Sequentially rhodium-catalyzed enantioselective cycloisomerization–hydrogenation syntheses of alkylidene butyrolactone β-hydroxyethanes and alkylidene tetrahydrofuran β-aminoethanes

Article abstract of DOI:10.1007/s10593-018-2267-1

[Figure not available: see fulltext.] The enantioselective Rh-catalyzed Alder-ene cycloisomerization of ester- and ether-tethered alkyne allyl alcohols is an excellent entry to subsequent Rh-catalyzed one-pot hydrogenations in the sense of sequentially Rh

Full text of DOI:10.1007/s10593-018-2267-1

DOI 10.1007/s10593-018-2267-1
Chemistry of Heterocyclic Compounds 2018, 54(3), 320–328
Sequentially rhodium-catalyzed enantioselective
cycloisomerization–hydrogenation syntheses
of alkylidene butyrolactone β-hydroxyethanes
and alkylidene tetrahydrofuran β-aminoethanes
Nadine Muschelknautz1, Frank Rominger2, Thomas J. J. Müller1*
1 Institut für Organische Chemie und Makromolekulare Chemie,
Lehrstuhl für Organische Chemie, Heinrich-Heine-Universität Düsseldorf,
Universitätsstraße 1, D-40225 Düsseldorf, Germany; e-mail: ThomasJJ.Mueller@hhu.de
2 Organisch-Chemisches Institut, Ruprecht-Karls-Universität Heidelberg,
Im Neuenheimer Feld 270, D-69120 Heidelberg, Germany
e-mail: frank.rominger@oci.uni-heidelberg.de
Submitted February 26, 2018
Accepted March 27, 2018
Published in Khimiya Geterotsiklicheskikh Soedinenii,
2018, 54(3), 320–328
The enantioselective Rh-catalyzed Alder-ene cycloisomerization of ester- and ether-tethered alkyne allyl alcohols is an excellent entry to
subsequent Rh-catalyzed one-pot hydrogenations in the sense of sequentially Rh-catalyzed processes to chiral alkylidene butyrolactone
β-hydroxyethanes and alkylidene tetrahydrofuran β-aminoethanes, respectively, with excellent levels of enantioselectivity.
Keywords: furanones, rhodium, tetrahydrofurans, asymmetric catalysis, cycloisomerization, homogeneous catalysis, hydrogenation,
one-pot reactions, sequential catalysis.
The invention of transition metal-catalyzed processes
has considerably enhanced the generation of complex
hetero- and carbocyclic structures starting from structurally
simple linear precursors. A further twist in these types of
cascading is the use of one catalyst for more than one
transformation in a one-pot fashion. This type of one-pot
methodology is generally referred to as sequential
catalysis.1–3 The catalytic cycloisomerization of enynes,4–13
i.e., the intramolecular and transition metal-catalyzed
version of the Alder-ene reaction,14,15 enables formation of
cycles bearing a diene functionality.
merizations of enyne substrates became increasingly
important.24–27
As part of our program to design new sequentially
catalyzed one-pot processes,28–31 we are particularly
interested in transition metal-catalyzed sequences initiated
by intramolecular cycloisomerization. In case of cyclo-
isomerization reactions with alkyne allyl alcohols, reactive
aldehyde functionalities are generated by virtue of the
tautomerism of the dienol intermediate. These resulting
enals set the stage for consecutive transformations particu-
larly in sequentially catalyzed one-pot processes (Scheme 1).
While Pd-catalyzed cycloisomerization of TMS-substituted
alkyne allyl alcohols proceeds smoothly, consecutive
concatenation as cycloisomerization–Wittig,32 cycloiso-
merization–Leuckart–Wallach,33 and a cycloisomerization–
Knoevenagel34 sequences were conducted in a one-pot
fashion. In the sense of a sequentially Pd-catalyzed process
a cycloisomerization–reductive amination sequence was per-
formed with hydrogen as the reductant.35 Also a
Rhodium(I)-catalyzed cycloisomerization processes,16
firstly pioneered by Zhang,17,18 allow enantioselective
generation of a chiral center upon transformation of
1,6-enynes by a cationic rhodium complex with chelating
enantiopure bisphosphane ligands furnishing five-
membered rings.19–22 Eventually rhodium–BINAP system
turned out to be most practical and efficacious.23 As
a consequence Rh-catalyzed enantioselective cycloiso-
0009-3122/18/54(3)-0320©2018 Springer Science+Business Media, LLC
320

Chemistry of Heterocyclic Compounds 2018, 54(3), 320–328
Scheme 1. Metal-catalyzed cycloisomerization of alkyne allyl alcohols and en route transformation
of the enal products in a one-pot fashion
sequentially iridium-catalyzed version with aryl-substituted
alkyne allyl alcohols furnished the corresponding conden-
sation products in the sense of a cycloisomerization–
Murahashi sequence under very mild reaction conditions in
absence of acids and bases.36 In addition, we could show
that Rh-catalyzed Alder-ene cycloisomerizations can be
successfully employed in one-pot sequences with Wittig
olefinations, giving a straightforward access to chiral
functionalized 4-alkyl 3-alkylidene tetrahydrofuran(on)es
in an enantioselective fashion.37
isomerization followed by hydrogenation (5 atm) at room
temperature for 24 h. Interestingly, instead of bicyclic
products, we exclusively obtained alkylidene butyrolactone
β-hydroxyethanes 2a–f in good to excellent yield and
excellent levels of enantioselectivity (Scheme 2). The
Scheme 2. Sequentially Rh–BINAP-catalyzed enantioselective
cycloisomerization–hydrogenation synthesis
of alkylidene butyrolactone β-hydroxyethanes 2a–f
Since rhodium has gained a superior role in catalytic
hydrogenation reactions38 sequential hydrogenation suggests
an intriguing sequel after rhodium-catalyzed cycloiso-
merization. Recently, we observed that cationic
Rh–(R)-BINAP complexes transform ether-tethered alkyne
allyl alcohols elegantly and enantioselectively into
2,7-dioxabicyclo[3.2.1]octanes via a cycloisomerization–
hydrogenation–isomerization–acetalization
(CIHIA)
sequence.39 Inspired by these findings we herein report the
enantioselective sequentially Rh-catalyzed cycloiso-
merization–hydrogenation
syntheses
of
alkylidene
butyrolactone β-hydroxyethanes and alkylidene tetrahydro-
furan β-aminoethanes.
As previously reported, a subsequent Rh-catalyzed
hydrogenation commences at a pressure of 5 bar, but in
contrast to the sodium borohydride reduction, the alcohols
were not isolated as products, and the isomeric 2,7-dioxa-
bicyclo[3.2.1]octanes were obtained as a result of a CIHIA
sequence.15 For shutting down the Rh-catalyzed allyl ether-
vinyl ether isomerization, which is considered to be
responsible for the concluding acetalization, we employed
(2Z)-4-hydroxybut-2-en-1-yl 3-(hetero)arylprop-2-ynoates
1a–f21 as substrates for the Rh–(R)-BINAP-catalyzed cyclo-
321

Chemistry of Heterocyclic Compounds 2018, 54(3), 320–328
Figure 1. Analytical chiral HPLC chromatograms of (rac)-3 (left) and (R)-3 (right) (HPLC: n-hexane–2-PrOH, 95:5, 0.8 ml/min,
λexc 254 nm, retention times: tS 33.3 min (minor), tR 40.2 min (major)).
structures of products 2 were unambiguously supported by
Scheme 3. Esterification of alcohol 2b to give acetate 3
13
1H, C, DEPT-135, COSY, and NOESY NMR experiments
as well as IR and mass spectrometry. The molecular composi-
tion was confirmed either by HRMS or elemental analysis.
The determination of the enantiomeric excesses by
analytical chiral GC and analytical chiral HPLC was
hampered by poor baseline separation for alcohol 2b.
Therefore, alcohol 2b was acetylated with acetyl chloride
in the presence of 4-(N,N-dimethylamino)pyridine (DMAP)
to give the corresponding acetate 3 (Scheme 3), which was
subjected to analytical chiral HPLC (Fig. 1).
of the new chiral center was presented and discussed
previously.39 The present cationic rhodium species further
on catalyzes the hydrogenation of the aldehyde to alcohol 2
in the presence of the α,β-unsaturated double bond and
various (hetero)aryl substituents of diverse electronic
nature. The tentative mechanism is outlined in Scheme 4.
After coordination of the enal intermediate to the cationic
The mechanistic rationale of the Rh–(R)-BINAP-
catalyzed cycloisomerization of alkyne allyl alcohols to
cyclic enals and the assignment of absolute configuration
Scheme 4. Mechanistic rationale for the Rh-catalyzed hydrogenation step in the sequentially Rh-catalyzed
cycloisomerization–hydrogenation synthesis of alkylidene butyrolactone β-hydroxyethanes 2
322

Chemistry of Heterocyclic Compounds 2018, 54(3), 320–328
Scheme 5. Sequentially Rh–BINAP-catalyzed
Rh–(R)-BINAP complex, the chelated complex A under-
goes oxidative addition to give the dihydrido complex B.
Hydride insertion furnishes the Rh-alcoholate C, which
undergoes reductive elimination to generate the alcohol
complex D. After decoordination of product 2, the
cationic Rh–(R)-BINAP complex is ready for a new
catalytic cycle.
Although the sequentially Rh-catalyzed cycloiso-
merization–hydrogenation of ether-tethered alkyne allyl
alcohols led into the CIHIA sequence, we became curious
to see what will happen in the presence of secondary
amines, since we had observed reductive amination in the
case of Pd-catalyzed sequences.35 Indeed, after cyclo-
isomerization of (Z)-4-[(3-arylprop-2-yn-1-yl)oxy]but-2-en-
1-ols 4a,b, the secondary amines were added to the reaction
mixture, which turned brownish immediately. After
purging the reaction mixture with hydrogen and stirring
under an ambient pressure at room temperature for 4
to 18 h, alkylidene tetrahydrofuran β-aminoethanes 5a–c
were obtained in yields of 25, 49, and 85%, respectively
enantioselective cycloisomerization–hydrogenation synthesis
of alkylidene tetrahydrofuran β-aminoethanes 5
R1
7
1 1. Cat. [RhCl(COD)] , (R)-BINAP
AgBF4, ClCH22CH2Cl
rt, 5 min
R
5
O
6
O
1
R3
3
2. R2R3NH (2 equiv)
H2 (1 atm), rt, 18 h
25–85%, >99% ee
4
N
2
R2
OH
5a–c
4a R1 = Ph
b R1 = p-anisyl
MeO
MeO
Ph
O
O
O
Ph
Bn
N
N
N
Me
(R)-5b
(25%, >99% ee)
Me
(R)-5c
(49%, >99% ee)
(R)-5a
(85%, >99% ee)
(Scheme 5). The structures of products
5
were
unambiguously supported by 1H, 13C, DEPT-135, and
COSY NMR experiments as well as IR and mass
spectrometry. The molecular composition was confirmed
by HRMS. In addition, the molecular structure of
compound 5a was corroborated by an X-ray structure
analysis (Fig. 2). The enantiomeric excesses of compounds
5 were directly determined by analytical HPLC with a
chiral cyclodextrin column (Fig. 3).
The yields of alkylidene tetrahydrofuran β-amino-
ethanes 5 are definitely affected by the nucleophilicity of
the secondary amines, i.e., morpholine is a stronger
nucleophile than N-benzylmethylamine and N-methyl-
aniline. Since alkylidene tetrahydrofuran β-amino-
ethanes are β-amino ethyl derivatives of heterocycles
they are potentially interesting in pharmaceutical appli-
cations.
Figure 2. Molecular structure of compound (R)-5a·HCl (thermal
ellipsoids shown at 50% probability).
Sequentially Rh-catalyzed cycloisomerization–hydro-
genation processes are ideally suited for rapid and
enantioselective preparation of alkylidene butyrolactone
cycloisomerization–reductive amination sequences to give
alkylidene tetrahydrofuran β-aminoethanes. Both substance
classes are in their own right interesting as building blocks
in the synthesis of lignans and their derivatives or as novel
β-aminoethyl-substituted pharmacophores.
β-hydroxyethanes
from
(2Z)-4-hydroxybut-2-en-1-yl
3-(hetero)arylprop-2-ynoates, whereas (Z)-4-[(3-arylprop-
2-yn-1-yl)oxy]but-2-en-1-ols are good substrates for
Figure 3. Analytical chiral HPLC chromatograms of (rac)-5b (left) and (R)-5b (right) (HPLC: n-hexane–2-PrOH 95:5, 0.8 ml/min,
λexc 266 nm, retention times: tR 15.2 min (major), tS 16.0 min (minor)).
323

Chemistry of Heterocyclic Compounds 2018, 54(3), 320–328
3-substituted (2Z)-4-hydroxybut-2-en-1-yl prop-2-ynoate
Experimental
1a–f was added, the solution stirred for a few minutes, and
finally the reaction was started by addition of a 0.05 M
solution of AgBF4 (0.1 equiv) in dry dichloroethane.
Immediately, the solution turned yellow and a yellow
precipitate of AgCl formed. The reaction was monitored by
TLC and after full conversion (t1), the reaction vessel was
set under hydrogen pressure (5 bar) and stirred for the time
t2. Then, the solvent was removed in vacuo and the residue
was chromatographed on silica gel (n-hexane – diethyl
ether).
IR spectra were recorded of solids as compressed KBr
pellets and of oils as films on a Bruker Vector 22 FT-IR
spectrometer. Optical rotation was measured on
a
PerkinElmer 341 polarimeter at λmax 589 nm. UV-Vis
spectra were recorded on a Hewlett Packard 84252 A diode
1
array spectrophotometer. H and 13C NMR spectra were
acquired on Bruker Avance III (300 and 75 MHz, respec-
tively) and Bruker Avance DRX500 (500 and 126 MHz,
respectively) spectrometers in CDCl3 using the CHCl3
resonance signal as internal standard (7.26 and 77.2 ppm,
respectively). The assignments of Cquat, CH, CH2, and CH3
nuclei were based on DEPT spectra. Atom numbering used
for assignment of NMR signals is shown on Schemes 2 and 3.
Mass spectra were recorded on a Bruker FTICR APEX III
spectrometer (EI, 70 eV). High-resolution mass spectra
were recorded on Jeol JMS-700 (EI, 70 eV) and Finnigan
TSQ 700 (EI, 70 eV) instruments and with Finnigan
MAT 95 (ESI) mass spectrometer. Elemental analyses were
performed on a PerkinElmer 2400 CHN elemental
analyzer. TLC was performed with silica gel-coated
aluminum plates 60 F154 (Merck) and visualization was
achieved by a handheld UV lamp (λmax,exc 254 or 365 nm) or
by immersion into an ethanolic solution of KMnO4. The
purification of products was performed on silica gel 60
(0.015–0.040 mm) by Macherey–Nagel using flash
technique and under a pressure of 2 bar. The crude
mixtures were adsorbed on Celite® 545 (0.02–0.10 mm)
before chromatographic purification. The reaction progress
was monitored qualitatively using TLC Silica gel 60 F254
aluminum sheets. Enantiomeric excesses were determined
by chiral HPLC on an HP 1090 Liquid Chromatograph
(Series II), Hewlett Packard, using a Chiralpak IA column
(Daicel Chemical Industries Ltd.). The evaluation was
performed with a HP ChemStations, Hewlett Packard.
(3Z,4R)-3-Ethylidene-4-(2-hydroxyethyl)dihydrofuran-
2(3H)-one (2a) was synthesized from (2Z)-4-hydroxybut-
2-en-1-yl but-2-ynoate (1a) (154 mg, 1.00 mmol), t1 5 min,
t2 18 h, eluent for flash chromatography n-hexane – diethyl
ether, 1:5 to diethyl ether. Yield 113 mg (72%), yellow oil.
20
Rf 0.39 (diethyl ether). (R)-enantiomer: [α]D +55.1°
(c 4.3 mg/ml, CHCl3). IR spectrum (film), ν, cm–1: 3433
(s), 2935 (s), 1751 (s), 1671 (m), 1439 (m), 1378 (m), 1211
1
(m), 1120 (m), 1020 (m), 864 (w), 776 (w). H NMR
spectrum (500 MHz, CDCl3), δ, ppm (J, Hz): 1.69–1.74
2
3
(2H, m, OH, 2-CH); 1.84 (1H, dt, J = 17.5, J = 5.8,
3
5
2-CH); 2.16 (3H, dd, J = 7.3, J = 2.1, CH3); 3.10–3.17
(1H, m, 3-CH); 3.69 (2H, dd, J = 11.5, J = 5.4, 1-CH);
2
3
3
4
3.99 (1H, dd, J = 9.0, J = 5.3, 4-CH); 4.42 (1H, dd,
2J = 14.7, 3J = 6.0, 4-CH); 6.26 (1H, qd, 3J = 7.3, 4J = 2.1,
7-CH). 13C NMR spectrum (125 MHz, CDCl3), δ, ppm:
14.2 (CH3); 36.6 (C-2); 37.8 (C-3); 60.1 (C-1); 71.3 (C-4);
129.0 (C-6); 139.1 (C-7); 170.7 (C-5). Mass spectrum
(70 eV), m/z (Irel, %): 156 [M]+ (4), 139 [M–OH]+ (9), 138
[M–H2O]+ (100), 130 (21), 112 (22), 111 [M–C2H5O]+
(47), 110 (20), 109 (13), 95 (14), 93 (13), 85 (15), 83
[C4H3O2]+ (36), 82 (12), 81 (30), 79 (20), 71 (11), 69 (18),
67 [C4H3O]+ (38), 55 (25), 53 (14), 43 [C2H3O]+ (12).
Found, m/z: 156.0786 [M]+. C8H12O3. Calculated, m/z:
156.0781.
The catalysis experiments were performed in degassed
dichloroethane which was dried using an MBraun system
MB-SPS-800. All rhodium-catalyzed cycloisomerization
reactions were carried out in oven-dried Schlenk glassware
using septa and syringes under argon atmosphere. All
rhodium-catalyzed one-pot sequences based on the cyclo-
isomerization reaction were performed in purpose-made
Schlenk tubes (8 ml volume, 4 mm wall thickness to resist
the excess hydrogen pressure). (2Z)-4-Hydroxybut-2-en-1-yl
(3Z,4R)-3-Benzylidene-4-(2-hydroxyethyl)dihydrofuran-
2(3H)-one (2b)39 was synthesized from (2Z)-4-hydroxybut-
2-en-1-yl 3-phenylprop-2-ynoate (1b) (108 mg, 0.50 mmol),
t1 30 min, t2 15 h, eluent for flash chromatography
n-hexane – diethyl ether, 1:2. Yield 107 mg (97%), yellow
oil. Rf 0.11 (n-hexane – diethyl ether, 1:2). (R)-enantiomer:
20
[α]D –2.2° (c 2.4 mg/ml, CHCl3). IR spectrum (film),
ν, cm–1: 3418 (s), 3059 (m), 3027 (m), 2912 (s), 1747 (s),
1644 (s), 1576 (w), 1494 (m), 1451 (m), 1382 (s), 1177 (s),
1113 (w), 1068 (w), 1027 (w), 972 (w), 953 (w), 899 (w),
3-(hetero)arylprop-2-ynoates
(1)
were
synthesized
according to the literature.21 The synthesis of (Z)-4-[(3-arylprop-
766 (m), 738 (m), 695 (s), 599 (m). H NMR spectrum
1
2-yn-1-yl)oxy]but-2-en-1-ols
4a,b
was
previously
(500 MHz, CDCl3), δ, ppm (J, Hz): 1.70–1.77 (1H, m,
2-CH); 1.83–1.89 (1H, m, 2-CH); 2.30 (1H, br. s, OH);
3.21–3.26 (1H, m, 3-CH); 3.65 (2H, t, 3J = 6.0, 1-CH); 4.00
reported.39 Piperidine, N-methylaniline, and N-benzyl-
methylamine were purchased from Sigma-Aldrich and used
without further purification.
3
4
(1H, dd, J = 9.0, J = 4.8, 4-CH); 3.98–4.01 (1H, m, 4-CH);
Sequentially rhodium-catalyzed cycloisomerization–
hydrogenation synthesis of alkylidene butyrolactone
alcohols 2a–f (General method). Under an argon
atmosphere [RhCl(COD)] (0.05 equiv) and (R)-BINAP
ligand (0.1 equiv) were placed in a Schlenk tube with a
magnetic stir bar. Then dried, degassed dichloroethane
(4.0 ml) was added, and the solution was stirred for several
minutes, until a dark-red solution was formed. Then,
6.85–6.87 (1H, m, 7-CH); 7.23–7.29 (3H, m, H Ar); 7.71
3
(2H, d, J = 6.7, H Ar). 13C NMR spectrum (125 MHz,
CDCl3), δ, ppm: 36.5 (C-2); 39.4 (C-3); 59.4 (C-1); 70.8 (C-4);
127.9 (CH Ph); 128.0 (Cquat Ph); 129.4 (CH Ph); 130.5 (CH
Ph); 133.4 (C-6); 139.8 (C-7); 169.4 (C-5). Mass spectrum
(70 eV), m/z (Irel, %): 218 [M]+ (33), 200 [M–H2O]+ (35),
199 [(M–H)–H2O]+ (100), 185 (19), 182 (13), 181 (22),
173 [M–CH3O]+ (23), 172 [M–CH3OH]+ (34), 156 (19),
324

Chemistry of Heterocyclic Compounds 2018, 54(3), 320–328
155 (95), 145 [C10H9O]+ (31), 141 (63), 129 [C7H13O2]+
Found, m/z: 248.1049 [M]+. C14H16O4. Calculated, m/z:
248.1043.
(3Z,4R)-4-(2-Hydroxyethyl)-3-(4-methylbenzylidene)-
(87), 128 [C7H12O2]+ (91), 127 (41), 117 (84), 115 (76),
104 (14), 91 [C7H7]+ (28), 77 (11). Found, m/z: 241.0835
[M+Na]+. C13H14NaO3. Calculated, m/z: 241.0835.
dihydrofuran-2(3H)-one (2d) was synthesized from
(2Z)-4-hydroxybut-2-en-1-yl 3-(4-methylphenyl)prop-2-yn-
oate (1d) (115 mg, 0.50 mmol), t1 60 min, t2 24 h, eluent
for flash chromatography diethyl ether. Yield 103 mg
(89%), yellow oil. Rf 0.16 (diethyl ether). (R)-enantiomer:
[α]D20 –3.3° (c 1.7 mg/ml, CHCl3). IR spectrum (film), ν, cm–1:
3417 (s), 2924 (s), 1747 (s), 1645 (m), 1607 (m), 1514 (m),
1380 (m), 1177 (m), 1080 (w), 814 (w). 1H NMR spectrum
(200 MHz, CDCl3), δ, ppm (J, Hz): 1.59 (1H, s, OH); 1.79–
1.89 (2H, m, 2-CH); 2.34 (3H, s, CH3); 3.25–3.39 (1H, m,
3-CH); 3.78 (2H, t, 3J = 6.1, 1-CH); 4.11 (1H, dd, 2J = 9.0,
rac-(3Z)-3-Benzylidene-4-(2-hydroxyethyl)dihydrofuran-
2(3H)-one ((rac)-2b) was synthesized from (2Z)-4-hydroxy-
but-2-en-1-yl 3-phenylprop-2-ynoate (1b) (108 mg,
0.50 mmol) using (rac)-BINAP as ligand instead of
(R)-BINAP, t1 5 min, 24 h, eluent for flash chromato-
graphy n-hexane – diethyl ether, 1:2. Yield 38 mg (34%),
yellow oil. IR spectrum (film), ν, cm–1: 3416 (s), 3057 (m),
3025 (m), 2914 (s), 1746 (s), 1645 (s), 1575 (w), 1494 (m),
1450 (m), 1381 (s), 1178 (s), 1112 (w), 1069 (w), 1026 (w),
972 (w), 953 (w), 900 (w), 767 (m), 737 (m), 694 (s), 600 (m).
1H NMR spectrum (500 MHz, CDCl3), δ, ppm (J, Hz): 1.70–
1.77 (1H, m, 2-CH); 1.82–1.89 (1H, m, 2-CH); 2.30 (1H,
br. s, OH); 3.21–3.25 (1H, m, 3-CH); 3.65 (2H, t, 3J = 6.0,
1-CH); 4.01 (1H, dd, 3J = 9.0, 4J = 4.8, 4-CH); 4.38–4.40 (1H,
m, 4-CH); 6.85–6.87 (1H, m, 7-CH); 7.22–7.29 (3H, m,
2
3
3J = 3.5, 4-CH); 4.49 (1H, dd, J = 9.0, J = 7.6, 4-CH);
4
3
6.89 (1H, d, J = 1.9, 7-CH); 7.16 (2H, d, J = 8.0, H Ar);
7.74 (2H, d, 3J = 8.2, H Ar). 13C NMR spectrum (125 MHz,
CDCl3), δ, ppm: 21.7 (CH3); 37.0 (C-2); 39.8 (C-3); 60.1
(C-1); 71.0 (C-4); 127.1 (C-6); 129.1 (CH Ar); 130.0
(Cquat Ar); 130.5 (Cquat Ar); 131.0 (CH Ar); 140.2 (C-7);
169.5 (C-5). Mass spectrum (70 eV), m/z (Irel, %): 232 [M]+
(94), 217 [M–CH3]+ (52), 199 (84), 187 [M–C2H5O]+ (12),
141 [C7H9O3]+ (89), 116 (82), 112 [C6H8O2]+ (51) 108
[C7H8O]+ (100). Found, m/z: 255.0992 [M+Na]+.
C14H16NaO3. Calculated, m/z: 255.0992.
3
H Ar); 7.72 (2H, d, J = 6.7, H Ar). 13C NMR spectrum
(125 MHz, CDCl3), δ, ppm: 36.5 (C-2); 39.3 (C-3); 59.4
(C-1); 70.8 (C-4); 127.9 (CH Ph); 128.0 (Cquat Ph); 129.3
(CH Ph); 130.4 (CH Ph); 133.4 (C-6); 139.9 (C-7); 169.5
(C-5). Mass spectrum (70 eV), m/z (Irel, %): 218 [M]+ (32),
200 [M–H2O]+ (34), 199 [(M–H)–H2O]+ (100), 185 (19),
182 (12), 181 (23), 173 [M–CH3O]+ (22), 172 [M–CH3OH]+
(33), 156 (19), 155 (94), 145 [C10H9O]+ (30), 141 (62), 129
[C7H13O2]+ (87), 128 [C7H12O2]+ (90), 127 (41), 117 (85),
115 (75), 104 (14), 91 [C7H7]+ (27), 77 (10). Found, m/z:
241.0835 [M+Na]+. C13H14NaO3. Calculated, m/z:
241.0835.
(3Z,4R)-3-(1,3-Benzodioxol-5-ylmethylidene)-4-(2-hydr-
oxyethyl)dihydrofuran-2(3H)-one (2e) was synthesized
from (2Z)-4-hydroxybut-2-en-1-yl 3-(1,3-benzodioxol-
5-yl)prop-2-ynoate (1e) (130 mg, 0.50 mmol), t1 15 min,
t2 66 h, eluent for flash chromatography diethyl ether.
Yield 113 mg (86%), yellow oil. Rf 0.29 (diethyl ether).
20
(3Z,4R)-4-(2-Hydroxyethyl)-3-(4-methoxybenzylidene)-
dihydrofuran-2(3H)-one (2c) was synthesized from
(R)-enantiomer: [α]D –16.3° (c 2.25 mg/ml, CHCl3).
IR spectrum (film), ν, cm–1: 3528 (s), 2914 (s), 1737 (s),
1706 (m), 1633 (m), 1597 (m), 1503 (s), 1448 (s), 1398 (m),
1341 (m), 1264 (s), 1210 (m), 1183 (m), 1108 (m), 1035 (s),
960 (w), 926 (m), 811 (m), 776 (m), 668 (w), 607 (w),
541 (w). 1H NMR spectrum (500 MHz, CDCl3), δ, ppm (J, Hz):
1.61 (1H, s, OH); 1.82–2.00 (2H, m, 2-CH); 3.23–3.37
(2Z)-4-hydroxybut-2-en-1-yl
3-(4-methoxyphenyl)prop-
2-ynoate (1c) (123 mg, 0.50 mmol), t1 300 min, t2 24 h,
eluent for flash chromatography diethyl ether. Yield 122 mg
(99%), yellow oil. Rf 0.27 (diethyl ether). (R)-enantiomer:
20
[α]D –16.9° (c 2.0 mg/ml, CHCl3). IR spectrum (film),
ν, cm–1: 3426 (s), 2934 (s), 2840 (w), 2048 (w), 1732 (s),
1634 (m), 1602 (s), 1573 (w), 1514 (s), 1429 (m), 1385
(m), 1304 (m), 1259 (s), 1172 (m), 1077 (m), 953 (w), 912
(w), 834 (m), 777 (w), 529 (m), 506 (w). 1H NMR
spectrum (500 MHz, CDCl3), δ, ppm (J, Hz): 1.75–1.77
(1H, m, OH); 1.83–1.88 (1H, m, 2-CH); 1.92–1.98 (1H, m,
2-CH); 3.28–3.34 (1H, m, 3-CH); 3.77–3.83 (5H, m, CH3,
(1H, m, 3-CH); 3.78 (2H, t, J = 6.0, 1-CH); 4.10 (1H, dd,
3
J = 9.0, J = 4.5, 4-CH); 4.48 (1H, dd, J = 9.0, J = 7.5,
4-CH); 5.97 (2H, s, OCH2O); 6.73–6.82 (2H, m, 7-CH,
H Ar); 7.20 (1H, dd, J = 8.1, J = 1.5, H Ar); 7.77 (1H, d,
J = 1.8, H Ar). 13C NMR spectrum (125 MHz, acetone-d6),
δ, ppm: 38.0 (C-2); 40.9 (C-3); 59.8 (C-1); 71.6 (C-4);
102.5 (CH2 dioxole); 108.6 (CH Ar); 111.4 (CH Ar); 127.9
(CH Ar); 128.0 (C-6); 129.6 (Cquat Ar); 139.6 (C-7); 148.4
(Cquat Ar); 149.7 (Cquat Ar); 170.0 (C-5). Mass spectrum
(70 eV), m/z (Irel, %): 262 [M]+ (67), 217 [M–C2H5O]+
(34), 192 (18), 171 [C11H7O2]+ (2) 159 (20), 143 (10), 136
(12), 125 [C7H9O2]+ (100), 131 (17), 115 (11), 77 [C6H5]+
(10), 45 [C2H5O]+ (14). Found, m/z: 262.0841 [M]+.
C14H14O5. Calculated, m/z: 262.0836.
2
3
1-CH); 4.10 (1H, dd, J = 9.0, J = 4.5, 4-CH); 4.48 (1H,
2
3
dd, J = 9.0, J = 7.8, 4-CH); 6.84–6.94 (3H, m, 7-CH,
H Ar); 7.85–7.93 (2H, m, H Ar). 13C NMR spectrum
(125 MHz, CDCl3), δ, ppm: 37.2 (C-2); 39.9 (C-3); 55.5
(OCH3); 60.0 (C-1); 71.0 (C-4); 113.8 (CH Ar); 114.7
(Cquat Ar); 125.5 (Cquat Ar); 126.7 (C-6); 132.4 (CH Ar);
140.0 (C-7); 160.9 (C-5). Mass spectrum (70 eV), m/z (Irel, %):
248 [M]+ (47), 246 (10), 230 [M–H2O]+ (10), 229 (13), 203
(74), 202 (10), 199 [M–H2O–OCH3]+ (10), 185 (21), 175
(28), 159 [C10H7O2]+ (31), 158 (17), 148 (14), 147
[C9H7O2]+ (100), 145 [C10H9O]+ (17), 144 (26), 141
[C7H9O3]+ (12), 135 (17), 134 (31), 132 (13), 131 (15), 129
[C7H13O2]+ (16), 128 [C6H8O3]+ (18), 127 (16), 121 (69),
115 (59), 108 [C7H8O]+ (15), 91 [C7H7]+ (56), 77 (24).
(3Z,4R)-4-(2-Hydroxyethyl)-3-(thiophen-2-ylmethyl-
idene)dihydrofuran-2(3H)-one (2f) was synthesized from
(2Z)-4-hydroxybut-2-en-1-yl 3-(thiophen-2-yl)prop-2-ynoate
(1f) (111 mg, 0.50 mmol), t1 5 min, t2 24 h, eluent for flash
chromatography diethyl ether. Yield 96 mg (86%), yellow
20
oil. Rf 0.21 (diethyl ether). [α]D +19.8° (c 2.4 mg/ml,
CHCl3). IR spectrum (film), ν, cm–1: 3419 (s), 3104 (w),
325

Chemistry of Heterocyclic Compounds 2018, 54(3), 320–328
2914 (s), 1732 (s), 1633 (s), 1479 (w), 1422 (w), 1392 (s),
dichloromethane (5 ml) under argon atmosphere and stirred
at room temperature for 2 h. After extraction with water
(3×6 ml), the solvents were removed in vacuo and the
residue was purified by flash chromatography on silica gel
(n-hexane – diethyl ether, 1:1). Yield 90 mg (69%), yellow
solid. Rf 0.56 (n-hexane – diethyl ether, 1:2). HPLC:
n-hexane–i-PrOH, 95:5, 0.8 ml/min, 254 nm, tS 33.3 min,
tR 40.2 min. IR spectrum (KBr), ν, cm–1: 2962 (m), 2912 (m),
1745 (s), 1643 (m), 1577 (w), 1492 (w), 1453 (w), 1367 (m),
1244 (s), 1177 (s), 1093 (m), 1063 (m), 1030 (m), 768 (m),
1330 (m), 1247 (m), 1174 (s), 1111 (m), 1026 (m), 859
(w), 776 (m), 717 (m), 609 (w), 503 (w). 1H NMR
spectrum (500 MHz, CDCl3), δ, ppm (J, Hz): 1.62 (1H, s,
OH); 1.76–1.98 (2H, m, 2-CH); 3.23–3.42 (1H, m, 3-CH);
3
2
3.78 (2H, t, J = 6.1, 1-CH); 4.12 (1H, dd, J = 9.0,
3J = 4.7, 4-CH); 4.51 (1H, dd, J = 9.0, J = 7.7, 4-CH);
2
3
3
7.02–7.07 (2H, m, 7-CH, H thienyl); 7.50 (1H, d, J = 5.2,
H thienyl); 7.55 (1H, d, J = 3.6, H thienyl). 13C NMR
3
spectrum (125 MHz, acetone-d6), δ, ppm: 38.0 (C-2); 39.8
(C-3); 59.9 (C-1); 72.0 (C-4); 125.4 (C-6); 127.6
(CH thienyl); 131.5 (CH thienyl); 132.6 (CH thienyl);
136.0 (C-7); 138.3 (Cquat thienyl); 170.4 (C-5). Mass
spectrum (70 eV), m/z (Irel, %): 224 [M]+ (22), 206 [M–H2O]+
(6), 205 (15), 179 [M–C2H5O]+ (15), 167 (18), 161 (9), 151
(18), 123 (11), 111 (10), 97 [C5H5O2]+ (18), 93 (12), 83
[C4H3S]+ (14), 73 (61), 71 (17), 45 [C2H5O]+ (100). Found,
m/z: 247.0399 [M+Na]+. C11H12O3NaS. Calculated, m/z:
247.0399.
1
737 (w), 695 (m), 601 (w), 515 (w), 502 (w). H NMR
spectrum (500 MHz, CDCl3), δ, ppm (J, Hz): 1.91–1.98
(1H, m, 2-CH); 2.01–2.09 (4H, m, 2-CH, CH3); 3.10–3.25
2
3
(1H, m, 3-CH); 4.09 (1H, dd, J = 9.0, J = 4.6, 4-CH);
4.12–4.28 (1H, m, 1-CH); 4.23 (1H, ddd, 2J = 11.9,
3
2
3
3J = 6.6, J = 5.6, 1-CH); 4.47 (1H, dd, J = 9.0, J = 7.5,
4-CH); 6.91 (1H, d, 4J = 2.0, 7-CH); 7.28–7.38 (3H, m, H Ar);
7.82 (2H, dd, J = 7.6, 4J = 1.6, H Ar). 13C NMR spectrum
3
(125 MHz, CDCl3), δ, ppm: 21.1 (CH3); 33.3 (C-2); 39.9
(C-3); 61.5 (C-1); 70.4 (C-4); 127.6 (Cquat Ph); 128.4
(CH Ph); 129.9 (CH Ph); 130.8 (CH Ph); 133.5
(C-6); 140.2 (C-7); 168.8 (C-5); 171.1 (Cquat acetyl). Mass
spectrum (70 eV), m/z (Irel, %): 260 [M]+ (7), 201
[M–CH3CO2]+ (6), 200 [M–CH3CO2H]+ (56), 199 (40), 185
[M–C2H3O3]+ (22), 182 (17), 181 (11), 172 [C11H8O2]+
(49), 171 (11), 156 (20), 155 [M–CH3–C7H7]+ (100), 154
(17), 153 (11), 143 (23), 142 (21), 141 (55), 129 (41), 128
[C6H8O3]+ (59), 127 (23), 117 (51), 116 (15), 115 (62), 102
(13), 91 [C7H7]+ (44), 78 (11), 77 [C6H5]+ (19), 65 (10), 51
(12). Found, %: C 69.04, H 6.45. C15H16O4. Calculated, %:
C 69.22, H 6.20.
Sequentially rhodium-catalyzed cycloisomerization–
reductive amination synthesis of alkylidene tetrahydro-
furan β-aminoethane 5a–c (General method). Under an
argon atmosphere [RhCl(cod)] and (R)-BINAP ligand were
placed into a Schlenk tube with a magnetic stirring bar.
Then dried, degassed dichloroethane was added and the
solution was stirred for several minutes, until a dark-red
solution was formed. Then (Z)-4-[(3-arylprop-2-yn-1-yl)-
oxy]but-2-en-1-ol (4) was added, the solution stirred for a
few minutes and finally the reaction was started by addition
of a 0.05 M solution of AgBF4 in dry dichloroethane.
Immediately, the solution turned yellow and a yellow
precipitate of AgCl formed. After 5 min, the secondary
amine was added to the reaction mixture and the reaction
vessel was flushed with hydrogen (1 atm) and stirred at
room temperature under hydrogen for 18 h. The reaction
mixture was then diluted with diethyl ether (100 ml), and
potassium carbonate (1 g) was added. After filtration, the
solvents were removed in vacuo and the residue was
chromatographed on alumina (basicity level IV) to give the
analytically pure alkylidene tetrahydrofuran β-amino-
ethanes 5a–c.
2-((3R,4Z)-4-Benzylidene-5-oxotetrahydrofuran-3-yl)-
ethyl acetate (3). Compound 2b (218 mg, 1.00 mmol),
acetyl chloride (0.1 ml, 1.4 mmol), and DMAP (170 mg,
1.40 mmol) were dissolved in dry dichloromethane (10 ml)
under argon atmosphere and stirred at room temperature for
2 h. After extraction with water (3×10 ml), the solvents
were removed in vacuo and the residue was purified by
flash chromatography on silica gel (n-hexane – diethyl
ether, 1:1). Yield 198 mg (76%), yellow solid. Rf 0.56
(n-hexane – diethyl ether, 1:2). (R)-enantiomer: [α]D20 –61.3°
(c 2.0 mg/ml, MeOH). HPLC: n-hexane–i-PrOH, 95:5,
0.8 ml/min, 254 nm, tS 33.3 min (minor), tR 40.2 min
(major): ee >99%. IR spectrum (KBr), ν, cm–1: 2964 (m),
2911 (m), 1747 (s), 1644 (m), 1576 (w), 1494 (w), 1453 (w),
1368 (m), 1243 (s), 1177 (s), 1092 (m), 1063 (m), 1030 (m),
767 (m), 738 (w), 695 (m), 602 (w), 516 (w), 503 (w).
1H NMR spectrum (500 MHz, CDCl3), δ, ppm (J, Hz): 1.91–
1.99 (1H, m, 2-CH); 2.02–2.10 (4H, m, 2-CH, CH3); 3.11–
2
3
3.26 (1H, m, 3-CH); 4.09 (1H, dd, J = 9.0, J = 4.7,
4-CH); 4.13–4.28 (1H, m, 1-CH); 4.23 (1H, ddd, 2J = 12.0,
3
2
3
3J = 6.6, J = 5.6, 1-CH); 4.48 (1H, dd, J = 9.0, J = 7.6,
4
4-CH); 6.91 (1H, d, J = 2.0, 7-CH); 7.28–7.38 (3H, m,
H Ar); 7.81 (2H, dd, J = 7.7, J = 1.6, H Ar). 13C NMR
spectrum (125 MHz, CDCl3), δ, ppm: 21.1 (CH3); 33.3
(C-2); 39.9 (C-3); 61.6 (C-1); 70.4 (C-4); 127.7 (Cquat Ph);
128.4 (CH Ph); 129.9 (CH Ph); 130.9 (CH Ph); 133.5
(C-6); 140.3 (C-7); 168.8 (C-5); 171.0 (Cquat acetyl). Mass
spectrum (70 eV), m/z (Irel, %): 260 [M]+ (8), 201
[M–CH3CO2]+ (7), 200 [M–CH3CO2H]+ (57), 199 (39), 185
[M–C2H3O3]+ (22), 182 (17) 181 (12), 172 [C11H8O2]+ (48),
171 (11), 156 (21), 155 [M–CH3–C7H7]+ (100), 154 (17), 153
(10), 143 (22), 142 (21), 141 (56), 129 (41), 128 [C6H8O3]+
(59), 127 (22), 117 (52), 116 (15), 115 (62), 102 (13), 91
[C7H7]+ (43), 78 (11), 77 [C6H5]+ (19), 65 (10), 51 (13).
Found, %: C 69.04, H 6.45. C15H16O4. Calculated, %:
C 69.22, H 6.20.
3
4
1-{2-[(3R,4Z)-4-Benzylidenetetrahydrofuran-3-yl]ethyl}-
piperidine (5a) was synthesized from (Z)-4-[(3-phenylprop-
2-yn-1-yl)oxy]but-2-en-1-ol (4a) (202 mg, 1.00 mmol)
using [RhCl(cod)] (12.3 mg, 0.03 mmol), (R)-BINAP
(31.1 mg, 0.05 mmol), dichloroethane (4.0 ml), 0.05 M
solution of AgBF4 in dry dichloroethane (1.0 ml, 0.05 mmol),
rac-2-((4Z)-4-Benzylidene-5-oxotetrahydrofuran-3-yl)-
ethyl acetate ((rac)-3). Compound (rac)-2b (110 mg,
0.50 mmol), acetyl chloride (50 μl, 0.7 mmol), and
4-DMAP (85 mg, 0.7 mmol) were dissolved in dry
326

Chemistry of Heterocyclic Compounds 2018, 54(3), 320–328
and piperidine (0.2 ml, 2.0 mmol). Eluent for flash chromato-
rac-N-{2-[(4Z)-4-(4-Methoxybenzylidene)tetrahydro-
furan-3-yl]ethyl}-N-methylaniline ((rac)-5b) was synthe-
sized from (Z)-4-{[3-(4-methoxyphenyl)prop-2-yn-1-yl]-
oxy}but-2-en-1-ol (4b) (116 mg, 0.50 mmol), using
[RhCl(cod)] (6.1 mg, 0.01 mmol), (rac)-BINAP (15.5 mg,
0.03 mmol) as ligand instead of (R)-BINAP, dichloro-
ethane (2.0 ml), 0.05 M solution of AgBF4 in dry dichloro-
ethane (0.5 ml, 0.03 mmol), and N-methylaniline (0.11 ml,
1.0 mmol). Eluent for flash chromatography n-hexane –
diethyl ether, 1:1 + 5 vol % of NEt3. Yield 132 mg (78%),
yellow oil. HPLC: (n-hexane–i-PrOH) 0.8 ml/min, 266 nm,
tR 15.2 min, tS 16.0 min. IR spectrum (film), ν, cm–1: 2932 (s),
2858 (s), 1602 (s), 1576 (w), 1509 (s), 1464 (m), 1368 (m),
1295 (m), 1253 (s), 1180 (m), 1115 (m), 1065 (m), 1033 (s),
991 (w), 909 (w), 825 (m), 750 (s), 731 (s), 692 (m), 532 (m).
1H NMR spectrum (300 MHz, CDCl3), δ, ppm (J, Hz): 1.66–
1.80 (1H, m, 2-CH); 1.93–2.03 (1H, m, 2-CH); 2.79–2.86
(1H, m, 3-CH); 2.92 (3H, s, NCH3); 3.33–3.45 (2H, m,
1-CH); 3.62 (1H, dd, 2J = 8.3, 3J = 5.6, 4-CH); 3.79 (3H, s,
graphy n-hexane – diethyl ether, 1:2 + 5 vol % of NEt3.
Yield 230 mg (85%), yellow oil. Rf 0.86 (diethyl ether).
20
(R)-enantiomer: [α]D –31.4° (c 4.5 mg/ml, CHCl3). HPLC:
n-hexane–i-PrOH, 0.8 ml/min, 266 nm, tR 18.2 min (major),
tS 25.5 min (minor): ee >99%. IR spectrum (film), ν, cm–1:
2933 (s), 2851 (s), 2802 (m), 1468 (m), 1059 (m), 738 (m),
1
694 (m). H NMR spectrum (300 MHz, CDCl3), δ, ppm
(J, Hz): 1.38–1.47 (2H, m, CH2 piperidinyl); 1.54–1.63
(5H, m, CH2 piperidinyl, 2-CH); 1.64–1.74 (1H, m, 2-CH);
2.28–2.46 (6H, m, CH2 piperidinyl, 1-CH); 2.80–2.90 (1H,
2
3
m, 3-CH); 3.55 (1H, dd, J = 8.5, J = 6.3, 4-CH); 4.03
2
3
(1H, dd, J = 8.5, J = 6.8, 4-CH); 4.62–4.63 (2H, m,
5-CH); 6.34–6.36 (1H, m, 7-CH); 7.11–7.22 (3H, m,
H Ph); 7.30–7.35 (2H, m, H Ph). 13C NMR spectrum
(75 MHz, CDCl3), δ, ppm: 24.5 (CH2 piperidinyl); 26.0
(CH2 piperidinyl); 30.4 (C-2); 44.0 (C-3); 54.7 (C-1); 57.4
(CH2 piperidinyl); 70.1 (C-5); 72.8 (C-4); 120.7 (C-7); 126.5
(CH Ph); 127.9 (CH Ph); 128.5 (CH Ph); 137.4 (Cquat Ph);
145.2 (C-6). Mass spectrum (70 eV), m/z (Irel, %): 271 [M]+
(1), 141 (14) 131 (15), 129 (23), 128 (35), 98 (100), 91
[C7H7]+ (100), 77 [C6H5]+ (8), 55 (19), 41 (16). Found, m/z:
271.1916 [M]+. C18H25NO. Calculated, m/z: 271.1931.
N-{2-[(3R,4Z)-4-(4-Methoxybenzylidene)tetrahydro-
furan-3-yl]ethyl}-N-methylaniline (5b) was synthesized
from (Z)-4-{[3-(4-methoxyphenyl)prop-2-yn-1-yl]oxy}but-
2-en-1-ol (4b) (116 mg, 0.50 mmol) using [RhCl(cod)]
(6.2 mg, 0.01 mmol), (R)-BINAP (15.6 mg, 0.03 mmol),
dichloroethane (2.0 ml), 0.05 M solution of AgBF4 in dry
dichloroethane (0.5 ml, 0.03 mmol), and N-methylaniline
(0.11 ml, 1.0 mmol). Eluent for flash chromatography
n-hexane – diethyl ether, 1:1 + 5 vol % of NEt3. Yield 40 mg
(25%), yellow oil. Rf 0.76 (n-hexane – diethyl ether, 1:1 +
2
3
OCH3); 4.03 (1H, dd, J = 8.3, J = 6.7, 4-CH); 4.59–4.61
3
4
(2H, m, 5-CH); 6.27 (1H, dd, J = 4.5, J = 2.2, 7-CH);
6.62–6.72 (3H, m, H aniline); 6.85–6.91 (2H, m, H p-anisyl);
7.03–7.07 (2H, m, H aniline); 7.19–7.25 (2H, m, H p-anisyl).
13C NMR spectrum (75 MHz, CDCl3), δ, ppm: 29.8 (C-2);
38.3 (N-CH3); 43.2 (C-3); 50.7 (C-1); 55.2 (O-CH3); 70.0
(C-5); 72.5 (C-4); 112.4 (CH aniline); 114.0 (CH p-anisyl);
116.2 (CH aniline); 120.3 (C-7); 129.1 (CH p-anisyl);
129.2 (CH aniline); 130.0 (Cquat aniline); 142.4 (Cquat p-anisyl);
149.1 (C-6); 158.2 (Cquat p-anisyl). Mass spectrum (70 eV),
m/z (Irel, %): 323 [M]+ (8), 216 [C14H16O2]+ (1), 188
[C12H12O2]+ (2), 162 [C10H10O2]+ (2), 149 (19), 146
[C10H10O]+ (4), 132 [C9H8O]+ (4), 121 [C8H9O]+ (10), 120
[C8H8O]+ (100). Found, m/z: 323.1890 [M]+. C21H25NO2.
Calculated, m/z: 323.1880.
20
+ 5 vol % of NEt3). [α]D –30.5° (c 1.4 mg/ml, CHCl3).
HPLC: (n-hexane–i-PrOH) 0.8 ml/min, 266 nm, tR 15.2 min
(major), tS 16.0 min (minor): ee >99%. IR spectrum (film),
ν, cm–1: 2933 (s), 2858 (s), 1603 (s), 1575 (w), 1509 (s),
1464 (m), 1367 (m), 1296 (m), 1252 (s), 1179 (m), 1116 (m),
1066 (m), 1034 (s), 992 (w), 910 (w), 826 (m), 750 (s),
733 (s), 693 (m), 531 (m). UV/Vis spectrum (CH2Cl2),
N-Benzyl-2-[(3R,4Z)-4-(4-methoxybenzylidene)tetra-
hydrofuran-3-yl]-N-methylethanamine (5c) was synthe-
sized from (Z)-4-{[3-(4-methoxyphenyl)prop-2-yn-1-yl]-
oxy}but-2-en-1-ol (4b) (232 mg, 1.00 mmol) using
[RhCl(cod)] (25 mg, 0.05 mmol), (R)-BINAP (63 mg,
0.1 mmol), dichloroethane (10.0 ml), 0.05 M solution of
AgBF4 in dry dichloroethane (2.0 ml, 0.1 mmol), and
N-benzylmethylamine (0.26 ml, 2.0 mmol). Eluent for flash
chromatography n-hexane – diethyl ether, 1:1 + 5 vol % of
NEt3. Yield 166 mg (49%), yellow oil. Rf 0.37 (n-hexane –
1
λmax, nm (ε): 262 (22600), 304 (2800). H NMR spectrum
(300 MHz, CDCl3), δ, ppm (J, Hz): 1.67–1.80 (1H, m, 2-CH);
1.93–2.04 (1H, m, 2-CH); 2.79–2.87 (1H, m, 3-CH); 2.93
(3H, s, NCH3); 3.33–3.46 (2H, m, 1-CH); 3.61 (1H, dd,
2J = 8.4, 3J = 5.6, 4-CH); 3.79 (3H, s, OCH3); 4.04 (1H, dd,
2J = 8.4, 3J = 6.7, 4-CH); 4.60–4.61 (2H, m, 5-CH); 6.28 (1H,
dd, 3J = 4.5, 4J = 2.2, 7-CH); 6.62–6.73 (3H, m, H aniline);
6.85–6.90 (2H, m, H p-anisyl); 7.03–7.08 (2H, m, H aniline);
7.19–7.26 (2H, m, H p-anisyl). 13C NMR spectrum (75 MHz,
CDCl3), δ, ppm: 29.8 (C-2); 38.3 (N-CH3); 43.3 (C-3); 50.8
(C-1); 55.2 (O-CH3); 70.0 (C-5); 72.6 (C-4); 112.4 (CH
aniline); 114.0 (CH p-anisyl); 116.3 (CH aniline); 120.3
(C-7); 129.1 (CH p-anisyl); 129.2 (CH aniline); 130.0 (Cquat
aniline); 142.3 (Cquat p-anisyl); 149.1 (C-6); 158.3 (Cquat
p-anisyl). Mass spectrum (70 eV), m/z (Irel, %): 323 [M]+
(9), 216 [C14H16O2]+ (1), 188 [C12H12O2]+ (2), 162
[C10H10O2]+ (2), 149 (20), 146 [C10H10O]+ (4), 132 [C9H8O]+
(4), 121 [C8H9O]+ (10), 120 [C8H8O]+ (100). Found, m/z:
323.1890 [M]+. C21H25NO2. Calculated, m/z: 323.1880.
20
diethyl ether, 1:2 + 5 vol % of NEt3). [α]D –23.9°
(c 2.8 mg/ml, CHCl3). IR spectrum (film), ν, cm–1: 3028 (w),
2940 (m), 2837 (m), 2790 (m), 1607 (s), 1511 (s), 1495 (w),
1454 (m), 1296 (m), 1251 (s), 1179 (m), 1113 (w), 1060 (m),
1035 (s), 933 (w), 872 (w), 825 (w), 739 (m), 700 (m),
531 (w). UV/Vis spectrum (CH2Cl2), λmax, nm (ε): 266
(23200), 276 (17400). 1H NMR spectrum (300 MHz,
CDCl3), δ, ppm (J, Hz): 1.60–1.72 (1H, m, 2-CH); 1.85–
1.97 (1H, m, 2-CH); 2.21 (3H, s, NCH3); 2.36–2.48 (2H, m,
1-CH); 2.81–2.93 (1H, m, 4-CH); 3.44–3.56 (3H, m, CH2
benzyl, 4-CH); 3.74–3.76 (1H, m, 5-CH); 3.79 (3H, s,
2
3
OCH3); 3.97 (2H, dd, J = 8.4, J = 6.7, 5-CH); 6.23–6.25
(1H, m, 7-CH); 6.87 (2H, d, 3J = 8.8, H p-anisyl); 7.04 (2H,
3
d, J = 8.7, H Ph); 7.24–7.32 (5H, m, H p-anisyl, H Ph).
13C NMR spectrum (75 MHz, CDCl3), δ, ppm: 30.9 (C-2);
327

Chemistry of Heterocyclic Compounds 2018, 54(3), 320–328
9. Chatani, N.; Inoue, H.; Morimoto, T.; Muto, T.; Murai, S.
42.3 (N-CH3); 43.4 (C-3); 55.3 (O-CH3); 62.5 (CH2
J. Org. Chem. 2001, 66, 4433.
benzyl); 70.0 (C-5); 72.8 (C-4); 113.9 (CH p-anisyl); 120.0
(C-7); 127.0 (CH Ph); 128.2 (CH Ph); 128.3 (CH Ph);
129.1 (CH p-anisyl); 130.2 (Cquat Ph); 139.2 (Cquat p-anisyl);
142.9 (C-6); 158.2 (Cquat p-anisyl). Mass spectrum (70 eV),
m/z (Irel, %): 337 [M]+ (15), 216 [C14H16O2]+ (1), 188
[C12H12O2]+ (2), 146 [C10H10O]+ (5), 135 (12), 134
[C9H10O]+ (100), 121 [C8H9O]+ (7), 120 (5), 91 [C7H7]+
(63). Found, m/z: 337.2056 [M]+. C22H27NO2. Calculated,
m/z: 337.2036.
10. Kezuka, S.; Okado, T.; Niou, E.; Takeuchi, R. Org. Lett.
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X-ray structural study of compound (R)-5a·HCl. The
single crystal of compound (R)-5a·HCl suitable for X-ray
crystallography was obtained by evaporation of the solution of
compound (R)-5a·HCl in dichloromethane kept at room
temperature for 7 days. The data were collected on a
Bruker SMART APEX diffractometer (radiation MoKa,
λ 0.71073 Å, 0.3 deg ω-scans with CCD area detector,
covering a whole sphere in reciprocal space) using a color-
less crystal (polyhedron), dimensions 0.36 × 0.16 × 0.05 mm3.
Crystal system orthorhombic; space group P212121; Z 4;
a 6.059(3), b 10.745(6), c 26.18(2) Å; α 90, β 90, γ 90°;
V 1704.3(19) Å3; ρ 1.200 g/cm3; T 200(2) K; θmax 28.54°;
17724 reflections measured, 4288 (R(int) 0.0741), observed
3623 (I > 2(I)), intensities were corrected for Lorentz and
polarization effects, an empirical absorption correction was
applied using the SADABS software40 based on the Laue
symmetry of the reciprocal space, μ 0.224 mm–1, Tmin 0.99,
Tmax 0.92. The structure was solved by direct methods and
refined against F2 with
a full-matrix least-squares
algorithm using the SHELXTL-PLUS (5.10) software
package,41 194 parameters refined, hydrogen atoms were
treated using appropriate riding models, goodness of fit
1.31 for observed reflections, final residual values
R1(F) 0.104, wR(F2) 0.164 for observed reflections,
residual electron density –0.33 to 0.59 eÅ–3. Crystallo-
graphic data of compound 5a is deposited at the Cambridge
Crystallographic Data Center (deposit CCDC 1825476).
Financial support of the Deutsche Forschungs-
gemeinschaft (SFB 623) and Fonds der Chemischen
Industrie is gratefully acknowledged. We also cordially
thank the BASF SE for the generous donation of chemicals.
34. Kressierer, C. J.; Müller, T. J. J. Synlett 2005, 1721.
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38. Chi, Y.; Tang, W.; Zhang X. In Modern Rhodium-Catalyzed
Organic Reactions; Evans, P. A., Ed.; Wiley-VCH:
Weinheim, 2005, p. 1.
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