Synthesis of β-keto sulfones via a multicomponent reaction through sulfonylation and decarboxylation

 

1-Phenyl-2-(phenylsulfonyl)ethan-1-one (2a) 1

1H NMR (400 MHz, CDCl3) δ 7.92 (m, 4H), 7.70 – 7.58 (m, 2H), 7.54 (t, J = 7.6 Hz, 2H), 7.48 (t, J = 7.3 Hz, 2H), 4.74 (s, 2H).

13C NMR (101 MHz, CDCl3) δ 187.9, 138.7, 135.7, 134.4, 134.2, 129.3, 129.2, 128.9, 128.6, 63.4.

References 1. Lu, Q.; Zhang, J.; Peng, P.; Zhang, G.; Huang, Z.; Yi, H.; Millercd, T. J.; Lei, A. Chem. Sci. 2015, 6, 4851.

Synthesis of β-keto sulfones via a multicomponent reaction through sulfonylation and decarboxylation

Jiyao Yu,b  Runyu Mao,a  Qingyu Wanga  and  Jie Wu*ac 

*Corresponding authors

aDepartment of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China
E-mail: jie_wu@fudan.edu.cn

bSchool of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive, Atlanta, USA

cState Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China

Abstract

A copper(I)-catalyzed synthesis of β-keto sulfones through a multicomponent reaction of aryldiazonium tetrafluoroborates, 3-arylpropiolic acids, sulfur dioxide, and water was developed. This reaction proceeds through a tandem radical process, and the sulfonyl radical, generated from the combination of aryldiazonium tetrafluoroborates with DABCO·(SO2)2, acts as the key intermediate. The transformation involves sulfonylation and decarboxylation, which allows for the efficient synthesis of the desired β-keto sulfones.

3-allyl-4H-chromen-4-one

3-allyl-4H-chromen-4-one

5b (8.4 g, 45 mmol, 91% yield) as a yellow oil. GC (retention time): 3.571 min

HRMS (EI): m/z calcd for [C12H10O2]: 186,0681 (M+ ); found 186.0657.

1H-NMR (400 MHz, CDCl3 ): δ/ppm = 8.18 (dd, J=8.0, 1.7 Hz, 1H), 7.70 (t, J=1.0, 1H), 7.58 (ddd, J=8.6, 7.1, 1.7 Hz, 1H), 7.43 – 7.28 (m, 2H), 5.92 (ddt, J=16.7, 10.1, 6.7 Hz, 1H), 5.22 – 5.04 (m, 2H), 3.20 (dt, J=6.7, 1.3, 2H).

13C NMR (75 MHz, CDCl3 ): δ/ppm = 177.5, 156.6, 152.7, 134.7, 133.5, 126.0, 125.0, 123.9, 123.1, 118.1, 117.2, 29.8.

IR (Diamond-ATR, neat): /cm-1 = 3077.00 (w), 3068.00 (w), 3017.00 (vw), 2970.00 (w), 2941.00 (vw), 2900.00 (w), 1632.00 (s), 1608.00 (s), 1573.00 (m), 1464.00 (s), 1429.00 (m), 1398.00 (s), 1353.00 (s), 1321.00 (m), 1297.00 (m), 1282.00 (m), 1264.00 (w), 1226.00 (w), 1210.00 (m), 1181.00 (m), 1156.00 (s), 1141.00 (s), 1111.00 (m), 1027.00 (w), 1005.00 (m), 961.00 (m), 924.00 (s), 909.00 (s), 896.00 (s), 868.00 (w), 846.00 (s), 802.00 (m), 769.00 (s), 756.00 (vs), 712.00 (m), 690.00 (s).

mp: 34.0 - 36.0 °C

Practical Large-Scale Regioselective Zincation of Chromone Using TMPZnCl·LiCl Triggered by the Presence or Absence of MgCl2

Lydia Klier†, Dorothée S. Ziegler†, René Rahimoff†, Marc Mosrin†‡, and Paul Knochel*† 

† Department Chemie, Ludwig-Maximilians-Universität, Butenandtstrasse. 5-13, 81377 München, Germany

‡ Research & Development, Crop Science, Bayer AG, Alfred-Nobel-Strasse 50, Building 6550, 2.08, 40789 Monheim am Rhein, Germany

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.7b00032

Chromones are efficiently zincated in position C(3) in THF by using the commercially available amide base TMPZnCl·LiCl (TMP = 2,2,6,6-tetramethylpiperidyl). Additionally, in the presence of a Lewis acid such as MgCl2, zincation using TMPZnCl·LiCl occurs at C(2). These metalation reactions are carried out on a 50 mmol scale, and the metalation selectivities have been compared with the corresponding small-scale reactions (2 mmol). The resulting zinc organometallics undergo smooth reactions with various electrophiles, for example, Pd-catalyzed cross-coupling reactions or Cu-catalyzed acylations or allylations.

/////////http://pubs.acs.org/doi/suppl/10.1021/acs.oprd.7b00032/suppl_file/op7b00032_si_001.pdf

Nickel-catalyzed carbonylation of arylboronic acids with DMF as a CO source

Bis(4-methoxyphenyl)methanone

 

bis(4-methoxyphenyl)methanone (3b) The title product was purified by column chromatography and was obtained in 83% yield (110 mg). Rf = 0.3 (petroleum ether/ethyl acetate 30:1), light yellow oil.

1H NMR (400 MHz, CDCl3) δ (ppm):

7.80 (d, J = 8.8 Hz, 2H),  AROM H ORTHO TO -C=0

6.97 (d, J = 8.8 Hz, 2H),  AROM H ORTHO TO -OCH3

3.89 (s, 6H); TWO -OCH3 GPS

13C NMR (100 MHz, CDCl3) δ (ppm): 194.4, 162.9, 132.2, 132.1, 113.4, 55.5;

IR (KBr): 2957, 1671, 1593, 1260, 1093, 806 cm-1; HRMS(ESI) calc. for (M + Na+ ) 265.0844; found 265.0835.

MOM CAN TEACH YOU NMR

Nickel-catalyzed carbonylation of arylboronic acids with DMF as a CO source

Org. Chem. Front., 2017, 4,569-572
DOI: 10.1039/C7QO00001D, Research Article

Yang Li, Dong-Huai Tu, Bo Wang, Ju-You Lu, Yao-Yu Wang, Zhao-Tie Liu, Zhong-Wen Liu, Jian Lu
By using N,N-dimethylformamide (DMF) as a CO source, nickel-catalyzed carbonylation of arylboronic acids was demonstrated as an efficient and facile protocol for the synthesis of diaryl ketones.

Nickel-catalyzed carbonylation of arylboronic acids with DMF as a CO source

Yang Li,ab  Dong-Huai Tu,a  Bo Wang,a  Ju-You Lu,a  Yao-Yu Wang,b  Zhao-Tie Liu,*c  Zhong-Wen Liuc  and  Jian Lu*a 

*Corresponding authors

aState Key Laboratory of Fluorine & Nitrogen Chemicals, Xi'an Modern Chemistry Research Institute, Xi'an, China
E-mail: lujian204@263.net

bKey Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an, 710069, China

cKey Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an, China
E-mail: ztliu@snnu.edu.cn

Abstract

By using N,N-dimethylformamide (DMF) as a CO source, the cheap metal nickel-catalyzed carbonylation of arylboronic acids was demonstrated as an efficient and facile protocol for the synthesis of diaryl ketones. Results indicated that NiBr2·diglyme was the best pre-catalyst among the investigated transitional metal salts, and excellent yields were achieved via C–H and C–N bond cleavage.

////////////http://www.rsc.org/suppdata/c7/qo/c7qo00001d/c7qo00001d1.pdf

 

Nanoscale graphene oxide sheets (NGO), as activated carbocatalysts, were synthesized by a reduction size strategy and used in chemoselective oxidative conversion of benzylic C–H to the corresponding carboxylic acid. On the basis of the results of the optimization process of different parameters, 3 equiv of H2O2 for each C–H group, 100 wt % of NGO in aqueous medium, acetone as a cosolvent, and a reaction temperature of 100 °C were selected as optimum parameters.

In this optimum condition, xylenes and toluene over 24 h with good yield were converted to the corresponding carboxylic acid, and in the case of diphenylmethane and ethylbenzene, these substrates with excellent yield were converted to benzophenone and acetophenone.

Selective Oxidation of Benzylic C–H Using Nanoscale Graphene Oxide as Highly Efficient Carbocatalyst: Direct Synthesis of Terephthalic Acid

Masoud Heidari, Alireza Sedrpoushan* , and Farajollah Mohannazadeh

Institute of Industrial Chemistry, Iranian Research Organization for Science and Technology (IROST), P.O. Box 33535-111, Tehran, Iran

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.7b00056

http://pubs.acs.org/doi/full/10.1021/acs.oprd.7b00056

 

*Tel.: +98 21 56276031. E-mail address: sedrpoushan1395@gmail.com (Alireza Sedrpoushan).

 

  

///////

A Brønsted acid catalysed enantioselective Biginelli reaction

A Bronsted acid catalysed enantioselective Biginelli reaction

Green Chem., 2017, 19,1529-1535
DOI: 10.1039/C6GC03274E, Paper

Margherita Barbero, Silvano Cadamuro, Stefano Dughera
A chiral derivative of 1,2-benzenedisulfonimide, namely (-)-4,5-dimethyl-3,6-bis(o-tolyl)-1,2-benzenedisulfonimide is herein proven to be an efficient chiral catalyst in a one pot three-component Biginelli reaction.

 

A Brønsted acid catalysed enantioselective Biginelli reaction

Margherita Barbero,a   Silvano Cadamuroa and  Stefano Dughera*a  

*Corresponding authors

aDipartimento di Chimica, Università di Torino, C.so Massimo d'Azeglio 48, 10125 Torino, Italy
E-mail: stefano.dughera@unito.it

Green Chem., 2017,19, 1529-1535

DOI: 10.1039/C6GC03274E

A chiral derivative of 1,2-benzenedisulfonimide, namely (−)-4,5-dimethyl-3,6-bis(o-tolyl)-1,2-benzenedisulfonimide is herein proven to be an efficient chiral catalyst in a one pot three-component Biginelli reaction. In fact the yields of the target dihydropyrimidines were very high (25 examples; average 91%) and enantiomeric excesses were always excellent (14 examples; average 97%). Ultimately, we herein propose a procedure that displays a number of benefits and advantages including the total absence of solvents, mild reaction conditions, relatively short reaction times and stoichiometric reagent ratios. Target dihydropyrimidines are obtained in adequate purity, making further chromatographic purification unnecessary. Moreover, the chiral catalyst was easily recovered from the reaction mixture and reused, without the loss of catalytic activity.

 

dihydropyrimidine-2-thiones 5

(R)-(-)-Ethyl 6-methyl-4-phenyl-2-thioxo-3,4-dihydropyrimidine-5-carboxylate (5a): pale grey solid (135 mg, 98% yield); mp 201–202 °C ( from EtOH; lit17 200–202 °C). 96.4% Ee (GC connected to a J&W Scientific Cyclosil-B column; stationary phase: 30% heptakis (2,3-di-Omethyl-6-O-t-butyldimethylsilyl)-β-cyclodextrin in DB-1701), tR= 12.11 min (major), tR= 12.54 min (minor); [a]D -65.4 (c 0.1 in MeOH). 1H NMR (200 MHz, DMSO-d6): δ = 10.24 (br s, 1H), 9.55 (br s, 1H), 7.31–7.12 (m, 5H), 5.09 (d, J = 3.9 Hz, 1H), 3.92 (q, J = 7.0 Hz, 2H), 2.21 (s, 3H), 1.01 (t, J = 7.0 Hz, 3H); 13C NMR (50 MHz, DMSO-d6): δ = 174.9, 165.8, 145.7, 129.3, 128.3, 127.0, 101.3, 60.2, 54.7, 17.8, 14.7. MS (m/z, EI): 276 [M+ ] (45), 247 (40), 199 (100). IR (neat) ν (cm−1): 3311 (NH), 3112 (NH), 1665 (CO), 1195 (CS).

 

 

 

Dughera Dott. Stefano

Tel: 0116707645
Email: stefano.dughera@unito.it
address: Department of Chemistry

Dipartimento di Chimica, Università di Torino, C.so Massimo d'Azeglio 48, 10125 Torino, Italy

R. Fu, Y. Yang, W. Lai, Y. Ma, Z. Chen, J. Zhou, W. Chai, Q. Wang, and R. Yuan, Synth. Comm., 2015, 45, 477.

 

//////////////Brønsted acid,  catalysed,  enantioselective,  Biginelli reaction, dihydropyrimidine-2-thiones

5-chloro-6-morpholinonicotinic acid

Preparation of 5-chloro-6-morpholinonicotinic acid (18)1
A solution of ethyl 5,6-dichloronicotinate (A-1, 1.1 g, 5.0 mmol), N,N-diisopropylethylamine (DIPEA, 0.97
g, 7.5 mmol) in acetonitrile (3.0 mL) was treated with morpholine (0.48 g, 6.0 mmol). The mixture was
stirred for 6 hours at 95 °C. The complete conversion of the starting material could be detected by
observing a change of the color from yellowish to deep orange. After complete conversion, the mixture was
evaporated to dryness, the residue diluted with water (20 mL), and extracted with dichloromethane (3x20
mL). The combined organic layer was dried over sodium sulfate and evaporated under reduced pressure to
yield 1.31 g (97 %) of A-2 as a red oil. The product was identified by LC/ESI-MS analysis and used for the
next synthetic step without further purification.
The ester A-2 (1.31 g, 4.83 mmol) was dissolved in a tetrahydrofurane/water mixture (1:1, 4.0 mL) and
treated with 2.0 M sodium hydroxide (0.33 g, 5.80 mmol). The reaction mixture was stirred for 5 h at 55 °C.
After complete conversion, the mixture was cooled to room temperature, diluted with water (20 mL) and
extracted with ethyl acetate (3x20 mL). The water layer was neutralized with an aqueous solution of
hydrochloric acid (2.0 N) until a white precipitate was observed. The product was collected by repeated
filtration and evaporation. The combined product fractions were dried at 70 °C yielding 1.17 g (100 %) of
18 as a white solid,

m.p. 185.2–186.2;

1H NMR (500 MHz, DMSO-d6) δ (ppm) 3.45 (t, J = 5.04 Hz, 2xCH2,4H), 3.72 (t, J = 4.41 Hz, 2xCH2, 4H), 8.08 (d, J = 1.89 Hz, CH, 1H), 8.66 (d, J = 1.90 Hz, CH, 1H), 13.01(s, CO2H, 1H). 13C (125 MHz, DMSO-d6) δ (ppm) 48.9 (2xCH2), 66.1 (2xCH2), 119.4, 139.7, 147.5, 159.3,
165.4;

LC/ESI-MS (m/z): 243.28 [M+H]+; Purity: 100.0 % (N).

Colandrea, V. J.; Doherty, G. A; Hale, J. J.; Huo, P.; Legiec, I. E.; Toth, L.; Vachal, P.; Yan, L. (3,4-
Disubstituted)propanoic carboxylates as S1P (EDG) receptor agonists. PCT Int. Appl. WO2005058848A1, 2005 (Merck & Co., Inc.).

Supporting Information

https://s3-eu-west-1.amazonaws.com/pstorage-acs-6854636/.../jm500729a_si_001.pdf

2-{[6-Chloro-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl]methyl}-4-fluorobenzonitrile

2-{[6-Chloro-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl]methyl}-4-fluorobenzonitrile (4)

white solid . Mp: 193–195 °C.

 

1H NMR (400 MHz, CDCl3) δ (ppm): 7.74–7.76(m, 1H), 7.14–7.17 (m, 1H), 6.95–6.97 (m, 1H), 6.05 (s, 1H), 5.51 (s, 2H), 3.40 (s, 3H).

2-({3-Methyl-6-[(3R)-3-piperidinylamino]-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl}methyl)-4-fluorobenzonitrile

 

2-({3-Methyl-6-[(3R)-3-piperidinylamino]-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl}methyl)-4-fluorobenzonitrile (8)

Mp: 90 °C decomposed.

 

1H NMR (400 MHz, CD3OD) δ (ppm): 7.85–7.89 (m, 1H), 7.25–7.28 (m, 1H), 6.96–6.99 (m, 1H), 5.37–5.51 (m, 2H), 4.84 (s, 1H), 3.42–3.49 (m, 1H), 3.28 (s, 3H), 3.11–3.15 (m, 1H), 2.89–2.93 (m, 1H), 2.46–2.58 (m, 2H), 1.92–1.95 (m, 1H), 1.48–1.70 (m, 3H).

 

MS (ESI+): m/z, 358.06 ([M + H]+).

A two-step efficient preparation of a renewable dicarboxylic acid monomer 5,5[prime or minute]-[oxybis(methylene)]bis[2-furancarboxylic acid] from D-fructose and its application in polyester synthesis

 

Green Chem., 2017, 19,1570-1575
DOI: 10.1039/C6GC03314H, Paper

Ananda S. Amarasekara, Loc H. Nguyen, Nnaemeka C. Okorie, Saad M. Jamal
A renewable monomer 5,5[prime or minute]-[oxybis(methylene)]bis[2-furancarboxylic acid] from D-fructose.

A two-step efficient preparation of a renewable dicarboxylic acid monomer 5,5′-[oxybis(methylene)]bis[2-furancarboxylic acid] from D-fructose and its application in polyester synthesis

Ananda S. Amarasekara,*a   Loc H. Nguyen,a  Nnaemeka C. Okoriea and   Saad M. Jamala  

*Corresponding authors

aDepartment of Chemistry, Prairie View A&M University, Prairie View, USA
E-mail: asamarasekara@pvamu.edu
Fax: +1 936 261 3117
Tel: +1 936 261 3107

Green Chem., 2017,19, 1570-1575

DOI: 10.1039/C6GC03314H

D-Fructose was converted to the dialdehyde 5,5′-[oxybis(methylene)]bis[2-furaldehyde] by heating at 110 °C in DMSO with the Dowex 50 W X8 solid acid catalyst in 76% yield without the isolation of the intermediate 5-hydroxymethylfurfural. This dialdehyde was then converted to the dicarboxylic acid monomer, 5,5′-[oxybis(methylene)]bis[2-furancarboxylic acid], using oxygen (1 atm.) and 5% Pt/C catalyst in 1.5 M aqueous NaOH at room temperature in 98% yield. The new dicarboxylic acid monomer can be considered as a renewable resource based alternative to terephthalic acid as demonstrated by the preparation of polyesters with 1,2-ethanediol and 1,4-butanediol in 87–92% yield.

 

Synthesis of 5,5'-[oxybis(methylene)]bis[2-furancarboxylic acid]

 

pale yellow crystals. 260 mg, 98 % yield. M.pt. 207-209 °C, Lit. M. pt. 209-210 °C 37 .

 

IR (ATR) 761, 891, 951, 1029, 1059, 1159, 1208, 1283, 1342, 1424, 1525, 1674, 3128 cm-1

 

1 H NMR (DMSO-d6 ) δ 3.38 (2H, bs, 2XCOOH), 4.51 (4H, s, 2X-CH2O ), 6.61 (2H, d, J = 3.6 Hz, C-4,4'), 7.15 (2H, d, J = 3.6 Hz, C-3,3').

 

13C NMR (DMSO-d6 ) δ 63.8, 112.2, 118.8, 145.3, 155.5, 159.6

37. T. Iseki and T. Sugiura, J. Biochem., 1939, 30, 113-118.

 

NMR PREDICT

1H NMR PREDICT

 

 

 

13C NMR PREDICT

 

 

//////////////O=C(O)c2ccc(COCc1ccc(o1)C(=O)O)o2

5,6-dihydropteridin-7(8H)-one

5,6-dihydropteridin-7(8H)-one

 

Org. Process Res. Dev., 2017, 21 (1), pp 11–17

DOI: 10.1021/acs.oprd.6b00219

/////////////

Regioselective access of alkylidendibenzo[c,f]oxocine framework via cyclocarbopalladation/cross-coupling cascade reactions and reductive Heck strategy

Regioselective access of alkylidendibenzo[c,f]oxocine framework via cyclocarbopalladation/cross-coupling cascade reactions and reductive Heck strategy

New J. Chem., 2017, Advance Article
DOI: 10.1039/C6NJ03825E, Paper

Tapas Ghosha  

a

Institute of Organic Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany
E-mail: tapas.ghosh@uni-wuerzburg.de,tapasghosh.chem@gmail.com
Tel: +49-931-31-81629

New J. Chem., 2017, Advance Article

DOI: 10.1039/C6NJ03825E
Palladium-catalyzed dual strategies of cascade cyclocarbopalladation/cross-coupling of alkynes and a reductive Heck reaction have been developed to construct dibenzo[c,f]oxocine frameworks with tri- and tetra-substituted exo-cyclic alkenes with high stereo- and regio-control.

Palladium-catalyzed dual strategies of cascade cyclocarbopalladation/cross-coupling of alkynes and a reductive Heck reaction have been developed to construct dibenzo[c,f]oxocine frameworks with tri- and tetra-substituted exo-cyclic alkenes with high stereo- and regio-control. The success of this efficient methodology has been demonstrated by the synthesis of a number of dibenzoxocines in moderate to good yields and in sufficient quantities to support their further development.

 

http://pubs.rsc.org/en/Content/ArticleLanding/2017/NJ/C6NJ03825E?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FNJ+%28RSC+-+New+J.+Chem.+latest+articles%29#!divAbstract

 

12-benzylidene-7,12-dihydro-5H-dibenzo[c,f]oxocine (8a): The material obtained after workup was subjected to column chromatography on silica gel with petroleum ether/EtOAc (19:1) as eluent to deliver pure 8a. Off white solid, yield = 82%,

 

mp. 134-136 oC,

 

IR (KBr): 2861, 1623, 1602 cm-1 , 1H NMR (400 MHz, CDCl3): δH = 7.47 (d, 1H, J = 7.2 Hz), 7.19-7.34 (m, 5H), 7.05-7.15 (m, 5H), 6.94-6.96 (m, 2H), 6.64 (s, 1H), 4.87 (s, 2H), 4.75 (s, 2H).

 

13C NMR (100 MHz, CDCl3): δC = 144.6, 142.1, 138.3, 137.4, 136.9, 129.9, 129.1, 128.9, 128.6, 128.3, 128.1, 127.9, 127.4, 127.0, 126.7, 73.0, 70.3.

 

HRMS (ESI [M+Na]+ ): for C22H18O calcd 321.1255; found 321.1245.

 

 

 

///////Regioselective, alkylidendibenzo[c,f]oxocine, cyclocarbopalladation/cross-coupling cascade reactions, reductive Heck strategy

Asymmetric total synthesis of (-)-δ-lycorane

1H NMR

13C NMR

Org. Chem. Front., 2017, Advance Article
DOI: 10.1039/C7QO00021A, Research Article

Junliang Wang, Jianneng Li, Xianwang Shen, Cong Dong, Jun Lin, Kun Wei
A first asymmetric synthesis of (-)-δ-lycorane by using a chiral bifunctional squaramide-catalysed cascade reaction is reported.

Asymmetric total synthesis of (−)-δ-lycorane

Junliang Wang,ab   Jianneng Li,a   Xianwang Shen,a  Cong Dong,a   Jun Lin*ab and   Kun Wei*a  

*Corresponding authors

aSchool of Chemical Science and Technology, Yunnan University, P. R. China

bSchool of Chemical Science and Technology, Yunnan University, Key Laboratory of Medicinal Chemistry for Natural Resource (Ministry of Education), Kunming, P. R. China
E-mail: weikun@ynu.edu.cn, linjun@ynu.edu.cn
Fax: +86871 65031633
Tel: +86871 65031633

Org. Chem. Front., 2017, Advance Article

DOI: 10.1039/C7QO00021A

A first asymmetric synthesis of the lycorine-type Amaryllidaceae alkaloid (−)-δ-lycorane by using a chiral bifunctional squaramide-catalysed cascade reaction as a powerful tool to construct the skeleton of the alkaloid on the basis of unsaturated β-ketoester and nitroalkene is reported. The sequence afforded a highly functionalized intermediate with three stereogenic centres with high diastereoselectivity (>20:1 dr) and high enantioselectivity (92% ee) in one step, which was converted into (−)-δ-lycorane in eight steps.

The residue was purified by flash silica 8 Please do not adjust margins Please do not adjust margins Please do not adjust margins gel chromatography (DCM/MeOH = 10/1) to give (−)-δ-lycorane (9 mg, 72%) as a white solid.

m.p.: 125-126 °C; [α] = -51.9, (c = 0.1, CHCl3);

IR (thin film, ν cm -1): 3551, 3477, 3414 , 1637, 1617, 619, 473;

1H-NMR (500 MHz, CDCl3), δ (ppm): 6.79 (s, 1H), 6.68 (s, 1H), 5.93 (s, 2H), 4.29 (d, J = 14.5 Hz, 1H), 3.95 (dd, J = 11.0, 8.5 Hz, 1H), 3.68 (d, J = 14.5 Hz, 1H), 3.52 (dd, J = 11.5, 4.0 Hz, 1H), 3.25 (s, 1H), 2.50 (m, 1H), 2.41 (d, J = 2.0 Hz, 1H), 1.86 (m, 1H), 1.77 (m, 2H), 1.66 (d, J = 14.5 Hz, 1H), 1.59 (m, 2H), 1.37 (m, 2H);

13C-NMR (125 MHz, CDCl3) δ (ppm): 149.0, 146.5, 131.3, 120.5, 109.5, 106.9, 101.5, 66.3, 55.1, 50.7, 39.7, 34.5, 29.6, 29.0, 24.8, 20.4;

HRMS (ESI): m/z calcd for C16H20NO2 + [M + H]+ : 258.1489, found: 258.1488.

////(−)-δ-lycorane