated such as trityl and TBDMS groups, and the unsaturated double yields of 86–92% and no diols were observed. In our parallel bond, nitro and cyano groups are intact in the process. AB is a experiments with NaBH4, we observed that diols are exclusive convenient reagent with remarkable thermal and hydrolytic stab- products (Table 2) or major product (Table 2, entry 33) if the ility, and easily handled, especially in large-scale manufacturing reaction was quenched in short time.
in neat water solvent. The advantages of the present method, To demonstrate the easy use of the reductant, a kilo scale including green and convenient reaction processes, excellent reduction of methyl benzoylformate with AB was conducted in yields, mild conditions and simple operation, readily available water. After vigorously stirring the mixture containing methyl and stable reagent, applicability to a wide range of substrates and benzoylformate 1A (1.0 kg, 6.1 mol), AB (189.1 g, 6.1 mol) in large-scale manufacturing, and the nontoxic and environmentally water (3 L) for 2 h, the completion of the reaction was monitored friendly nature of the reductant, make this new method a valu- by TLC. Thereafter, the reaction mixture was thoroughly able addition to existing options.
extracted with EtOAc, and the combined organic layers werethen washed with saturated brine, dried over anhydrous mag-nesium sulfate, and concentrated. The residue was distilled under reduced pressure to give mandelate 2A (951 g, 94% yield) as awhite solid.
General procedure for the reduction of carbonyl compounds toalcohols A mixture of carbonyl compound 1 (0.5 mmol), AB (0.5 mmol)in neat water (2 mL) was stirred at rt for an appropriate time. The In conclusion, the present work describes a selective and con- reaction was monitored by TLC. Upon completion, the reaction venient green procedure for the reduction of a variety of alde- mixture was extracted with ethyl acetate (3 × 5 mL). The com- hydes and ketones to corresponding alcohols using AB as bined organic extracts were dried over anhydrous magnesium reductant. This method is applicable to a broad range of carbonyl sulfate and concentrated by rotary evaporation, the residue was 1374 Green Chem., 2012, 14, 1372–1375 This journal is The Royal Society of Chemistry 2012 purified by silica gel column chromatography to obtain the 1153; (c) I. A. Kaluzna, T. Matsuda, A. K. Sewell and J. D. Stewart, J.
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