MnO2as a terminal oxidant in Wacker oxidation of homoallyl alcohols and terminal olefins

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ARTICLE

MnO₂as Terminal Oxidant in Wacker Oxidation of Homoallyl

Alcohols and Terminal Olefins

Rodney A. Fernandes,*^aGujjula V. Ramakrishna^aand Venkati Bethi^a

Received 00th January 20xx,

Accepted 00th January 20xx

An efficient and mild reaction conditions for Wacker-type oxidation of terminal olefins of less explored homoallyl alcohols

to -hydroxy-methyl ketones has been developed by using Pd(II) catalyst and MnO₂as co-oxidant. The method involves mild

reaction conditions and shows good functional group compatibility along with high regio- and chemoselectivity. While our

earlier system of PdCl₂/CrO₃/HCl produced ,-unsaturated ketones from homoallyl alcohols, the present method provided

orthogonally the -hydroxy-methyl ketones. No overoxidation or elimination of benzylic and/or -hydroxy group was

observed. The method could be extended to oxidation of simple terminal olefins as well, to methyl ketones displaying its

versatility. A application to the regioselective synthesis of gingerol is demonstrated.

DOI: 10.1039/x0xx00000x

Introduction



-Hydroxy-keto compounds are key building blocks for 1,3-

diketones, 1,3-diols and polyketides present in many natural

products, pharmaceuticals, and bioactive compounds.¹The

conventional aldol addition reaction used for the synthesis of -

hydroxy-keto compounds sometimes suffers from substrate

scope, selectivity, and a number of by-products formation,

especially the self-aldol and aldol condensation products with

facile elimination of hydroxy group. The Wacker-type oxidation

has been extensively studied for several years to convert

terminal olefins to methyl ketones.^2,3The traditional Cu-

mediated Wacker process has limitations, such as corrosive

reaction medium, isomerization of the double bond and

chlorinated by-products.⁴To overcome this, alternative

methods are developed based on solvents (DMF, DMA,

sulfolane, CO₂, PEG, ethylene carbonate, etc),⁵organic

oxidants,^5a,6inorganic oxidants,⁷nitrogen-based ligands,⁸

nitrates,⁹and organic peroxides.¹⁰We recently explored the

traceless OH-directed Wacker oxidation, one-pot elimination of

homoallyl alcohols

condensation (Scheme 1A).¹¹This led to the synthesis of

unsaturated ketones . We visualized an orthogonal chemo

1 as an alternative to Wittig olefination/aldol

,-

2

selective oxidation of only terminal olefin of homoallyl alcohol

by the Wacker process. The selectivity in Wacker oxidation of

homoallyl alcohol depends on the substrate and the oxidant.^6a

To the best of our knowledge there exists few reports on such

reaction of homoallyl alcohols as substrates for Wacker

oxidation.^6a,8c,12,13In 1988, Nokami and co-workers explored the

Wacker oxidation [PdCl₂(10 mol%), p-benzoquinone (p-BQ,

Scheme 1 Wacker oxidation of homoallyl alcohols.

3.0equiv), DMF-H₂O] of C-3 substituted homoallyl alcohols 1 to

result largely in the hemiacetals

4 (aldehyde selective, Scheme

1B).^6aWith no C-3 substituent, the reaction gave methyl ketone

^aDepartment of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai

400076, Maharashtra, India. E-mail: rfernand@chem.iitb.ac.in; Fax: +91 22

25767152; Tel: +91 22 25767174

(e.g. 3a, R = H, only example). In 2006, Cornell and Sigman

disclosed the use of Pd[(

−)-sparteine]Cl₂(2 mol%)/O₂-based

system for ketone-selective Wacker oxidation of homoallyl

Electronic Supplementary Information (ESI) available: [details of any supplementary

information available should be included here]. See DOI: 10.1039/x0xx00000x

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alcohols 1b (only 1 example of unprotected homoallyl alcohol, alcohol oxidation was observed with higher loading of MnO₂(6

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Scheme 1C).^8cIn a subsequent report in 2011, Sigman et al.¹²equivalent). Normal MnO₂is used in superstoichiometric

DOI: 10.1039/D0OB01344G

showed Pd(Quinox)Cl₂(3-10 mol%), AgSbF₆(7.5-25 mol%) and quantity, being heterogenous reaction for allylic and benzylic

TBHP (12 equiv)-based Wacker oxidation of homoallyl alcohols oxidations.¹⁷Increase in PdCl₂loading (20 mol%, entry 20) did

1

(Scheme 1D). However, the latter reaction conditions failed not affect the yield much (80%). Also, lowering of MnO₂amount

for 1-phenyl-but-3-en-ol 1b and was explored though on limited (2-1 equivalent) along with 20 mol% of PdCl₂did not yield

substrates (only 5 examples). A recent report by Runeberg and superior results. Hence we concluded to have PdCl₂(10 mol%),

Eklund displayed the Wacker oxidation of unprotected MnO₂(4 equiv) in MeCN/H₂O (7:1) at 60

carbohydrate-based homoallyl alcohols, unfortunately conditions.

requiring higher catalyst [Pd(OAc)₂(30 mol%)] and ligand

[pyridine (60 mol%)] loading and resulting in product Table 1 Optimization of reaction conditions.^a

mixtures.¹³



C as optimum

In continuation to our efforts^6b,7f,gin developing new oxidants

for Wacker chemistry, we explored MnO₂as a terminal oxidant

in heterogenous Wacker process. We aimed at orthogonal

selectivity with regard to earlier results.¹¹MnO₂and related Mn-

based compounds are well recognized oxidant in organic

synthesis, used specially in allylic oxidations.^14,15There has been

a report¹⁶on the use of Mn²⁺salts of heteropoly acids

Entry Pd-catalyst

(x mol%)

Oxidant

(y equiv)

MnO₂(3)

Solvent

(7:1)

Time Yield^b

(h)

3b (%)

67

1

2

3

4

5

6

7

8

9

PdCl₂(10)

MeCN:H₂O 24

[H_3+xPMo₁₂V O (0  x  3)] containing PdCl₂and supported on

−

x

x 40

Mn(SO₄).4H₂O (3) MeCN:H₂O 30

40

silica for oxidation of ethene. The manganese salts of hetero

poly acids were prepared using HPA and Mn(NO₃)₂or Mn(CO₃)₂

in aqueous solution. PdCl₂was first supported on silica and then

impregnated with hetero poly compounds from aqueous

solutions. However, the catalytic activity was affected by the

catalyst preparation procedure. The heterogenous reaction also

required the presence of molybdenum and vanadium atoms in

HPA for the activity. The direct use of MnO₂is not reported to

the best of our knowledge in Wacker process as oxidant for

Pd(0) for an excellent oxidation of varied types of homoallyl

Mn(SO₄).H₂O (3)

KMnO₄(3)

MeCN:H₂O 36

MeCN:H₂O 48

35

18

Mn(OAc)₂.4H₂O (3) MeCN:H₂O 24

MnCl₂.4H₂O (3) MeCN:H₂O 32

Mn(NO₃)₂.4H₂O (3) MeCN:H₂O 15

21

30

58

Pd(OAc)₂(10) MnO₂(3)

Pd(OCOCF₃)₂MnO₂(3)

(10)

MeCN:H₂O 36

MeCN:H₂O 22

53

57

10 Pd(MeCN)₂MnO₂(3)

(10)

MeCN:H₂O 26

46

11 Pd(dba)₂(10) MnO₂(3)

MeCN:H₂O 23

CH₂Cl₂:H₂O 40

53

36

55

47

38

51

78

79

80

74

60

alcohols

1 to -hydroxy ketones 3 (X = OH) with a wider

12 PdCl₂(10)

13 PdCl₂(10)

14 PdCl₂(10)

15 PdCl₂(10)

16^cPdCl₂(10)

17 PdCl₂(10)

18 PdCl₂(10)

19 PdCl₂(10)

20 PdCl₂(20)

21 PdCl₂(20)

22 PdCl₂(20)

MnO₂(3)

MnO₂(4)

MnO₂(5)

MnO₂(6)

MnO₂(4)

MnO₂(2)

MnO₂(1)

substrate scope, generality and milder reaction conditions

(Scheme 1E). No competing alcohol oxidation/elimination by

MnO₂was observed under this protocol. This methods was also

applicable to both activated and non-activated terminal olefins

DMF:H₂O

DMSO:H₂O 48

THF:H₂O 30

36

MeCN:H₂O 48

MeCN:H₂O 22

MeCN:H₂O 26

CH₃CN:H₂O 26

CH₃CN:H₂O 22

CH₃CN:H₂O 28

CH₃CN:H₂O 32

giving methyl ketones 3 (X = H).

Results and Discussion

We began the investigation by optimizing the reaction

conditions using the homoallyl alcohol 1b as a model substrate

(Table 1). Initially we examined various Mn-based oxidants (3

equiv, entries 1-7) along with PdCl₂(10 mol%) to find that MnO₂

^aAll reactions were carried on 0.5 mmol of olefin 1b in a closed flask.

^bIsolated yield. ^cReaction under N₂.

was the best giving -hydroxy ketone 3b in 67% yield (entry 1).

No oxidation of benzylic alcohol by MnO₂or other oxidants was

observed showing a good level of chemoselectivity.^14,15

Similarly, the reaction was also ketone selective and no

aldehyde or lactol was detected.^6aThe requirement of 3

equivalents of MnO₂can be interpreted based on the

heterogenous nature of reaction. We next examined the

commonest other Pd-catalysts used in Wacker oxidation

(entries 8-11), to reveal that PdCl₂was superior. A change in

solvent mixtures (entries 12-15) showed MeCN/H₂O in 7:1 ratio

was the best. A reaction under nitrogen atmosphere (entry 16)

took longer time to complete and gave diminished yield of 3b

(51%). Increasing the amount of MnO₂(4-6 equiv, entries 17-19)

indicated 4 equivalent was optimum giving 3b in 78% yield. No

We further investigated the scope of this reaction conditions

on various homoallyl alcohols

1 as shown in Scheme 2 to give

the -hydroxy ketones in good yields. Compounds with aryl



3

ring having both electron withdrawing and donating groups like

Me, O-alkyl, OH, Cl, NO₂or Ph at different positions, all worked

well giving the

Similarly the anthracene, naphthalene, cinnamyl, and furyl-

based substrates 1n-s gave the -hydroxy ketones 3n-s in 68-

-hydroxy ketones 3b-m in 61-80% yields.



78% yields. The cinnamyl cases 3p-r were noteworthy that only

the terminal olefin bond was oxidized leaving chemoselectively

the internal double bond intact. No allylic alcohol oxidation nor

elimination was observed in all cases, which is remarkable in

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this process knowing that MnO₂is an oxidant for allylic alcohol group was observed in all cases even though there could be a

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DOI: 10.1039/D0OB01344G

oxidation. Also, the tertiary homoallyl alcohols 1t-w furnished drive for more substituted double bond formation. Further, the

the

case of 3v, the water addition occurred at the benzylic position provided the

considering the stability of benzylic cation giving the -hydroxy and 66% yields. The product 2-methyl-

product regioselectively. Also, no elimination of -hydroxy selectively obtained in 60% yield unlike the aldehyde selective

hemiacetal formation reported in the literature for



-hydroxy ketones 3t-w, respectively, in 68-75% yields. In aliphatic secondary and tertiary homoallyl alcohols 1x and 1y

-hydroxy ketones 3x and 3y, respectively in 65%

-hydroxy ketone 3z was







-

substituted homoallyl alcohols.^6aSince the substrate homoallyl

alcohol 1z was used as diastereomer mixture, the ketone

compound 3z was obtained as 70:30 diastereomer mixture. A

reaction of 1b at 1.5 mmol scale resulted in 3b in 67% yield after

a 28 h reaction. In all reactions we did not observe the

formation of regioisomeric aldehyde and also allylic/benzylic

alcohol oxidation products within the detection limit of NMR.

The pure products were isolated by chromatographic

purification and the remaining material was observed as trail of

inseparable and unidentifiable mixtures. The MnO₂oxidations

normally require over 15 equivalents¹⁷of the oxidants due to

heterogenous media. With upto 6 equivalents of MnO₂, no

benzylic alcohol oxidation was observed (Table 1, entry 19).

Scheme 3 Wacker-type oxidation of styrenes and aliphatic terminal olefins.

The substrate scope was extended to styrenes and

unactivated aliphatic terminal olefins (Scheme 3). Thus,

Scheme 2 Substrate scope for Wacker-type oxidation of homoallyl alcohols.

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styrenes with electron donating and withdrawing groups all General information

worked well in giving the methyl ketones 3a-m in 50-79% performed on EM 250 Kieselgel 60 F254 silica gel plates. The

.

Thin-layer chromatography was

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DOI: 10.1039/D0OB01344G

yields. No aldehyde products were detected in all cases. The spots were visualized by staining with KMnO₄or by using a UV

ortho-substituted compounds

h-l were all obtained lamp. ¹HNMR and ¹³CNMR were recorded with a spectrometer

successfully without any difficulty. The unactivated terminal operating at 400 or 500 and 100 or 125 MHz for proton and

3



olefins

ketones

1

3



n-r and diene

n-r and diketone

1

3



s



gave the corresponding methyl carbon nuclei, respectively. The chemical shifts are based on the

in moderate to good yields. Good CHCl₃peak at = 7.26 ppm for proton NMR and = 77.00 ppm

s



functional group compatibility was observed with substrates (t) for carbon NMR. IR spectra were obtained on an FT-IR

having free hydroxy or ester groups in obtaining the methyl spectrometer by evaporating compounds dissolved in CHCl₃on

ketones

3



t-x in 50-63% yields.

CsCl pellet or by preparing KBr pellet for solid. HRMS (ESI-TOF)

The chemoselective homoallylic Wacker oxidation was spectra were recorded using positive electrospray ionization by

18

applied in the synthesis of the natural product gingerol (

8

)

the TOF method.

(Scheme 4). The latter was isolated from rhizomes of Zingiber General Procedure for synthesis of homoallylalcohols: A flame dry

officinale by Connell and Sutherland and later by Nakatani et round-bottom flask was charged with a solution of requisite allyl

al.¹⁹It shows potent anticancer, antimicrobial, anti- bromide (3.50 mmol) in anhydrous THF (5 mL) under argon

inflammatory, antioxidant, antidiabetic, antiallergic, and atmosphere. Zinc dust (0.230 g, 3.50 mmol) was added slowly at 0 ^oC.

antiaging activities.²⁰Toward the synthesis of

metathesis of eugenol (

) with homoallyl alcohol 6¹²provided added to the stirring solution. The resulting suspension was stirred

the internal homoallyl alcohol

in 72% yield as 8:1 (E/Z) for 2 h at 0 ^oC and then overnight at room temperature. The reaction

mixture. This on Wacker oxidation under present protocol mixture was quenched with saturated aq. NH₄Cl at 0 ^oC, the mixture

regioselectively gave (±)-gingerol in 61% yield. The then filtered and extracted with EtOAc (3 x 10 mL). The combined

enantiopure version of easily obtainable by various organic layers were washed with brine, dried (Na₂SO₄) and

8, the cross The aldehyde (1.0 mmol) dissolved in anhydrous THF (5 mL) was

1p

7

8

6

asymmetric allylation protocols²¹and also the variation of side concentrated. The residue was purified by silica gel column

chain can lead conveniently to other gingerols and related chromatography using petroleum ether/EtOAc (9:1 to 4:1) as an

compounds.^18e

eluent to afford the homoallylalcohols. The known products

obtained by this procedure, 1b-d,^22a1e,^22b1f,^22c1g,^22b1h,^22a1i-l,^22d

1m,^22e1n,^22f1o,^22e1p,^22a1q,^22a1r,^22g1s,^22a1t,^22h1u,²²ⁱ1v,^22j1w,^22f

1x,^22k1y¹²and 1z^22lhave analytical data consistent with the

literature.

Styrenes 1a-m and olefins 1n, 1p (eugenol), 1q-x were

commercially procured (Aldrich Chem. Co.). Preparation of 1o is

given below.

1-Benzyloxy-4-(but-3-en-1-yl)-2-methoxybenzene (1o). To the

stirred solution of 1-benzyloxy-4-(bromomethyl)-2-methoxybenzene

(1 g, 3.26 mmol, 1.0 equiv) in Et₂O (20 mL) was added freshly

prepared solution of allyl magnesium bromide (3.6 mL, 3.6 mmol, 1.1

equiv) in Et₂O at 0 ^oC and the resulting suspension was stirred for 16

h. The reaction was quenched with saturated aq. NH₄Cl and the

solution extracted with EtOAc (2 × 20 mL). The combined organic

layers were washed with brine, dried (Na₂SO₄), and concentrated.

The residue was purified by silica gel column chromatography using

petroleum ether/EtOAc (19:1) as an eluent to give 1o (0.613 g, 70%)

as colorless oil. IR (CHCl₃): ν_max= 3062, 3030, 2923 2856, 1637, 1611,

1582, 1511, 1453, 1381, 1297, 1238, 1175, 1119, 1025, 912, 826, 756,

696, 542 cm^-1; ¹H NMR (500 MHz, CDCl₃): δ = 7.56–7.16 (m, 5H), 6.96–

6.55 (m, 3H), 5.98–5.66 (m, 1H), 5.14 (s, 2H), 5.08–4.98 (m, 2H), 3.89

(s, 3H), 2.66 (t, J = 7.7 Hz, 2H), 2.38–2.33 (m, 2H) ppm; ¹³C{¹H} NMR

(125 MHz, CDCl₃): δ = 149.5, 146.2, 138.2, 137.5, 135.2, 128.5, 127.8,

127.3, 120.2, 114.9, 114.1, 112.3, 71.2, 56.0, 35.7, 35.0 ppm; HRMS

(ESI-TOF) m/z: [M+Na]⁺calcd for C₁₈H₂₀NaO₂291.3391; Found

291.3396.

Scheme 4 Short synthesis of (±)-gingerol (8).

Conclusion

In summary, in this paper, we have developed an efficient

Wacker-type orthogonal chemoselective oxidation of homoallylic

alcohols to

catalysis. Our earlier version led to



-hydroxy ketones using MnO₂as co-oxidant in PdCl₂

-unsaturated ketones.¹¹

,

Various long-chain terminal olefins, dienes, substituted styrenes

have been explored in this paper. A wide spectrum of functional-

group tolerance, mild reaction conditions, good regio- and chemo

selectivity are key features of the present methodology (50

examples). The presented work gains significance considering not

many reports in chemoselective Wacker-type oxidation of

homoallyl alcohols selectively to methyl ketones are known. A

short synthesis of gingerol using the present Wacker oxidation

method has also been achieved

.

Experimental Section

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TOF) m/z: [M+Na]⁺calcd for C₁₂H₁₆NaO₄247.0941; Found

247.0938.

General procedure for Wacker oxidation of terminal olefins 1

or 1

To a stirred solution of olefin or 1 (0.5 mmol) in CH₃CN (3.5

mL) and H₂O (0.5 mL) were added PdCl₂(8.9 mg, 0.05 mmol, 10

mol%) and MnO₂(174 mg, 2.0 mmol, 4.0 equiv) at room

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DOI: 10.1039/D0OB01344G



1

4-(2,5-Dimethoxyphenyl)-4-hydroxybutan-2-one(3f).^23c

Reaction time = 19 h, colorless oil (68.6 mg, 61%). IR (CHCl₃):

ν_max= 3489, 3091, 3081, 3020, 1715, 1602, 1521, 1415, 1163,

temperature. The reaction mixture was warmed to 60 C and

1

1111, 1078, 1014, 973, 922, 857, 698, 668, 627 cm^-1; H NMR

stirred for specified time in a closed flask. The reaction mixture

was then filtered through a small pad of Celite/silica gel and

washed with EtOAc and the filtrate concentrated. The residue

was purified by silica gel column chromatography using

petroleum ether/EtOAc (9:1 to 4:1) as an eluent to afford the

(400 MHz, CDCl₃):δ = 7.04 (d, J = 2.5 Hz, 1H), 6.79–6.74 (m, 2H),

5.37 (dd, J = 9.3, 2.8 Hz, 1H), 3.78 (s, 3H), 3.77 (s, 3H), 2.92 (dd,

J = 17.3, 2.8 Hz, 1H), 2.75 (dd, J = 17.3, 9.4 Hz, 1H), 2.19 (s, 3H)

ppm; ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 209.5, 153.9, 149.9,

132.0, 112.9, 112.3, 111.3, 65.5, 55.8, 55.8, 50.4, 30.6 ppm;

HRMS (ESI-TOF) m/z: [M+Na]⁺calcd for C₁₂H₁₆NaO₄247.0941;

Found 247.0939.

methyl ketones 3 or 3, respectively.

4-Hydroxy-4-phenylbutan-2-one (3b).^23aReaction time = 22 h,

colorless oil (64 mg, 78%). IR (CHCl₃): ν_max= 3444, 3063, 3031,

2928, 1714, 1605, 1495, 1454, 1416, 1361, 1331, 1258, 1165,

4-(Benzo[1,3]dioxol-5-yl)-4-hydroxybutan-2-one

Reaction time = 18 h, white solid (76 mg, 73%). M.p. 53‒55

(3g).^23d

C;

1

1062, 1028, 1000, 941, 916, 701, 541 cm^-1; H NMR (500 MHz,



IR (CHCl₃): ν_max= 3446, 3013, 2902, 1713, 1608,1505, 1488,

CDCl₃): δ = 7.38−7.29 (m, 5H), 5.16 (dd, J = 9.0, 3.4 Hz, 1H), 2.92–

1445, 1360, 1249, 1095, 1039, 933, 868, 814, 758, 632, 563 cm^-

2.79 (m, 2H), 2.19 (s, 3H) ppm; ¹³C{¹H} NMR: (125 MHz, CDCl₃):

δ = 209.0, 142.7, 128.5, 127.7, 125.6, 69.9, 52.0, 30.7 ppm;

HRMS (ESI-TOF) m/z: [M+Na]⁺calcd for C₁₀H₁₂NaO₂187.0730;

Found 187.0740.

1

¹; H NMR (500 MHz, CDCl₃): δ = 6.86 (d, J = 1.5 Hz, 1H), 6.79–

6.74 (m, 2H), 5.93 (s, 2H), 5.05−5.03 (m, 1H), 2.85 (dd, J = 17.3,

9.3 Hz, 1H), 2.75 (dd, J = 17.3, 3.2 Hz, 1H), 2.18 (s, 3H) ppm;

¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 209.0, 147.8, 147.0, 136.8,

119.0, 108.1, 106.3, 101.0, 69.7, 52.0, 30.7 ppm; HRMS (ESI-

TOF) m/z: [M+Na]⁺calcd for C₁₁H₁₂NaO₄231.0628; Found

231.0633.

4-Hydroxy-4-(p-tolyl)butan-2-one (3c).^23bReaction time = 20 h,

colorless oil (71.3 mg, 80%). IR (CHCl₃): ν_max= 3437, 3011, 2923

1712, 1666, 1612, 1515, 1420, 1361, 1321, 1307, 1288, 1257,

1179, 1163, 1071, 1020, 980, 948, 821, 759, 600, 568, 542 cm^-

¹; ¹H NMR (500 MHz, CDCl₃): δ = 7.24 (d, J = 8.0 Hz, 2H), 7.16 (d,

J = 8.0 Hz, 2H), 5.12 (dd, J = 9.3, 3.2 Hz, 1H), 2.88 (dd, J = 17.3,

5.9 Hz, 1H), 2.79 (dd, J = 17.4, 3.2 Hz, 1H), 2.34 (s, 3H), 2.19 (s,

3H) ppm; ¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 209.1, 139.8, 137.4,

129.2, 125.6, 69.7, 52.0, 30.7, 21.1 ppm; HRMS (ESI-TOF) m/z:

[M+Na]⁺calcd for C₁₁H₁₄NaO₂201.0886; Found 201.0885.

4-Hydroxy-4-(4-hydroxyphenyl)butan-2-one (3h). Reaction

time = 26 h, colorless oil (69.4 mg, 77%). IR (CHCl₃): ν_max= 3484,

3017, 2971, 2900, 1713, 1661, 1609, 1592, 1566, 1491, 1406,

1360, 1316, 1257, 1183, 1162, 1092, 1042, 1014, 975, 945, 832,

800, 776, 668, 632, 540 cm^-1; ¹H NMR (400 MHz, CDCl₃): δ = 7.14

(d, J = 8.4 Hz, 2H), 6.71 (d, J = 8.4 Hz, 2H), 5.05 (dd, J = 9.1, 3.1

Hz, 1H), 3.68 (brs, 1H), 2.89 (dd, J = 17.3, 9.2 Hz, 1H), 2.76 (dd, J

= 17.3, 3.2 Hz, 1H), 2.16 (s, 3H) ppm; ¹³C{¹H} NMR (100 MHz,

CDCl₃): δ = 209.9, 155.6, 134.1, 127.2, 115.5, 69.7, 51.6, 30.7

ppm; HRMS (ESI-TOF) m/z: [M+Na]⁺calcd for C₁₀H₁₂NaO₃

203.0679; Found 203.0685.

4-Hydroxy-4-(3-methoxyphenyl)butan-2-one (3d).^23aReaction

time = 26 h, colorless oil (74 mg, 76%). IR (CHCl₃): ν_max= 3465,

3002, 2933, 2837, 1710, 1602, 1586, 1488, 1436, 1361, 1319,

1288, 1264, 1160, 1044, 953, 870, 782, 756, 699, 665, 552 cm^-1;

¹H NMR (500 MHz, CDCl₃): δ = 7.27–7.24 (m, 1H), 6.93–6.90 (m,

4-(4-Chlorophenyl)-4-hydroxybutan-2-one (3i).^23aReaction

time = 20 h, pale yellow solid (69.5 mg, 70%). M.p. 45‒48 C; IR

(CHCl₃): ν_max= 3483, 3020, 2976, 2915, 2891, 1712, 1661, 1609,

2H), 6.82−6.80 (m, 1H), 5.13 (dd, J = 9.1, 3.2 Hz, 1H), 3.80 (s, 3H),

2.88 (dd, J = 17.5, 9.3 Hz, 1H), 2.80 (dd, J = 17.5, 2.9 Hz, 1H), 2.19

(s, 3H) ppm; ¹³C{¹H} NMR (125MHz, CDCl₃): δ = 209.0, 159.8,

144.4, 129.6, 117.8, 113.2, 111.1, 69.8, 55.2, 51.9, 30.7 ppm;

HRMS (ESI-TOF) m/z: [M+Na]⁺calcd for C₁₁H₁₄NaO₃217.0835;

Found 217.0835.

1567, 1492,1406, 1360, 1313, 1186, 1159, 1092, 1014, 975, 928,

1

877, 823, 667, 626, 540 cm^-1; H NMR (400 MHz, CDCl₃): δ =

7.32–7.26 (m, 5H), 5.11 (dd, J = 8.6, 3.8 Hz, 1H), 3.00 (br s, 1H),

2.88–2.73 (m, 2H), 2.18 (s, 3H) ppm; ¹³C{¹H} NMR (100 MHz,

CDCl₃): δ = 208.9, 141.2, 133.3, 128.6, 127.0, 69.1, 51.8, 30.7

ppm; HRMS (ESI-TOF) m/z: [M+Na]⁺calcd for C₁₀H₁₁ClNaO₂

221.0340; Found 221.0340.

4-(3,4-Dimethoxyphenyl)-4-hydroxybutan-2-one(3e).

Reaction time = 23 h, pale yellow solid (72mg, 64%). M.p. 94

−98



C; IR (CHCl₃): ν_max= 3436, 3002, 2940, 2837, 1713, 1602, 1586,

1543, 1488, 1465, 1456, 1435, 1361, 1318, 1288, 1264, 1159,

1044, 956, 871, 785, 750, 699, 645, 551 cm^-1; ¹H NMR (500 MHz,

CDCl₃): δ = 6.92 (s, 1H), 6.87−6.81 (m, 2H), 5.10 (dd, J = 9.2, 2.1

4-Hydroxy-4-(4-nitrophenyl)butan-2-one (3j).^23aReaction time

= 28 h, pale yellow solid (74.3 mg, 71%). M.p. 59‒64 C; IR

(CHCl₃): ν_max= 3481, 3019, 2905, 2854, 1712, 1602, 1521, 1413,

1348, 1163, 1109, 1076, 975, 924, 857, 698, 668, 626, 537 cm^-1;

¹H NMR (500 MHz, CDCl₃): δ = 8.17 (dd, J = 8.6, 1.8 Hz, 2H), 7.52

(d, J = 8.5 Hz, 2H), 5.24 (t, J = 6.1 Hz, 1H), 2.84 (d, J = 6.7 Hz, 2H),

2.20 (s, 3H) ppm; ¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 208.4,

Hz, 1H), 3.89 (s, 3H), 3.86 (s, 3H), 3.25 (s, 1H), 2.91 (dd, J = 17.5,

9.3 Hz, 1H), 2.82 (dd, J = 17.5, 2.9 Hz, 1H), 2.19 (s, 3H) ppm;

¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 209.1, 149.1, 148.5, 135.4,

117.8, 111.0, 108.8, 69.7, 55.9, 55.8, 52.0, 30.8 ppm; HRMS (ESI-

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Journal Name

150.0, 147.2, 126.4, 123.7, 68.8, 51.5, 30.6 ppm; HRMS (ESI- 3H) ppm; ¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 209.1,_V1_ie5_w7_A._r7_ti,_cl1_e3_O7_nl._in8_e,

TOF) m/z: [M+Na]⁺calcd for C₁₀H₁₁NNaO₄232.0580; Found 134.1, 129.4, 128.7, 127.2, 124.3, 119.0, ^D1^O05^I:.¹6⁰,^.17⁰0³.⁹0^/,^D5⁰5^O.^B3⁰,¹5³1⁴⁴.9^G,

232.0575.

30.8 ppm; HRMS (ESI-TOF) m/z: [M+Na]⁺calcd for C₁₅H₁₆NaO₃:

267.0992;Found 267.1001

4-Hydroxy-4-(2-nitrophenyl)butan-2-one (3k).^23aReaction time

= 30 h, colorless oil (68 mg, 65%). IR (CHCl₃): ν_max= 3505, 3071, (E)-4-Hydroxy-6-phenylhex-5-en-2-one (3p).²⁴Reaction time =

3013, 2962, 2938, 1677, 1598, 1573, 1466, 1358, 1295, 1249, 24 h, colorless oil (69.4 mg, 73%). IR (CHCl₃): ν_max= 3450, 3020,

1217, 1185, 1154, 1126, 1070, 1044, 1022, 967, 807, 669, 596, 2926, 2855, 1710, 1491, 1405, 1357, 1309, 1092, 1014, 1014,

1

534 cm^-1; H NMR (400 MHz, CDCl₃): δ = 7.91–7.70 (m, 2H), 973, 829, 805, 726, 668, 541 cm^-1; ¹H NMR (400 MHz, CDCl₃): δ

7.67–7.61 (m, 1H), 7.48–7.38 (m, 1H), 5.64 (d, J = 9.4 Hz, 1H), = 7.37–7.24 (m, 5H), 6.64 (d, J = 15.9 Hz, 1H), 6.20 (dd, J = 15.9,

3.40 (br s, 1H), 3.06 (d, J = 17.6 Hz, 1H), 2.72 (dd, J = 17.6, 9.4 6.1 Hz, 1H), 4.76 (q, J = 6.0 Hz, 1H), 2.76 (d, J = 6.1 Hz, 2H), 2.21

Hz, 1H), 2.20 (s, 3H) ppm; ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = (s, 3H) ppm; ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 209.0, 136.4,

208.6, 147.0, 138.5, 133.7, 128.2, 128.1, 124.3, 65.4, 51.1, 30.3 130.4, 130.0, 128.5,127.7, 126.4, 68.4, 49.9, 30.8 ppm; HRMS

ppm; HRMS (ESI-TOF) m/z: [M+Na]⁺calcd for C₁₀H₁₁NNaO₄(ESI-TOF) m/z: [M+ H]⁺calcd for C₁₂H₁₅O₂191.1067; Found

232.0580; Found 232.0578.

191.1058.

4-Hydroxy-4-(3-nitrophenyl)butan-2-one (3l). Reaction time = (E)-4-Hydroxy-6-(4-methoxyphenyl)hex-5-en-2-one(3q).²⁴

36 h, colorless oil (73.2 mg, 70%). IR (CHCl₃): ν_max= 3468, 3081, Reaction time = 24 h, colorless oil (79.4 mg, 77%). IR (CHCl₃):

2926, 2847, 1712, 1583, 1530, 1485, 1351, 1261, 1166, 1095, ν_max= 3450, 3018, 2927, 2847, 2837, 1711, 1598, 1489, 1465,

1

1066, 1022, 959, 900, 809, 738, 690 cm^-1; H NMR (500 MHz, 1435, 1362, 1291, 1246, 1163, 1105, 1028, 975, 796, 668 cm^-1;

CDCl₃): δ = 8.23 (d, J = 2.5 Hz, 1H), 8.12 (d, J = 8.0 Hz, 1H), 7.70 ¹H NMR (500 MHz, CDCl₃): δ = 7.30 (d, J = 8.0 Hz, 2H), 6.84 (d, J

(d, J = 7.6 Hz, 1H), 7.52 (t, J = 7.9 Hz, 1H), 5.25 (dd, J = 7.6, 4.5 = 8.3 Hz, 2H), 6.58 (d, J = 15.9 Hz, 1H), 6.05 (dd, J = 15.9, 6.5 1H),

Hz, 1H), 2.87 (d, J = 4.7 Hz, 2H), 2.22 (s, 3H)ppm; ¹³C{¹H} NMR 4.72 (q, J = 5.8 Hz, 1H), 3.80 (s, 3H), 2.74 (d, J = 5.9 Hz, 2H), 2.20

(125 MHz, CDCl₃): δ = 208.6, 148.3, 144.8, 131.8, 129.5, 122.6, (s, 3H) ppm; ¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 209.0, 159.3,

120.7, 68.7, 51.5, 30.7 ppm; HRMS (ESI-TOF) m/z: [M+Na]⁺calcd 130.0, 129.2, 127.8, 127.7, 114.0, 68.6, 55.2, 50.1, 30.8 ppm;

for C₁₀H₁₁NNaO₄232.0580; Found 232.0574.

HRMS (ESI-TOF) m/z: [M+Na]⁺calcd for C₁₃H₁₆NaO₃243.0992;

Found 243.0997.

4-([1,1'-Biphenyl]-4-yl)-4-hydroxybutan-2-one (3m). Reaction

time = 20 h, colorless oil (96 mg, 80%). IR (CHCl₃): ν_max= 3447, (E)-4-Hydroxy-6-(2-methoxyphenyl)hex-5-en-2-one(3r).

3020, 2925, 1769, 1485, 1466, 1437, 1415, 1288, 1216, 1156, Reaction time = 28 h, colorless oil (77.3 mg, 75%). IR (CHCl₃):

1120, 995, 861, 817, 776, 753, 722, 694, 666, 634, 542 cm^-1; ¹H ν_max= 3446, 3006, 2930, 2854, 1713, 1596, 1490, 1468, 1432,

NMR (400 MHz, CDCl₃): δ = 7.63–7.55 (m, 4H), 7.47–7.41 (m, 1368, 1291, 1246, 1168, 1110, 1053, 1025, 976, 726, 670 cm^-1;

4H), 7.34–7.32 (m, 1H), 5.22 (dd, J = 8.9, 3.5 Hz, 1H), 2.97–2.84 ¹H NMR (400 MHz, CDCl₃): δ = 7.42 (d, J = 7.6 Hz, 1H), 7.40–7.20

(m, 2H), 2.22 (s, 3H) ppm; ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = (m, 1H), 7.01–6.85 (m, 3H), 6.23 (dd, J = 16.1, 6.4 Hz, 1H), 4.76

209.0, 141.7, 140.8, 140.7, 128.8, 127.3, 127.1, 126.1, 69.6, (q, J = 5.7 Hz, 1H), 3.84 (s, 3H), 2.76 (d, J = 6.1 Hz, 2H), 2.21 (s,

51.9, 30.8 ppm; HRMS (ESI-TOF) m/z: [M+Na]⁺calcd for 3H) ppm; ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 209.0, 156.8,

C₁₆H₁₆NaO₂263.1043; Found 263.1046.

130.7, 128.8, 126.9, 125.4, 120.6, 110.8, 69.0, 55.4, 50.1, 30.8

ppm; HRMS (ESI-TOF) m/z: [M+Na]⁺calcd for C₁₃H₁₆NaO₃

4-(Anthracen-9-yl)-4-hydroxybutan-2-one (3n). Reaction time 243.0992; Found 243.1007.

= 26 h, pale yellow solid (99 mg, 75%). M.p. 107–109 C; IR



(CHCl₃): ν_max= 3444, 3050, 3016, 2925, 2854, 1711, 1681, 1593, 4-(Furan-2-yl)-4-hydroxybutan-2-one (3s).^23dReaction time =

1444, 1357, 1329, 1305, 1158, 1085, 931,887, 809, 732, 694, 25 h, colorless oil (52.4 mg, 68%). IR (CHCl₃): ν_max= 3442, 3021,

1

666, 555cm^-1; H NMR (400 MHz, CDCl₃) : δ = 8.64 (s, 2H), 8.41 2945, 2861, 1715, 1505, 1413, 1362, 1261, 1164, 1066, 1013,

1

(s, 1H), 8.00 (d, J = 8.0 Hz, 2H), 7.52‒7.43 (m, 4H), 6.79 (dd, J = 915, 888, 813, 599 cm^-1; H NMR (500 MHz, CDCl₃): δ = 7.35–

10.3, 2.6 Hz, 1H), 3.72 (dd, J = 18.1, 10.3 Hz, 1H), 2.89 (dd, J = 7.22 (m, 1H), 6.32–6.31 (m, 1H), 6.25–6.24 (m, 1H), 5.15 (dd, J =

18.1, 2.4 Hz, 1H), 2.24 (s, 3H) ppm; ¹³C{¹H} NMR (100 MHz, 8.9, 3.2 Hz, 1H), 3.05 (dd, J = 17.6, 8.9 Hz, 1H), 2.91 (dd, J = 17.6,

CDCl₃): δ = 209.0, 132.6, 131.6, 129.3, 129.1, 128.3, 125.8, 3.2 Hz, 1H), 2.20 (s, 3H) ppm; ¹³C{¹H} NMR (125 MHz, CDCl₃): δ

124.8, 66.4, 50.3, 30.7 ppm; HRMS (ESI-TOF) m/z: [M+Na]⁺calcd = 208.4, 154.9, 142.1, 110.2, 106.2, 63.7, 48.0, 30.6 ppm; HRMS

for C₁₈H₁₆NaO₂287.1043; Found 287.1043.

(ESI-TOF) m/z: [M+Na]⁺calcd for C₈H₁₀NaO₃177.0522; Found

177.0518.

4-Hydroxy-4-(6-methoxynaphthalen-2-yl)butan-2-one

(3o). 1-(9-Hydroxy-9H-fluoren-9-yl)propan-2-one (3t). Reaction

Reaction time = 21 h, colorless oil (95.3 mg, 78%). IR (CHCl₃): time = 22 h, colorless oil (89.4 mg, 75%). IR (CHCl₃): ν_max= 3451,

ν_max= 3469, 3020, 2929, 2857, 1712, 1596, 1490, 1459, 1361, 3065, 3043, 2928, 1775, 1698, 1608, 1588, 1477, 1450, 1421,

1288, 1241, 1164, 1112, 1053, 1027, 975, 804, 756 cm^-1; ¹H NMR 1393, 1360, 1329, 1302, 1252, 1234, 1168, 1105, 1088, 1047,

(500 MHz, CDCl₃) : δ = 7.74‒7.71 (m, 3H), 7.42 (d, J = 8.4 Hz, 1H), 1028, 990, 940, 904, 879, 854, 737, 710, 665, 622, 575 cm^-1; ¹H

7.16‒7.12 (m, 2H), 5.29 (dd, J = 9.1, 2.6 Hz, 1H), 3.92 (s, 3H), 2.97 NMR (500 MHz, CDCl₃): δ = 7.63 (d, J = 7.5 Hz, 2H), 7.54 (d, J =

(dd, J = 17.5, 9.2 Hz, 1H), 2.89 (dd, J = 17.5, 2.9 Hz, 1H), 2.21 (s, 7.5 Hz, 2H), 7.38–7.35 (m, 2H), 7.30–7.26 (m, 2H), 3.05 (s, 2H),

6 | J. Name., 2012, 00, 1-3

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2.15 (s, 3H) ppm; ¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 210.5, (ESI-TOF) m/z: [M+Na]⁺calcd for C₁₇H₃₄NaO₂293.2451; Found

View Article Online

DOI: 10.1039/D0OB01344G

148.0, 139.2, 129.2, 128.1, 123.9, 120.1, 80.5, 51.4, 31.8 ppm; 293.2451.

HRMS (ESI-TOF) m/z: [M+Na]⁺calcd for C₁₆H₁₄NaO₂261.0886;

Found 261.0886.

4-Hydroxy-3-methylnonan-2-one (3z).¹²Reaction time = 26 h,

colorless oil (51.7 mg, 60%). Diastereomer mixture (dr = 65:35).

1

1-(1-Hydroxy-1,2,3,4-tetrahydronaphthalen-1-yl)propan-2-

Major diastereomer: H NMR (400 MHz, CDCl₃): δ = 3.97–3.89

one (3u). Reaction time = 24 h, colorless oil (76.6 mg, 75%). IR (m, 1H), 2.65–2.51 (m, 1H), 2.19 (s, 3H), 1.51–1.27 (m, 8H), 1.14

(CHCl₃): ν_max= 3476, 3023, 2931, 2855, 1734, 1486, 1466, 1437, (d, J = 4.6 Hz, 3H), 0.87 (t, J = 6.7 Hz, 3H) ppm; ¹³C{¹H} NMR (100

1378, 1287, 1159, 1120, 1071, 1042, 997, 928, 821, 723, 694, MHz, CDCl₃): δ = 214.0, 70.9, 50.8, 34.0, 31.8, 29.3, 26.0, 22.6,

668, 542 cm^-1; ¹H NMR (400 MHz, CDCl₃): δ = 7.53 (d, J = 7.9 Hz, 14.1, 9.6. ppm.

1H), 7.23–7.14 (m, 2H), 7.04 (d, J = 7.2 Hz, 1H), 2.94 (s, 2H),

2.88–2.68 (m, 2H), 2.18 (s, 3H), 2.13–2.02 (m, 1H), 2.02–1.87 (m, Acetophenone (3'a).^6bReaction time = 24 h, colorless oil (47.5

1

2H), 1.79–1.68 (m, 1H) ppm; ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = mg, 79%). H NMR (400 MHz, CDCl₃): δ

= 7.97–7.92 (m, 2H),

210.5, 141.0, 136.3, 128.8, 127.3, 126.4, 126.3, 71.8, 53.5, 36.2, 7.57–7.51 (m, 1H), 7.48–7.41 (m, 2H), 2.59 (s, 3H) ppm; ¹³C{¹H}

32.1, 29.4, 20.1 ppm. HRMS (ESI-TOF) m/z: [M+K]⁺calcd for NMR (100 MHz, CDCl₃): δ = 198.1, 137.0, 133.0, 128.5, 128.2,

C₁₃H₁₆KO₂243.0782; Found 243.0780.

26.5 ppm.

4-Hydroxy-1,4-diphenylpentan-1-one (3v).^25aReaction time = 1-(p-Tolyl)ethan-1-one (3'b).^9bReaction time = 22 h, colorless

25 h, colorless oil (89 mg, 70%). IR (CHCl₃): ν_max= 3469, 3060, oil (45.6 mg, 68%). ¹H NMR (400 MHz, CDCl₃): δ = 7.85 (d, J = 8.2

3027, 2975, 2928, 1722, 1683, 1599, 1581, 1494, 1447, 1373, Hz, 2H), 7.25 (d, J = 8.0 Hz, 2H), 2.56 (s, 3H), 2.40 (s, 3H) ppm;

1

1278, 1174, 1026, 914, 888, 764, 700, 560 cm^-1; H NMR (500 ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 197.8, 143.8, 134.6, 129.2,

MHz, CDCl₃) : δ = 7.88–7.86 (m, 2H), 7.54–7.51 (m, 1H), 7.47– 128.4, 26.4, 21.5 ppm; HRMS (ESI-TOF) m/z: [M + Na]⁺calcd for

7.45 (m, 2H), 7.43–7.39 (m, 2H), 7.36–7.33 (m, 3H), 3.03–2.97 C₉H₁₀ONa 157.0624; Found 157.0623 ppm.

(m, 1H), 2.90‒2.84 (m, 1H), 2.33–2.24 (m, 2H), 1.63 (s, 3H) ppm;

¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 201.2, 147.2, 136.7, 133.1, 1-(4-tert-Butylphenyl)ethan-1-one (3'c).^6bReaction time = 24 h,

128.5, 128.3, 128.1, 126.7, 124.8, 74.2, 37.7, 33.8, 31.3 ppm; colorless oil (56.4 mg, 64%). ¹H NMR (500 MHz, CDCl₃): δ

= 7.90

HRMS (ESI-TOF) m/z: [M+Na]⁺calcd for C₁₇H₁₈NaO₂(d, J = 8.7 Hz, 2H), 7.48 (d, J = 8.7 Hz, 2H), 2.58 (s, 3H), 1.34 (s,

277.1199;Found 277.1194.

9H) ppm; ¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 197.8, 156.8, 134.6,

128.3, 125.5, 35.1, 31.1, 26.5 ppm; HRMS (ESI-TOF) m/z: [M +

4-Hydroxy-4-phenylpentan-2-one(3w).¹²Reaction time = 28 h, H]⁺calcd for C₁₂H₁₇O 177.1274; Found 177.1276.

colorless oil (60.6 mg, 68%). H NMR (500 MHz, CDCl₃) : δ =

1

7.50–7.25 (m, 5H), 3.19 (d, J = 17.0 Hz, 1H), 2.85 (d, J = 17.1 Hz, 1-(4-Methoxyphenyl)ethan-1-one (3'd).^6bReaction time = 16 h,

1H), 2.08 (s, 3H), 1.52 (s, 3H) ppm; ¹³C{¹H} NMR (125 MHz, colorless semi-solid (52.6 mg, 70%). ¹H NMR (400 MHz, CDCl₃):

CDCl₃): δ = 203.7, 140.2, 121.3, 119.7, 117.3,66.3, 46.9, 24.9, δ = 7.93 (s, 2H), 6.92 (s, 2H), 3.85 (s, 3H), 2.54 (s, 3H) ppm;

23.7 ppm; HRMS (ESI-TOF) m/z: [M+Na]⁺calcd for C₁₁H₁₄NaO₂: ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 196.8, 163.4, 130.5, 113.6,

201.0886; Found 201.0892.

55.4, 26.3 ppm.

4-Hydroxydecan-2-one (3x).^23dReaction time = 30 h, colorless 1-(4-Chlorophenyl)ethan-1-one (3'e).^9bReaction time = 36 h,

oil (56 mg, 65%). IR (CHCl₃): ν_max= 3434, 2959, 2930, 2857, colorless oil (45.6 mg, 59%). IR (CHCl₃): ν_max= 3020, 2928, 2855,

1712, 1671, 1625, 1530, 1468, 1359, 1163, 1017, 976, 912, 863, 1688, 1591, 1572, 1488, 1429, 1398, 1360, 1098, 1013, 958,

1

808, 736, 689, 649, 546 cm^-1; H NMR (400 MHz, CDCl₃): δ = 832, 670 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ

=

7.85 (d, J = 8.6 Hz,

4.07–3.99 (m, 1H), 2.64 (dd, J = 17.4, 3.4 Hz, 1H), 2.52 (dd, J = 2H),7.38 (dJ = 8.7 Hz, 2H), 2.54 (s, 3H) ppm; ¹³C{¹H} NMR (100

17.4, 8.4 Hz, 1H), 2.39 (br s, 1H), 2.19 (s, 3H), 1.53−1.15 (m, MHz, CDCl₃): δ = 196.6, 139.4, 135.3, 129.6, 128.7, 26.4 ppm.

10H), 0.87 (t, J = 6.8 Hz, 3H) ppm; ¹³C{¹H} NMR (125 MHz,

CDCl₃): δ = 210.1, 67.5, 49.9, 36.3, 31.7, 30.7, 29.1, 25.4, 22.5, 1-(4-Nitrophenyl)ethan-1-one (3'f).^6bReaction time = 25 h, pale

1

14.0 ppm; HRMS (ESI-TOF) m/z: [M+Na]⁺calcd for yellow solid (58 mg, 70%). M.p. 77−79 °C; H NMR (400 MHz,

C₁₀H₂₀NaO₂195.1356; Found 195.1349.

CDCl₃): δ = 8.32 (d, J = 8.8 Hz, 2H), 8.11 (d, J = 8.8 Hz, 2H), 2.68

(s, 3H) ppm; ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 196.3, 150.7,

4-Hydroxy-4-methylhexadecan-2-one (3y). Reaction time = 24 141.6, 129.3, 123.9, 27.0 ppm.

h, colorless oil (89.3 mg, 66%). IR (CHCl₃): ν_max= 3464, 3111,

3019, 2929, 2855, 2796, 1709, 1465, 1408, 1377, 1303, 1128, 1-(4-Bromophenyl)ethan-1-one (3'g).^9bReaction time = 27 h,

1

1054, 926, 891, 717, 667 cm^-1; H NMR (500 MHz, CDCl₃): δ = colorless solid (63.7 mg, 64%). M.p. 46

−

48



C; IR (CHCl₃): ν_max

=

2.63 (d, J = 17.1 Hz, 1H), 2.54 (d, J = 17.4 Hz, 1H), 2.19 (s, 3H), 3020, 2924, 2857, 1677, 1606, 1573, 1406, 1358, 1309, 1272,

1.41

−

1.18 (m, 23H), 1.18 (s, 3H), 0.87 (t, J = 6.9 Hz, 3H) ppm; 1181, 1122, 1075, 1042, 1018, 954, 927, 878, 841, 817, 772, 668,

1

¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 211.1, 71.6, 52.2, 42.2, 31.9, 637, 591, 567 cm^–1; H NMR (400 MHz, CDCl₃): δ

= 7.80 (d, J =

30.1, 29.64, 29.62, 29.6, 29.3, 26.7, 24.0, 22.7, 14.1 ppm; HRMS 8.5 Hz, 2H), 7.59 (d, J = 8.5 Hz, 2H), 2.57 (s, 3H) ppm; ¹³C{¹H}

This journal is © The Royal Society of Chemistry 20xx

J. Name., 2013, 00, 1-3 | 7

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Organic & Biomolecular Chemistry

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Journal Name

NMR (100 MHz, CDCl₃): δ = 197.0, 135.8, 131.8, 129.8, 128.3,

26.5 ppm.

View Article Online

4-(4-Benzyloxy-3-methoxyphenyl)butan^D-2^O-^Io^{: 1}n⁰e^.10(³3⁹'o^/D).^0OR^Be⁰a¹c³t⁴io^4Gn

time = 19 h, colorless oil (99.5 mg, 70%). IR (CHCl₃): ν_max= 3019,

1-(2-Bromophenyl)ethan-1-one (3'h).²⁶Reaction time = 25 h, 2922, 1714, 1666, 1626, 1608, 1591, 1492, 1406, 1359, 1330,

1

colorless oil (53 mg, 53%). H NMR (400 MHz, CDCl₃): δ = 7.61 1161, 1091, 1014, 976, 945, 833, 797, 775, 731, 668, 584, 540

1

(d, J = 7.8 Hz, 1H), 7.46 (dd, J = 7.6, 1.7 Hz, 1H), 7.37 (td, J = 7.5, cm^-1; H NMR (400 MHz, CDCl₃): δ = 7.44–7.27 (m, 5H), 6.81–

0.8 Hz, 1H), 7.29 (td, J = 7.7, 1.7 Hz, 1H), 2.63 (s, 3H) ppm; ¹³C{¹H} 6.73 (m, 2H), 6.65 (d, J = 8.1 Hz, 1H), 5.12 (s, 2H), 3.87 (s, 3H),

NMR (100 MHz, CDCl₃): δ = 201.4, 141.4, 133.8, 131.8, 128.9, 2.83 (t, J = 7.1 Hz, 2H), 2.73 (t, J = 7.1 Hz, 2H), 2.13 (s, 3H) ppm;

127.4, 118.9, 30.3 ppm. HRMS (ESI-TOF) m/z: [M + Na]⁺calcd for ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 208.1, 149.5, 146.5, 137.3,

C₇H₈BrNaO 220.9572; Found 220.9567.

134.2, 128.5, 127.7, 127.2, 120.0, 114.2, 112.2, 71.1, 55.9, 45.3,

30.1, 29.3 ppm; HRMS (ESI-TOF) m/z: [M+Na]⁺calcd for

1-(2-Chlorophenyl)ethan-1-one (3'i).^9bReaction time = 28 h, C₁₈H₂₀NaO₃307.1305; Found 307.1310.

colorless oil (43.3 mg, 56%). ¹H NMR (400 MHz, CDCl₃): δ = 7.52

(d, J =7.6 Hz, 1H), 7.41–7.22 (m, 3H), 2.63 (s, 3H) ppm; ¹³C{¹H} 1-(4-Hydroxy-3-methoxyphenyl)propan-2-one (3'p). Reaction

NMR (100 MHz, CDCl₃): δ = 200.4, 139.0, 131.9, 131.2, 130.6, time = 20 h, colorless oil (63 mg, 70%). IR (CHCl₃): ν_max= 3528,

129.3, 126.9, 30.6 ppm;

3020, 2979, 2935, 2857, 1708, 1603, 1515, 1468, 1434, 1363,

1268, 1207, 1151, 1120, 1036, 956, 914, 880, 820, 726, 646 cm^-

1-(2-Methoxyphenyl)ethan-1-one (3'j).^9bReaction time = 23 h, ¹; H NMR (500 MHz, CDCl₃): δ = 6.87 (d, J = 7.8 Hz, 1H), 6.71–

colorless semi-solid (46 mg, 61%). IR (CHCl₃): ν_max= 3019, 2840, 6.67 (m, 2H), 5.63 (s, 1H), 3.86 (s, 3H), 3.60 (s, 2H), 2.14 (s, 3H)

1676, 1596, 1574, 1485, 1437, 1359, 1294, 1251, 1185, 1071, ppm; ¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 207.0, 146.6, 144.7,

1042, 967, 851, 751, 668, 595 cm^–1; ¹H NMR (400 MHz, CDCl₃): 126.0, 122.2, 114.5, 111.6, 55.9, 50.6, 29.0 ppm; HRMS (ESI-

δ = 7.72 (dd, J = 7.7, 1.7 Hz, 1H), 7.47–7.42 (m, 1H), 6.97 (dd, J = TOF) m/z: [M+Na]⁺calcd for C₁₀H₁₂NaO₃203.0679; Found

8.0, 7.6 Hz, 2H), 3.90 (s, 3H), 2.60 (s, 3H) ppm; ¹³C{¹H} NMR (100 203.0680.

1

MHz, CDCl₃): δ = 199.9, 158.8, 133.6, 130.3, 128.1, 120.4, 111.5,

55.4, 31.8 ppm.

Decan-2-one (3'q). Reaction time = 24 h, colorless oil (57 mg,

73%). IR (CHCl₃): ν_max= 3022, 2952, 2921, 1714, 1464, 1400,

1-(2,4,6-Trimethylphenyl)ethan-1-one (3'k). Reaction time = 26 1361, 1162, 670 cm^-1; ¹H NMR (400 MHz, CDCl₃): δ

= 2.41 (t, J =

h, colorless oil (55 mg, 68%). IR (CHCl₃): ν_max= 3019, 2918, 2850, 7.5 Hz, 2H), 2.13 (s, 3H), 1.54–1.52 (m, 2H), 1.32–1.20 (m, 10H),

1698, 1606, 1418, 1353, 1253, 1164, 1058, 1037, 1015, 911, 0.87 (t, J = 6.9 Hz, 3H) ppm; ¹³C{¹H} NMR (100 MHz, CDCl₃): δ =

848, 670, 643, 597 cm^-1; ¹H NMR (400 MHz, CDCl₃): δ = 6.84 (s, 209.4, 43.8, 31.8, 29.8, 29.3, 29.1, 29.08, 23.8, 22.6, 14.0 ppm;

2H), 2.46 (s, 3H), 2.28 (s, 3H), 2.22 (s, 6H) ppm; ¹³C{¹H} NMR (100 HRMS (ESI-TOF) m/z: [M+Na]⁺calcd for C₁₀H₂₀NaO 179.1406;

MHz, CDCl₃): δ = 208.5, 139.8, 138.2, 132.2, 128.4, 32.1, 20.9, Found 179.1409.

19.0 ppm; HRMS (ESI-TOF) m/z: [M+K]⁺calcd for C₁₁H₁₄KO:

201.0676; Found 201.0684.

Tetradecan-2-one (3'r). Reaction time = 28 h, colorless oil (81

mg, 76%). IR (CHCl₃): ν_max= 3020, 2931, 2844, 1717, 1449, 1414,

1-(2,4-dichlorophenyl)ethan-1-one (3'l).^9bReaction time = 28 h, 1361, 1162, 1120, 966, 722, 668 cm^–1; ¹H NMR (500 MHz,

colorless oil (57 mg, 60%). ¹H NMR (400 MHz, CDCl₃): δ = 7.51 CDCl₃): δ

= 2.40 (t, J = 7.5 Hz, 2H), 2.12 (s, 3H), 1.61–1.52 (m, 2H

(d, J = 8.3 Hz, 1H), 7.40 (d, J = 1.9 Hz, 1H), 7.28 (dd, J = 14.3, 12.4 ), 1.36–1.19 (m, 18H), 0.88 (t, J = 6.8 Hz, 3H) ppm; ¹³C{¹H} NMR

Hz, 1H), 2.61 (s, 1H) ppm; ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = (125 MHz, CDCl₃): δ = 209.5, 43.8, 31.9, 29.8, 29.63, 29.61, 29.6,

198.8, 137.6, 137.0, 132.4, 130.6, 130.4, 127.2, 30.6 ppm.

29.5, 29.4, 29.3, 29.2, 23.9, 22.7, 14.1 ppm; HRMS (ESI-TOF)

m/z: [M+Na]⁺calcd for C₁₄H₂₈ONa 235.2032; Found 235.2030.

1-(3-Nitrophenyl)ethan-1-one (3'm). Reaction time = 32 h,

colorless oil (41.3 mg, 50%). IR (CHCl₃): ν_max= 3019, 2928, 2850, Octane-2,7-dione (3's). Reaction time = 24 h, colorless oil (37

1692, 1616, 1534, 1474, 1432, 1353, 1254, 1112, 1019, 910, mg, 52%). IR (CHCl₃): ν_max= 3019, 2935, 2853, 1711, 1584, 1462,

1

848, 670, 597 cm^-1; H NMR (400 MHz, CDCl₃): δ = 8.73 (d, J = 1408, 1374, 1301, 1127, 927, 812, 724, 667 cm^–1; ¹H NMR (400

8.0 Hz, 1H), 8.39 (t, J = 6.9 Hz, 1H), 8.27 (dd, J = 7.0, 1.8 Hz, 1H), MHz, CDCl₃): δ = 2.42 (t, J = 2.8 Hz, 4H), 2.11 (s, 6H), 1.53 (t, J =

7.69–7.65 (m, 1H), 2.67 (s, 3H) ppm; ¹³C{¹H} NMR (100 MHz, 2.8 Hz, 4H) ppm; ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 208.6, 43.3,

CDCl₃): δ = 195.6, 148.4, 138.2, 133.7, 129.9, 127.3, 123.1, 26.6 29.8, 23.1 ppm. HRMS (ESI-TOF) m/z: [M+Na]⁺calcd for

ppm. HRMS (ESI-TOF) m/z: [M + Na]⁺calcd for C₈H₇NNaO₃C₈H₁₄O₂Na 165.0886; Found 165.0889.

188.0318; Found 188.0312.

10-Hydroxydecan-2-one (3't). Reaction time = 24 h, colorless oil

1-Phenylpropan-2-one (3'n).^25bReaction time = 24 h, colorless (50 mg, 63%). IR (CHCl₃): ν_max= 3465, 3162, 3013, 2929, 2856,

oil (42.3 mg, 63%). ¹H NMR (500 MHz, CDCl₃): δ = 7.57–7.23 (m, 1711, 1466, 1371, 1299, 1219, 1200, 1120, 1044, 929, 822, 770,

5H), 3.74 (s, 2H), 2.19 (s, 3H) ppm; ¹³C{¹H} NMR (125 MHz, 760, 726, 669 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ

= 3.63 (t, J = 6.7

CDCl₃): δ = 206.4, 134.2, 129.3, 128.7, 127.0, 51.1, 29.2 ppm; Hz, 2H), 2.41 (t, J = 7.4 Hz, 2H), 2.13 (s, 3H), 1.60–1.50 (m, 4H),

HRMS (ESI-TOF) m/z: [M+Na]⁺calcd for C₉H₁₀NaO: 157.0625; 1.39–1.25 (m, 8H) ppm; ¹³C{¹H} NMR (100 MHz, CDCl₃): δ =

Found 157.0624.

209.5, 63.0, 43.8, 32.7, 29.9, 29.4, 29.3, 29.1, 25.7, 23.8 ppm;

8 | J. Name., 2012, 00, 1-3

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HRMS (ESI-TOF) m/z: [M+Na]⁺calcd for C₁₀H₂₀O₂Na: 195.1356; 5-Hydroxy-1-(4-hydroxy-3-methoxyphenyl)decan_V-3_ie-_wo_An_rte_ic,_{le Online}

(



)

Found 195.1351.

gingerol (8).¹⁷The titled compound was^Dp^Or^Ie^:p¹⁰a^.1r⁰e³d^9/f^Dro⁰m^OB01344G

7

(100

mg, 0.36 mmol) following similar procedure as described for

3

11-Hydroxyundecan-2-one (3′u). Reaction time = 21 h, colorless to give 8 (64.6 mg, 48%) as colorless oil. IR (CHCl₃): ν_max= 3534,

oil (53 mg, 57%). IR (CHCl₃): ν_max= 3416, 2926, 2854, 1711, 1464, 3410, 2959, 2933, 2858, 2252, 1704, 1612, 1215, 1465, 1431,

1361, 1171, 1054, 912, 668 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ

1369, 1272, 1208, 1153, 1124, 1035, 909, 852, 818, 795, 735,

=

3.60 (t, J = 6.7 Hz, 2H), 2.39 (t, J = 7.4 Hz, 2H), 2.10 (s, 3H), 1.86 648, cm^-1; ¹H NMR (400 MHz, CDCl₃): δ = 6.79 (d, J= 8.0 Hz, 1H),

(s, 1H), 1.58–1.50 (m, 4H), 1.38–1.20 (m, 10H) ppm; ¹³C{¹H} 6.71–6.56 (m, 2H), 5.85 (brs, 1H), 4.02 (d, J = 4.0 Hz, 1H), 3.83

NMR (100 MHz, CDCl₃): δ = 209.6, 62.9, 43.7, 32.7, 29.8, 29.3, (s, 3H), 3.17 (br s, 1H), 2.81 (t, J = 6.8 Hz, 2H), 2.71 (t, J = 7.0 Hz,

29.27, 29.2, 29.1, 25.6, 23.8 ppm; HRMS (ESI-TOF) m/z: [M+Na]⁺2H), 2.57–2.43 (m, 2H), 1.54–1.19 (m, 8H), 0.87 (t, J = 6.7 Hz, 3H)

calcd for C₁₁H₂₂O₂Na 209.1512; Found 209.1510.

ppm; ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 211.4, 146.4, 143.9,

132.5, 120.6, 114.4, 111.0, 67.6, 55.7, 49.2, 45.3, 36.3, 31.6,

Ethyl 5-oxohexanoate (3′v). Reaction time = 36 h, colorless oil 29.1, 25.0, 22.5, 13.9 ppm; HRMS (ESI-TOF) m/z: [M+Na]⁺calcd

(39.5 mg, 50%). IR (CHCl₃): ν_max= 3028., 2945, 2844, 1750, 1718, for C₁₇H₂₆NaO₄317.1723; Found 317.1723.

1648, 1439, 1363, 1321, 1286, 1202, 1152, 1042, 821, 798, 754,

1

697, 663, 627, 543 cm^–1; H NMR (400 MHz, CDCl₃): δ

=

4.12 (q,

J = 7.1 Hz, 2H), 2.51 (t, J = 7.2 Hz, 2H), 2.32 (t, J = 7.2 Hz, 2H),

2.14 (s, 3H), 1.89–1.84 (m, 2H), 1.25 (t, J = 7.1 Hz, 3H) ppm;

¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 208.1, 173.2, 60.4, 42.5, 33.2,

29.9, 18.9, 14.2 ppm; HRMS (ESI-TOF) calcd for C₈H₁₄O₃Na

181.0835; Found 181.0840.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

We thank SERB New Delhi, Grant No. EMR/2017/000499 for

financial support. G.V.R. and V.B. thank CSIR New Delhi, India

for research fellowships.

Ethyl 3-oxobutanoate (3′w) ^6b

. Reaction time = 24 h, colorless oil

(42 mg, 58%).; ¹H NMR (400 MHz, CDCl₃): δ = 4.15 (q, J = 7.2 Hz,

2H), 3.41 (s, 2H), 2.23 (s, 3H), 1.24 (t, J = 7.1 Hz, 3H) ppm; ¹³C{¹H}

NMR (100 MHz, CDCl₃): δ = 200.6, 167.0, 61.3, 50.0, 30.0, 14.0

ppm.

REFERENCES

1. (a) R. Mestres, Green Chem. 2004, 6, 583. (b) J. Sukumaran and

U. Hanefeld, Chem. Soc. Rev. 2005, 34, 530. (c) C. Hertweck,

Angew. Chem., Int. Ed. 2009, 48, 4688. (d) P. Clapés, W.-D.

Fessner, G. A. Sprenger, and A. K. Samland, Curr. Opin. Chem.

Biol. 2010, 14, 154.

Methyl 3-oxobutanoate (3′x) ²⁷

. Reaction time = 26 h, colorless

1

oil (30 mg, 52%); H NMR (400 MHz, CDCl₃): δ = 3.68 (s, 3H),

3.42 (s, 2H), 2.21 (s, 3H) ppm; ¹³C{¹H} NMR (100 MHz, CDCl₃): δ

= 200.5, 167.5, 52.2, 49.7, 30.0 ppm.

2. (a) J. Smidt, W. Hafner, R. Jira, R. Sieber, J. Sedlmeier, and A.

Sabel, Angew. Chem., Int. Ed. 1962, 1, 80. (b) J. Tsuji, Synthesis

1984, 369. (c) J. M. Takacs, and X.-T. Jiang, Curr. Org. Chem.

2003, 7, 369. (d) T. V. Baiju, E. Gravel, E. Doris, and I. N. N.

Namboothiri, Tetrahedron Lett. 2016, 57, 3993.

3. (a) E. Monflier and A. Mortreux, In Aqueous-Phase

Organometallic Catalysis, 2nd ed. B. Cornils, W. A. Herrmann,

Wiley-VHC: Weinheim, Germany, 2004; pp 481−487. (b) L.

Hintermann, In Transition Metals for Organic Synthesis, 2nd ed.

M. Beller, and C. Bolm, Wiley-VHC: Weinheim, Germany, 2004;

Vol. 2, pp 379. (c) R. Jira, In Applied Homogeneous Catalysis with

Organometallic Compounds, 2nd ed. B. Cornils, W. A. Herrmann,

Wiley-VHC: Weinheim, Germany, 2002; Vol. 1, pp 386.

4. J. Aguado, D. P. Serrano, R. Van Grieken, J. M. Escola, R. García,

and S. Carretero, Modified Wacker of Long-chain Terminal

Olefins. In Book of Extended Abstracts of the Fourth World

Congress on Oxidation Catalysis; Berlin, Potsdam, Germany,

2001; pp 493.

5. (a) W. H. Clement and C. M. Selwitz, J. Org. Chem. 1964, 29, 241.

(b) D. R. Fahey and E. A. Zuech, J. Org. Chem. 1974, 39, 3276. (c)

H. Jiang, L. Jia, and J. Li, Green Chem. 2000, 2, 161. (d) T.

Mitsudome, T. Umetani, N. Nosaka, K. Mori, T. Mizugaki, K.

Ebitani, and K. Kaneda, Angew. Chem., Int. Ed. 2006, 45, 481. (e)

J.-L. Wang, L.-N. He, C.-X. Miao, and Y.-N. Li, Green Chem. 2009,

11, 1317. (f) K. Mitsudo, S. Fukunaga, T. Fujita, H. Mandai, S.

Suga, and H. Tanaka, Electrochemistry 2013, 81, 347.

(E)-4-(5-Hydroxydec-2-en-1-yl)-2-methoxyphenol (7). To

stirred and degassed solution of phenol ( 100 mg, 0.609

mmol, 1.0 equiv) and homoallyl alcohol (87 mg, 0.609 mmol,

1.0 equiv) in dry CH₂Cl₂(10 mL) was added Grubbs second-

generation catalyst (10.4 mg, 0.0122 mmol, 2 mol%) at room

temperature, and the mixture was refluxed for 48 h. The

mixture was then cooled and filtered through a small pad of

silica gel, and the filtrate was concentrated under vacuum. The

residue was purified by silica gel column chromatography using

petroleum ether/EtOAc (5:1) as an eluent to provide (8:1)

a

1p

6

mixture of (E/Z)-7 (122 mg, 72%) as a colorless oil. IR (CHCl₃):

ν_max= 3444, 3054, 2979, 2928, 2857, 1649, 1608, 1514, 1464,

1434, 1374, 1265, 1234, 1208, 1153, 1122, 1036, 971, 912, 888,

822, 733, 705, 651 cm^-1; ¹H NMR (500 MHz, CDCl₃): δ = 6.84 (d,

J = 7.9 Hz, 1H), 6.71–6.64 (m, 2H), 5.81 (s, 1H), 5.74–5.59 (m,

1H), 5.58–5.48 (m, 1H), 3.84 (s, 3H), 3.64–3.60 (m, 1H), 3.29 (d,

J = 6.4 Hz, 2H), 2.30–2.24 (m, 1H), 2.16–2.09 (m, 1H), 1.50–1.42

(m, 2H), 1.32–1.23 (m, 6H), 0.89 (t, J = 6.9 Hz, 3H) ppm; ¹³C{¹H}

NMR (125 MHz, CDCl₃): δ = 146.4, 143.8, 133.0, 132.3, 127.2,

120.9, 114.3, 111.0, 71.0, 55.7, 40.4, 38.6, 36.6, 31.8, 25.2, 22.5,

13.9 ppm; HRMS (ESI-TOF) m/z: [M+Na]⁺calcd for C₁₇H₂₆NaO₃

301.1774;Found 301.1774.

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ARTICLE

Journal Name

6. (a) J. Nokami, H. Ogawa, S. Miyamoto, T. Mandai, S.

Wakabayasi, and J. Tsuji, Tetrahedron Lett. 1988, 29, 5181. (b)

D. A. Chaudhari, and R. A. Fernandes, J. Org. Chem. 2016, 81,

2113.

7. (a) H. Takayama, T. Koike, N. Aimi, and S. Sakai, J. Org. Chem.

1992, 57, 2173. (b) R. A. T. M. van Benthem, H. Hiemstra, and

W. N. Speckamp, J. Org. Chem. 1992, 57, 6083. (c) N. I.

Kuznetsova, M. A. Fedotov, V. A. Likholobov, and Y. I. Yermakov,

J. Mol. Catal. 1986, 38, 263. (d) L. Eberson and L. Jӧnsson, J.

Chem. Soc., Chem. Commun. 1974, 885. (e) K. I. Matveev, Kinet.

Katal. 1977, 18, 862. (f) R. A. Fernandes, and V. Bethi,

Tetrahedron 2014, 70, 4760. (g) R. A. Fernandes, and D. A.

Chaudhari, J. Org. Chem. 2014, 79, 5787.

Reddy, M. Narender, Y. V. D. Nageswar, and K. R. Rao, Synth.

Commun. 2007, 37, 1983. (d) R. T_Do_Om_I:if₁u₀j_.i₁,₀₃S^V₉.ⁱ_/^e_D^wM₀^Aa_O^rts_B^icu₀^led₁a^O₃,₄^nl₄ⁱⁿT_G^e.

Kurahashi, and S. Matsubara, Org. Lett. 2019, 21, 3834. (e) T.

Hamaguchi, Y. Takahashi, H. Tsuji, and M. Kawatsura, Org. Lett.

2020, 22, 1124. (f) J.-X. Wang, X. Jia, T. Meng, and L. Xin,

Synthesis 2005, 2838. (g) T. Naicker, P. I. Arvidsson, H. G. Kruger,

G. E. M. Maguire, and T. Govender, Eur. J. Org. Chem. 2011,

6923. (h) K. Takenaka, Y. D. Dhage, and H. Sasai, Chem.

Commun. 2013, 49, 11224. (i) R. S. Vasconcelos, L. F. Silva Jr, and

A. Giannis, J. Org. Chem. 2011, 76, 1499. (j) L.-M. Zhao, H.-S.

Gao, D.-F. Li, J. Dong, L.-L. Sang, and J. Ji, Org. Biomol. Chem.

2017, 15, 4359. (k) B. Das, D. B. Shinde, B. S. Kanth, A. Kamle,

and C. G. Kumar, Eur. J. Med. Chem. 2011, 46, 3124. (l) K.-T. Tan,

S.-S. Chng, H.-S. Cheng, and T.-P. Loh, J. Am. Chem. Soc. 2003,

125, 2958.

8. (a) J.-H. Ahn and D. C. Sherrington, Macromolecules 1996, 29,

4164. (b) G.-J. Ten Brink, I. W. C. E. Arends, G. Papadogianakis,

and R. A. Sheldon, Appl. Catal. A: General 2000, 194, 435. (c) C. 23. (a) R. Fernandez-Lopez, J. Kofoed, M. Machuqueiro, and T.

N. Cornell and M. S. Sigman, Org. Lett. 2006, 8, 4117.

9. (a) S. Uchiumi, K. Ataka, and T. Matsuzaki, J. Organomet. Chem.

1999, 576, 279. (b) G. Zhang, X. Xie, Y. Wang, X. Wen, Y. Zhao,

and C. Ding, Org. Biomol. Chem. 2013, 11, 2947.

10. (a) J. Tsuji, H. Nagashima, and K. Hori, Chem. Lett. 1980, 9, 257.

(b) H. Mimoun, R. Charpentier, A. Mitschler, J. Fischer, and R.

Darbre, Eur. J. Org. Chem. 2005, 5268. (b) V. Ashokkumar, C.

Chithiraikumar, and A. Siva, Org. Biomol. Chem. 2016, 14, 9021.

(c) P. S. Mainkar, V. Chippala, R. Chegondi, and S.

Chandrasekhar, Synlett 2016, 1969. (d) V. Maslak, Z. Tokic-

Vujosevic, Z. Ferjancic, and R. N. Saicic, Tetrahedron Lett. 2009,

50, 6709.

Weiss, J. Am. Chem. Soc. 1980, 102, 1047. (c) C. N. Cornell, and 24. H. Shulman, C. Makarov, A. K. Ogawa, F. Romesberg, and E.

M. S. Sigman, J. Am. Chem. Soc. 2005, 127, 2796. (d) B. W. Keinan, J. Am. Chem. Soc. 2000, 122, 10743.

Michel, A. M. Camelio, C. N. Cornell, and M. S. Sigman, J. Am. 25. (a) E. Speckmeier, P. J. W. Fuchs, and K. Zeitler, Chem. Sci. 2018,

Chem. Soc. 2009, 131, 6076.

11. V. Bethi and R. A. Fernandes, J. Org. Chem. 2016, 81, 8577.

9, 7096. (b) J.-L. Wang, H.-J. Li, H.-S. Wang, and Y.-C. Wu, Org.

Lett. 2017, 19, 3811.

12. J. R. McCombs, B. W. Michel, and M. S. Sigman, J. Org. Chem. 26. N. Schröder, J. Wencel-Delord, and F. Glorius, J. Am. Chem. Soc.

2011, 76, 3609.

2012, 134, 8298.

13. P. A. Runeberg, and P. Eklund, Org. Lett. 2019, 21, 8145.

14. (a) A. J. Fatiadi, Synthesis 1976, 65. (b) A. J. Fatiadi Synthesis

1976, 133.

27. B. Wahl, H. Bonin, A. Mortreux, S. Giboulot, F. Liron, G. Poli, and

M. Sauthier, Adv. Synth. Catal. 2012, 354, 3105.

15. (a) R. J. K. Taylor, M. Reid, J. Foot, and S. A. Raw, Acc. Chem.

Res. 2005, 38, 851. (b) C. C. Cosner, P. J. Cabrera, K. M. Byrd, A.

M. Adams, and P. Helquist, Org. Lett. 2011, 13, 2071.

16. K. Nowińska, D. Dudko, and R. Golon, Chem. Commun. 1996,

277.

17. (a) T. Aoyama, N. Sonoda, M. Yamauchi, K. Toriyama, M. Anzai,

A. Ando, and T. Shioiri, Synlett, 1998, 35. (b) S. P. Gholap, D.

Jangid, R. A. Fernandes, R. A. J. Org. Chem. 2019, 84, 3537.

18. For recent synthesis see: (a) G. Solladié and C. Ziani-Chérif, J.

Org. Chem. 1993, 58, 2181. (b) S. A. Fleming, C. W. Dyer, and J.

Eggington, Synth. Commun. 1999, 29, 1933. (c) G. Sabitha, C.

Srinivas, T. R. Reddy, K. Yadagiri, and J. S. Yadav, Tetrahedron:

Asymmetry 2011, 22, 2124. (d) N. V. Kumar, S. C. S. Kumar, P.

Srinivas, and B. K. Bettadaiah, Org. Prep. Proc. Int. 2015, 47, 443.

(e) S. Paladhi, I.-S. Hwang, E. J. Yoo, D. H. Ryu, and C. E. Song,

Org. Lett. 2018, 20, 2003.

19. (a) D. W. Connell and M. D. Sutherland, Aust. J. Chem. 1969, 22,

1033. (b) H. Kikuzaki, S.-M. Tsai, and N. Nakatani,

Phytochemistry 1992, 31, 1783.

20. R. B. Semwal, D. K. Semwal, S. Combrinck, and A. M. Viljoen,

Phytochemistry 2015, 117, 554.

21. (a) H. C. Brown, and P. K. Jadhav, J. Am. Chem. Soc. 1983, 105,

2092. (b) W. R. Roush, A. E. Walts, and L. K. Hoong, J. Am. Chem.

Soc. 1985, 107, 8186. (c) U. S. Racherla, and H. C. Brown, J. Org.

Chem. 1991, 56, 401. (d) G. E. Keck, K. H. Tarbet, and L. S. Geraci,

J. Am. Chem. Soc. 1993, 115, 8467. (e) K. Kubota, J. L. Leighton,

Angew. Chem., Int. Ed. 2003, 42, 946.

22. (a) Z. Du, Y. Li, F. Wang, W. Zhou, and J.-X. Wang, Synth.

Commun. 2011, 41 , 1664. (b) S. C. Cosgrove, S. Hussain, N. J.

Turner, and S. P. Marsden, ACS Catal. 2018, 8, 5570. (c) M. S.

10 | J. Name., 2012, 00, 1-3

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Organic & Biomolecular Chemistry

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DOI: 10.1039/D0OB01344G

Abstract

PdCl₂(10 mol%)

CH₃CN/H₂O (7:1)

PdCl₂(10 mol%)

CH₃CN/H₂O (7:1)

OH

R

O

R

O

CrO₃(0.5 equiv)

60 ^oC, 8-18 h

then conc. HCl, 1 h

MnO₂(4.0 equiv)

60 ^oC, 18-36 h

this work

50 examples

R = alkyl, aryl

previous work

orthogonal Wacker oxidation

chemoselective olefin oxidation

2016

J. Org. Chem.

, 81, 8577

An efficient and mild reaction conditions for Wacker-type oxidation of terminal olefins

of less explored homoallyl alcohols to -hydroxy-methyl ketones has been developed by

using Pd(II) catalyst and MnO₂as co-oxidant.

Article Doi

MnO2as a terminal oxidant in Wacker oxidation of homoallyl alcohols and terminal olefins

DOI: 10.1039/d0ob01344g

Source and publish data:

Authors:

Article abstract of DOI:10.1039/d0ob01344g

Full text of DOI:10.1039/d0ob01344g

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