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Tetrahedron 70 (2014) 2088e2095

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Tetrahedron

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Commutative reduction of aromatic ketones to arylmethylenes/alcohols by hypophosphites catalyzed by Pd/C under biphasicconditions

Carole Guyon a, Marc Baron a, Marc Lemaire a, Florence Popowycz b,*, Estelle M�etay a,*

a Equipe Catalyse Synth�ese Environnement, Institut de Chimie et Biochimie Mol�eculaires et Supramol�eculaires, UMR-CNRS 5246, Universit�e de Lyon,Universit�e Claude Bernard-Lyon 1, Batiment Curien, 43 boulevard du 11 Novembre 1918, F-69622 Villeurbanne Cedex, Franceb Equipe Chimie Organique et Bioorganique, Institut de Chimie et Biochimie Mol�eculaires et Supramol�eculaires, UMR-CNRS 5246,Institut National des Sciences Appliqu�ees (INSA Lyon), Batiment Jules Verne, 20 Avenue Albert Einstein, F-69621 Villeurbanne Cedex, France

a r t i c l e i n f o

Article history:Received 2 December 2013Received in revised form 4 February 2014Accepted 5 February 2014Available online 14 February 2014

Keywords:DeoxygenationReductionPalladiumHypophosphiteKetones

* Corresponding authors. Tel.: þ33 (0)4 7244850(E.M.); tel.: þ33 (0)4 72 43 82 21; fax: þ33 (0)4 72 43Florence.Popowycz@insa-lyon.fr (F. Popowycz), estelly_estelle@voila.fr (E. M�etay).

0040-4020/$ e see front matter � 2014 Elsevier Ltd.http://dx.doi.org/10.1016/j.tet.2014.02.014

a b s t r a c t

An efficient method is reported to reduce aromatic ketones selectively into arylmethylenes or alcoholswith hypophosphites and Pd/C, depending on the selected conditions. This study could representa promising alternative to the classical uses of standard hydrides or molecular hydrogen involved inreduction and deoxygenation procedures.

� 2014 Elsevier Ltd. All rights reserved.

1. Introduction

While the reduction of ketones into alcohols has been largelyimplemented by an impressive number of methods and reagents,the over-reduction of C]O into CH2 was studied to a lesser extent.And yet, the ketone deoxygenation into methylene is a pivotal stepin the synthesis of some molecules of industrial interest. The two-step acylation/reduction procedure has been previously used toaccess amongst others, ibuprofen (synthesis of starting materialisobutylbenzene), piperonyl butoxide (insecticide), hexyl resorcinol(displaying anaesthesic, antiseptic, and anthelmintic properties).Classical key reactions of ketone deoxygenation are well known asClemmensen,1 WolffeKishner,2 and Mozingo reductions.3 Otheralternative methods propose the reduction of ketone into alkanewith molecular hydrogen4 (Pd/C,4a,b Pt,4c Co,4d Cu,4e and Ru4f),hydrides,5 hydroxysilanes,6 and isopropanol or formates as hy-drogen donors7 (Ni7a and Pd7b). However, the major drawbackslinked to some of the described conditions are the difficulty to

7; fax: þ33 (0)4 7243140888 96 (F.P.); e-mail addresses:e.metay@univ-lyon1.fr, meta-

All rights reserved.

handle reactants and the utilization of toxic or expensive reagents.For example, though the high toxicity, potential flammability, andinstability of hydrazine, Merck & co recently reported a practical,kilogram-scale implementation of the WolffeKishner reduction fora synthetic intermediate of high added value.8

In the search of new methodological tools to reduce organicfunctions, the reactivity of hypophosphite derivatives was studied.Hypophosphites have been already identified as efficient reactantsto promote reductions in the presence of transition metals (Pd, Ni,Ru.) or under radical activation.9 In association with iodine, thereduction of diarylketones and benzyl alcohols into arylmethyleneswas reported.10 The efficiency of the reaction was limited to dia-rylketones and few examples of activated acetophenones. Ketoneswere reduced selectively to alcohols11 with hypophosphites in thepresence of Ir11a or Ru11bed complexes, and also with good enan-tioselectivity in our group.11d When palladium on carbon was usedin combination with sodium hypophosphite, the over-reduction ofketones to alkanes was mainly observed as co-product of thealcohol.11k,l Synthetic use to prepare alkanes is only reported onspecific examples of activated ketones.11eej In the presence ofa base, only the alcohol was observedwith a slow kinetics.11m Theseobservations were not valorized to develop a method of generalapplicability to selectively prepare alkanes. During our previousinvestigation on the reduction of the nitro group by

C. Guyon et al. / Tetrahedron 70 (2014) 2088e2095 2089

hypophosphite,12 we noticed the peculiar reactivity of 40-nitro-acetophenone leading to 4-ethylaniline as a co-product when2.5 mol % of Pd/C was added in biphasic 2-MeTHF/water solventmixture (Scheme 1).

Table 2Sonication versus thermal activation

Entry Activation T [�C] Conv. [%] 1a/1ba

1 Sonication 20 99 0:1002 Thermal 60 94 4:963 Thermal 100 99 0:100

a Conversions and 1a/1b ratios were determined by 1H NMR analysis.

Scheme 1. Preliminary results.

In the literature, this metal was previously employed for thedeoxygenation of alcohols.13 All these results prompted us toevaluate the potential combination of the hypophosphite de-rivatives and Pd/C in the deoxygenation reaction of ketones toarylmethylenes.

This communication aims to report here an efficient method toreduce aromatic ketones selectively into arylmethylenes withhypophosphites catalyzed by heterogeneous Pd/C. The break-through reported in this paper aims to develop a commutativestrategy based on hypophosphites to reduce the ketone alterna-tively either into alcohol or into arylmethylene by performing mi-nor changes of the experimental protocol. Thus, selecting onemethod amongst the two specific conditions should providea powerful and helpful toolbox for selective functionalization.

2. Results and discussion

From the preliminary observations (Scheme 1), we decided toevaluate the possibility to orientate completely the selectivitytoward the formation of the deoxygenated product. To investigatethe pivotal role of the reaction parameters, the scope and thelimitations of the deoxygenation reaction, the choice of the sub-strate was essential. To implement the study, methyl 4-acetylbenzoate was selected on electronic criteria: the electron-withdrawing effect of ester group promoting easily the reductioninto alcohol but rendering tough the deoxygenation. The conditionsdescribed in Scheme 1 were thus applied in a first attempt tomethyl 4-acetylbenzoate (Table 1, entry 1), leading to a partialconversion of 34% with an excellent selectivity directed toward thealcohol 1a. An increase of the loading of the palladium catalyst,respectively, to 5 and 10 mol % has an influence on the selectivity,

Table 1Optimization of the deoxygenation

Entry Pd/C [mol %] Solvent Conv. [%] 1a/1ba

1 2.5 2-MeTHF 34 93:72 5 2-MeTHF 99 73:273b 5 2-MeTHF 18 100:04 10 2-MeTHF 99 27:735c 10 2-MeTHF 99 50:506 10 EtOAc 99 42:587 10 THF 99 77:238 10 DMCd 99 43:579 10 DECd 99 8:9210 10 CPMEd 99 0:100

a Conversions and 1a/1b ratios were determined by 1H NMR analysis.b H2O was replaced by glycerol as a co-solvent.c In this case, NaH2PO2$H2O (2 equiv), H3PO2 (2 equiv) were used.d DMC¼dimethylcarbonate; DEC¼diethylcarbonate; CPME¼cyclopentyl methyl

ether.

which is inverted in favor of the arylmethylene (Table 1, entry 2).Replacing water by glycerol as a co-solvent of 2-MeTHF led toa significant decrease of the conversion and the selectivity (Table 1,entry 3). It is noticeable that with 10mol % of Pd/C (Table 1, entry 4),the selectivity was inverted toward the arylmethylene 1b detectedas the major product (ratio alcohol/arylmethylene: 27:73). The pHinfluences the reaction balance as a slight change in the ratio ofsodium hypophosphite and its conjugate acid modified the selec-tivity, without affecting the conversion: the use of NaH2PO2(2 equiv) and H3PO2 (2 equiv) led to a more acidic pH activatingboth ketone and intermediate alcohol affording an equal mixture ofthe alcohol 1a and the arylmethylene 1b (Table 2, entry 5).

The influence of the solvent on the transformation was evalu-ated. Ethyl acetate and THF, respectively, provided no selectivity(Table 1, entry 6) or an inverted selectivity in favor of the alcohol 1a(Table 1, entry 7). The selectivity in favor of the arylmethylenes 1bwas intensified with the hydrophobic character of the solvent.Dimethylcarbonate exhibited a low selectivity between 1a and 1b(Table 1, entry 8). DEC and CPME allow, respectively, 92% and 100%selectivity in 1b (Table 1, entries 9 and 10). Additional screeningconditions were evaluated under optimized conditions includingthe nature of the metals14 or other sources of hypophosphites.15

The conversion under the best conditions (Table 1, entry 10) wascomplete after only 1 h with a ratio of alcohol/arylmethylenes of74:26.

This ratio evolves over time to afford only arylmethylene after5 h. With other solvents the selectivity did not increase witha longer reaction time as well as with a large excess ofhypophosphites.

In order to evaluate the effect of the sonication on the reactionconditions, the reduction of compound 1 in a CPME/H2O biphasicmixture in the presence of 10 mol % of Pd/C, was realized underthermal activation at 60 �C (Table 2). At this temperature, after thesame reaction time of 5 h, the conversion of the starting materialwas 94% with a good selectivity for the arylmethylene (96%) (Table2, entry 2). Running the reaction at 100 �C prompted total con-version with a high selectivity toward arylmethylene 1b (Table 2,entry 3).

In view of the results obtained in Table 2, both conditionsretained for the deoxygenation reaction were: Pd/C (10 mol %),NaH2PO2$H2O/H3PO2 (3:1 equiv), CPME, 5 h at 100 �C or undersonication.

Once, the deoxygenation parameters identified, the relativecommutation of the hypophosphite potential reduction appearedto be an important issue to be addressed. As alcohol was mostlyidentified during the reduction of ketone into arylmethylene, wewere interested in orientating the reduction selectively in favor ofthe alcohol.

In that case, p-methoxyacetophenonewas selected on electronicparameters: the electron-donating effect of p-methoxy group dis-criminating the reduction into alcohol but facilitating the de-oxygenation. Experimental conditions of Table 1 (5 mol % Pd,3 equiv NaH2PO2, 1 equiv H3PO2, 2-MeTHF/H2O, sonication, 5 h)

C. Guyon et al. / Tetrahedron 70 (2014) 2088e20952090

giving a good selectivity in favor of the alcohol (Table 1, Entry 2)were thus applied to p-methoxyacetophenone 2 (Table 3, entry 1):total conversion was observed in favor of the deoxygenationproduct 2b. Changing the method of activation by the classicalthermal conditions provided the same results (Table 3, entry 2). Theconcomitant use of only sodium hypophosphite (influence on thepH reaction medium) and a phase transfer agent (due to the bi-phasic medium 2-MeTHF/water) such as tetrabutylammoniumchloride permitted in less than 3 h an excellent conversion of 96%with an excellent selectivity in 2a (Table 3, entry 3). In these con-ditions, the alcohol was less activated by the acidic source, slowingdown the deoxygenation. To control the alkaline pH of the reactionmedium, the combination of tetrabutyl ammonium chloride TBACand NaOH (Table 3, entry 4) led to a similar selectivity but a slightdecrease of the conversion, which is probably due to the compe-tition between phase transfer catalysis between NaOH andNaH2PO2, regarding TBAC. The conversion/selectivity in 2b waspreserved when the load of the catalyst in Pd/C was only 2.5 mol %(Table 3, entry 5). Decreasing the load of catalyst up to 1 mol %impacted the conversion (Table 3, entry 6): alcohol 2awas obtainedwith 72% conversion and complete selectivity. Under prolongedreaction times (21 h), the deoxygenation process appeared, limitingthus the selectivity (Table 3, entry 6). The conditions retained forthe selective reduction into alcohol were: Pd/C (2.5 mol %), NaH2-PO2$H2O (4 equiv), TBAC (7 mol %) under thermal activation asa compromise between the kinetics of reduction/deoxygenationand selectivity. The optimized conditions described above werealso evaluated under ultrasonic activation, leading to a lower con-version (only 61%) with a total selectivity in favor of the alcohol.

Table 3Optimization of the reduction to alcohol

Entry Pd/C [mol %] x Additive Time [h] Conv [%] 2a/2bb

1a 5 1 None 5 100 0:1002 5 1 None 14 93 0:1003 5 0 TBACc 2.75 96 96:44 5 0 TBACc 5 63 100:0

NaOHd

5 2.5 0 TBACc 3 98 98:26 1 0 TBACc 5 72 100:07 1 0 TBACc 21 83 87:13

a Sonication activation.b Conversions and 2a/2b ratio were determined by 1H NMR analysis.c Tetrabutylammonium chloride (7 mol %).d NaOH (4 equiv).

Taking advantage of the dual conditions to orientate either thereduction (method A) or the deoxygenation reactions (method Band method C), the scope was extended to a large diversity of ke-tones to explore the potential switch of hypophosphite sodium salt.Miscellaneous ketones were considered: p-substituted acetophe-nones, a-substituted acetophenones, aryl and heteroaryl ketones.

Previous substrates 1 and 2 were both submitted to method A(reduction), methods B and C (deoxygenation) providing excellentselectivities and isolated yields (Table 4, entries 1 and 2). Electron-rich substituents on aryl ring gave excellent yields in the corre-sponding arylmethylenes while selective stop to the alcohol wasdifficult. Following method A, both the methoxy and methyl sub-stituents successfully provided the alcohols 2a and 3a with a com-plete selectivity while methods B and C validated the commutativeaspect of the strategy with complete deoxygenation (Table 4, en-tries 2 and 3). In the case of 40-aminoacetophenone 4 and 40-hydroxyacetophenone 5, method A required the addition of2e4 equiv of NaOH to adjust the pH of the reaction medium and to

facilitate the reduction (without NaOH, only the correspondingarylmethylenes 4b and 5bwere obtained) (Table 4, entries 4 and 5).Compound 4b was also prepared via the reduction of 4-nitroacetophenone in 89% isolated yield with the method C. Inthe case of dimethylamino substituent (Table 4, entry 6), the se-lectivity in favor of the alcohol 6awas relatively moderate, whereasthe arylmethylene 6b was obtained with a complete selectivity bymethod B with a moderate conversion 67%. Reaction performedwith method B in a sealed tube at 100 �C allowed a completeconversion (72% of isolated yield).

Electron-withdrawing substituents provided excellent sub-strates to point out the commutative effect between reduction anddeoxygenation methods. Deoxygenation of 40-cyanoacetophenone7 gave a complexmixturewith partial reduction of both ketone andnitrile functions. In order to render the reaction selective, themethod B was applied in the presence of a large excess of re-ductants (NaH2PO2 (6 equiv)/H3PO2 (2 equiv)). p-Ethylbenzylamine7c, resulting from the over-reduction, was obtained in 67% yield(Table 4, entry 7). 4-Acetyl benzoic acid 8 and 40-(trifluoromethyl)acetophenone 9 were successfully submitted to the reduction anddeoxygenation conditions. It is also noticeable that 4-ethylbenzoicacid was obtained with a high yield while this compound was notdescribed from the classical deoxygenation methods (Table 4, en-tries 8 and 9). Withmore hydrophobic aromatic moiety, incompleteconversions were observed and 10-acetonaphthone 10 was lessreactive than 20-acetonapthone 11. This difference of reactivity is inagreement with the literature. Indeed, the reaction time for thereduction of 10-acetonaphthone was generally longer than for the20-acetonaphthone to reach similar conversions and yields.16 Thereduction into alcohol was selective, as well as the deoxygenation(Table 4, entries 10 and 11, methods A and B, respectively). In orderto increase the conversion of the 10-acetonaphthone, an additionalexperiment was run for 48 h with the method A. The conversionreached 73% but the selectivity dropped with the apparition of thedeoxygenation product (selectivity 87:13). Finally, the alcohol wasobtained in 59% yield. Sonochemical activation (method C) for eachsubstrate, provided a mixture of alcohol and arylmethylene. Thesame observations were pointed out with fluorene derivatives 12and 13 (Table 4, entries 12 and 13). The reaction with a-substitutedacetophenones such as benzophenone 14 or methyl oxo(phenyl)acetate 15 provided excellent conversion under both methods(Table 4, entries 14 and 15). In the case of a-CO2Me substrate,a partial hydrolysis occurred justifying a moderate isolated yield of55% in arylmethylene 15b (Table 4, entry 15). An exception wasnoticed for 2,2,2-trifluoroacetophenone 16, which gave only thealcohol, the strong electron-withdrawing effect of the vicinal tri-fluoromethyl group hinders the loss of water (Table 4, entry 16).This result is in agreement with literature data since the access tothe deoxygenated product is described only in several steps.17

Heterocyclic systems such as 1-(1-benzothien-3-yl)ethanone 17and 3-acetylindole 18 were subjected to the reduction and de-oxygenation conditions (Table 4, entries 17 and 18).

The reduction conditions A allowed only poor conversion withno trace of the alcohol (only deoxygenation product). For the benzo[b]thiophene derivative, only method B furnished the aryl-methylenes 17b in modest yield of 41%, whereas for the indolederivative, the impact of methods B and C was similar in terms ofconversion, yield, and selectivity (60% of 18b for both methods).Even though not shown in Table 4, it was noticed that under theseconditions, p-chloroacetophenone was dehalogenated. As pre-viously observed when palladium on charcoal was associated withhypophosphites a dehalogenation can occur especially when thequantity of palladium is higher than 2.5 mol %. In the case of 2,6-diacetylpyridine a complex mixture was observed, whatevermethod B or C used, due to partial over-reduction of aromatic ringand the presence of ketone/alcohol/arylmethylene mixture was

Table 4Substrate scope and limitations

Entry/Compound Ketone Reduction in a (method A)a Deoxygenation in b (methods B and C)b

a/bc Yieldd [%] (conv. [%])c Method a/bc Yieldd [%] (conv. [%])c

1 100:0 94 (>99) B 0:100 85 (>99)C 80 (>99)

2 98:2 93 (98) B 0:100 89 (>99)C 88 (>99)

3 100:0 97 (>99) B 0:100 84 (>99)C 83 (>99)

4e 90:10 60 (71) B 0:100 76 (>99)C 86 (>99)

5f 97:3 50 (60) Bg 0:100 88 (>99)C 95 (>99)

6 62:38 44 (90) Bg 0:100 72 (>99)

7 100:0 69 (>99)h B 67C Complex mixture

8 100:0 61 (>99) B 0:100 91 (>99)C 90 (>99)

9 100:0 89 (97) B 0:100 80 (>99)

10 100:0 55 (56) B 0:100 75 (89)C 34:66 NI (83)

11 100:0 98 (>99) B 0:100 90 (>99)C 41:59 NI (>99)

12 100:0 82 (86) B 0:100 91 (>99)

13 100:0 80 (>99) B 0:100 85 (>99)

14 91:9 87 (>99) B 0:100 83 (>99)C 0:100 77 (>99)

15 100:0 80 (>99) B 0:100 55 (>99)

16 100:0 77 (>99) B 100:0 79 (>99)

(continued on next page)

C. Guyon et al. / Tetrahedron 70 (2014) 2088e2095 2091

Table 4 (continued )

Entry/Compound Ketone Reduction in a (method A)a Deoxygenation in b (methods B and C)b

a/bc Yieldd [%] (conv. [%])c Method a/bc Yieldd [%] (conv. [%])c

17 0:100 NI (7) Bg 0:100 41 (50)C 24:76 NI (16)

18 0:100 NI (26)

B 7:93 60 (82)C 5:95 60 (83)

a Method A: NaH2PO2$H2O (4 equiv), Pd/C 5% (2.5 mol %), TBAC (7 mol %), H2O ([NaH2PO2$H2O]¼1.6 M)/2-MeTHF, 60 �C, 1.5e29 h.b Method B: NaH2PO2$H2O (3 equiv)/H3PO2 (50% w/w in H2O, 1 equiv), Pd/C 5% (10 mol %), H2O ([NaH2PO2$H2O]¼1.6 M)/CPME, 100 �C, 5 h; method C: NaH2PO2$H2O

(3 equiv)/H3PO2 (50% w/w in H2O, 1 equiv), Pd/C 5% (10 mol %), H2O ([NaH2PO2$H2O]¼1.6 M)/CPME, sonication, 5 h.c Conversion of the starting material as well as a/b ratio were estimated by 1H NMR.d Isolated yield.e Additive: NaOH (4 equiv).f Additive: NaOH (2 equiv).g Reaction in sealed tube.h Yield (25%) of the amino alcohol was observed when extracting the aqueous phase under basic conditions.

C. Guyon et al. / Tetrahedron 70 (2014) 2088e20952092

noticed. However, these expected alcohols could be synthesizedusing sodium hypophosphite and ruthenium catalyst following thealready published method.11d

From the results obtained in the deoxygenation methods, bothmethods gave similar results when the reaction was conducted inabout 5 h (Table 4, entries 1e5). But the selectivity could be im-proved with a longer reaction time as depicted for the thermalactivation. A monitoring of the reaction has shown a rapid re-duction of the ketone in alcohol and the hydrogenolysis of the in-termediate to the corresponding deoxygenation product. Asreported, the hydrogenolysis varied with the nature of thesubstituents.18

Recycling test of heterogeneous palladium catalyst was achievedon 4-methoxyacetophenone under the optimized conditions ofmethod C. After reaction the crude was filtered off (MilliporeDurapore filter 0.1 mm), Pd/C was washed with water, MeOH, andCH2Cl2. After drying, Pd/C was used for another reaction. After eachrun, Pd/C was recovered and engaged in another life cycle withoutadditional drying. Along the four first runs, both yield and the se-lectivity in favor of arylmethylene 1b were intact. In the fifth run,the conversion decreased to 95% but selectivity was still intact.

3. Conclusion

In conclusion, we have shown that the combination of hypo-phosphite derivatives and Pd/C could be used efficiently for thedeoxygenation of aromatic ketone to arylmethylene as well as forthe selective reduction to the corresponding alcohol. The reactionparameters were investigated and the scope of the reaction wasdemonstrated, pointing out the potential of hypophosphite in re-duction in organic synthesis as an alternative to hydrides andmolecular hydrogen. Considering the recycling potential of thecatalyst associated to the phosphate by-products generated andeasily separable, further development should be expected.

4. Experimental section

4.1. General

Unless otherwise stating, all reagents were obtained fromcommercial sources and used as received. H3PO2 50wt % solution inwater and tetrabutylammonium chloride were purchased fromSigma Aldrich�. NaH2PO2$H2O was purchased from Alfa Aesar. Thepalladium references are as follows: Pd/C 5% 50% H2O fromHeraeus

Katalysator, Typ: K-0219, Dat: 19/03.97, Charge, M9/97, Netto. Silicagel (40e63 micron) was used for column chromatography. Con-version and ratio alcohol/alkane were calculated on the crudemixture after extraction and evaporation by NMR of an aliquot. Thereaction under sonication activation was carried out in an ultra-sonic cleaning bath (Bransonic, Branson 2510EMT) at 42 kHzfrequency.

4.2. General procedure for the ketone reduction in alcohol1e19a,c (method A)

In a Schlenk tube (10 mL), a solution of ketone compound(1mmol), tetrabutylammonium chloride (20mg, 72 mmol, 7 mol %),and Pd/C 5% wt (50% in water) (55 mg, 26 mmol, 2.6 mol %) in 2-MeTHF (1 mL) was stirred at room temperature (20 �C) for10e20 min. To this mixture was added a solution of sodiumhypophosphite monohydrate (424 mg, 4 mmol, 4 equiv) in water(2.5 mL). The reaction mixture was heated at 60 �C. After dilution inCH2Cl2 (10 mL), water (10 mL) was added. The aqueous phase wasextracted with CH2Cl2 (2�20 mL). The combined organic layerswere dried (Na2SO4), filtered, and concentrated. Purification byflash chromatography on silica gel was performed for products 4a,5a, 10a, 12a, 15a, and 19c.

4.2.1. 4-(1-Hydroxyethyl)benzoic acid methyl ester [84851-56-9]11d

(1a). Procedure A; 2.7 h; colorless oil (170 mg, 94%). 1H NMR(300MHz, CDCl3) d (ppm)¼1.51 (d, 3H, J¼6.5 Hz, CH3), 1.84 (br s, 1H,OH), 3.91 (s, 3H, OCH3), 4.97 (q, 1H, J¼6.5 Hz, CHeOH), 7.45 (d, 2H,J¼8.3 Hz, Harom), 8.02 (d, 2H, J¼8.3 Hz, Harom).

4.2.2. 1-(40-Methoxyphenyl)ethanol [3319-15-1]11d (2a). ProcedureA; 3.3 h; colorless oil (141 mg, 93%). 1H NMR (300 MHz, CDCl3)d (ppm)¼1.48 (d, 3H, J¼6.5 Hz, CH3), 1.68 (br s, 1H, OH), 3.81 (s, 3H,OCH3), 4.86 (q, 1H, J¼6.5 Hz, CHeOH), 6.89 (d, 2H, J¼8.7 Hz, Harom),7.31 (d, 2H, J¼8.7 Hz, Harom).

4.2.3. 1-(40-Methylphenyl)ethanol [536-50-5]11d (3a). Procedure A;1.5 h; oil (132 mg, 97%). 1H NMR (300MHz, CDCl3) d (ppm)¼1.49 (d,3H, J¼6.4 Hz, CH3), 1.75 (br s, 1H, OH), 2.34 (s, 3H, CH3), 4.87 (q, 1H,J¼6.4 Hz, CHeOH), 7.16 (d, 2H, J¼7.8 Hz, Harom), 7.27 (d, 2H,J¼7.8 Hz, Harom).

4.2.4. 1-(40-Aminophenyl)ethanol [14572-89-5]19 (4a). Method Amodified: addition of sodium hydroxide (160 mg, 4 mmol, 4 equiv)

C. Guyon et al. / Tetrahedron 70 (2014) 2088e2095 2093

to the sodium hypophosphite solution. This solution was added intwo times in 1 h delay; 4 h; treatment: after dilution with NaOH(1 M), the aqueous phase (pH>10) was extracted with CH2Cl2;purification: flash chromatography (dichloromethane/meth-anol¼98:2); colorless oil (82 mg, 60%). 1H NMR (300 MHz, CDCl3)d (ppm)¼1.47 (d, 3H, J¼6.4 Hz, CH3), 1.65 (br s, 1H, OH), 3.66 (br s,2H, NH2), 4.80 (q, 1H, J¼6.4 Hz, CHeOH), 6.67 (d, 2H, J¼8.5 Hz,Harom), 7.17 (d, 2H, J¼8.5 Hz, Harom). 13C NMR (75 MHz, CDCl3)d (ppm)¼24.8 (CH3), 69.9 (CHeOH), 115.1 (2 CH), 126.6 (2 CH), 136.1(Cq), 145.6 (Cq).

4 .2 .5 . 1- (4-Hydroxyphenyl ) -1-e thano l [2380-91-8 1]2 0

(5a). Method A modified: addition of sodium hydroxide (80 mg,2 mmol, 2 equiv) to the sodium hypophosphite solution; 4 h;treatment: after dilution with water (pH¼5e6), the aqueous phasewas extracted with CH2Cl2. The aqueous phase was acidified(pH¼3e4) and extracted with CH2Cl2; purification: flash chroma-tography (cyclohexane/ethyl acetate¼100:0 to 50:50); white solid(75 mg, 54%). 1H NMR (300 MHz, DMSO-d6) d (ppm)¼1.26 (d, 3H,J¼6.4 Hz, CH3), 4.59 (qd, 1H, J¼4.0, 6.4 Hz, CHeOH), 4.91 (d, 1H,J¼4.0 Hz, OH), 6.68 (d, 2H, J¼8.4 Hz, Harom), 7.11 (d, 2H, J¼8.4 Hz,Harom), 9.19 (br s, 1H, AreOH). 13C NMR (75 MHz, DMSO-d6)d (ppm)¼25.9 (CH3), 67.8 (CHeOH), 114.7 (2 CH), 126.5 (2 CH), 137.7(Cq), 156.0 (Cq).

4.2.6. 1-[40-(N,N0-Dimethylamino)phenyl]ethanol [5338-94-3]21

(6a). Procedure A; 3 h; oil (74 mg, 44%). 1H NMR (300 MHz,CDCl3) d (ppm)¼1.48 (d, 3H, J¼6.5 Hz, CH3), 1.64 (br s, 1H, OH), 2.94(s, 6H, 2 CH3), 4.83 (q, 1H, J¼6.5 Hz, CHeOH), 6.73 (d, 2H, J¼8.6 Hz,Harom), 7.26 (d, 2H, J¼8.6 Hz, Harom). 13C NMR (75 MHz, CDCl3)d (ppm)¼24.8 (CH3), 40.8 (2 CH3), 70.1 (CHeOH),112.7 (2 CH),126.5(2 CH), 133.9 (Cq), 150.2 (Cq).

4.2.7. 1-(40-Cyanophenyl)ethanol [52067-35-3]11d (7a). ProcedureA; 18 h; colorless oil (101 mg, 69%). 1H NMR (300 MHz, CDCl3)d (ppm)¼1.50 (d, 3H, J¼6.6 Hz, CH3), 1.72 (br s, 1H, OH), 4.97 (q, 1H,J¼6.6 Hz, CHeOH), 7.49 (d, 2H, J¼8.3 Hz, Harom), 7.65 (d, 2H,J¼8.3 Hz, Harom).

4.2 .8 . 4 0-(1-Hydroxyethyl)-benzo ic ac id [97364-15-3]22

(8a). Procedure A; 3 h 50; extraction: CH2Cl2 and HCl (1 M);white solid (100 mg, 61%). 1H NMR (300 MHz, CDCl3) d (ppm)¼1.52(d, 3H, J¼6.5 Hz, CH3), 4.99 (q, 1H, J¼6.5 Hz, CHeOH), 7.49 (d, 2H,J¼8.3 Hz, Harom), 8.09 (d, 2H, J¼8.3 Hz, Harom). 13C NMR (75 MHz,DMSO-d6) d (ppm)¼25.8 (CH3), 67.9 (CHeOH), 125.5 (2 CH), 129.2(Cq), 129.3 (2 CH), 152.5 (Cq), 167.4 (Cq).

4.2.9. 1-[4 0-(Trifluoromethyl)phenyl]ethanol [1737-26-4]11d

(9a). Procedure A; 4 h; colorless oil (169 mg, 89%). 1H NMR(300MHz, CDCl3) d (ppm)¼1.51 (d, 3H, J¼6.4 Hz, CH3),1.66 (br s,1H,OH), 4.99 (q, 1H, J¼6.4 Hz, CHeOH), 7.49 (d, 2H, J¼8.1 Hz, Harom),7.61 (d, 2H, J¼8.1 Hz, Harom).

4.2.10. 1-(10-Naphthyl)ethanol [1517-72-2] (10a). Procedure A;29 h; purification: flash chromatography (cyclohexane/ethylacetate¼100:0 to 50:50); white solid (96 mg, 54%). 1H NMR(300 MHz, CDCl3) d (ppm)¼1.68 (d, 3H, J¼6.4 Hz, CH3), 1.89 (d, 1H,J¼3.6 Hz, OH), 5.70 (qd, 1H, J¼3.6, 6.4 Hz, CHeOH), 7.47e7.56 (m,3H, Harom), 7.69 (d, 1H, J¼7.1 Hz, Harom), 7.79 (d,1H, J¼8.1 Hz, Harom),7.88 (d, 1H, J¼7.1 Hz, Harom), 8.13 (d, 1H, J¼8.1 Hz, Harom). 13C NMR(75 MHz, CDCl3) d (ppm)¼24.4 (CH3), 67.0 (CHeOH), 122.0 (CH),123.2 (CH), 125.6 (CH), 125.6 (CH), 126.0 (CH), 127.9 (CH), 128.9(CH), 130.3 (Cq), 133.8 (Cq), 141.4 (Cq).

4.2.11. 1-(20-Naphthyl)ethanol [7228-47-9]11d (11a). Procedure A;5.7 h; white solid (174 mg, 98%). 1H NMR (300 MHz, CDCl3)

d (ppm)¼1.57 (br s, 1H, OH), 1.59 (d, 3H, J¼6.5 Hz, CH3), 5.08 (q, 1H,J¼6.5 Hz, CHeOH), 7.45e7.53 (m, 3H, Harom), 7.81e7.86 (m, 4H,Harom).

4.2.12. 1-(9H-Fluoren-2-yl)ethanol [1001043-05-5] (12a). ProcedureA; 7 h; purification: flash chromatography (cyclohexane/ethylacetate¼100:0 to 60:40); white solid (173 mg, 82%). 1H NMR(300 MHz, CDCl3) d (ppm)¼1.56 (d, 3H, J¼6.6 Hz, CH3), 1.82 (d, 1H,J¼3.3 Hz, CHeOH), 3.90 (s, 2H, CH2), 4.99 (qd, 1H, J¼3.3, 6.6 Hz,CHeOH), 7.30 (td,1H, J¼1.4, 7.4 Hz, Harom), 7.35e7.39 (m, 2H, Harom),7.54 (d, 1H, J¼7.4 Hz, Harom), 7.58 (s, 1H, Harom), 7.74e7.79 (m, 2H,Harom). 13C NMR (75 MHz, CDCl3) d (ppm)¼25.4 (CH3), 37.0 (CH2),70.7 (CHeOH), 119.9 (CH), 120.0 (CH), 122.2 (CH), 124.3 (CH), 125.1(CH), 126.7 (CH), 126.8 (CH), 141.2 (Cq), 141.5 (Cq), 143.5 (Cq), 143.7(Cq), 144.6 (Cq). HRMS (CI) calcd for C15H14O [MþH]þ 211.1117 found211.1114.

4.2.13. (9H-Fluoren-2-yl)methanol23 (13a). Procedure A; 6 h10 min; purification: flash chromatography (dichloromethane);white solid (155 mg, 80%). 1H NMR (300 MHz, CDCl3) d (ppm)¼1.67(t, 1H, J¼5.8 Hz, OH), 3.91 (s, 2H, CH2), 4.77 (d, 2H, J¼5.8 Hz,CH2eOH), 7.30 (dt, 1H, J¼1.32, 7.4 Hz, Harom), 7.36e7.41 (m, 2H,Harom), 7.53e7.57 (m, 2H, Harom), 7.76e7.80 (m, 2H, Harom). 13C NMR(75 MHz, CDCl3) d (ppm)¼36.8 (CH2), 65.3 (CH2eOH), 119.8 (CH),119.9 (CH), 123.8 (CH), 125.0 (CH), 125.8 (CH), 126.6 (CH), 126.7(CH), 139.7 (Cq), 141.1 (Cq), 141.4 (Cq), 143.4 (Cq), 143.6 (Cq). HRMS(CI) calcd for C14H12O [M�H]þ. 193.0804 found 195.0804.

4.2.14. Diphenylmethanol [91-01-0]11d (14a). Procedure A; 5 h;white solid (162 mg, 87%). 1H NMR (300 MHz, CDCl3) d (ppm)¼1.55(br s, 1H, OH), 5.86 (s, 1H, CHeOH), 7.17e7.40 (m, 10H, Harom).

4.2.15. Methyl DL-mandelate [4358-87-6]11d (15a). Procedure A;1.3 h; purification: flash chromatography (cyclohexane/ethylacetate¼100:0 to 60:40); white solid (133 mg, 80%). 1H NMR(300 MHz, CDCl3) d (ppm)¼3.42 (d, 1H, J¼5.7 Hz, OH), 3.77 (s, 3H,COOCH3), 5.18 (d, 1H, J¼5.7 Hz, CHeOH), 7.34e7.42 (m, 5H, Harom).

4.2.16. 2,2,2-Trifluoro-1-phenylethanol [340-04-5]11d (16a). ProcedureA; 3 h; oil (135 mg, 77%). 1H NMR (300 MHz, CDCl3) d (ppm)¼2.63(br s, 1H, OH), 5.03 (q, 1H, J¼6.8 Hz, CHeOH), 7.40e7.49 (m, 5H,Harom).

4.3. General procedures for the ketone reduction in alkane1e19b

Method B: in a round bottom flask, to a solution of ketone(1 mmol) and Pd/C 5 wt % (50% in water) (212 mg, 0.1 mmol,10 mol %) in CPME (1 mL) was added a mixture of sodium hypo-phosphite monohydrate (3 mmol), hypophosphorous acid 50% inwater (1 mmol) inwater (2mL). The reactionmixturewas heated at100 �C between 2 and 16 h. Same treatment as Method A wasperformed.

Method C: the same procedure was followed replacing thethermal activation by a sonochemical activation during 5 h.

4.3.1. Methyl 4-ethylbenzoate [7364-20-7]6e (1b). Procedure C; 5 h;colorless liquid (131 mg, 80%). 1H NMR (300 MHz, CDCl3) d (ppm)¼1.24 (t, 3H, J¼7.5 Hz, CH3), 2.68 (q, 2H, J¼7.5 Hz, CH2), 3.89 (s, 3H,OCH3), 7.25 (d, 2H, J¼8.4 Hz, Harom), 7.95 (d, 2H, J¼8.4 Hz, Harom). 13CNMR (75 MHz, CDCl3) d (ppm)¼15.3 (CH3), 29.0 (CH2), 52.0 (OCH3),127.7 (Cq), 127.9 (2 CH), 129.8 (2 CH), 149.8 (Cq), 167.2 (Cq).

4.3.2. 1-Ethyl-4-methoxybenzene [1515-95-3]25 (2b). Procedure C;2 h; colorless liquid (121 mg, 88%). 1H NMR (300 MHz, CDCl3)d (ppm)¼1.28 (t, 3H, J¼7.5 Hz, CH3), 2.66 (q, 2H, J¼7.5 Hz, CH2), 3.84

C. Guyon et al. / Tetrahedron 70 (2014) 2088e20952094

(s, 3H, OCH3), 6.89 (d, 2H, J¼8.4 Hz, Harom), 7.18 (d, 2H, J¼8.4 Hz,Harom). 13C NMR (75 MHz, CDCl3) d (ppm)¼16.0 (CH3), 28.1 (CH2),55.3 (OCH3), 113.8 (2CH), 128.8 (2CH), 136.5 (Cq), 157.7 (Cq).

4.3.3. 1-Ethyl-4-methylbenzene [622-96-8] (3b). Procedure C; 5 h;GC yield with internal standard: dodecane (83%). GC: ZB-5-MS(30 m�0.25 mm�0.25 mm), H2 (40 mL/min), N2 (400 mL/min),injection temperature: 250 �C, detection temperature: 280 �C,column temperature: 2 min at 70 �C then 70e280 �C at 15 �C/min,retention time: 4.80 min.

4.3.4. 4-Ethylaniline [589-16-2]25 (4b). Procedure C; 4 h; brownliquid (105 mg, 86%). 1H NMR (300 MHz, CDCl3) d (ppm)¼1.22 (t,3H, J¼7.5 Hz, CH3), 2.57 (q, 2H, J¼7.5 Hz, CH2), 3.51 (br s, 2H, NH2),6.66 (d, 2H, J¼8.3 Hz, Harom), 7.02 (d, 2H, J¼8.3 Hz, Harom). 13C NMR(75 MHz, CDCl3) d (ppm)¼16.0 (CH3), 28.1 (CH2), 115.3 (2CH), 128.7(2CH), 134.5 (Cq), 144.1 (Cq).

4.3.5. 4-Ethylphenol [123-07-9]29 (5b). Procedure C; 1.5 h; brownsolid (116 mg, 95%). 1H NMR (300 MHz, CDCl3) d (ppm)¼1.22 (t, 3H,J¼7.5 Hz, CH3), 2.59 (q, 2H, J¼7.5 Hz, CH2), 5.17 (br s, 1H, OH), 6.77(d, 2H, J¼8.3 Hz, Harom), 7.08 (d, 2H, J¼8.3 Hz, Harom). 13C NMR(75 MHz, CDCl3) d (ppm)¼16.0 (CH3), 28.1 (CH2), 115.3 (2 CH), 129.0(2 CH), 136.7 (Cq), 153.4 (Cq).

4.3.6. 4-Ethyl-N,N-dimethylaniline26 (6b). Procedure B in sealedtube; 16 h, purification: flash chromatography (pentane 100%);clear liquid (107 mg, 72%). 1H NMR (300 MHz, DMSO-d6) d (ppm)¼1.12 (t, 3H, J¼7.5 Hz, CH3), 2.47 (q, 2H, J¼7.5 Hz, CH2), 2.83 (s, 6H,CH3), 6.65 (d, 2H, J¼7.5 Hz, Harom), 7.01 (d, 2H, J¼7.5 Hz, Harom). 13CNMR (75 MHz, DMSO-d6) d (ppm)¼16.1 (CH3), 27.2 (CH2), 40.5 (2CH3), 112.8 (2 CH), 128.1 (2 CH), 131.5 (Cq), 148.8 (Cq).

4.3.7. 4-Ethylbenzylamine hydrochloride (7c). Procedure B in sealedtube with NaH2PO2 (6 equiv) and H3PO2 (2 equiv); 16 h, purifica-tion: precipitation with HCl (2 M) in Et2O (2 mL); white solid(111 mg, 65%). 1H NMR (300 MHz, CD3OD-d4) d (ppm)¼1.22 (t, 3H,J¼7.5 Hz, CH3), 2.66 (q, 2H, J¼7.5 Hz, CH2), 4.09 (s, 2H, CH2), 5.02 (brs, 3H, NHþ

3 ), 7.28 (d, 2H, J¼8.2 Hz, Harom), 7.39 (d, 2H, J¼8.2 Hz,Harom). 13C NMR (75 MHz, CD3OD-d4) d (ppm)¼16.1 (CH3), 29.5(CH2), 44.1 (CH2), 129.6 (2CH), 130.2 (2CH), 131.7 (Cq), 146.7 (Cq).

4.3.8. 4-Ethylbenzoic acid [619-64-7]27 (8b). Procedure C; whitesolid (135 mg, 90%). 1H NMR (300 MHz, CDCl3) d (ppm)¼1.27 (t, 3H,J¼7.5 Hz, CH3), 2.73 (q, 2H, J¼7.5 Hz, CH2), 7.30 (d, 2H, J¼8.3 Hz,Harom), 8.03 (d, 2H, J¼8.3 Hz, Harom). 13C NMR (75 MHz, CDCl3)d (ppm)¼15.3 (CH3), 29.2 (CH2), 127.0 (Cq), 128.2 (2 CH), 130.5 (2CH), 151.0 (Cq), 172.6 (Cq).

4.3.9. 1-Ethyl-4-trifluoromethylbenzene24 (9b). Procedure B; 16 h;pale yellow oil (139 mg, 80%). 1H NMR (400 MHz, CDCl3) d (ppm)¼1.18 (t, 3H, J¼7.6 Hz, CH3), 2.62 (q, 2H, J¼7.6 Hz, CH2), 7.21 (d, 2H,J¼8.1 Hz, Harom), 7.45 (d, 2H, J¼8.1 Hz, Harom). 13C NMR (100 MHz,CDCl3) d (ppm)¼15.4 (CH3), 28.9 (CH2), 124.6 (q, J¼280 Hz, CF3),125.3 (q, J¼4.4 Hz, 2CH), 128.2 (q, J¼31.4 Hz, Cq), 128.3 (2CH), 148.4(Cq). 19F NMR (376 MHz, CDCl3) d (ppm)¼�62.74 (CF3).

4.3.10. 1-Ethylnaphthalene [1127-76-0]29 (10b). Procedure B; 16 h;purification: flash chromatography (pentane 100%); clear liquid(117 mg, 75%). 1H NMR (300 MHz, CDCl3) d (ppm)¼1.24 (t, 3H,J¼7.5 Hz, CH3), 2.96 (q, 2H, J¼7.5 Hz, CH2), 7.18e7.36 (m, 4H, Harom),7.56 (d, 1H, J¼8.1 Hz, Harom), 7.70 (m,1H, Harom), 7.92 (m,1H, Harom).13C NMR (75 MHz, CDCl3) d (ppm)¼15.2 (CH3), 26.0 (CH2), 123.8(CH), 125.0 (CH), 125.5 (CH), 125.8 (2CH), 126.5 (CH), 128.9 (CH),131.9 (Cq), 134.0 (Cq), 140.4 (Cq).

4.3.11. 2-Ethylnaphthalene [939-27-5]28 (11b). Procedure B; 16 h;liquid (141 mg, 90%). 1H NMR (300 MHz, CDCl3) d (ppm)¼1.20 (t,

3H, J¼7.5 Hz, CH3), 2.67 (q, 2H, J¼7.5 Hz, CH2), 7.21 (d, 1H, J¼8.6 Hz,Harom), 7.24-7.32 (m, 2H, Harom), 7.49 (s, 1H, Harom), 7.61e7.68 (m,3H, Harom). 13C NMR (75 MHz, CDCl3) d (ppm)¼15.7 (CH3), 29.2(CH2), 125.1 (CH), 125.7 (CH), 125.9 (CH), 127.2 (CH), 127.5 (CH),127.7 (CH), 127.9 (CH), 132.1 (Cq), 133.8 (Cq), 141.9 (Cq).

4.3.12. 2-Ethyl-9H-fluorene (12b). Procedure B; 16 h; yellow solid(176 mg, 91%). 1H NMR (400 MHz, CDCl3) d (ppm)¼1.27 (t, 3H,J¼7.6 Hz, CH3), 2.70 (q, 2H, J¼7.6 Hz, CH2CH3), 3.83 (s, 2H, CH2), 7.17(t, 1H, J¼7.8 Hz, Harom), 7.24 (t, 1H, J¼7.4 Hz, Harom), 7.33 (d, 1H,J¼7.6 Hz, Harom), 7.35 (s, 1H, Harom), 7.48 (d, 1H, J¼7.4 Hz, Harom),7.66 (d, 1H, J¼7.8 Hz, Harom), 7.72 (d, 1H, J¼7.4 Hz, Harom). 13C NMR(100 MHz, CDCl3) d (ppm)¼16.1 (CH3), 29.2 (CH2), 36.9 (CH2), 119.7(CH),119.8 (CH),124.6 (CH), 125.1 (CH),126.3 (CH),126.6 (CH),126.8(CH), 139.5 (Cq), 141.9 (Cq), 143.2 (Cq), 143.3 (Cq), 143.6 (Cq).

4.3.13. 2-Methyl-9H-fluorene [2523-39-9]29 (13b). Procedure B;16 h; yellow solid (153 mg, 85%). 1H NMR (300 MHz, CDCl3)d (ppm)¼2.54 (s, 3H, CH3), 3.94 (s, 2H, CH2), 7.29 (d, 1H, J¼7.7 Hz,Harom), 7.36e7.50 (m, 3H, Harom), 7.62 (d, 1H, J¼7.1 Hz, Harom), 7.77(d, 1H, J¼7.7 Hz, Harom), 7.85 (d, 1H, J¼7.5 Hz, Harom). 13C NMR(75 MHz, CDCl3) d (ppm)¼21.7 (CH3), 36.8 (CH2), 119.6 (CH), 119.7(CH),125.0 (CH),125.8 (CH),126.3 (CH),126.7 (CH),127.7 (CH),136.6(Cq), 139.2 (Cq), 141.9 (Cq), 143.2 (Cq), 143.6 (Cq).

4.3.14. Diphenylmethane [101-81-5]30 (14b). Procedure B; 16 h;white solid (139 mg, 83%). 1H NMR (300 MHz, CDCl3) d (ppm)¼4.04(s, 2H, CH2), 7.23e7.27 (m, 6H, Harom), 7.31e7.37 (m, 4H, Harom). 13CNMR (75 MHz, CDCl3) d (ppm)¼42.1 (CH2), 126.2 (2 CH), 128.6 (4CH), 129.1 (4 CH), 141.2 (2Cq).

4.3.15. Methyl 2-phenylacetate [101-41-7]31 (15b). Procedure B;16 h; gray solid (83 mg, 55%). 1H NMR (300 MHz, CDCl3) d (ppm)¼3.66 (s, 2H, CH2), 3.71 (s, 3H, CH3), 7.26e7.38 (m, 5H, Harom). 13CNMR (75 MHz, CDCl3) d (ppm)¼41.3 (CH2), 52.1 (CH3), 127.2 (CH),128.7 (2 CH), 129.4 (2 CH), 134.1 (Cq), 172.1 (Cq).

4.3.16. 3-Ethylbenzo[b]thiophene32 (17b). Procedure B in sealedtube; 16 h; purification: flash chromatography (pentane 100%);white solid (67 mg, 41%). 1H NMR (300 MHz, CDCl3) d (ppm)¼1.41(t, 3H, J¼7.5 Hz, CH3), 2.90 (qd, 2H, J¼1.0, 7.5 Hz, CH2), 7.11 (s, 1H,Harom), 7.34e7.44 (m, 2H, Harom), 7.78 (dd, 1H, J¼1.6, 6.7 Hz, Harom),7.88 (dd, 1H, J¼1.6, 6.7 Hz, Harom). 13C NMR (75 MHz, CDCl3)d (ppm)¼13.5 (CH3), 21.8 (CH2), 120.3 (CH), 121.8 (CH), 123.0 (CH),123.9 (CH), 124.3 (CH), 138.8 (Cq), 139.1 (Cq), 140.7 (Cq).

4.3.17. 3-Ethylindole [1484-19-1]33 (18b). Procedure B; 5 h; purifi-cation: flash chromatography (pentane/CH2Cl2 9:1); white solid(87 mg, 60%). 1H NMR (300 MHz, CDCl3) d (ppm)¼1.31 (t, 3H,J¼7.5 Hz, CH3), 2.76 (qd, 2H, J¼1.0, 7.5 Hz, CH2), 6.88 (t, 1H, J¼1.0 Hz,Harom), 7.09 (td, 1H, J¼7.9, 8.0 Hz, Harom), 7.16 (td, 1H, J¼7.9, 8.0 Hz,Harom), 7.27 (d, 1H, J¼8.0 Hz, Harom), 7.59 (d, 1H, J¼7.9 Hz, Harom),7.70 (br s, 1H, NH). 13C NMR (75 MHz, CDCl3) d (ppm)¼14.6 (CH3),18.5 (CH2), 111.2 (CH), 118.9 (Cq), 119.1 (CH), 119.2 (CH), 120.6 (CH),122.0 (CH), 127.5 (Cq), 136.5 (Cq).

Acknowledgements

M.B. and C.G. have an equal contribution in this publication. TheMinist�ere de l’Enseignement Sup�erieur et de la Recherche isgratefully acknowledged for grant to M.B. C.G. held a doctoral fel-lowship from La R�egion Rhone-Alpes financed to the amount of32,116 euros. The authors are grateful for the access to the MSanalysis at the Centre Commun de Spectroscopie de Masse andNMR facilities at the Universit�e Lyon 1.

C. Guyon et al. / Tetrahedron 70 (2014) 2088e2095 2095

Supplementary data

Supplementary data associated with this article can be found inthe online version, at http://dx.doi.org/10.1016/j.tet.2014.02.014.

References and notes

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Samec;, J. S. M. ACS Catal. 2013, 3, 635.14. Reaction conditions: metal (10 mol %), NaH2PO2$H2O/H3PO2 (3:1 equiv), CPME,

5 h under sonication. No conversion was observed with: Fe(OAc)2, FeBr3,[RuCl2(p-cymene)]2, Co(OAc)2, Co(acac)3, Cu(OAc)2, CuBr, Ni(OAc)2, MoO2(a-cac)2, V(O)(OiPr)3, Co oxideeMo oxide/Al2O3, Ti(OiPr)4, Pt/C, Ir/C, Ru/C, Rh/C, Ni/SiO2, Cu. Only Pd(OAc)2 and Ni(Ra) provided poor conversions

15. Use of calcium hypophosphite or iron hypophosphite provided similar resultsthan sodium hypophosphite, but a lower conversion was obtained with am-monium hypophosphite

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