Synthesis of Alkynyl-Glycinols by Lewis Acid Catalyzed Propargylic Substitution of Bis-Imidates

Article abstract of DOI:10.1002/ejoc.201500937

Racemic and enantioenriched alkynyl-glycinols can be synthesized by Lewis acid catalyzed cyclization reaction of bis-trichloracetimidates derived from alkynyl-glycols. The cyclization proceeds selectively to give 4-alkynyl-oxazolines as the propargylic substitution products. Enantioenriched bis-imidates that contain an alkyl or trimethylsilyl substituent at the acetylene gave oxazolines with complete inversion of configuration. In turn, considerable racemization was observed in the cyclization of bis-imidates that contain a phenyl substituent. The racemization for these substrates can be suppressed by introduction of the electronegative substituent at the phenyl ring. Oxazolines prepared by bis-imidate cyclization reaction can be readily transformed to protected alkynyl-glycol derivatives. Racemic and enantioenriched alkynyl-glycinol derivatives can be synthesized by Lewis acid catalyzed cyclization reaction of bis-trichloroacetimidates into oxazolines.

Full text of DOI:10.1002/ejoc.201500937

FULL PAPER
DOI: 10.1002/ejoc.201500937
Synthesis of Alkynyl-Glycinols by Lewis Acid Catalyzed Propargylic
Substitution of Bis-Imidates
Jekaterina Sirotkina,[a] Liene Grigorjeva,[a] and Aigars Jirgensons*[a]
Keywords: Synthetic methods / Nucleophilic substitution / Alkynes / Cyclization / Lewis acids
Racemic and enantioenriched alkynyl-glycinols can be syn-
thesized by Lewis acid catalyzed cyclization reaction of bis-
trichloracetimidates derived from alkynyl-glycols. The cycli-
zation proceeds selectively to give 4-alkynyl-oxazolines as
the propargylic substitution products. Enantioenriched bis-
imidates that contain an alkyl or trimethylsilyl substituent at
the acetylene gave oxazolines with complete inversion of
configuration. In turn, considerable racemization was ob-
served in the cyclization of bis-imidates that contain a phenyl
substituent. The racemization for these substrates can be
suppressed by introduction of the electronegative substituent
at the phenyl ring. Oxazolines prepared by bis-imidate cycli-
zation reaction can be readily transformed to protected alk-
ynyl-glycol derivatives.
Introduction
Results and Discussion
Alkynyl-glycinols 3 (Figure 1) have found application as
important multifunctional building blocks for the construc-
tion of complex molecules.[1–10] Nevertheless, the literature
review revealed that there is a limited number of methods
for the synthesis of such compound types.[11–19] Of particu-
lar interest is the access to enantioenriched alkynyl-glycin-
ols that typically relies on derivatization of Garner’s alde-
hyde[5,11,12,20,21] and Ellman-type addition reactions of ter-
minal alkynes to N-sulfinyl imines.[14,17]
Racemic alkynyl-glycols 6a–6j required for the synthesis
of bis-imidate 1 were prepared by addition of magnesium
or lithium acetylenides to protected acetaldehydes 4a and
4b followed by deprotection of intermediates 5a–5j.
For the synthesis of diinyl-glycols 6k and 6l, intermediate
5b was first de-silylated and then subjected to Glaser cou-
pling with bromoalkynes (Table 1). For the synthesis of vin-
ylacetylenyl-glycol 6m, de-silylation of intermediate 5b was
followed by Sonogashira coupling with vinyl bromide
(Table 1).[28]
Enantioenriched ethynyl-glycols R-6a–6e were prepared
by using Noyori asymmetric hydrogenation reaction of pro-
tected hydroxyl ketones 7a–7f as a key step (Table 2).[29]
Ketones 7a–7e were prepared by oxidation of protected di-
ols 5a–5e.
Carreira’s asymmetric addition of alkynes to protected
hydroxy ketone 4b[30] was found to be the method of choice
for the synthesis of enantioenriched aryl-substituted eth-
ynyl-glycols R-6h–6j (Table 3).
The absolute configuration for representative diols R-6b
and R-6j was determined by analysis of the 1H NMR spec-
troscopic data of the diastereoisomeric diesters that resulted
from derivatization with R- and S-α-metoxyphenylacetic
acids (see Supporting Information).[31]
Diols 6a–6m were converted into bis-imidates 1a–1m in
good yields by the reaction with trichloroacetonitrile in the
presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU;
Table 4).
Figure 1. Alkynyl-glycinols 3 by propargylic substitution of bis-im-
idates 1.
Previously we developed the synthesis of unsaturated
amino alcohols based on allylic substitution in bis-imid-
ates.[22–27] In these systems, one of the imidates serves as an
N-nucleophile and the other as a leaving group when acti-
vated by the acid catalyst. Here we report investigation of
the propargylic substitution reaction of bis-imidates 1 de-
rived from alkynyl-glycols (Figure 1). Both regioselectivity
and chirality transfer of the cyclization were explored with
an aim to prepare alkynyl-oxazolines 2, which are precur-
sors of alkynyl-glycinols 3.
Cyclization of bis-imidates 1a–1m was achieved in good
yields with a wide range of Lewis acid catalysts: trimethyl-
silyl (TMS)OTf, BF3·Et2O, AlCl3, FeCl3 (Table 5). In this
reaction, 4-alkynyloxazolines 2a–2m typically were ob-
tained with high selectivity over regioisomers 7a–7m. In the
[a] Latvian Institute of Organic Synthesis,
Aizkraukles 21, Riga 1006, Latvia
E-mail: aigars@osi.lv
http://osmg.osi.lv/
Supporting Information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201500937.
6900
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 6900–6908

Synthesis of Alkynyl-Glycinols
Table 1. Preparation of racemic alkynyl-glycols 6.[a]
Table 3. Preparation of enantioenriched alkynyl-glycols by using
Carreira’s asymmetric alkynylation.[a]
Entry
R
6, yield [%] (ee [%])[b]
1
2
3
Ph
R-6h, 79 (88)
R-6i, 88 (90)
R-6j, 60 (93)
2-ClC6H4
3,5-ClC6H3
Entry
R
5, yield [%]
6, yield [%]
[a] Reagents and conditions: (a) RCϵCH (2.5 equiv.), (–)-N-
methylephedrine (2.2 equiv.), Zn(OTf)2 (2.0 equiv.), TEA
(2.2 equiv.), toluene room temp. then pTsOH·H2O (15 mol-%),
MeOH, CH2Cl2, room temp. [b] ee was determined by HPLC by
chiral column Chiralpak IB.
1
2
3
4
5
6
7
8
Me
TMS
BnOCH2
BnOCH2CH2
tBu
Pent
TIPS
Ph
2-ClC6H4
3,5-ClC6H3
PentCϵC
TIPSCϵC
CH2=CH
5a, 87
5b, 81
5c, 27
5d, 45
5e, 78
5f, 76
5g, 60
5h, 70
5i, 70
5j, 56
–
6a, 81
6b, 94
6c, 93
6d, Ͼ 99
6e, 88
6f, 90
Table 4. Preparation of bis-imidates 1 from alkynyl-glycols 6.[a]
6g, 97
6h, 91
6i, 95
9
10
11
12
13
6j, 82
6k, 88[b]
6l, 79[b]
6m, 88[b]
–
–
[a] Reagents and conditions: (a) 4a, MeCϵCMgBr, Et2O, 0 °C for
5a; (b) 4a or 4b, RCϵCH, nBuLi, THF, –78 °C for 5b–5j; (c) 5a and
5c–5f, TBAF, AcOH, THF room temp. for 6a and 6c–6f; (d) 5b, g,
1% HCl, MeOH, room temp. for 6b, g; (e) 5h–5j, 15 mol-%
pTsOH·H2O, MeOH, CH2Cl2, room temp. for 6h–6j; (f) 5b, KF,
MeOH 50 °C then PentCϵCBr or triisopropylsilyl (TIPS)CϵCBr,
NH2OH·HCl, 20 mol-% CuCl, BuNH2, room temp. for 6k and 6l;
(g) 5b, KF, MeOH 50 °C then 10 mol-% CuI, 2 mol-% Pd(PPh3)4,
diethanolamine, vinyl bromide, THF, room temp. for 6m. [b] Diols
6k–6m were prepared from intermediate 5b.
Entry
R
1, yield [%][b]
1
2
3
4
5
6
7
8
Me
TMS
BnOCH2
BnOCH2CH2
tBu
Pent
TIPS
Ph
2-ClC6H4
3,5-ClC6H3
Pent–CϵC
TIPS–CϵC
CH2=CH
1a, 73
1b, 85
1c, 92
1d, 97
1e, 90
1f, 88
1g, 99
1h, 80
1i, 85
1j, 88
1k, 83
1l, 50
1m, 85
9
Table 2. Preparation of enantioenriched alkynyl-glycols 6 by using
10
11
12
13
Noyori asymmetric reduction reaction.[a]
[a] Reagents and conditions: (a) CCl3CN, 20 mol-% DBU, molecu-
lar sieves (4 Å), CH2Cl2, 0 °C. [b] Enantioenriched bis-imidates R-
1 were prepared by the same procedure as the racemic compound
in similar yields.
Chirality transfer in the cyclization reaction of enanti-
oenriched bis-imidates R-1 was investigated. Substrates R-
1a–1e that contained an alkyl or TMS substituent gave ox-
azolines S-2a–2e with complete inversion of configuration
at the stereocenter (Table 6, Entries 1–5). This stereochemi-
cal outcome indicates that the SN2 type substitution of the
Lewis acid complexed propargylic imidate with the uncom-
plexed imidate (Figure 2). Notably, this is different from all-
ylic substitution reaction with bis-imidates, which proceed
by an SN1 type reaction mechanism.[22,24,26] In turn, phenyl-
Entry
R
7, yield [%]
6, yield [%] (ee [%])[b]
1
2
3
4
5
Me
TMS
BnOCH2
BnOCHCH2
tBu
7a, 70
7b, 70
7c, 83
7d, 70
7e, 50
R-6a, 72 (90)
R-6b, 68 (96)
R-6c, 61 (92)
R-6d, 43 (93)
R-6e, 63 (93)
[a] Reagents and conditions: (a) Dess–Martin periodinane, CH2Cl2,
room temp. (b) Cat. 8 (6 mol-%), iPrOH room temp., then TBAF,
AcOH, THF room temp. [b] ee was determined by chiral GC for substituted bis-imidate R-1h formed oxazoline 2h with a
6a, 6b, and 6e, or by HPLC by using chiral column Chiralpak IB
for 6c and 6d.
considerable degree of racemization (Table 6, Entry 6). One
chlorine substituent in the phenyl ring in substrate R-1i
slightly suppressed the racemization in the cyclization to
case of TMS-substituted substrate 1b, the desired selectivity oxazoline 2i (Table 6, Entries 7–9). With two chlorines in
for oxazoline 2b formation was improved by replacing the the phenyl ring in substrate R-1j the racemization was mini-
TMSOTf catalyst with AlCl3 (Table 5, Entries 2 and 3).
mal with all the catalysts explored and oxazoline S-2j was
Eur. J. Org. Chem. 2015, 6900–6908
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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6901

J. Sirotkina, L. Grigorjeva, A. Jirgensons
FULL PAPER
Scheme 1. Transformation of oxazolines 2 into amino alcohol derivatives 3, 9, and 10. Reagents and conditions: (a) Aqueous HCl (6 m),
MeOH, room temp.; (b) Aqueous HCl (6 m), MeOH room temp. then Boc2O, NaHCO3, THF room temp.; (c) pTsOH, pyridine, H2O
80 °C.
Table 5. Substrate scope in the cyclization reaction of bis-imidates
1 to oxazolines 2.[a]
Figure 2. Proposed mechanisms for bis-imidate 1 cyclization reac-
tion in the case of alkyl and aryl substitution.
Entry
R
Cat.[b]
2/7
2, yield [%]
observed in high enantiopurity (Table 6, Entries 10–12).
These results indicate a mixed SN1/SN2 type mechanism in
the case of substrates that bear a phenyl group in acetylenic
position (Figure 2). The SN1 pathway is obviously dimin-
ished by decreasing the carbenium ion stabilizing effect of
the phenyl group in substrates R-1i and R-1j.
1
2
3
4
5
6
7
8
Me
TMS
TMS
BnOCH2
BnOCH2CH2 AlCl3
tBu
Pent
TIPS
Ph
2-ClC6H4
3,5-ClC6H3 AlCl3
PentCϵC
TIPSCϵC
CH2=CH
TMSOTf
TMSOTf
AlCl3
Ͼ 50:1
9:1
35:1
8:1
41:1
Ͼ 50:1
Ͼ 50:1
23:1
25:1
Ͼ 50:1
32:1
2a, 71
2b, 82
2b, 91
2c, 75
2d, 80
2e, 84
2f, 82
2g, 73
2h, 79
2i, 70
2j, 95
2k, 86
2l, 69
2m, 80
AlCl3
AlCl3
TMSOTf
AlCl3
TMSOTf
TMSOTf
The synthetic utility of oxazolines 2 was demonstrated
by transforming them into alkynyl-glycinol derivatives
(Scheme 1). Strong acidic hydrolysis of oxazolines S-2b–2e
and S-2j led to alkynyl-glycinols S-3b–3e and S-3j. The ab-
solute configuration for the representative amino alcohols
9
10
11
12
13
14
AlCl3
AlCl3
AlCl3
11:1
Ͼ 50:1
Ͼ 50:1
1
S-3b and S-3j was determined by analysis of the H NMR
spectra of the diastereoisomeric arylamines resulting from
derivatization with R- and S-1-fluoro-2,4-dinitrophenyl-5-
phenylethylamines (see Supporting Information).[32]
The hydrolysis of oxazoline 2h was followed by tert-
butoxycarbonyl (Boc)-protection without isolation of an in-
termediate to give protected amino alcohol 9. Mild acidic
hydrolysis of oxazoline 2b provided N-trichloroacetyl
amino alcohol 10.
[a] Reagents and conditions: (a) Lewis acid, CH2Cl2, room temp.
[b] From the range of catalysts screened (TMSOTf, BF3·Et2O,
AlCl3, FeCl3) only the result for the best performing catalyst is
shown.
Table 6. Chirality transfer in the cyclization reaction of enantioen-
riched bis-imidates 1 to oxazolines 2.
Entry
R
1, (ee [%]) Cat.
2, yield [%] (ee [%])
1
2
3
4
5
6
7
8
Me
TMS
BnOCH2
BnOCHCH2 R-1d, (93) AlCl3
tBu
Ph
2-ClC6H4
R-1a, (90) AlCl3
R-1b, (96) AlCl3
R-1c, (92) AlCl3
S-2a, 80 (90)
S-2b, 90[a] (96)
S-2c, 70 (92)
S-2d, 75 (92)
Conclusions
In summary, we have developed a new approach to en-
antioenriched alkynyl-glycinols based on cyclization reac-
tion of bis-trichloroacetimidates derived from alkynyl-
glycols. The cyclization reaction of bis-imidates proceeds se-
lectively to give 4-alkynyl-oxazolines as propargylic substi-
tution products. Enantioenriched bis-imidates that contain
an alkyl or TMS substituent at acetylene give oxazolines
with complete inversion of configuration. In turn, consider-
able racemization was observed in the cyclization reaction
of bis-imidates that contain a phenyl substituent. The race-
R-1e, (93) TMSOTf S-2e, 84 (93)
R-1h, (88) BF3·Et2O S-2h, 80 (36)
R-1i, (90)
R-1j, (93)
BF3·Et2O S-2i, 90 (52)
TMSOTf S-2i, 75 (57)
AlCl3 S-2i, 89 (52)
BF3·Et2O S-2j, 56 (86)
TMSOTf S-2j, 50 (89)
AlCl3
9
10
11
12
3,5-ClC6H3
S-2j, 79 (76)
[a] 1H NMR yield. 1,4-bis(trichloromethyl)benzene was used as an
internal standard.
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Synthesis of Alkynyl-Glycinols
1-(tert-Butyldimethylsilyloxy)non-3-yn-2-ol (5f): Colorless oil. 1H
NMR (400 MHz, CDCl3): δ = 4.41–4.34 (m, 1 H, -CHO-), 3.74
(dd, J = 10.0, 3.7 Hz, 1 H, -CH2O-), 3.60 (dd, J = 10.0, 7.5 Hz, 1
H, -CH2O-), 2.54 (d, J = 4.2 Hz, 1 H, -OH), 2.20 [td, J = 7.2,
2.0 Hz, 2 H, -CH2(CH2)3CH3], 1.54–1.46 [m, 2 H, -CH2CH2-
(CH2)2CH3], 1.40–1.25 [m, 4 H, -CH2CH2(CH2)2CH3], 0.93–0.87
[two signals overlapping, 12 H, -SiC(CH3)3, -(CH2)4CH3], 0.09 [s,
6 H, -Si(CH3)2] ppm. 13C NMR (100 MHz, CDCl3): δ = 86.5, 77.9,
67.5, 63.5, 31.2, 28.4, 26.0, 22.3, 18.8, 18.5, 14.1, –5.2 ppm. GC–
MS (EI): m/z = 270 [M]+. No ionization under HRMS conditions.
mization for these substrates can be suppressed by introduc-
tion of electronegative substituents in the phenyl ring. The
oxazolines prepared by bis-imidate cyclization can be read-
ily transformed into alkynyl-glycinol derivatives.
Experimental Section
General Information: Commercially available reagents were used
without further purification. Ru(p-cymene)[(S,S)-TsDPEN] cata-
lyst S,S-8[33] and protected aldehydes 4a[34] and 4b[35] were prepared
in accordance with the procedures described in the literature. iP-
rOH was distilled from CaH2. All air- or moisture-sensitive reac-
tions were carried out under an argon atmosphere with oven-dried
glassware. Flash chromatography was carried out with Merck Kie-
selgel 60 (230–400 mesh). Thin-layer chromatography was per-
formed on silica gel and was visualized by staining with KMnO4.
NMR spectra were recorded with a Varian Mercury spectrometer
(400 MHz) and a Bruker Fourier spectrometer (300 MHz) with
chemical shift values reported relative to tetramethylsilane by using
the residual chloroform signal as an internal standard. Elemental
analyses were performed with a Carlo-Erba EA1108 Elemental An-
alyzer. HRMS were obtained with a Q-TOF micro high-resolution
mass spectrometer with ESI (ESI+/ESI–). Chiral HPLC was car-
ried out with a Chiralpak IB column. Chiral GC was carried out
with 6-TBDMS-2,3-Me-β-CD 50%, 25 m as the chiral stationary
phase.
1-[(tert-Butyldimethylsilyl)oxy]-4-(triisopropylsilyl)but-3-yn-2-ol
(5g): Colorless oil. 1H NMR (400 MHz, CDCl3): δ = 4.46–4.38 (m,
1 H, -CHO-), 3.77 (dd, J = 9.9, 3.9 Hz, 1 H, -CH2O-), 3.65 (dd, J
= 9.9, 6.5 Hz, 1 H, -CH2O-), 2.53 (d, J = 5.4 Hz, 1 H, -OH), 1.11–
1.02 {m, 23 H, -Si[CH(CH3)2]3} 0.91 [s, 9 H, -SiC(CH3)3], 0.10 [s,
6 H, -Si(CH3)2] ppm. 13C NMR (100 MHz, CDCl3): δ = 105.78,
86.29, 67.21, 63.75, 25.99, 18.72, 18.45, 11.26, –5.23 ppm. GC–MS
(EI): m/z = 299.1[M – tBu]+.
4-Phenyl-1-(trityloxy)but-3-yn-2-ol (5h): Viscous colorless oil. 1H
NMR (400 MHz, CDCl3): δ = 7.57–7.21 [m, 20 H, C6H5-,
-C(C6H5)3], 4,78–4.69 (br., 1 H, -CHO-), 3.50–3.36 (m, 2 H,
-CH2O-), 2.68–2.56 (br., 1 H, -OH) ppm. 13C NMR (100 MHz,
CDCl3): δ = 143.6, 131.8, 128.7, 128.5, 128.3, 128.0, 127.2, 122.4,
87.4, 86.9, 85.5, 67.3, 62.6 ppm. HRMS (ESI-TOF): m/z calcd. for
C29H25O2 405.1849; found 405.1846 [M + H]+.
4-(2-Chlorophenyl)-1-(trityloxy)but-3-yn-2-ol (5i): Viscous colorless
oil. 1H NMR (400 MHz, CDCl3): δ = 7.39 [m, 19 H, 2-ClC6H4-,
-C(C6H5)3], 4.77 (m, 1 H, -CHO-), 3.50 (dd, J = 9.3, 6.1 Hz, 1 H,
-CH2O-), 3.43 (dd, J = 9.3, 4.1 Hz, 1 H, -CH2O-), 2.68 (d, J =
5.5 Hz, 1 H, -OH) ppm. 13C NMR (100 MHz, CDCl3): δ = 143.7,
136.1, 133.7, 129.6, 129.3, 128.8, 128.0, 127.3, 126.5, 122.5, 93.0,
87.0, 82.2, 67.2, 62.7 ppm. No ionization under HRMS conditions.
General Procedure for the Synthesis of Protected Diols 5a–5j: nBuLi
solution in hexanes (2.5 m, 0.44 mL, 1.2 mmol) was added dropwise
to a solution of alkyne (1.1 mmol) in tetrahydrofuran (THF; 8 mL)
at –78 °C. The resulting reaction mixture was stirred at –78 °C for
30 min, then a solution of aldehyde 4a (174 mg, 1.0 mmol) in THF
(2 mL) was added dropwise. The reaction mixture was stirred at
–78 °C for 2 h (TLC control) then saturated aqueous NH4Cl
(5 mL) and Et2O (10 mL) were added. The organic phase was sepa-
rated and the aqueous phase was extracted with Et2O (2ϫ 20 mL).
The combined organic phase was washed with brine, dried with
Na2SO4, filtered, and the solvents evaporated. The crude residue
was purified by chromatography on silica gel (ethyl acetate/hexanes,
1:10–1:6) to afford alcohols rac-5.
4-(3,5-Dichlorophenyl)-1-(trityloxy)but-3-yn-2-ol (5j): Viscous col-
orless oil. 1H NMR (400 MHz, CDCl3): δ = 7.49–7.43 [m, 6 H,
3,5-ClC6H3-, -C(C6H5)3], 7.34–7.22 [m, 12 H, -C(C6H5)3], 4.66 (td,
J = 6.0, 4.3 Hz, 1 H, -CHO-), 3.43–3.35 (m, 2 H, -CH2O-), 2.57
(d, J = 5.7 Hz, 1 H, -OH) ppm. 13C NMR (100 MHz, CDCl3): δ =
143.6, 135.0, 130.1, 129.1, 128.8, 128.1, 127.4, 125.4, 90.0, 87.2,
83.0, 67.1, 62.6 ppm. HRMS (ESI-TOF): m/z calcd. for
C29H22Cl2O2Na [M + Na]+ 495.0889; found 495.0891.
Compounds 5a,[36] 5b,[37] and 5e[38] are known.
General Procedure for the Synthesis of Diols 6a, 6c–6f: To a solution
of substrate 5a, or 5c–5f (1.00 mmol) in THF (12 mL), AcOH
(0.17 mL, 3.00 mmol) and tetra-n-butylammonium fluoride
(TBAF; 0.95 g, 3.00 mmol) were added. The reaction mixture was
stirred until complete conversion (TLC control). Then triethyl-
amine (TEA; 0.40 mL) and silica gel were added and the solvent
was evaporated. The residue was purified by chromatography on a
short silica gel column (light petroleum ether/ethyl acetate, 2:1) to
afford the product.
5-(Benzyloxy)-1-(tert-butyldimethylsilyloxy)pent-3-yn-2-ol
(5c):
Colorless oil. 1H NMR (400 MHz, CDCl3): δ = 7.39–7.26 (m, 5
H, -C6H5), 4.59 (s, 2 H, -OCH2Ph), 4.49–4.43 (m, 1 H, -CHO-),
4.21 (d, J = 1.7 Hz, 2 H, -CH2OBn), 3.79 (dd, J = 10.0, 3.8 Hz, 1
H, -CH2O-), 3.67 (dd, J = 10.0, 7.1 Hz, 1 H, -CH2O-), 2.74–2.62
(m, 1 H, -OH), 0.91 [s, 9 H, -SiC(CH3)3], 0.11 [s, 6 H, -Si-
(CH3)2] ppm. 13C NMR (100 MHz, CDCl3): δ = 137.5, 128.5,
128.2, 128.0, 84.6, 81.5, 71.7, 67.0, 63.3, 57.5, 25.8, 18.5, –5.2 ppm.
HRMS (ESI-TOF): m/z calcd. for C18H29O3Si [M + H]+ 321.1880;
found 321.1889.
Compound R-6a[39] is known. NMR spectroscopic data for racemic
compound 6a matched these reported for enantioenriched com-
pound R-6a.
6-(Benzyloxy)-1-(tert-butyldimethylsilyloxy)hex-3-yn-2-ol (5d): Col-
orless oil. 1H NMR (400 MHz, CDCl3): δ = 7.38–7.26 (m, 5 H,
-C6H5), 4.54 (s, 2 H, -OCH2Ph), 4.41–4.34 (m, 1 H, -CHO-), 3.74
(dd, J = 10.0, 3.7 Hz, 1 H, -CH2OTBS), 3.63–3.55 (m, 3 H, two
signals overlapping, -CH2OTBS, -CH2CH2OBn), 2.53 (td, J = 7.1,
2.0 Hz, 2 H, -CH2CH2OBn), 0.91 [s, 9 H, -SiC(CH3)3], 0.09 [s, 6
H, -Si(CH3)2] ppm. 13C NMR (100 MHz, CDCl3): δ = 138.2, 128.6,
128.2, 128.0, 83.0, 79.1, 73.1, 68.4, 67.4, 63.4, 26.0, 20.3, 18.5,
–5.2 ppm. HRMS (ESI-TOF): m/z calcd. for C19H31O3Si
[M + H]+ 335.2037; found 335.2034.
5-(Benzyloxy)pent-3-yne-1,2-diol (6c): Colorless oil. 1H NMR
(400 MHz, CDCl3): δ = 7.38–7.26 (m, 5 H, -CH2C6H5), 4.57 (s, 2
H, -OCH2Ph), 4.51–4.44 (m, 1 H, -CHOH), 4.19 (d, J = 1.7 Hz, 2
H, -CH2OBn), 3.76–3.60 (m, 2 H, -CH2OH), 3.45–3.33 (br., 1 H,
-OH), 3.12–3.00 (br., 1 H, -OH) ppm. 13C NMR (100 MHz,
CDCl3): δ = 137.2, 128.6, 128.2, 128.1, 84.6, 82.0, 72.1, 66.5, 63.3,
57.5 ppm. (R-6c): [α]2D0 = –13.1 (c = 1, CH2Cl2).
6-(Benzyloxy)hex-3-yne-1,2-diol (6d): Colorless oil. 1H NMR
(300 MHz, CDCl3): δ = 7.39–7.33 (m, 5 H, -CH2C6H5), 4.57 (s, 2
Eur. J. Org. Chem. 2015, 6900–6908
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6903

J. Sirotkina, L. Grigorjeva, A. Jirgensons
FULL PAPER
H, -OCH2Ph), 4.50–4.40 (m, 1 H, -CHOH), 3.77–3.64 (m, 2 H, = –13.3 (c = 0.7, CH2Cl2). No ionization under HRMS conditions.
-CH2OH), 3.60 (t, J = 6.9 Hz, 2 H, -CH2CH2OBn), 2.56 (td, J =
4-(3,5-Dichlorophenyl)but-3-yne-1,2-diol (6j): White powder, m.p.
115–117 °C. H NMR (400 MHz, CDCl3): δ = 7.35–7.29 (m, 3 H,
-C6H3), 4.67 (dd, J = 6.4, 3.7 Hz, 1 H, -CHOH), 3.84 (dd, J = 11.4,
6.9, 1.9 Hz, 2 H, -CH2CH2OBn), 2.16 (br., 1 H, -OH), 2.06–1.97
1
(br., 1 H, -OH) ppm. 13C NMR (100 MHz, CDCl3): δ = 137.8,
128.5, 127.9, 127.8, 83.4, 79.4, 73.0, 68.2, 66.7, 63.3, 20.1 ppm. (R-
3.7 Hz, 1 H, -CH2OH), 3.77 (dd, J = 11.4, 6.4 Hz, 1 H, -CH2OH),
6d): [α]2D0 = –9.3 (c = 0.8, CH2Cl2).
2.46–2.33 (br., 1 H, -OH), 2.16–1.96 (br., 1 H, -OH) ppm. 13C
NMR (100 MHz, CDCl3): δ = 135.1, 130.131, 129.3, 125.0, 89.2,
83.7, 66.4, 63.7 ppm. No ionization under HRMS conditions. (R-
6j): [α]2D0 = –5.4 (c = 0.7, MeOH).
5,5-Dimethylhex-3-yne-1,2-diol (6e): White powder, m.p. 74–76 °C.
1H NMR (300 MHz, CDCl3): δ = 4.37 (dd, J = 7.5, 3.6 Hz, 1 H,
-CHOH), 3.62 (dd, J = 11.4, 3.6 Hz, 1 H, -CH2OH), 3.53 (dd, J
= 11.4, 7.5 Hz, 1 H, -CH2OH), 3.47–3.19 (br., 2 H, two signals
overlapping, -OH), 1.15 [s, 9 H, -C(CH3)3] ppm. 13C NMR
(100 MHz, CDCl3): δ = 95.5, 76.2, 67.0, 63.5, 31.0, 27.5 ppm. No
ionization under HRMS conditions. (R-6e): [α]2D0 = –18.6 (c = 1,
CH2Cl2). C8H14O2: C 67.57, H 9.92; found C 67.16, H 9.96.
Undeca-3,5-diyne-1,2-diol (6k): To a solution of substrate 5b
(0.20 g, 0.73 mmol) in MeOH (8 mL) KF (0.11 g, 1.83 mmol) was
added. The reaction mixture was heated at 50 °C for 7 h. After
the desilylation reaction was complete (TLC control), the reaction
mixture was cooled to room temp. and CuCl (14 mg, 0.15 mmol),
NH2OH·HCl (76 mg, 1.1 mmol), and PentNH2 (0.85 mL) were
added. The reaction mixture was stirred at room temp. for 10 min.
A solution of 1-bromoalkyne (0.19 g, 1.1 mmol) in MeOH (3 mL)
was added and stirring was continued for an additional 40 min un-
til TLC showed complete conversion. The reaction mixture was
poured into water (15 mL) and extracted with Et2O (3ϫ 15 mL).
The combined organic phase was washed with saturated aqueous
KHSO4 (10 mL), saturated aqueous NaCl (10 mL), dried with
Na2SO4, filtered, and concentrated under reduced pressure. The
residue was purified by flash column chromatography on silica gel
(petroleum ether/EtOAc, 1:1) to give diol 6k (115 mg, 88%) as an
oil. 1H NMR (400 MHz, CDCl3): δ = 4.52–4.47 (m, 1 H, HOCH-),
3.70–3.57 (m, 2 H, HOCH2-), 2.47–2.37 (br., 1 H, HO-), 2.28 [td,
J = 7.0, 0.9 Hz, 2 H, -CH2(CH2)3CH3], 2.21–2.09 (m, 1 H, HO-),
1.53 [m, 2 H, -CH2CH2(CH2)2CH3], 1.42–1.27 [m, 4 H, -(CH2)2-
(CH2)2CH3], 0.90 [t, J = 7.1 Hz, 3 H, -(CH2)4CH3] ppm. 13C NMR
(100 MHz, CDCl3): δ = 82.3, 72.9, 71.3, 66.3, 64.1, 63.6, 30.9, 27.7,
22.1, 19.2, 13.9 ppm.
Non-3-yne-1,2-diol (6f): Colorless oil. 1H NMR (400 MHz, CDCl3):
δ = 4.47–4.40 (br., 1 H, HOCH-), 3.75–3.67 (br., 1 H, HOCH2-),
3.63 (dd, 1 H, HOCH2-), 2.39–2.28 (m, 1 H, HO-), 2.20 [td, J =
7.2, 2.0 Hz,
3 H, two signals overlapping: HO- un -CH2-
(CH2)3CH3], 1.56–1.45 [m, 2 H, -CH2CH2(CH2)2CH3], 1.40–1.25
[m, 4 H, -(CH2)2(CH2)2CH3], 0.89 [t, J = 7.1 Hz, 3 H, -(CH2)4-
CH3] ppm. 13C NMR (101 MHz, CDCl3): δ = 87.6, 77.9, 67.1, 63.7,
31.3, 28.4, 22.4, 18.9, 14.2 ppm. No ionization under HRMS condi-
tions.
General Procedure for the Synthesis of Diols 6b, and 6g: Substrate
5b, or 5g (1.00 mmol) was dissolved in a methanolic HCl solution
(1%, 10 mL). The reaction mixture was stirred until complete con-
version (TLC control). Then TEA (0.40 mL) and silica gel were
added and the solvent was evaporated. The residue was purified by
chromatography on a short silica-gel column (light petroleum
ether/ethyl acetate, 1:1) to afford the product.
Compound 6g[40] is known.
6-(Triisopropylsilyl)hexa-3,5-diyne-1,2-diol (6l): Prepared similar to
compound 6k from but-3-yne-1,2-diol (41 mg), yield 101 mg (79%),
slightly yellow oil. H NMR (400 MHz, CDCl3): δ = 4.50–4.41 (m,
1 H, HOCH-), 3.76–3.61 (m, 2 H, HOCH2-), 2.45–2.33 (br., 1 H,
HO-), 2.14–2.02 (br., 1 H, HO-), 1.02 (s, 21 H, 3 iPr) ppm. 13C
NMR (100 MHz, CDCl3): δ = 90.5, 87.3, 76.0, 73.2, 68.1, 65.5,
20.5, 13.2 ppm. No ionization under HRMS conditions.
4-(Trimethylsilyl)but-3-yne-1,2-diol (6b): White powder, m.p. 53–
54 °C. 1H NMR (300 MHz, CDCl3): δ = 4.52–4.39 (br., 1 H,
-CHOH), 3.81–3.59 (m, 2 H, -CH2OH), 2.36–2.22 (br., 1 H, -OH),
2.15–1.98 (br., 1 H, -OH), 0.18 [s, 9 H, -Si(CH3)3] ppm. 13C NMR
(75 MHz, CDCl3): δ = 103.1, 91.7, 66.6, 63.9, –0.1 ppm. No ioniza-
tion under HRMS conditions. (R-6b): [α]2D0 = –24.3 (c = 1, CH2Cl2).
C7H14O2Si: C 53.12, H 8.92; found C 53.00, H 8.91.
1
Hex-5-en-3-yne-1,2-diol (6m): Following the reported procedure,[28]
CuI (12.8 mg, 0.067 mmol, 10 mol-%) and Pd(PPh3)4 (15.6 mg,
0.013 mmol, 2 mol-%) were dissolved in diethylamine (0.6 mL) at
room temp. under an argon atmosphere. To this reaction mixture,
a solution of but-3-yne-1,2-diol (58 mg, 0.67 mmol, 1.0 equiv.) in
THF and vinyl bromide in THF (1 m, 1.0 mL, 1.01 mmol,
1.5 equiv.) were sequentially added dropwise and the resulting sus-
pension was stirred at room temp. for 4 h. The reaction mixture
was concentrated under reduced pressure. The residue was purified
by flash column chromatography (petroleum ether/EtOAc, 1:1) as
an eluent to give diol 6m (66 mg, 88%) as a colorless oil. 1H NMR
(400 MHz, CD3OD): δ = 5.84 (ddd, J = 17.6, 11.1, 1.8 Hz, 1 H,
-CH=CH2), 5.59 (dd, J = 17.6, 2.2 Hz, 1 H, -CH=CH2), 5.46 (dd,
J = 11.1, 2.2 Hz, 1 H, -CH=CH2), 4.40 (ddd, J = 6.9, 4.9, 1.8 Hz,
1 H, -CHO-), 3.58 (dd, J = 11.2, 4.9 Hz, 1 H, -CH2O-), 3.53 (dd,
J = 11.2, 6.9 Hz, 1 H, -CH2O-) ppm. 13C NMR (100 MHz,
CD3OD): δ = 127.6, 118.0, 89.7, 84.5, 67.3, 64.5 ppm. No ioniza-
tion under HRMS conditions.
General Procedure for the Synthesis of Diols 6h–6j: To a solution
of substrate 5h–5j (1 mmol) in a mixture of CH2Cl2 and MeOH
(2.5 mL/1.35 mL), pTsOH·H2O (0.15 mmol) was added. The reac-
tion mixture was stirred until complete conversion (TLC control),
typically overnight. Then TEA (20 μL) and silica gel were added
and the solvent evaporated. The residue was purified by
chromatography on a short silica-gel column (light petroleum
ether/ethyl acetate, 1:1) to afford the product.
Racemic compound 6h[41] is known.
4-(Phenyl)but-3-yne-1,2-diol (R-6h): NMR spectroscopic data cor-
responded to these reported in the literature for the racemic com-
pound. White powder, m.p. 60–62 °C. [α]2D0 = –26.8 (c = 1.0,
CH2Cl2). No ionization under HRMS conditions. C10H10O2·
1/6H2O: C 72.71, H 6.31; found C 72.94, H 6.24.
4-(2-Chlorophenyl)but-3-yne-1,2-diol (6i): White powder, m.p. 110–
112 °C. 1H NMR (400 MHz, CD3OD): δ = 7.51 (dd, J = 7.4,
2.0 Hz, 1 H, -C6H4), 7.43 (dd, J = 7.7, 1.5 Hz, 1 H, -C6H4), 7.32
(td, J = 7.7, 2.0 Hz, 1 H, -C6H4), 7.26 (td, J = 7.4, 1.5 Hz, 1 H, General Procedure for the Synthesis of Ketones 7a–7e: To a solution
-C6H4), 4.59 (dd, J = 7.2, 4.7 Hz, 1 H, -CHOH), 3.73 (dd, J = 11.2,
4.7 Hz, 1 H, -CH2OH), 3.67 (dd, J = 11.2, 7.2 Hz, 1 H,
of alcohol 5a–5e (0.28 g, 1.31 mmol) in CH2Cl2 (7 mL) Dess–Mar-
tin periodinane (0.406 m in CH2Cl2, 4.8 mL, 1.97 mmol) was slowly
-CH2OH) ppm. 13C NMR (100 MHz, CDCl3): δ = 136.8, 134.6, added. The reaction mixture was stirred until complete conversion
130.8, 130.3, 127.8, 123.9, 94.6, 82.4, 67.3, 64.7 ppm. (R-6i): [α]2D0
(TLC control). Then the mixture was diluted with Et2O (15 mL),
6904
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© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 6900–6908

Synthesis of Alkynyl-Glycinols
filtered through a short Celite® column and the filtrate was evapo-
rated. The residue was purified by flash column chromatography
(petroleum ether/EtOAc, 15:1) to give ketone 7a–7e.
vacuum was released and (–)-N-methylephedrine (2.2 mmol,
2.2 equiv.) was added. The vacuum was applied for 30 min and then
released. Toluene (3 mL) and triethylamine (2.2 mmol, 2.2 equiv.)
were added and the reaction mixture was stirred at room tempera-
ture for 2 h (in some cases overnight). Alkyne (3.0 mmol, 3.0 equiv.)
was added dropwise and the reaction mixture was stirred at room
temp. for 15 min. A solution of aldehyde (1.0 mmol, 2.2 equiv.) in
toluene (1 mL) was added slowly by means of a syringe pump
(within 1 h). The reaction mixture was stirred until TLC showed
complete conversion. The reaction mixture was filtered through a
short silica gel column (toluene) to afford products 5h–5j.
Compounds 7b,[37] and 7e[38] are known.
1-[(tert-Butyldimethylsilyl)oxy]pent-3-yn-2-one (7a): Colorless oil.
1H NMR (400 MHz, CDCl3): δ = 4.30 (s, 2 H, -CH2OTBS), 2.03
(s, 3 H, -CH3), 0.92 [s, 9 H, -SiC(CH3)3], 0.10 [s, 6 H, -Si-
(CH3)2] ppm. 13C NMR (100 MHz, CDCl3): δ = 186.8, 93.3, 78.2,
70.6, 25.9, 18.6, 4.3, –5.2 ppm.
5-(Benzyloxy)-1-(tert-butyldimethylsilyloxy)pent-3-yn-2-one
(7c):
Colorless oil. 1H NMR (300 MHz, CDCl3): δ = 7.42–7.28 (m, 5
H, -C6H5), 4.62 (s, 2 H, -CH2OTBS), 4.38–4.31 (m, 4 H, two signals
overlapping, -CH2OBn, -OCH2Ph), 0.93 [s, 9 H, -SiC(CH3)3], 0.11
[s, 6 H, -Si(CH3)2] ppm. 13C NMR (100 MHz, CDCl3): δ = 186.1,
136.8, 128.7, 128.3, 128.2, 90.6, 83.4, 72.3, 70.5, 57.1, 25.9, 18.5,
–5.3 ppm.
4-Phenyl-1-(trityloxy)but-3-yn-2-ol (R-5h): [α]2D0 = 12.4 (c = 1.0,
CH2Cl2). Enantiomeric excess (88%) was determined by SFC
analysis on chiral phase [Chiralpak IB; 4.6ϫ250 mm; F = 1 mL/
min, 10% IPA + 90% Hex; T = 25 °C; tr (major) 11.0 min, tr
(minor) 8.0 min].
4-(3-Chlorophenyl)-1-(trityloxy)but-3-yn-2-ol (R-5i): [α]2D0 = 2.6 (c =
1.2, CH2Cl2). Enantiomeric excess (90%) was determined by SFC
analysis on chiral phase [Lux Cellulose 1; 4.6ϫ150 mm; F = 1 mL/
min, 10% IPA + 90% Hex; T = 25 °C; tr (major) 7.0 min, tr (minor)
9.1 min].
4-(3,5-Dichlorophenyl)-1-(trityloxy)but-3-yn-2-ol (R-5j): [α]2D0 = 19.9
(c = 1.7, CH2Cl2). Enantiomeric excess (93%) was determined by
SFC analysis on chiral phase [Lux Cellulose 1; 4.6ϫ150 mm; F =
2 mL/min, 10% IPA + 90% Hex; T = 25 °C; tr (major) 6.1 min, tr
(minor) 10.2 min].
6-(Benzyloxy)-1-(tert-butyldimethylsilyloxy)hex-3-yn-2-one
(7d):
Colorless oil. 1H NMR (300 MHz, CDCl3): δ = 7.32–7.14 (m, 5
H, -C6H5), 4.45 (s, 2 H, -CH2OTBS), 4.22 (s, 2 H, -OCH2Ph), 3.54
(t, J = 6.8 Hz, 2 H, -CH2CH2OBn), 2.58 (t, J = 6.8 Hz, 2 H,
-CH2CH2OBn), 0.83 [s, 9 H, -SiC(CH3)3], 0.00 [s, 6 H, -Si-
(CH3)2] ppm. 13C NMR (100 MHz, CDCl3): δ = 186.4, 137.8,
128.5, 127.9, 127.8, 93.7, 79.3, 73.2, 70.6, 67.1, 25.8, 20.7, 18.5,
–5.3 ppm.
General Procedure for the Synthesis of Enantioenriched Alcohols R-
5a–5e: To a solution of catalyst 8 (20 mg, 0.03 mmol) in degassed
iPrOH (8 mL) a solution of ketone 7a–7e (0.49 mmol) in iPrOH
(2 mL) was added. The reaction mixture was stirred until TLC
showed complete conversion (from 40 min to 15 h). Then the reac-
tion mixture was evaporated and the residue was purified by flash
column chromatography (petroleum ether/EtOAc, 15:1) to give diol
R-5a–5e.
General Procedure for the Synthesis of Bis-imidates 1: To a solution
of diol 6a–6m (1.0 mmol) in CH2Cl2 or THF (10 mL) molecular
sieves (4 Å) were added. The reaction mixture was cooled to 0 °C
and DBU (0.25 mmol, 25 mol-%) was added. The solution was
stirred at 0 °C for 30 min, trichloroacetonitrile (4 mmol, 4 equiv.)
was added. The reaction mixture was stirred until complete conver-
sion of the starting material (TLC control). The solvent was re-
moved and the residue was purified by filtering through a short
silica-gel column (CH2Cl2). If needed, the product was purified by
flash column chromatography on silica gel (petroleum ether/
EtOAc, 10:1) to give bis-trichloroacetimidate 1a–1m.
1-[(tert-Butyldimethylsilyl)oxy]pent-3-yn-2-ol (R-5a): Enantiomeric
excess (90%) was determined by chiral GC analysis [β-DEXTM 120;
30 mϫ0.25 mm, df 0.25 μm; 160 °C to 220 °C; tr (major) 19.4 min,
tr (minor) 19.6 min].
Pent-3-yne-1,2-diyl Bis-trichloroacetimidate (1a): Colorless oil. 1H
NMR (400 MHz, CDCl3): δ = 8.50 (s, 1 H, =NH), 8.43 (s, 1 H,
=NH), 5.88–5.84 (m, 1 H, -CHO-), 4.67–4.53 (m, 2 H, CH2O-),
1.89 (s, 3 H, -CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 162.3,
161.6, 91.1, 91.1, 84.7, 71.9, 69.2, 66.6, 3.7 ppm. HRMS (ESI-
TOF): m/z calcd. for C9H9Cl6N2O2 [M + H]+ 386.8790; found
386.8786.
1-[(tert-Butyldimethylsilyl)oxy]-4-(trimethylsilyl)but-3-yn-2-ol (R-
5b): [α]2D0 = –9.0 (c = 1.0, CH2Cl2). Enantiomeric excess (96%) was
determined by chiral GC analysis [β-DEXTM 120; 30 mϫ0.25 mm,
df 0.25 μm; 160 °C to 220 °C; tr (major) 26.5 min, tr (minor)
26.2 min].
5-(Benzyloxy)-1-(tert-butyldimethylsilyloxy)pent-3-yn-2-ol (R-5c):
[α]2D0 = –2.6 (c = 0.4, CH2Cl2). Enantiomeric excess (92%) was de-
termined by supercritical fluid chromatography (SFC) analysis on
chiral phase [Lux Cellulose 1; 4.6ϫ150 mm; F = 2 mL/min, 10%
IPA + 90% Hex; T = 25 °C; tr (major) 9.3 min, tr (minor) 7.2 min].
4-(Trimethylsilyl)but-3-yne-1,2-diyl Bis-trichloroacetimidate (1b):
White powder, m.p. 46–48 °C. 1H NMR (400 MHz, CDCl3): δ =
8.54 (s, 1 H, =NH), 8.43 (s, 1 H, =NH), 5.93 (dd, J = 7.7, 4.1 Hz,
1 H, -CHO-), 4.68–4.57 (m, 2 H, -CH2O-), 0.17 [s, 9 H, -Si-
(CH3)3] ppm. 13C NMR (100 MHz, CDCl3): δ = 162.5, 161.5, 97.3,
93.8, 77.4, 69.0, 66.6, –0.2 ppm. HRMS (ESI-TOF): m/z calcd. for
C11H15Cl6N2O2Si [M + H]+ 444.9028; found 444.9029.
6-(Benzyloxy)-1-(tert-butyldimethylsilyloxy)hex-3-yn-2-ol
(R-5d):
[α]2D0 = –2.6 (c = 0.3, CH2Cl2). Enantiomeric excess (93%) was de-
termined by SFC analysis on chiral phase [Chiralpak IB;
4.6ϫ250 mm; F = 1 mL/min, 10% IPA + 90% Hex; T = 25 °C; tr
(major) 7.6 min, tr (minor) 6.6 min].
5-(Benzyloxy)pent-3-yne-1,2-diyl Bis-trichloroacetimidate (1c): Col-
1
orless oil. H NMR (400 MHz, CDCl3): δ = 8.57 (s, 1 H, =NH),
1-[(tert-Butyldimethylsilyl)oxy]-5,5-dimethylhex-3-yn-2-ol
(R-5e):
8.46 (s, 1 H, =NH), 7.37–7.26 (m, 5 H, -C6H5), 6.00–5.94 (m, 1
H, -CHO-), 4.68 (dd, J = 11.7, 3.9 Hz, 1 H, -CH2O-), 4.62 (dd, J
= 11.7, 7.7 Hz, 1 H, -CH2O-), 4.58 (s, 2 H, -CH2Ph), 4.21 (d, J =
1.7 Hz, 2 H, -CH2OBn) ppm. 13C NMR (100 MHz, CDCl3): δ =
162.3, 161.4, 137.2, 128.6, 128.3, 128.1, 90.9, 84.0, 79.5, 71.6, 68.8,
66.0, 57.2 ppm. Unstable under HRMS analysis conditions.
[α]2D0 = –4.2 (c = 0.3, CH2Cl2) Enantiomeric excess (93%) was deter-
mined by chiral GC analysis [β-DEXTM 120; 30 mϫ0.25 mm, df
0.25 μm; 160 °C to 220 °C; tr (major) 31.0 min, tr (minor)
30.8 min].
General Procedure for the Synthesis of Enantioenriched Alcohols R-
5h–5j: Zn(OTf)2 (2.0 mmol, 2.0 equiv.) was dried under vacuum at
125 °C for 2 h. Then the flask was cooled to room temperature, the
6-(Benzyloxy)hex-3-yne-1,2-diyl Bis-trichloroacetimidate (1d): Col-
1
orless oil. H NMR (400 MHz, CDCl3): δ = 8.50 (s, 1 H, =NH),
Eur. J. Org. Chem. 2015, 6900–6908
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6905

J. Sirotkina, L. Grigorjeva, A. Jirgensons
H, -(CH2)2(CH2)2CH3], 1.41–1.24 [m, H,
FULL PAPER
8.42 (s, 1 H, =NH), 7.37–7.24 (m, 5 H, -C6H5), 5.90 (ddt, J = 5.9,
4.0, 2.0 Hz, 1 H, -CHO-), 4.64–4.56 (m, 2 H, -CH2O-), 4.52 (s, 2
H, -OCH2Ph), 3.57 (t, J = 7.0 Hz, 2 H, -CH2CH2OBn), 2.55 (td, J
1.48 [m,
4
4
-CH2CH2(CH2)2CH3], 0.90 [t, J = 7.1 Hz, 3 H, -(CH2)4CH3] ppm.
13C NMR (101 MHz, CDCl3): δ = 162.4, 161.4, 90.9, 90.8, 83.3,
= 7.0, 2.0 Hz, 2 H, -CH2CH2OBn) ppm. 13C NMR (100 MHz, 73.0, 68.7, 67.7, 66.7, 64.2, 31.1, 27.8, 22.3, 19.4, 14.0 ppm. HRMS
CDCl3): δ = 162.7, 161.9, 138.4, 128.9, 128.2, 128.1, 91.3, 86.2,
74.3, 73.4, 69.5, 68.3, 66.9, 20.7 ppm. Unstable under HRMS
analysis conditions.
(ESI-TOF): m/z calcd. for C15H17Cl6N2O2 [M + H]+ 466.9416;
found 466.9413.
6-(Triisopropylsilyl)hexa-3,5-diyne-1,2-diyl Bis-trichloroacetimidate
1
5,5-Dimethylhex-3-yne-1,2-diyl Bis-trichloroacetimidate (1e): Color-
less oil. 1H NMR (400 MHz, CDCl3): δ = 8.49 (s, 1 H, =NH), 8.41
(s, 1 H, =NH), 5.91 (dd, J = 7.0, 4.8 Hz, 1 H, -CHO-), 4.61–4.53
(m, 2 H, -CH2O-), 1.21 [s, 9 H, -C(CH3)3] ppm. 13C NMR
(100 MHz, CDCl3): δ = 162.6, 161.5, 97.2, 91.2, 91.1, 71.4, 69.4,
66.7, 30.8, 27.6 ppm. HRMS (ESI-TOF): m/z calcd. for
C12H15Cl6N2O2 [M + H]+ 428.9259; found 428.9248.
(1l): Colorless oil. H NMR (400 MHz, CDCl3): δ = 8.53 (s, 1 H,
=NH), 8.40 (s, 1 H, =NH), 5.91 (dd, J = 8.0, 3.8 Hz, 1 H,
-CHO-), 4.62 (dd, J = 11.7, 3.8 Hz, 1 H, -CH2O-), 4.56 (dd, J =
11.7, 8.0 Hz, 1 H, -CH2O-), 1.01 {s, 21 H, -Si[CH(CH3)2]3} ppm.
13C NMR (100 MHz, CDCl3): δ = 162.1, 161.2, 90.7, 90.6, 88.2,
86.7, 72.9, 68.6, 68.4, 66.3, 18.5, 11.2 ppm. Unstable under HRMS
analysis conditions.
Non-3-yne-1,2-diyl Bis-trichloroacetimidate (1f): Colorless oil. 1H
NMR (400 MHz, CDCl3): δ = 8.49 (s, 1 H, =NH), 8.40 (s, 1 H,
=NH), 5.87 (dd, J = 9.2, 4.3 Hz, 1 H, -CHO-), 4.63–4.56 (m, 2 H,
-CH2O-), 2.21 [td, J = 7.1, 2.0 Hz, 2 H, -CH2(CH2)3CH3], 1.54–
Hex-5-en-3-yne-1,2-diyl Bis-trichloroacetimidate (1m): Colorless oil.
1H NMR (400 MHz, CDCl3): δ = ppm. 1H NMR (400 MHz,
CDCl3): δ = 8.55 (s, 1 H, =NH), 8.45 (s, 1 H, =NH), 6.03 (ddd, J
= 7.7, 4.1, 1.6 Hz, 1 H, -CHO-), 5.82 (ddd, J = 17.5, 10.8, 1.6 Hz,
1 H, -CH=CH2), 5.72 (dd, J = 17.5, 2.5 Hz, 1 H, -CH=CH2), 5.57
(dd, J = 10.8, 2.5 Hz, 1 H, -CH=CH2), 4.70–4.60 (m, 2 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 162.5, 161.6, 129.4, 116.1, 91.0,
91.0, 86.4, 82.2, 68.9, 66.7 ppm. HRMS (ESI-TOF): m/z calcd. for
C10H8Cl6N2O2 [M + H]+ 398.8790; found 398.8793.
1.45 [m,
2 H, -CH2CH2(CH2)2CH3], 1.38–1.22 [m, 4 H,
-CH2CH2(CH2)2CH3], 0.87 [t, J = 7.1 Hz, 3 H, -(CH2)4CH3] ppm.
13C NMR (100 MHz, CDCl3): δ = 162.5, 161.7, 89.4, 72.9, 69.4,
66.9, 31.1, 28.1, 22.3, 18.9, 14.1 (-CCl3 not detected) ppm. HRMS
(ESI-TOF): m/z calcd. for C13H17Cl6N2O2 [M + H]+ 442.9416;
found 442.9408.
General Procedure for the Cyclization Reaction of Bis-trichloroacet-
imidates 1a–1m: Molecular sieves (4 Å) and a Lewis acid catalyst
(0.05 mmol, 10 mol-%) were added to a stirred solution of bis-imid-
ate 1a–1m (0.50 mmol) in solvent (5 mL) at room temp. After the
reaction was complete (TLC control in the first minute of the reac-
tion), TEA (50 mol-%) was added to the reaction mixture and the
solvent was evaporated. The residue was purified by chromatog-
raphy on a short silica-gel column (light petroleum ether/ethyl acet-
ate, 10:1) to afford product 2a–2m.
4-(Triisopropylsilyl)but-3-yne-1,2-diyl Bis-trichloroacetimidate (1g):
Colorless oil. 1H NMR (400 MHz, CDCl3): δ = 8.53 (s, 1 H, =NH),
8.41 (s, 1 H, =NH), 5.90 (dd, J = 7.6, 4.2 Hz, 1 H, -CHO-), 4.70–
4.55 (m, 2 H, -CH2O-), 1.04 {s, 21 H, -Si[CH(CH3)2]3} ppm. 13C
NMR (100 MHz, CDCl3): δ = 162.5, 161.3, 110.2, 99.4, 91.1, 90.2,
69.0, 66.7, 18.6, 11.2 ppm. Unstable under HRMS analysis condi-
tions.
4-Phenylbut-3-yne-1,2-diyl Bis-trichloroacetimidate (1h): Colorless
1
oil. H NMR (400 MHz, CDCl3): δ = 8.57 (s, 1 H, =NH), 8.45 (s,
4-(Prop-1-yn-1-yl)-2-(trichloromethyl)oxazoline (2a): Colorless oil.
1H NMR (400 MHz, [D6]dimethyl sulfoxide): δ = 5.19–5.12 (m, 1
H, -CHN-), 4.86 (dd, J = 10.0, 8.2 Hz, 1 H, -CH2O-), 4.47 (t, J =
8.2 Hz, 3 H, -CH2O-), 1.84 (d, J = 2.3 Hz, 3 H, -CH3) ppm. 13C
NMR (100 MHz, CDCl3 dried with K2CO3): δ = 163.7, 86.5, 82.7,
75.8, 58.0, 3.9 ppm. GC–MS (EI): m/z = 225 [M]+. Enantiomeric
excess (90%) was determined by chiral GC analysis [β-DEXTM 120;
30 mϫ0.25 mm, df 0.25 μm; 160 °C to 220 °C; tr (major) 19.2 min,
tr (minor) 18.8 min].
1 H, =NH), 7.56–7.41 (m, 2 H, -C6H5), 7.41–7.25 (m, 3 H, -C6H5),
6.13 (dd, J = 7.6, 4.1 Hz, 1 H, -CHO-), 4.79–4.65 (m, 2 H, -CH2O-
) ppm. 13C NMR (100 MHz, CDCl3): δ = 162.5, 161.6, 132.2,
129.2, 128.5, 121.8, 91.1, 87.8, 81.7, 69.0, 66.9 ppm. HRMS (ESI-
TOF): m/z calcd. for C12H9Cl3NO [M – C2HNOCl3]+ 287.9752;
found 287.9750.
4-(2-Chlorophenyl)but-3-yne-1,2-diyl Bis-trichloroacetimidate (1i):
1
Colorless oil. H NMR (400 MHz, cdcl3): δ = 8.55 (s, 1 H, =NH),
8.41 (s, 1 H, =NH), 7.40 (d, J = 7.6 Hz, 1 H, -C6H4Cl), 7.31 (d, J
= 8.0 Hz, 1 H, -C6H4Cl), 7.24–7.17 (m, 1 H, -C6H4Cl), 7.17–7.10
(m, J = 7.5 Hz, 1 H, -C6H4Cl), 6.12 (dd, J = 7.7, 4.0 Hz, 1 H,
-CHO-), 4.76–4.63 (m, 2 H, -CH2O-) ppm. 13C NMR (100 MHz,
CDCl3): δ = 162.4, 161.5, 136.5, 133.8, 130.2, 129.5, 126.5, 121.8,
91.0, 91.0, 86.9, 84.4, 68.8, 66.8 ppm. HRMS (ESI-TOF): m/z
4-[(Trimethylsilyl)ethynyl]-2-(trichloromethyl)oxazoline (2b): White
powder, m.p. 53–54 °C. 1H NMR (400 MHz, CDCl3): δ = 5.07 (dd,
J = 10.2, 9.1 Hz, 1 H, -CHN-), 4.82 (dd, J = 10.2, 8.2 Hz, 1 H,
-CH2O-), 4.54 (dd, J = 9.1, 8.2 Hz, 1 H, -CH2O-), 0.19 [s, 9 H,
-Si(CH3)3] ppm. 13C NMR (100 MHz, CDCl3): δ = 164.0, 101.2,
91.2, 86.2, 76.4, 58.3, –0.3 ppm. GC–MS (EI): m/z = 283 [M]+.
HRMS (ESI-TOF): m/z calcd. for C9H13Cl3NOSi [M + H]+
283.9827; found 283.9833. Enantiomeric excess (96%) was deter-
mined by chiral GC analysis [β-DEXTM 120; 30 mϫ0.25 mm, df
0.25 μm; 160 °C to 220 °C; tr (major) 23.4 min, tr (minor)
22.9 min].
calcd. for C12H8NOCl4 [M
321.9360.
–
C2HNOCl3]+ 321.9360; found
4-(3,5-Dichlorophenyl)but-3-yne-1,2-diyl
Bis-trichloroacetimidate
1
(1j): Colorless oil. H NMR (400 MHz, CDCl3): δ = 8.60 (s, 1 H,
=NH), 8.48 (s, 1 H, =NH), 7.39–7.27 (m, 3 H, -C6H3), 6.10 (dd, J
= 7.5, 4.1 Hz, 1 H, -CHO-), 4.72 (dd, J = 11.7, 4.1 Hz, 1 H,
-CH2O-), 4.68 (dd, J = 11.7, 7.5 Hz, 1 H, -CH2O-) ppm. 13C NMR
(100 MHz, CDCl3): δ = 162.4, 161.5, 135.1, 130.3, 129.7, 124.5,
91.0, 90.9, 85.0, 84.2, 68.6, 66.5 ppm. Unstable under HRMS
analysis conditions.
4-[3-(Benzyloxy)prop-1-yn-1-yl]-2-(trichloromethyl)oxazoline (2c):
Colorless oil. 1H NMR (400 MHz, CDCl3): δ = 7.37–7.27 (m, 5
H, -C6H5), 5.12 (ddt, J = 10.3, 8.7, 1.8 Hz, 1 H, -CHO-), 4.82 (dd,
J = 10.3, 8.3 Hz, 1 H, -CH2O-), 4.59–4.53 (two signals overlapping,
3 H, -OCH2Ph, -CH2O-), 4.23 (d, J = 2.0 Hz, 2 H, -CH2OBn) ppm.
Undeca-3,5-diyne-1,2-diyl Bis-trichloroacetimidate (1k): Colorless 13C NMR (100 MHz, CDCl3): δ = 164.4, 137.3, 128.6, 128.2, 128.1,
1
oil. H NMR (400 MHz, CDCl3): δ = 8.57 (s, 1 H, =NH), 8.46 (s,
1 H, =NH), 5.94 (dd, J = 7.8, 3.9 Hz, 1 H, -CHO-), 4.71–4.57 (m,
82.9, 82.3, 77.4, 76.5, 72.1, 57.9, 57.6 ppm. HRMS (ESI-TOF): m/z
calcd. for C14H13Cl3NO2 [M + H]+ 332.0006; found 332.0011. En-
2 H, -CH2O-), 2.28 [t, J = 7.1 Hz, 2 H, -CH2(CH2)3CH3], 1.58– antiomeric excess (92%) was determined by SFC analysis on chiral
6906
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 6900–6908

Synthesis of Alkynyl-Glycinols
phase [Chiralpak IB; 4.6ϫ250 mm; F = 1 mL/min, 10% IPA + 4-[(3,5-Dichlorophenyl)ethynyl]-2-(trichloromethyl)oxazoline
90% Hex; T = 25 °C; tr (major) 13.0 min, tr (minor) 14.0 min].
(2j):
Colorless oil. 1H NMR (400 MHz, CDCl3): δ = 7.27 (m, 3 H,
-C6H3), 5.24–5.17 (m, 1 H, -C6H3), 4.83 (dd, J = 10.1, 8.4 Hz, 1 H,
-CHN-), 4.62–4.54 (m, 1 H, -CH2O-) ppm. 13C NMR (100 MHz,
CDCl3): δ = 164.7, 135.1, 130.2, 129.4, 124.9, 87.8, 86.2, 83.4, 76.4,
58.2 ppm. Unstable under HRMS analysis conditions. Enantio-
meric excess (76–89%) was determined by SFC analysis on chiral
phase [Chiralpak IB; 4.6ϫ250 mm; F = 1 mL/min, 10% IPA +
90% Hex; T = 25 °C; tr (major) 5.8 min, tr (minor) 6.4 min].
4-[4-(Benzyloxy)but-1-yn-1-yl]-2-(trichloromethyl)oxazoline
(2d):
Colorless oil. 1H NMR (400 MHz, CDCl3): δ = 7.38–7.26 (m, 5
H, -C6H5), 5.04 (ddt, J = 10.1, 9.0, 2.1 Hz, 1 H, -CHN-), 4.78 (dd,
J = 10.1, 8.2 Hz, 1 H, -CH2O-), 4.56–4.46 (two signals overlapping,
3 H, -CH2O-, -OCH2Ph), 3.59 (t, J = 6.9 Hz, 2 H, -CH2CH2OBn),
2.55 (td, J = 6.9, 2.1 Hz, 2 H, -CH2CH2OBn) ppm. 13C NMR
(100 MHz, CDCl3): δ = 164.0, 138.1, 128.6, 127.9, 127.8, 86.4, 83.8,
77.7, 76.8, 73.1, 68.1, 58.0, 20.4 ppm. HRMS (ESI-TOF): m/z
calcd. for C15H15Cl3NO2 [M + H]+ 346.0163; found 346.0160. En-
antiomeric excess (92%) was determined by SFC analysis on chiral
phase [Chiralpak IB; 4.6ϫ250 mm; F = 1 mL/min, 10% IPA +
90% Hex; T = 25 °C; tr (major) 11.9 min, tr (minor) 9.7 min].
4-(Nona-1,3-diyn-1-yl)-2-(trichloromethyl)oxazoline (2k): Colorless
1
oil. H NMR (400 MHz, CDCl3): δ = 5.13–5.07 (m, 1 H, -CHN-),
4.79 (dd, J = 10.1, 8.4 Hz, 1 H, -CH2O-), 4.56 (t, J = 8.4 Hz, 1
H, -CH2O-), 2.27 [td, J = 7.1, 0.8 Hz, 2 H, -CH2(CH2)3CH3], 1.53
[p, J = 7.1 Hz, 2 H, -CH2CH2(CH2)2CH3], 1.42–1.24 [m, 4 H,
-(CH2)2(CH2)2CH3], 0.89 [t, J = 7.1 Hz, 3 H, -(CH2)4CH3] ppm.
13C NMR (100 MHz, CDCl3): δ = 164.6, 86.2, 82.7, 76.2, 71.4,
71.3, 64.5, 58.3, 31.1, 27.9, 22.3, 19.4, 14.1 ppm. GC–MS (EI): m/z
290 [M+ – Me]. Unstable under HRMS analysis conditions.
4-(3,3-Dimethylbut-1-yn-1-yl)-2-(trichloromethyl)oxazoline
(1e):
Colorless oil. 1H NMR (400 MHz, CDCl3): δ = 5.02 (dd, J = 10.0,
9.1 Hz, 1 H, -CHN-), 4.78 (dd, J = 10.0, 8.1 Hz, 1 H, -CH2O-),
4.43 (dd, J = 9.1, 8.1 Hz, 1 H, -CH2O-), 1.20 [s, 9 H, -C-
(CH3)3] ppm. 13C NMR (100 MHz, CDCl3): δ = 163.7, 95.0, 86.5,
77.1, 75.1, 58.1, 30.9, 27.6 ppm. HRMS (ESI-TOF): m/z calcd. for
C10H13Cl3NO [M + H]+ 268.0057; found 268.0064. Enantiomeric
excess (93%) was determined by chiral GC analysis [β-DEXTM 120;
30 mϫ0.25 mm, df 0.25 μm; 160 °C to 220 °C; tr (major) 26.3 min,
tr (minor) 26.1 min].
4-[(Triisopropylsilyl)buta-1,3-diyn-1-yl]-2-(trichloromethyl)oxazoline
1
(2l) Colorless oil. H NMR (400 MHz, CDCl3): δ = 5.13 (dd, J =
10.2, 8.5 Hz, 1 H, -CHN-), 4.81 (dd, J = 10.2, 8.5 Hz, 1 H, -CH2O-
), 4.60 (t, J = 8.5 Hz, 1 H, -CH2O-), 1.08 {s, 21 H, -Si[CH-
(CH3)2]3} ppm. 13C NMR (100 MHz, CDCl3): δ = 164.6, 88.5,
86.0, 85.9, 75.8, 72.2, 71.2, 58.0, 18.5, 11.2 ppm. Unstable under
HRMS analysis conditions.
4-(Hept-1-yn-1-yl)-2-(trichloromethyl)oxazoline (2f): Colorless oil.
1H NMR (400 MHz, CDCl3): δ = 5.02 (ddt, J = 9.9, 8.8, 2.1 Hz,
1 H, -CHN-), 4.77 (dd, J = 9.9, 8.2 Hz, 1 H, -CH2O-), 4.47 (dd, J
= 8.8, 8.2 Hz, 1 H, -CH2O-), 2.19 [td, J = 7.2, 2.1 Hz, 3 H,
-CH2(CH2)3CH3], 1.50 [p, J = 7.2 Hz, 2 H, -CH2CH2(CH2)2CH3],
1.38–1.22 [m, 4 H, -(CH2)2(CH2)2CH3], 0.92–0.81 [m, 3 H, -(CH2)4-
CH3] ppm. 13C NMR (100 MHz, CDCl3): δ = 163.9, 87.3, 86.5,
77.0, 76.6, 58.1, 31.2, 28.2, 22.3, 18.9, 14.1 ppm. HRMS (ESI-
TOF): m/z calcd. for C11H15Cl3NO [M + H]+ 282.0214; found
282.0219.
4-(But-3-en-1-yn-1-yl)-2-(trichloromethyl)oxazoline (2m): Colorless
oil. 1H NMR (400 MHz, CDCl3): δ = 5.82 (ddd, J = 17.6, 10.9,
1.8 Hz, 1 H, -CH=CH2), 5.70 (dd, J = 17.6, 2.3 Hz, 1 H,
-CH=CH2), 5.54 (dd, J = 10.9, 2.3 Hz, 1 H, -CH=CH2), 5.18 (ddd,
J = 10.1, 8.6, 1.8 Hz, 1 H, -CHN-), 4.83 (dd, J = 10.1, 8.6 Hz, 1
H, -CH2O-), 4.56 (t, J = 8.6 Hz, 1 H, -CH2O-) ppm. 13C NMR
(100 MHz, CDCl3): δ = 164.3, 128.6, 116.4, 86.4, 86.0, 84.7, 76.6,
58.3 ppm. HRMS (ESI-TOF): m/z calcd. for C8H7Cl3NO [M +
H]+ 237.9593; found 237.9593.
4-[(Triisopropylsilyl)ethynyl]-2-(trichloromethyl)oxazoline (2g): Col-
orless oil. 1H NMR (400 MHz, CDCl3): δ = 5.06 (dd, J = 9.9,
8.2 Hz, 1 H, -CHN-), 4.79 (dd, J = 9.9, 8.2 Hz, 1 H, -CH2O-), 4.53
(t, J = 8.2 Hz, 1 H, -CH2O-), 1.05 {s, 21 H, -Si[CH(CH2)]3} ppm.
13C NMR (100 MHz, CDCl3): δ = 164.2, 103.6, 87.9, 86.5, 77.1,
58.6, 18.7, 11.2 ppm. GC–MS: 368 [M]+.
General Procedure for the Synthesis of Alkynyl-Glycinols (S-3):
Aqueous HCl (6 m, 1 mL) was added dropwise to a solution of
oxazoline S-2 (0.15 mmol) in MeOH (1.5 mL) at room temperature.
The reaction mixture was stirred at room temperature for 2 h and
the solvent was evaporated. Toluene (1 mL) was added to the reac-
tion mixture and the solvents evaporated. This procedure was re-
peated one more time. The residue was suspended in EtOAc and
filtered to give amino alcohol S-3.
4-(Phenylethynyl)-2-(trichloromethyl)oxazoline (2h): Colorless oil.
1H NMR (400 MHz, CDCl3): δ = 7.49–7.43 (m, 2 H, o-C6H5-),
7.37–7.28 (m, 3 H, p,m-C6H5-), 5.30 (dd, J = 10.0, 8.5 Hz, 1 H,
-CHN-), 4.90 (dd, J = 10.0, 8.5 Hz, 1 H, -CH2O-), 4.66 (t, J =
8.5 Hz, 1 H, -CH2O-) ppm. 13C NMR (100 MHz, CDCl3): δ =
164.3, 132.0, 129.0, 128.5, 122.2, 86.4, 86.1, 85.4, 76.7, 58.5 ppm.
2-Amino-4-(trimethylsilyl)but-3-yn-1-ol Hydrochloride (S-3b): White
powder, yield 90%, m.p. 136–139 °C. 1H NMR (400 MHz,
CD3OD): δ = 4.11 (dd, J = 8.2, 4.2 Hz, 1 H, -NCH-), 3.85 (dd, J
= 11.6, 4.2 Hz, 1 H, -CH2OH), 3.65 (dd, 1 H, -CH2OH), 0.20 [s, 9
H, -Si(CH3)3] ppm. 13C NMR (100 MHz, CD3OD): δ = 98.5, 94.4,
63.2, 49.6, 46.6, –0.5 ppm. HRMS (ESI-TOF): m/z calcd. for
C7H16NOSi [M]+ 158.1001; found 158.0994. [α]2D0 = 15.6 (c = 1.0,
MeOH).
HRMS (ESI-TOF): m/z calcd. for C12H9Cl3NO [M
+
H]+
287.9750; found 287.9749. Enantiomeric excess (36%) was deter-
mined by SFC analysis on chiral phase [Chiralpak IB;
4.6ϫ250 mm; F = 1 mL/min, 10% IPA + 90% Hex; T = 25 °C; tr
(major) 6.9 min, tr (minor) 11.8 min].
2-Amino-7-(benzyloxy)hepta-3,5-diyn-1-ol Hydrochloride (S-3c):
White powder, yield 75%, m.p. 110–114 °C. H NMR (400 MHz,
4-[(3-Chlorophenyl)ethynyl]-2-(trichloromethyl)oxazoline (2i): Col-
orless oil. 1H NMR (300 MHz, CDCl3): δ = 7.43 (dd, J = 7.4,
2.0 Hz, 1 H, -C6H4), 7.32 (dd, J = 7.9, 1.3 Hz, 1 H, -C6H4), 7.25–
7.10 (m, 2 H, -C6H4), 5.27 (dd, J = 10.0, 8.5 Hz, 1 H, -CHN-), 4.85
(dd, J = 10.0, 8.5 Hz, 1 H, -CH2O-), 4.63 (t, J = 8.5 Hz, 1 H,
-CH2O-) ppm. 13C NMR: δ = 164.5, 136.4, 133.8, 130.0, 129.4,
126.6, 122.2, 90.6, 86.4, 82.8, 58.6 ppm. HRMS (ESI-TOF): m/z
calcd. for C12H7Cl4NO [M + H]+ 321.9355; found 321.9346. Enan-
tiomeric excess (52–57%) was determined by SFC analysis on chi-
ral phase [Chiralpak IB; 4.6ϫ250 mm; F = 1 mL/min, 10% IPA +
90% Hex; T = 25 °C; tr (major) 9.7 min, tr (minor) 10.9 min].
1
CD3OD): δ = 7.39–7.27 (m, 5 H, -C6H5), 4.59 (s, 2 H, -OCH2Ph),
4.26 (d, J = 1.8 Hz, 2 H, -CH2OBn), 4.18 (ddt, J = 7.7, 4.0, 1.8 Hz,
1 H, -CHN-), 3.87 (dd, J = 11.6, 4.0 Hz, 1 H, -CH2O), 3.70 (dd, J
= 11.6, 7.7 Hz, 1 H, -CH2O) ppm. 13C NMR (100 MHz, CD3OD):
δ = 137.3, 128.0, 127.7, 127.6, 84.0, 78.3, 71.5, 61.7, 56.5, 44.7 ppm.
HRMS (ESI-TOF): m/z calcd. for C12H16NO2 [M]+ 206.1181;
found 206.1175. [α]2D0 = 4.1 (c = 0.4, MeOH).
2-Amino-8-(benzyloxy)octa-3,5-diyn-1-ol Hydrochloride (S-3d):
1
White powder, yield 81%, m.p. 120–124 °C. H NMR (400 MHz,
Eur. J. Org. Chem. 2015, 6900–6908
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6907

J. Sirotkina, L. Grigorjeva, A. Jirgensons
FULL PAPER
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[22] L. Grigorjeva, A. Jirgensons, Eur. J. Org. Chem. 2011, 2421–
2425.
CD3OD): δ = 7.38–7.25 (m, 5 H, -C6H5), 4.54 (s, 2 H, -OCH2Ph),
4.05 (ddt, J = 8.3, 4.1, 2.1 Hz, 1 H, -CHOH), 3.83 (dd, J = 11.6,
4.1 Hz,
1 H, -CH2N-), 3.69–3.57 (m, 3 H, -CH2CH2OBn,
-CH2OH), 2.57 (td, J = 6.5, 2.1 Hz, 2 H, -CH2CH2OBn) ppm. 13C
NMR (100 MHz, CD3OD): δ = 137.9, 128.0, 127.5, 127.4 ppm.
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Received: July 15, 2015
Published Online: September 30, 2015
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