Iridium-catalyzed asymmetric allylic substitutions with bulky amines/oxidative double bond cleavage - Entry into the reetz synthesis of amino alcohols

Article abstract of DOI:10.1002/ejoc.201501333

Branched allylic amines were prepared by Ir-catalyzed enantioselective allylic aminations with the bulky N-nucleophiles HN(Boc)₂ and HNBn₂. The products were transformed into N-protected amino aldehydes, which were either reduced or coupled diastereoselectively with organometallic compounds to give vicinal amino alcohols. A formal synthesis of the neurokinin receptor antagonist (+)-L-733060 was carried out as an application. Ir-catalyzed enantioselective allylic aminations with bulky N-nucleophiles HN(Boc)₂ and HNBn₂ gave N-protected allylic amines, which were transformed into N-protected chiral amino aldehydes. These are useful chiral building blocks as previously demonstrated by Reetz et al. A formal synthesis of the neurokinin receptor antagonist (+)-L-733060 was carried out as an application.

Full text of DOI:10.1002/ejoc.201501333

DOI: 10.1002/ejoc.201501333
Full Paper
Amino Aldehydes
Iridium-Catalyzed Asymmetric Allylic Substitutions with Bulky
Amines/Oxidative Double Bond Cleavage – Entry into the Reetz
Synthesis of Amino Alcohols
Kai Seehafer,[a] Chandi C. Malakar,[a] Markus Bender,[a] Jianping Qu,[a] Chen Liang,[a] and
Günter Helmchen*[a]
Abstract: Branched allylic amines were prepared by Ir-cata- or coupled diastereoselectively with organometallic com-
lyzed enantioselective allylic aminations with the bulky N-nu- pounds to give vicinal amino alcohols. A formal synthesis of the
cleophiles HN(Boc)2 and HNBn2. The products were transformed neurokinin receptor antagonist (+)-L-733060 was carried out as
into N-protected amino aldehydes, which were either reduced an application.
Introduction
als. In view of the limited set of substituents and the preference
for enantiomers of this compound class, it appears desirable
L
Many natural products, drugs, and peptidomimetics are β-
amino alcohols.[1] Particularly versatile procedures for the syn-
thesis of β-amino alcohols were developed by Reetz and co-
workers, who have shown that reactions between organometal-
lic compounds and α-amino aldehydes can display high dia-
stereoselectivity controlled by N-protecting groups.[2,3] Thus, N-
Boc-α-amino aldehydes preferentially proceed under chelate
control to give syn-β-amino alcohols, whereas N,N-dibenzyl-
amino aldehydes, which contain sterically shielded nitrogen
atoms, do not form chelated intermediates and preferentially
yield anti-β-amino alcohols (Scheme 1).
to broaden the structural space.
We have now investigated the preparation of N-protected α-
amino aldehydes by oxidation of branched allylic amines, which
can be prepared by Ir-catalyzed allylic amination. This approach
is obvious, but there were challenges involved: (a) preparation
of allylamines with very bulky N-protecting groups by Ir-cata-
lyzed allylic substitution has so far not been sufficiently investi-
gated, and (b) oxidative cleavage of the double bond required
conditions that would not give rise to racemization or deteriora-
tion of the resulting sensitive α-amino aldehydes.
Oxidative cleavage of the double bond in branched allylic
amination products has previously been carried out with RuCl3/
NaIO4, to give protected amino acids.[4,6c] To the best of our
knowledge, aldehydes or alcohols have so far only been pre-
pared from allylic alkylation products by ozonolysis followed by
reduction.[5]
Results and Discussion
The Boc-protected allylic amines were prepared with excellent
selectivities by treatment of HN(Boc)2 with allylic carbonates 1
under “salt-free“ reaction conditions (Table 1).[6] The catalysts
were either prepared in situ by adding a base (DMAP) to a
mixture of [Ir(dbcot)Cl]2 and the phosphoramidite L2[7,8] (Fig-
ure 1) or by mixing isolated (π-allyl)Ir complex C1 with DBU.[9]
Enantiomeric excesses were determined after partial deprotec-
tion by treatment either with TFA (compounds 4a–f) or with
KOH/ethanol (compound 4g) to give the mono-Boc-protected
amines 4.[10] Use of dbcot as ancillary ligand is advantageous
because of generally superior regioselectivity.
Scheme 1. Diastereoselective syntheses of syn- and anti-β-amino alcohols.
The Reetz approach relies almost exclusively on α-amino
aldehydes derived from natural amino acids as starting materi-
[a] Organisch-Chemisches Institut, Ruprecht-Karls-Universität Heidelberg,
Im Neuenheimer Feld 270, 69120 Heidelberg, Germany
E-mail: g.helmchen@oci.uni-heidelberg.de
http://www.uni-heidelberg.de/institute/fak12/OC/helmch/
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/ejoc.201501333.
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Table 1. Ir-catalyzed asymmetric allylic substitution with HN(Boc)2 as pro-
nucleophile.
Table 2. Ir-catalyzed asymmetric allylic substitution with HNBn2 as pronucleo-
phile.
Entry
1
Time [h] Yield[a] [%]
5/6[b]
ee[c] [%]
Entry
1
Catalyst[a] Time [h]
Yield[c] [%]
2/3[d]
ee[e] [%]
1[d]
2[f]
3
1a
1b
1c
1d
1e
1f
0.5
2
89
88
74
73
71
82
65
96:4
98:2
99
94
96
1
1a
1b
1c
1d
1e
1f
A
A
A
A
B
B
B
2
1
20
1
2.5
4
2.5
87
84
69
85
76
73
78
92:8
99:1
94:6
94:6
92:8
93:7
98:2
99
98
98
99
93
89
98
2[b]
3
2.5
2.5
6
82:18
84:16
86:14
86:14
75:25
4[f]
5[d],[e]
6
91
4
95
5[b]
6[b]
7
3.5
3
97[g]
94
7
1g
1g
[a] Isolated yields of 5. [b] Determined by 1H NMR examination of the crude
products. [c] Determined by chiral HPLC. [d] 4 mol-% of Ir were used. [e] ent-
L2 was used. [f] Reaction was performed at 40 °C. [g] Determined by chiral
HPLC after O-deprotection.
[a] Catalyst A: C1 (1–2 mol-%), DBU (8 mol-%). Catalyst B: [Ir(dbcot)Cl]2 (2 mol-
%). L2 (4 mol-%) and DMAP (8 mol-%). [b] ent-L2 was used. [c] Isolated yields
of 2. [d] Determined by 1H NMR examination of the crude products. [e] Deter-
mined by chiral HPLC examination of carbamates 4.
Scheme 2. Preparation of β-amino alcohols 8 and 9 by oxidative cleavage/
reduction.
Figure 1. Ligands and (π-allyl)Ir complex C1 used in this work.
The N,N-dibenzyl-allylamines 5a–g were similarly obtained
with good to high selectivities by enantioselective Ir-catalyzed
allylic amination with HNBn2 as nucleophile (Table 2).[11] The
catalysts were prepared in situ as described above.
Representative examples of allylic derivatives 4 and 5 were
converted into β-amino alcohols 8 or 9 via aldehydes 7
(Scheme 2). Both ozonolysis and dihydroxylation by treatment
with OsO4 (cat.)/NMO and subsequent periodide cleavage were
probed as oxidation procedures. The latter procedure gave su-
perior results. Racemization was minimal because purification
was possible at the diol stage; the aldehydes were sufficiently
pure for further steps. For precise assessment of racemization,
aldehydes were reduced to the amino alcohols 8 or 9 with
NaBH4 at room temperature (yields: 74–98 %, 87–98 % ee,
Schemes 3, 4).
Scheme 3. Preparation of N-Boc-amino alcohols. [a] Compound 4a (97 % ee)
was used in conjunction with Method A. [b] ee was determined after transfor-
mation into the 4-nitrobenzoate. [c] Compound ent-4b was used.
To test the oxidation procedure in conjunction with the
Ozonolysis furnished less satisfactory results because purifi- Reetz method, reactions between Grignard compounds and
cation of the aldehydes by column chromatography was neces- aldehydes derived from allylic derivatives 4a or 4g were carried
sary for ee determination or addition of organometallic com- out. In the latter case, the aldehyde 7g (Scheme 5) was pre-
pounds, and this led to partial racemization.
pared from 4g by both Method A and Method B. The aldehyde
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cause the starting aldehyde 7a is particularly prone to racemi-
zation. The amide 4a was transformed into the aldehyde 7a by
Method B; the aldehyde was treated with but-3-en-1-ylmagne-
sium bromide at room temperature, initially in THF as solvent.
The product 11 was obtained with satisfactory diastereoselect-
ivity (92:8), but with a considerably diminished ee of 77 %
(Table 3). Fortunately, results were much improved by use of
Et2O as solvent (Table 3, Entry 1).
Table 3. Addition of but-3-en-1-ylmagnesium bromide to the aldehyde 7a
(see Scheme 6).
syn/anti[a]
Yield [%][b]
ee 11-syn[c]
Scheme 4. Preparation of N,N-dibenzylamino alcohols.
Entry
Solvent
1
2
3
Et2O
THF
Et2O/THF
96:4
92:8
96:6
62 (60)
51 (49)
48
97
77
n.d.
obtained by the latter procedure was sufficiently pure for the
ee (97 %) to be determined reliably by HPLC. Treatment with
nBuMgCl/THF was carried out with the crude aldehyde after
fast workup and furnished the amino alcohols 10 with up to
98 % ee. The results given in Scheme 5 clearly demonstrate that
oxidation procedure B is the superior procedure. The preference
for the syn-amino alcohol 10a was as anticipated according to
the results of the Reetz group.[3]
[a] Determined by HPLC examination of the crude product. [b] Refers to over-
all yields, with the isolated yields of 11 in parentheses. [c] Determined by
chiral HPLC.
Further steps in the synthesis of 12 (Scheme 6) involved
chromatographic isolation of pure 11-syn, oxidative cleavage of
the double bond (Method B), deprotection by treatment with
TFA, and reductive amination (H2/Pd/C) to give (2S,3S)-2-phenyl-
piperidin-3-ol (12) in 56 % yield over four steps.
Conclusions
In summary, Ir-catalyzed asymmetric allylic substitutions with
the particularly bulky (pro)nucleophiles HN(Boc)2 and HNBn2
proceed with excellent yields and enantioselectivities. The
branched products were subjected to oxidative double bond
cleavage, preferably by dihydroxylation followed by periodate
treatment to give N-protected α-amino aldehydes with a high
degree of conservation of enantiomeric excess, as determined
either directly or after reduction to alcohols with NaBH4. By use
of methods developed by Reetz et al., two representative N-
Boc-α-amino aldehydes were treated with Grignard reagents to
give syn-β-amino alcohols with ee ≥ 97 %. As an application, a
synthesis of (2S,3S)-2-phenylpiperidin-3-ol (12), an intermediate
in the syntheses of the non-peptide substance P antagonist (+)-
L-733060, was carried out.
Scheme 5. Addition of a Grignard reagent to the aldehyde 7g.
As an application in medicinal chemistry, we prepared the
piperidine derivative 12 (Scheme 6), which has been used as
an intermediate in the syntheses of the neurokinin receptor
antagonist (+)-L-733060.[12,13] This example is of interest be-
Experimental Section
General: All reactions requiring exclusion of air and moisture were
performed in dried glassware under argon. Absolute solvents were
purchased from Sigma–Aldrich. But-3-enylmagnesium bromide was
purchased from Acros Organics as a 0.5
M solution in THF. For addi-
tion reactions with this compound in Et2O, THF was evaporated off
and the Grignard reagent was dissolved again in Et2O. Catalytic
hydrogenations were carried out with an autoclave Roth model II.
Ozonolysis was carried out with a Fischer Ozone-Generator Mod-
ell 503. Macherey–Nagel Polygram Sil G/UV precoated sheets were
used for TLC; spots were visualized with aqueous KMnO4 solution
or under UV. Macherey–Nagel silica gel 60 was used for flash chro-
matography. Preparative HPLC was carried out with a Gilson 305
instrument coupled with a Knauer UV/Vis filter photometer and a
1
silica gel Latek column (250 × 21 mm, 5 μm). H NMR spectra were
Scheme 6. Addition of but-3-en-1-ylmagnesium bromide to the aldehyde 7a
and synthesis of (2S,3S)-2-phenylpiperidin-3-ol (12).
recorded with Bruker DRX 200, Avance 300, Avance II 400, or Av-
495 © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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ance 500 instruments. Chemical shifts are reported in δ units (ppm)
gel (petroleum ether/ethyl acetate) to give the corresponding α-
relative to the solvent residual peak or TMS; coupling constants are amino aldehyde 7.
given in Hertz. 13C NMR spectra were recorded with Bruker Av-
General Procedure 4/B – Dihydroxylation/Periodide Cleavage: A
solution of a branched allylic amine derivative 4 or 5 (1.0 equiv.) in
acetone (0.1 ) at room temperature was treated dropwise with a
mixture of K2OsO4·2 H2O (2.5 mol-%) and NMO (2.2 equiv.) in water
(1:10 of acetone volume used). When complete conversion was
reached (16 h, TLC monitoring, petroleum ether/ethyl acetate,
KMnO4), Na2S2O4 was added, and the mixture was stirred for
30 min. Subsequently, the solution was filtered through a pad of
Celite®, the solvent was removed from the filtrate in vacuo, and the
ance 300, Avance II 400, or Avance 500 instruments. Chemical shifts
are reported in δ units (ppm) relative to the solvent residual peak.
High-resolution mass spectra were recorded with Bruker ApexQe
FT-ICR (ESI+), ZAB-2F (EI+), or JEOL JMS-700 (FAB+) instruments. Opti-
cal rotations were measured at 20 °C with a Perkin–Elmer 341 in-
strument. Enantiomeric excesses were determined with a HP 1100
liquid chromatograph and chiral Daicel columns (Chiralpak AD-H,
AS-H, OD-H, OJ-H, IB, 250 × 4.6 mm, 5 μm); diastereomeric ratios
were determined with a silica gel column from Merck (LiChroCART,
250 × 4.6 mm, 7 μm). Melting points (m.p.) were determined with
a Büchi Tottoli apparatus and are not corrected.
M
residue was dissolved in Et2O/H2O (2:1, 0.1
M). Then NaIO4
(2.1 equiv.) was added, and the mixture was vigorously stirred at
room temperature until TLC monitoring (1–2 h, petroleum ether/
ethyl acetate, KMnO4) showed complete conversion. Phosphate
buffer/Et2O (1:1) was added, and the aqueous layer was separated
and extracted twice with Et2O. The combined organic layers were
dried with Na2SO4, filtered, and concentrated in vacuo to give the
corresponding α-amino aldehyde 7. The crude product was directly
used for further reactions without analysis (unless otherwise men-
tioned).
General Procedure 1 – Iridium-Catalyzed Allylic Substitutions
with Catalyst Activation in situ: Success with the following proce-
dures requires dry THF (<35 μg of H2O mL–1, Karl Fischer titration).
Under argon, in a heat-gun-dried Schlenk tube, a solution of
[Ir(dbcot)Cl]2 (2–2.5 mol-%), L2 or ent-L2 (4–5 mol-%), and DMAP
(8 mol-%) in dry THF (0.4
M with respect to the carbonate) was
stirred for 5–10 min at room temperature until a white precipitate
had formed at the glass wall above the solution. The allylic carbon-
ate 1 (1.0 equiv.) and, after a further 5 min, HN(Boc)2 (1.2 equiv.) or
HNBn2 (1.5 equiv.) were added, and the mixture was stirred at the
stated temperature and for the stated time until TLC monitoring
(petroleum ether/ethyl acetate, KMnO4) indicated complete conver-
sion. The solvent was removed under reduced pressure, and the
residue was analyzed with respect to content of branched and lin-
ear product by 1H NMR spectroscopy. The pure reaction products
were obtained by flash column chromatography on silica gel (petro-
leum ether/ethyl acetate).
General Procedure 5 – Reduction of Crude α-Amino Aldehydes
7 to Give α-Amino Alcohols 8: A crude α-amino aldehyde 7
(1.0 equiv.) was dissolved in Et2O/MeOH (6:1, 0.02
M), and NaBH4
(2.0 equiv.) was added. The mixture was stirred at room temperature
until TLC monitoring (petroleum ether/ethyl acetate, KMnO4)
showed complete conversion. Water was added, and the mixture
was extracted three times with ethyl acetate. The combined organic
layers were dried with Na2SO4. The solvent was removed under
reduced pressure to give the crude product, which was purified by
flash column chromatography on silica gel (petroleum ether/ethyl
acetate) to afford the α-amino alcohol 8.
General Procedure 2 – Iridium-Catalyzed Allylic Substitutions
with (π-Allyl)Ir-Complex C1 as Catalyst: Success with the follow-
ing procedures requires dry THF (<35 μg of H2O mL–1, Karl Fischer
titration). Under argon, in a heat-gun-dried Schlenk tube, (π-Allyl)Ir
complex C1 (1–2 mol-%) and DBU (8 mol-%) were dissolved in dry
General Procedure 6 – Reduction of Crude α-Amino Aldehydes
7 to Give α-Amino Alcohols 9: The crude α-amino aldehyde 7
(1.0 equiv.) was dissolved in THF/H2O (6:1, 0.2
M), and NaBH4
(1.5 equiv.) was added. The mixture was stirred at room temperature
until TLC monitoring (petroleum ether/ethyl acetate, KMnO4)
showed complete conversion (15 min). Water was added, and the
mixture was extracted three times with ethyl acetate. The combined
organic layers were dried with Na2SO4. The solvent was removed
under reduced pressure to give the crude product, which was puri-
fied by flash column chromatography on silica gel (petroleum
ether/ethyl acetate) to afford α-amino alcohol 9.
THF (0.4
M
with respect to the carbonate). The allylic carbonate 1
(1.0 equiv.) and, after a further 5 min, HN(Boc)2 (1.1 equiv.) were
added, and the mixture was stirred at 50 °C and for the stated
time until TLC monitoring (petroleum ether/ethyl acetate, KMnO4)
indicated complete conversion. The solvent was removed under re-
duced pressure, and the residue was analyzed with respect to con-
1
tent of branched and linear product by H NMR spectroscopy. The
pure reaction products were obtained by flash column chromatog-
raphy on silica gel (petroleum ether/ethyl acetate).
(–)-Di-tert-butyl [(1S)-1-Phenylprop-2-en-1-yl]imidodicarbonate
(2a): This compound was prepared as described in General Proce-
dure 2; yield 580 mg (1.74 mmol), 87 %, colorless oil, 99 % ee (deter-
mined after mono-Boc removal), 2a/3a = 92:8. [α]D20 (99 % ee) =
–36.6 [c = 1.0, CHCl3, (S)], ref.[14] [α]D20 (99 % ee) = +49.1 [c = 1.16,
CHCl3, (R)]. The analytical data were in agreement with the litera-
ture.
General Procedure 3 – Mono-Boc Removal: Except in the case of
2d, a solution of the di-Boc-protected amine 2 (1.0 equiv.) in CH2Cl2
(0.1 M) was treated dropwise with TFA (1.5 equiv.) at room tempera-
ture. The mixture was stirred for 1.5 h until TLC monitoring (petro-
leum ether/ethyl acetate, KMnO4) showed complete conversion of
the starting material. The solvent was removed in vacuo, and the
crude product was subjected to flash column chromatography on
silica gel (petroleum ether/ethyl acetate).
[(2E)-3-Phenylprop-2-en-1-yl]imidodicarbonate (3a): The analyti-
cal data were in agreement with the literature.[14]
General Procedure 4/A – Ozonolysis: Ozone was bubbled through
a cooled (–78 °C) solution of a branched allylic amine derivative 4
or 5 (1.0 equiv.) and a small amount of Sudan® III in CH2Cl2 (0.1 M)
until the red color of the solution disappeared. Then O2 was
bubbled through for further 3 min, SMe2 (10 equiv.) was added,
and the mixture was stirred first for 10 min at –78 °C and then for
(–)-Di-tert-butyl [(1S)-1-Methylprop-2-en-1-yl]imidodicarbonate
(2b): This compound was prepared as described in General Proce-
dure 2; yield 456 mg (1.68 mmol), 84 %, colorless solid, m.p. 30–
33 °C, 98 % ee (determined after mono-Boc removal), 2b/3b = 99:1.
[α]D20 (95 % ee) = +9.5 [c = 1.03, CHCl3, (R)]. 1H NMR (CDCl3, 500 MHz):
δ = 1.39 (d, J = 6.9 Hz, 3 H), 1.48 (s, 18 H), 4.76–4.85 (m, 1 H), 5.07
30 min at room temperature. The solvent was removed in vacuo, (d, J = 10.5 Hz, 1 H), 5.13 (d, J = 17.4 Hz, 1 H), 6.00 (ddd, J = 17.1,
and the residue was subjected to flash chromatography on silica
10.4, 5.5 Hz, 1 H) ppm. 13C NMR (CDCl3, 125 MHz): δ = 18.1, 28.2,
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54.2, 82.3, 115.0, 139.2, 153.0 ppm. HRMS (ESI+) calcd. for
C17H35N2O4 [M + Me3NH]+ 331.2597; found 331.2592.
Di-tert-butyl ((2E)-4-{[tert-Butyl(dimethyl)-silyl]oxy}but-2-en-1-
yl)imidodicarbonate (3f): H NMR (CDCl3, 400 MHz): δ = 0.06 (s, 6
1
H), 0.90 (s, 9 H), 1.49 (s, 18 H), 4.13–4.17 (m, 4 H), 5.65–5.77 (m, 2
H) ppm. 13C NMR (CDCl3, 100 MHz): δ = –5.1, 18.5, 26.1, 28.2, 47.6,
63.3, 82.4, 125.6, 132.2, 152.4 ppm. HRMS (ESI+) calcd. for
Di-tert-butyl (2E)-But-2-en-1-ylimidodicarbonate (3b): The ana-
lytical data were in agreement with the literature.[15]
(–)-Di-tert-butyl [(1R)-1-Hexylprop-2-en-1-yl]imidodicarbonate
(2c): This compound was prepared as described in General Proce-
dure 2; yield 471 mg (1.38 mmol), 69 %, colorless oil, 98 % ee (deter-
mined after mono-Boc removal), 2c/3c = 94:6. [α]D20 (95 % ee) = +2.6
[c = 1.00, CHCl3, (S)]. 1H NMR (CDCl3, 400 MHz): δ = 0.87 (t, J =
6.8 Hz, 3 H), 1.23–1.34 (m, 8 H), 1.48 (s, 18 H), 1.63–1.73 (m, 1 H),
1.79–1.90 (m, 1 H), 4.56–4.65 (m, 1 H), 5.09 (td, J = 10.3, 1.3 Hz, 1
H), 5.15 (td, J = 17.3, 1.4 Hz, 1 H), 6.00 (ddt, J = 17.2, 10.3, 6.7 Hz, 1
H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 14.2, 22.7, 26.5, 28.2, 29.1,
31.9, 32.6, 59.3, 82.2, 116.2, 138.2, 153.2 ppm. HRMS (ESI+) calcd. for
C
20H39NO5SiNa [M + Na]+ 424.2495; found 424.2489.
(–)-Di-tert-butyl [(1R)-1-(2-Phenylethyl)prop-2-en-1-yl]imidodi-
carbonate (2g): This compound was prepared as described in Gen-
eral Procedure 1; yield 384 mg (1.06 mmol), 78 %, colorless oil,
98 % ee (determined after mono-Boc removal), 2g/3g = 98:2. [α]D20
(98 % ee) = –0.4 [c = 1.03, CHCl3, (R)], ref.[16] [α]D20 (93 % ee) = –0.5
[c = 1.09, CHCl3, (S)]. The analytical data were in agreement with
the literature.
Di-tert-butyl
[(2E)-5-Phenylpent-2-en-1-yl]imidodicarbonate
C
19H35NO4Na [M + Na]+ 364.2464; found 364.2465.
1
(3g): H NMR (CDCl3, 300 MHz): δ = 1.49 (s, 18 H), 2.34 (dt, J = 7.3,
6.9 Hz, 1 H), 2.68 (t, J = 7.3 Hz, 2 H), 4.10 (dd, J = 5.9, 0.8 Hz, 1 H),
5.51 (dtt, J = 15.3, 6.0, 1.2 Hz, 1 H), 5.67 (dt, J = 15.4, 6.7 Hz, 1 H),
7.13–7.31 (m, 5 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 28.2, 34.2,
35.8, 48.0, 82.3, 126.0, 126.0, 128.4, 128.5, 132.8, 141.9, 152.6 ppm.
HRMS (ESI+) calcd. for C21H31NO4Na [M + Na]+ 384.2151; found
384.2148.
Di-tert-butyl (2E)-Non-2-en-1-ylimidodicarbonate (3c): 1H NMR
(CDCl3, 400 MHz): δ = 0.87 (t, J = 6.8 Hz, 3 H), 1.23–1.37 (m, 8 H),
1.49 (s, 18 H), 2.00 (q, J = 6.9, 6.8 Hz, 2 H), 4.09 (d, J = 6.0 Hz, 2 H),
5.40–5.50 (m, 1 H), 5.55–5.65 (m, 1 H) ppm. 13C NMR (CDCl3,
100 MHz): δ = 14.1, 22.6, 28.8, 29.2, 31.7, 28.1, 32.2, 48.0, 82.0, 125.1,
133.9, 152.4 ppm. HRMS (ESI+) calcd. for C19H35NO4Na [M + Na]+
364.2464; found 364.2464.
(–)-tert-Butyl [(1S)-1-Phenylprop-2-en-1-yl]carbamate (4a): This
compound was prepared as described in General Procedure 3; yield
551 mg (2.36 mmol), 96 %, colorless solid, m.p. 56–57 °C, ref.[14]
54–55 °C. [α]D20 (99 % ee) = –64.4 [c 1.00, CHCl3, (S)], ref.[14] [α]D20
(99 % ee) = +62.2 [c = 1.00, CHCl3, (R)]. The analytical data were in
(+)-Di-tert-butyl [(2S)-1-(Trityloxy)but-3-en-2-yl]imidodicarbon-
ate (2d): This compound was prepared as described in General
Procedure 2; yield 450 mg (0.85 mmol), 85 %, colorless solid, m.p.
140–143 °C, ref.[6d] 143–146 °C, 99 % ee (determined after mono-
Boc removal), 2d/3d = 94:6. [α]D20 (99 % ee) = +24.5 [c = 1.12, CHCl3, agreement with the literature.
(S)], ref.[6d] [α]D20 (97 % ee) = +25.7 [c = 0.97, CHCl3, (S)]. The analytical
data were in agreement with the literature.
(–)-tert-Butyl [(1S)-1-Methylprop-2-en-1-yl]carbamate (4b): This
compound was prepared as described in General Procedure 3; yield
126 mg (0.74 mmol), 95 %; colorless solid, m.p. 56–57 °C.
[α]D20 (98 % ee) = –4.9 [c = 1.09, CHCl3, (S)], ref.[17] [α]D20 = –6.3 [c =
1.2, CHCl3, (S)]. The analytical data were in agreement with the liter-
ature.
Di-tert-butyl [(2E)-4-(Trityloxy)but-2-en-1-yl]imidodicarbonate
(3d): The analytical data were in agreement with the literature.[6d]
(–)-Di-tert-butyl
{(1R)-1-[(Benzyloxy)methyl]prop-2-en-1-yl}-
imidodicarbonate (2e): This compound was prepared as described
in General Procedure 1; yield 122 mg (0.32 mmol), 76 %, colorless
oil, 93 % ee (determined after mono-Boc removal), 2e/3e = 92:8. [α]
(–)-tert-Butyl [(1R)-1-Hexylprop-2-en-1-yl]carbamate (4c): This
compound was prepared as described in General Procedure 3; yield
80.5 mg (0.33 mmol), 97 %, colorless oil. [α]D20 (98 % ee) = –12.4 [c =
1.55, CHCl3, (R)]. HPLC (Chiralpak AS-H, n-hexane/2-propanol
99.5:0.5, flow 0.5 mL min–1, room temp., λ = 205 nm), tR[(–)-(R)-4c] =
12.8 min, tR[(+)-(S)-4c] = 16.9 min. 1H NMR (CDCl3, 400 MHz): δ =
0.87 (t, J = 6.9 Hz, 3 H), 1.20–1.36 (m, 8 H), 1.40–1.54 (m, 2 H), 1.44
(s, 9 H), 4.07 (br. s, 1 H), 4.44 (br. s, 1 H), 5.06 (td, J = 10.4, 1.3 Hz, 1
H), 5.13 (td, J = 17.2, 1.3 Hz, 1 H), 5.73 (ddd, J = 17.1, 10.4, 5.7 Hz,
1 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 14.2, 22.7, 25.8, 28.5, 29.2,
31.9, 35.4, 52.9, 79.3, 114.3, 139.3, 155.5 ppm. HRMS (ESI+) calcd. for
C14H27NO2Na [M + Na]+ 264.1939; found 264.1934.
20 (93 % ee) = –10.4 [c = 1.01, CHCl3, (R)]. 1H NMR (CDCl3, 400 MHz):
D
δ = 1.48 (s, 18 H), 3.70 (dd, J = 9.8, 6.4 Hz, 1 H), 3.88 (dd, J = 9.8,
8.2 Hz, 1 H), 4.52 (d, J = 12.0 Hz, 1 H), 4.56 (d, J = 12.0 Hz, 1 H),
4.96–5.05 (m, 1 H), 5.18 (td, J = 10.6, 1.2 Hz, 1 H), 5.25 (td, J = 17.4,
1.2 Hz, 1 H), 5.96 (ddd, J = 17.1, 10.5, 6.1 Hz, 1 H), 7.22–7.36 (m, 5
H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 28.2, 58.1, 70.7, 72.9, 82.4,
117.5, 127.6, 127.7, 128.4, 134.8, 138.5, 153.1 ppm. HRMS (ESI+)
calcd. for C21H31NO5Na [M + Na]+ 400.2100; found 400.2093.
Di-tert-butyl [(2E)-4-(Benzyloxy)but-2-en-1-yl]imidodicarbonate
1
(3e): H NMR (CDCl3, 400 MHz): δ = 1.50 (s, 18 H), 3.97–4.04 (m, 2
H), 4.15–4.22 (m, 2 H), 4.50 (s, 2 H), 5.66–5.84 (m, 2 H), 7.24–7.38
(m, 5 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 28.2, 47.6, 70.2, 72.0,
82.5, 127.7, 127.8, 128.5, 128.9, 129.2, 138.4, 152.5 ppm. HRMS (ESI+)
calcd. for C21H31NO5Na [M + Na]+ 400.2100; found 400.2093.
(–)-tert-Butyl (S)-[1-(Trityloxy)but-3-en-2-yl]carbamate (4d): A
solution of 2d (185 mg, 0.35 mmol) in a mixture of toluene (1 mL)
and EtOH (10 mL) was treated with KOH (39.2 mg, 0.51 mmol). Then
the mixture was stirred under reflux until TLC monitoring showed
complete conversion [petroleum ether/diethyl ether (10:1); Rf(2d) =
(–)-Di-tert-butyl [(1R)-1-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-
prop-2-en-1-yl]imidodicarbonate (2f): This compound was pre- 0.38, Rf(4d) = 0.23, KMnO4]. The solvent was removed in vacuo, and
pared as described in General Procedure 1; yield 108 mg
the crude product was subjected to flash column chromatography
(0.27 mmol), 73 %, colorless oil, 89 % ee (determined after mono-
on silica gel [petroleum ether/diethyl ether (20:1)] to give 4d
Boc removal), 2f/3f = 93:7. [α]D20 (89 % ee) = –8.2 [c = 1.02, CHCl3, (133.8 mg, 0.31 mmol, 89 %) as a colorless oil. [α]D20 (99 % ee) =
1
(R)]. H NMR (CDCl3, 400 MHz): δ = 0.04 (s, 6 H), 0.88 (s, 9 H), 1.49
–18.5 [c = 1.05, CHCl3, (S)]. HPLC (Chiralpak AD-H, n-hexane/2-
(s, 18 H), 3.76 (dd, J = 9.9, 6.4 Hz, 1 H), 4.00 (dd, J = 9.9, 8.5 Hz, 1
propanol 95:5, flow 0.5 mL min–1, room temp., λ = 220 nm), tR[(+)-
H), 4.78–4.84 (m, 1 H), 5.16 (td, J = 10.5, 1.4 Hz, 1 H), 5.18 (td, J = (R)-4d] = 12.6 min, tR[(–)-(S)-4d] = 15.2 min. 1H NMR (CDCl3,
17.4, 1.4 Hz, 1 H), 5.92 (ddd, J = 17.4, 10.5, 6.2 Hz, 1 H) ppm. 13C 500 MHz): δ = 1.48 (s, 18 H), 3.20–3.26 (m, 2 H), 4.42 (br. s, 1 H),
NMR (CDCl3, 100 MHz): δ = –5.2, 18.4, 26.0, 28.2, 60.9, 63.9, 82.2, 4.87 (br. s, 1 H), 5.23 (td, J = 10.0, 1.5 Hz, 1 H), 5.29 (td, J = 17.3,
117.4, 134.7, 153.2 ppm. HRMS (ESI+) calcd. for C20H39NO5SiNa [M
+ Na]+ 424.2495; found 424.2488.
1.3 Hz, 1 H), 5.94 (ddd, J = 17.1, 10.5, 5.0 Hz, 1 H), 7.27–7.30 (m, 3
H), 7.34–7.37 (m, 6 H), 7.48–7.50 (m, 6 H) ppm. 13C NMR (CDCl3,
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125 MHz): δ = 28.5, 52.9, 65.7, 79.5, 86.6, 115.6, 127.2, 127.9, 128.8,
136.7, 143.9, 155.5 ppm. HRMS (ESI+) calcd. for C28H31NNaO3 [M +
Na]+ 452.2196; found 452.2198.
2 H), 3.02 (d, J = 5.9 Hz, 2 H), 3.58 (s, 4 H), 5.52 (td, J = 15.4, 5.9 Hz,
1 H), 5.60 (td, J = 15.5, 6.2 Hz, 1 H), 7.20–7.42 (m, 10 H) ppm. 13C
NMR (CDCl3, 100 MHz): δ = 14.2, 22.8, 29.0, 29.5, 31.9, 32.6, 55.7,
57.8, 126.9, 127.2, 128.3, 129.0, 134.4, 140.1 ppm. HRMS (ESI+) calcd.
for C23H32N [M + H]+ 322.2535; found 322.2529.
(+)-tert-Butyl {(1R)-1-[(Benzyloxy)methyl]prop-2-en-1-yl}carb-
amate (4e): This compound was prepared as described in General
Procedure 3; yield 76.9 mg (0.28 mmol), 97 %, colorless oil. [α]D20
(93 % ee) = +32.2 [c = 1.01, CHCl3, (R)], ref.[10a]: [α]D20 (98 % ee) =
+30.9 [c = 0.62, CHCl3, (R)]. The analytical data were in agreement
with the literature.
(–)-(2S)-N,N-Dibenzyl-1-(trityloxy)but-3-en-2-amine (5d): This
compound was prepared as described in General Procedure 1; yield
191 mg (0.38 mmol), 73 %, colorless oil, 91 % ee, 5d/6d = 84:16.
[α]D20 (91 % ee) = –45.0 [c = 0.95, CHCl3, (S)], ref.[22] [α]D20 (97 % ee) =
+56.2 [c = 0.93, CHCl3, (R)]. The analytical data were in agreement
with the literature.
(–)-tert-Butyl
[(1S)-1-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-
prop-2-en-1-yl]carbamate (4f): This compound was prepared as
described in General Procedure 3; yield 22.7 mg (75.3 μmol), 38 %,
colorless oil. [α]D20 (89 % ee) = –32.2 [c = 0.77, CHCl3, (S)], ref.[18]
[α]D20 (98 % ee) = –35.0 [c = 1.05, CHCl3, (S)]. The analytical data were
in agreement with the literature.
(2E)-N,N-Dibenzyl-4-(trityloxy)but-2-en-1-amine (6d): The ana-
lytical data were in agreement with the literature.[22]
(+)-(2R)-N,N-Dibenzyl-1-(benzyloxy)but-3-en-2-amine (5e): This
compound was prepared as described in General Procedure 1; yield
52.7 mg (0.15 mmol), 71 %, colorless oil, 95 % ee, 5e/6e = 86:14.
[α]D20 (95 % ee) = –27.2 [c = 1.07, CHCl3, (S)]. HPLC (Chiralpak IB, n-
hexane/2-propanol 99:1, flow 0.5 mL min–1, room temp., λ =
(–)-tert-Butyl [(1R)-1-(2-Phenylethyl)prop-2-en-1-yl]carbamate
(4g): This compound was prepared as described in General Proce-
dure 3; yield 27.4 mg (105 μmol), 98 %, colorless solid, m.p. 76–
77 °C. [α]D20 (98 % ee) = –25.3 [c = 1.04, CHCl3, (R)], ref.[19]
[α]D20 (90 % ee) = +22.5 [c = 1.9, CHCl3, (S)]. HPLC (Chiralpak OD-H,
n-hexane/2-propanol 95:5, flow 0.8 mL min–1, room temp., λ =
1
210 nm), tR[(+)-(R)-5e] = 9.2 min, tR[(–)-(S)-5e] = 11.4 min. H NMR
(CDCl3, 400 MHz): δ = 3.42–3.50 (m, 1 H), 3.57 (d, J = 13.9 Hz, 2 H),
3.64 (dd, J = 9.8, J = 6.5 Hz, 1 H), 3.76 (dd, J = 9.8, 6.2 Hz, 1 H), 3.83
(d, J = 13.9 Hz, 2 H), 4.50 (s, 2 H), 5.23 (ddd, J = 17.3, 1.7, 1.2 Hz, 1
H), 5.34 (ddd, J = 10.7, 1.8, 1.0 Hz, 1 H), 5.93 (ddd, J = 17.5, 10.5,
7.5 Hz, 1 H), 7.18–7.44 (m, 10 H) ppm. 13C NMR (CDCl3, 100 MHz):
δ = 54.6, 60.1, 71.5, 73.1, 118.6, 126.9, 127.6, 127.7, 128.3, 128.4,
128.7, 135.0, 138.6, 140.5 ppm. HRMS (ESI+) calcd. for C25H28NO [M
+ H]+ 358.2171; found 358.2166.
1
210 nm), tR[(–)-(R)-4g] = 7.6 min, tR[(+)-(S)-4g] = 10.7 min. H NMR
(CDCl3, 300 MHz): δ = 1.45 (s, 9 H), 1.70–1.92 (m, 2 H), 2.56–2.75 (m,
2 H), 4.15 (br. s, 1 H), 4.47 (br. s, 1 H), 5.12 (d, J = 10.4 Hz, 1 H), 5.18
(d, J = 17.2 Hz, 1 H), 5.78 (ddd, J = 17.0, 10.4, 5.6 Hz, 1 H), 7.13–7.34
(m, 5 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 28.6, 32.3, 37.1, 52.8,
79.5, 114.9, 126.11, 128.5, 128.6, 138.9, 141.8, 155.5 ppm. HRMS
(ESI+) calcd. for C32H46N2O4Na [2 M + Na]+ 545.3355; found
545.3348.
(2E)-N,N-Dibenzyl-4-(benzyloxy)but-2-en-1-amine (6e): The ana-
lytical data were in agreement with the literature.[23]
(–)-(1S)-N,N-Dibenzyl-1-phenylprop-2-en-1-amine (5a): This
compound was prepared as described in General Procedure 1; yield
151 mg (0.48 mmol), 89 %; colorless oil, 99 % ee, 5a/6a = 96:4.
[α]D20 (99 % ee) = –111 [c = 1.03, CHCl3, (S)], ref.[11] [α]D20 (95 % ee) =
–111 [c = 1.06, CHCl3, (S)]. The analytical data were in agreement
with the literature.
(–)-(2S)-N,N-Dibenzyl-1-{[tert-butyl(dimethyl)silyl]oxy}but-3-en-
2-amine (5f): This compound was prepared as described in General
Procedure 1; yield 139 mg (0.36 mmol), 82 %, colorless oil, 97 % ee
(determined after TBS removal with TBAF), 5f/6f
= 86:14.
[α]D20 (97 % ee) = +7.4 [c = 1.02, CHCl3, (R)], ref.[24] [α]D20 = +5.5 [c =
1.00, CHCl3, (R)]. The analytical data were in agreement with the
literature.
(2E)-N,N-Dibenzyl-3-phenylprop-2-en-1-amine (6a): The analyti-
cal data were in agreement with the literature.[11]
(2E)-N,N-Dibenzyl-4-{[tert-butyl(dimethyl)silyl]-oxy}but-2-en-1-
amine (6f): H NMR (CDCl3, 400 MHz): δ = 0.08 (2 × s, 6 H), 0.92 (s,
(+)-(2R)-N,N-Dibenzylbut-3-en-2-amine (5b): This compound was
prepared as described in General Procedure 1; yield 341 mg
1
9 H), 3.07 (d, J = 4.7 Hz, 2 H), 3.58 (s, 4 H), 4.18 (d, J = 3.7 Hz, 2 H),
5.68–5.83 (m, 2 H), 7.20–7.44 (m, 10 H) ppm. 13C NMR (CDCl3,
100 MHz): δ = –5.0, 18.6, 26.1, 55.0, 57.9, 63.7, 126.9, 127.8, 128.3,
128.9, 132.6, 139.8 ppm. HRMS (ESI+) calcd. for C24H36NOSi [M + H]+
382.2566; found 382.2562.
(1.36 mmol), 88 %, colorless oil, 94 % ee, 5b/6b
= 98:2.
[α]D20 (94 % ee) = +13.4 [c = 0.53, CHCl3, (R)], ref.[20] [α]D20 = –11.6 [c =
8.3, CHCl3, (S)]. The analytical data were in agreement with the liter-
ature.
(E)-N,N-Dibenzylbut-2-en-1-amine (6b): The analytical data were
in agreement with the literature.[21]
(–)-(3R)-N,N-Dibenzyl-5-phenylpent-1-en-3-amine (5g): This
compound was prepared as described in General Procedure 1; yield
81.2 mg (0.24 mmol), 65 %, colorless oil, 94 % ee, 5g/6g = 75:25.
[α]D20 (94 % ee) = +27.7 [c = 1.03, CHCl3, (S)]. HPLC (Chiralpak IB, n-
hexane/2-propanol 99.9:0.1, flow 1.0 mL min–1, room temp., λ =
210 nm), tR[(+)-(S)-5g] = 7.3 min, tR[(–)-(R)-5g] = 7.8 min. 1H NMR
(CDCl3, 400 MHz): δ = 1.79 (dddd, J = 13.6, 10.7, 6.9, 5.5 Hz, 1 H),
2.04 (dddd, J = 13.4, 10.8, 7.5, 5.8 Hz, 1 H), 2.55 (ddd, J = 13.9, 10.8,
5.4 Hz, 1 H), 2.81 (ddd, J = 13.9, 10.7, 5.8 Hz, 1 H), 3.09–3.17 (m, 1
H), 3.42 (d, J = 13.8 Hz, 2 H), 3.85 (d, J = 13.8 Hz, 2 H), 5.09 (ddd,
J = 17.2, 2.0, 0.8 Hz, 1 H), 5.32 (ddd, J = 10.6, 2.2, 0.5 Hz, 1 H), 5.88
(ddd, J = 17.2, 10.3, 8.6 Hz, 1 H), 7.09–7.45 (m, 15 H) ppm. 13C NMR
(CDCl3, 100 MHz): δ = 33.1, 34.3, 53.9, 60.8, 118.1, 125.7, 126.9, 128.3,
128.4, 128.5, 128.9, 136.3, 140.5, 142.8 ppm. HRMS (ESI+) calcd. for
C25H28N [M + H]+ 342.2222; found 342.2217.
(–)-(3R)-N,N-Dibenzylnon-1-en-3-amine (5c): This compound was
prepared as described in General Procedure 1; yield 120 mg
(0.37 mmol), 74 %; colorless oil, 96 % ee, 5c/6c 82:18.
[α]D20 (96 % ee) = –15.0 [c = 1.01, CHCl3, (R)]. HPLC (Chiralpak OD-H,
n-hexane/2-propanol 95:5, flow 0.5 mL min–1, room temp., λ =
210 nm), tR[(+)-(S)-5c] = 5.1 min, tR[(–)-(R)-5c] = 6.2 min. 1H NMR
(CDCl3, 400 MHz): δ = 0.88 (t, J = 6.9 Hz, 3 H), 1.15–1.32 (m, 7 H),
1.34–1.51 (m, 2 H), 1.64–1.77 (m, 1 H), 2.97–3.05 (m, 1 H), 3.38 (d,
J = 13.8 Hz, 2 H), 3.81 (d, J = 13.8 Hz, 2 H), 5.03 (ddd, J = 17.2, 2.1,
0.8 Hz, 1 H), 5.26 (ddd, J = 10.3, 2.1, 0.4 Hz, 1 H), 5.81 (ddd, J = 17.2,
10.3, 8.6 Hz, 1 H), 7.19–7.42 (m, 10 H) ppm. 13C NMR (CDCl3,
100 MHz): δ = 14.3, 22.8, 26.6, 29.4, 32.0, 32.2, 53.8, 61.0, 117.6,
126.8, 128.3, 128.8, 136.9, 140.8 ppm. HRMS (ESI+) calcd. for C23H32
[M + H]+ 322.2535; found 322.2528.
N
(2E)-N,N-Dibenzylnon-2-en-1-amine (6c): 1H NMR (CDCl3,
400 MHz): δ = 0.85–0.92 (m, 3 H), 1.22–1.40 (m, 8 H), 2.00–2.07 (m,
(2E)-N,N-Dibenzyl-5-phenylpent-2-en-1-amine (6g): The analyti-
cal data were in agreement with the literature.[23]
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(+)-tert-Butyl [(1S)-2-Oxo-1-phenylethyl]carbamate (7a): This
compound was prepared as described in General Procedure 4/B;
(R)-8d] = 12.1 min, tR[(–)-(S)-8d] = 16.8 min. 1H NMR (CD2Cl2,
500 MHz): δ = 1.43 (s, 9 H), 2.34 (br. s, 1 H), 3.21–3.22 (m, 2 H), 3.63–
yield 118 mg (0.44 mmol), quant., colorless oil. [α]D20 (99 % ee accord- 3.67 (m, 1 H), 3.70–3.77 (m, 2 H), 5.04 (br. s, 1 H), 7.24–7.27 (m, 3
ing to the starting material) = +214, [c = 1.08, CHCl3, (S)], ref.[25a] H), 7.30–7.33 (m, 6 H), 7.42–7.44 (m, 6 H) ppm. 13C NMR (CD2Cl2,
[α]D20 = +272 [c = 0.9, CH2Cl2, (S)]. The analytical data were in agree- 125 MHz): δ = 28.5, 52.6, 63.9, 64.0, 79.7, 87.2, 127.6, 128.3, 128.9,
ment with the literature.[25b]
144.2, 156.3 ppm. HRMS (ESI+) calcd. for C27H31NNaO4 [M + Na]+
456.2145; found 456.2158.
(–)-tert-Butyl [(1R)-1-Formyl-3-phenylpropyl]carbamate (7g):
This compound was prepared as described in General Procedure 4/
A; yield 124 mg (0.47 mmol), 87 %. It was also prepared as de-
scribed in General Procedure 4/B; yield 243 mg (0.92 mmol), 96 %,
(+)-(2R)-2-[Bis(phenylmethyl)amino]-2-phenylethanol (9a): This
compound was prepared as described in General Procedure 4/B
plus General Procedure 6: 5a (99 % ee) was used, yield 107 mg
colorless oil, 97 % ee. [α]D20 (97 % ee) = –62.3 [c = 0.92, CHCl3, (R)]. (0.34 mmol), 88 %, colorless oil, 98 % ee. [α]D20 (98 % ee) = +148 [c =
HPLC (Chiralpak OD-H, n-hexane/2-propanol 96:4, flow 0.8 mL min–1,
0.52, CHCl3, (R)]. HPLC (Chiralpak AD-H, n-hexane/2-propanol 88:12,
flow 0.7 mL min–1, room temp., λ = 210 nm), tR[(–)-(S)-9a] =
11.3 min, tR[(+)-(R)-9a] = 12.1 min. 1H NMR (CDCl3, 300 MHz): δ =
3.02 (br. s, 1 H), 3.15 (d, J = 13.4 Hz, 2 H), 3.61 (dd, J = 10.7, 5.2 Hz,
1
λ = 210 nm), tR[(–)-(R)-7g] = 29.2 min, tR[(+)-(S)-7g] = 33.6 min. H
NMR (CDCl3, 300 MHz): δ = 1.46 (s, 9 H), 1.80–1.97 (m, 1 H), 2.10–
2.34 (m, 1 H), 2.61–2.80 (m, 2 H), 4.24 (br. s, 1 H), 5.08 (br. s, 1 H),
7.12–7.35 (m, 5 H), 9.55 (s, 1 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 1 H), 3.9 (d, J = 13.4 Hz, 2 H), 3.94 (m, 12 H), 4.14 (dd, J = 11.3,
28.4, 31.0, 31.6, 59.7, 80.3, 126.5, 128.6, 128.8, 140.7, 155.7,
199.6 ppm. HRMS (ESI+) calcd. for C15H21NO3Na [M + Na]+ 286.1419;
found 286.1415.
10.7 Hz, 1 H), 7.23–7.45 (m, 15 H) ppm. 13C NMR (CDCl3, 75 MHz):
δ = 53.5, 60.5, 63.0, 127.3, 128.1, 128.3, 128.6, 129.0, 129.3, 135.1,
139.1 ppm. HRMS (EI+) calcd. for C22H24NO [M + H]+ 318.1852; found
318.1852.
(–)-tert-Butyl [(1R)-2-Hydroxy-1-phenylethyl]carbamate (8a):
This compound was prepared as described in General Procedure 4/
A plus General Procedure 5: 4a (97 % ee) was used, yield 106 mg
(0.45 mmol), 70 %, 91 % ee. This compound was also prepared as
described in General Procedure 4/B plus General Procedure 5: 4a
(–)-(2R)-2-[Bis(phenylmethyl)amino]propan-1-ol (9b): This com-
pound was prepared as described in General Procedure 4/B plus
General Procedure 6: 5b (94 % ee) was used, yield 61 mg
(0.24 mmol), 80 %, colorless oil, 94 % ee. [α]D20 (94 % ee) = –62.3 [c =
(99 % ee) was used, yield 89.6 mg (0.38 mmol), 84 %, colorless oil, 0.68, CHCl3 (R)]. HPLC (Chiralcel OD-H, n-hexane/2-propanol 90:10,
95 % ee. [α]D20 (94 % ee) = –27.9 [c = 1.03, CHCl3, (R)], ref.[26] [α]D25
–31.3 [c = 0.4, CHCl3, (R)]. The analytical data were in agreement
=
flow 0.7 mL min–1, λ = 205 nm), tR[(–)-(R)-9b] = 8.8 min, tR[(+)-(S)-
9b] = 11.9 min. H NMR (CDCl3, 300 MHz): δ = 0.90 (d, J = 6.9 Hz,
1
with the literature.
3 H), 2.86–3.04 (m, 1 H), 3.03 (br. s, 1 H), 3.25 (dd, J = 10.7, 4.9 Hz,
1 H), 3.28 (d, J = 13.4 Hz, 2 H), 3.39 (dd, J = 11.3, 10.6 Hz, 1 H), 3.74
(d, J = 13.4 Hz, 2 H), 7.13–7.27 (m, 10 H) ppm. 13C NMR (CDCl3,
75 MHz): δ = 7.6, 51.9, 53.2, 61.7, 126.2, 127.5, 128.0, 138.2 ppm.
HRMS (EI+) calcd. for C17H21NO [M]+ 255.1623; found 255.1604.
(–)-tert-Butyl [(2S)-1-Hydroxypropan-2-yl]carbamate (8b): This
compound was prepared as described in General Procedure 4/B
plus General Procedure 5: ent-4b (98 % ee) was used, yield 51.8 mg
(0.30 mmol), 80 %, yellowish oil, 94 % ee (determined after conver-
sion into the p-nitrobenzoate ester), [α]D20 (96 % ee) = +3.6 [c = 1.0, (–)-(2R)-2-[Bis(phenylmethyl)amino]octan-1-ol (9c): This com-
CHCl3, (R)], ref.[27] [α]D20 = +8.6 [c = 0.8, CHCl3, (R)]. HPLC (Chiral- pound was prepared as described in General Procedure 4/B plus
pak OD-H, n-hexane/2-propanol 95:5, flow 1.0 mL min–1, λ =
General Procedure 6: 5c (96 % ee) was used, yield 123 mg
254 nm), tR[(R)-p-nitrobenzoate ester 8b] = 14.6 min, tR[(S)-p-nitro- (0.38 mmol), 74 %, colorless oil, 96 % ee. [α]D20 (96 % ee) = –79.1 [c =
1
benzoate ester 8b] = 18.0 min. H NMR (CDCl3, 500 MHz): δ = 1.12
0.47, CHCl3, (R)]. The analytical data were in agreement with the
(d, J = 17.3 Hz, 3 H), 1.42 (s, 9 H), 3.15 (br. s, 1 H), 3.46–3.49 (m, 1 literature.[28]
H), 3.58–3.60 (m, 1 H), 3.72 (br. s, 1 H), 4.80 (br. s, 1 H) ppm. 13C
(+)-(2S)-2-[Bis(phenylmethyl)amino]-3-(trityloxy)propan-1-ol
NMR (CDCl3, 125 MHz): δ = 17.4, 28.5, 48.5, 66.9, 79.6, 156.4 ppm.
HRMS (EI+) calcd. for C7H14O3N [M – CH3]+ 160.0974; found
160.0981.
(9d): This compound was prepared as described in General Proce-
dure 4/B plus General Procedure 6: 5d (91 % ee) was used, yield
109 mg (0.21 mmol), 85 %, colorless oil, 87 % ee. [α]D20 (87 % ee) =
+65.5 [c = 0.4, CHCl3 (S)], ref.[29] [α]D20 = +58.4 [c = 1.0, CHCl3 (S)].
HPLC (Chiralcel OD-H, n-hexane/2-propanol 95:5, flow 0.7 mL min–1,
(+)-tert-Butyl [(2R)-1-Hydroxyoctan-2-yl]carbamate (8c): This
compound was prepared as described in General Procedure 4/B
plus General Procedure 5: 4c (98 % ee) was used, yield 135 mg
(0.55 mmol), 94 %, colorless oil, 94 % ee (determined after conver-
1
λ = 200 nm), tR[(–)-(R)-9d] = 10.2 min, tR[(+)-(S)-9d] = 14.2 min. H
NMR (CDCl3, 500 MHz): δ = 2.83 (br. s, 1 H), 3.11 (br. s, 2 H), 3.35
sion into the p-nitrobenzoate ester). [α]D20 (94 % ee) = +16.4 [c = (m, 4 H), 3.48 (br. s, 1 H), 3.68 (d, J = 12.5 Hz, 2 H), 7.13–7.26 (m, 19
1.00, CHCl3, (R)]. HPLC (Chiralpak AD-H, n-hexane/2-propanol 97:3,
flow 1.0 mL min–1, λ = 254 nm), tR[(R)-p-nitrobenzoate ester 8c] =
30.4 min, tR[(S)-p-nitrobenzoate ester 8c] = 37.0 min. 1H NMR (CDCl3,
500 MHz): δ = 0.86 (t, J = 6.2 Hz, 3 H), 1.26–1.33 (m, 10 H), 1.43 (s,
9 H), 2.85 (br. s, 1 H), 3.50–3.52 (m, 1 H), 3.59–3.3.65 (m, 2 H), 4.67
(br. s, 1 H) ppm. 13C NMR (CDCl3, 125 MHz): δ = 14.1, 22.7, 26.1,
28.5, 29.3, 31.6, 31.8, 52.9, 66.0, 79.6, 156.7 ppm. HRMS (EI+) calcd.
for C13H27NNaO3 [M + Na]+ 268.1893; found 268.1881.
H), 7.37 (m, 6 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 54.0, 58.9, 59.8,
60.3, 87.3, 127.2, 128.0, 128.5, 128.7, 129.0, 139.5, 143.8 ppm. HRMS
(EI+) calcd. for C36H36NO2 [M + H]+ 514.2743; found 514.2740.
(+)-tert-Butyl [(1R,2R)-2-Hydroxy-1-(2-phenylethyl)hexyl]carb-
amate (10a) and (+)-tert-Butyl [(1R,2S)-2-Hydroxy-1-(2-phenyl-
ethyl)hexyl]carbamate (10b): Under argon, n-BuMgCl (2.0
M in
THF, 295 μL, 0.59 mmol) was added to a cooled (0 °C) solution of
7g (51.6 mg, 0.20 mmol, obtained by General Procedure 4/B,
98 % ee) in dry THF (2 mL). After addition the mixture was allowed
to warm to room temperature and stirred overnight (15 h). Then
water (5 mL) and Et2O (5 mL) were added, and the aqueous layer
was separated and extracted with Et2O (3 × 5 mL). The combined
(–)-tert-Butyl
[(2S)-1-Hydroxy-3-(trityloxy)propan-2-yl]carb-
amate (8d): This compound was prepared as described in General
Procedure 4/B plus General Procedure 5: 4d (99 % ee) was used,
yield 106 mg (0.24 mmol), 98 %, colorless oil, 95 % ee.
[α]D20 (95 % ee) = –2.3 [c = 1.00, CHCl3, (S)]. HPLC (Chiralpak OD-H, organic layers were dried with Na2SO4 and filtered through a pad
n-hexane/2-propanol 95:5, flow 1.0 mL min–1, λ = 215 nm), tR[(+)- of Celite®, the solvent was removed in vacuo, and the ratio of dia-
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Full Paper
stereoisomers was determined by analytical HPLC [silica gel, n-hex-
ane/2-propanol (99:1), flow 0.8 mL min–1] of the crude product
(10a/10b = 85:15). The diastereoisomers were separated by prepar-
ative HPLC [petroleum ether/ethyl acetate (5:1); Rf(10a) = 0.21,
Rf(10b) = 0.18, Ce(SO4)2] to give 10a (38.5 mg, 0.12 mmol, 60 %,
98 % ee) as a colorless oil and 10b (8.1 mg, 25.2 μmol, 13 %,
98 % ee) as a colorless solid (m.p. 118–122 °C).
ethyl acetate (1:1); Rf(11-syn) = 0.48, Rf(diol) = 0.10, UV]. Na2S2O4
(35 mg) was added, the mixture was stirred for 30 min and then
filtered through a pad of Celite®, and the solvent was removed in
vacuo. The crude product was dissolved in Et2O/H2O (2:1, 3 mL).
NaIO4 (43.0 mg, 0.20 mmol) was added, and the mixture was vigor-
ously stirred for 1 h at room temperature [TLC monitoring: petro-
leum ether/ethyl acetate (1:1); Rf(aldehyde) = 0.35, KMnO4]. Water
(5 mL) and ethyl acetate (5 mL) were added, and the aqueous layer
was separated and extracted with ethyl acetate (3 × 5 mL). The
combined organic layers were dried with Na2SO4, filtered, and con-
centrated in vacuo. Then, the yellowish solid was dissolved in
CH2Cl2 (0.5 mL)/trifluoroacetic acid (500 μL, 6.50 mmol), and the
mixture was stirred for 45 min at room temperature. The solvent
was removed in vacuo, and the residue was dissolved in MeOH
(1.5 mL), before addition of a mixture of Pd(OH)2/C (5.8 mg, 20 wt.-
%) and Rh/C (1.5 mg, 5 wt.-%). The black suspension was placed in
an autoclave and stirred for 15 h under H2 (10 bar). The mixture
Compound 10a: [α]D20 (90 % ee) = +8.7 [c = 1.02, CHCl3, (1R,2R)].
HPLC (Chiralpak IB, n-hexane/2-propanol 95:5, flow 0.8 mL min–1
,
λ = 210 nm), tR[(+)-(1R,2R)-10a] = 8.2 min, tR[(–)-(1S,2S)-10a] =
14.3 min. 1H NMR (CDCl3, 300 MHz): δ = 0.89 (t, J = 7.0 Hz, 3 H),
1.22–1.39 (m, 4 H), 1.45 (s, 9 H), 1.86 (dd, J = 15.2, 7.8 Hz, 2 H), 2.03
(br. s, 1 H), 2.57–2.80 (m, 2 H), 3.42–3.65 (m, 2 H), 4.76 (d, J = 9.1 Hz,
1 H), 7.14–7.32 (m, 5 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 14.1,
22.8, 28.0, 28.5, 32.8, 34.2, 34.8, 54.3, 73.9, 79.4, 126.0, 128.5, 142.1,
156.6 ppm. HRMS (ESI+) calcd. for C19H32NO3 [M + H]+ 322.2382;
found 322.2377.
was filtered through a pad of Celite® (ethyl acetate), and NaOH (1 M,
Compound 10b: [α]D20 (93 % ee) = +16.3 [c = 1.00, CHCl3, (1R,2S)].
5 mL) was added to the filtrate. The aqueous layer was separated
and extracted with ethyl acetate (3 × 5 mL). The combined organic
layers were dried with Na2SO4, filtered, and concentrated in vacuo.
The crude product was subjected to flash chromatography on silica
gel [petroleum ether/triethylamine/methanol (80:15:5); Rf(12) =
0.15, UV] to give 12 (9.9 mg, 55.9 mmol, 56 %) as colorless needles
(m.p. 86–88 °C, ref.[13] 90–93 °C). [α]D20 (97 % ee according to the
HPLC (Chiralpak IB, n-hexane/2-propanol 95:5, flow 0.8 mL min–1
,
λ = 210 nm), tR[(+)-(1R,2S)-10b] = 7.0 min, tR[(–)-(1S,2R)-10b] =
10.0 min. 1H NMR (CDCl3, 300 MHz): δ = 0.88 (t, J = 7.0 Hz, 3 H),
1.20–1.44 (m, 4 H), 1.46 (s, 9 H), 1.56–1.74 (m, 1 H), 1.75–1.90 (m, 1
H), 2.29 (br. s, 1 H), 2.55–2.69 (m, 1 H), 2.70–2.84 (m, 1 H), 3.50–3.75
(m, 2 H), 4.73 (d, J = 8.0 Hz, 1 H), 7.14–7.34 (m, 5 H) ppm. 13C NMR
(CDCl3, 75 MHz): δ = 14.1, 22.8, 28.3, 28.6, 31.3, 32.8, 33.1, 55.2, 74.9,
79.7, 126.1, 128.5, 128.6, 141.9, 156.6 ppm. HRMS (ESI+) calcd. for
starting material) = +50.1 [c = 0.42, CHCl3, (2S,3S)], ref.[13] [α]D23
=
+66.4 [c = 0.62, CHCl3, (2S,3S)]. The analytical data were in agree-
ment with the literature.
C
19H32NO3 [M + H]+ 322.2382; found 322.2378.
(+)-tert-Butyl [(1S,2S)-2-Hydroxy-1-phenylhex-5-en-1-yl]-carb-
amate (11): Under argon, but-3-enylmagnesium bromide (1.0 in
M
Acknowledgments
Et2O, 600 μL, 0.60 mmol) was added to a solution of 7a (47.1 mg,
0.20 mmol, obtained by General Procedure 4/B) in dry Et2O (1.4 mL),
and the mixture was stirred at room temperature overnight (15 h).
Then water (3 mL), brine (3 mL), and Et2O (5 mL) were added, and
the aqueous layer was separated and extracted with Et2O (3 ×
5 mL). The combined organic layers were dried with Na2SO4 and
filtered through a pad of Celite®, the solvent was removed in vacuo,
and the ratio of diastereoisomers was determined by analytical
HPLC [silica gel, n-hexane/2-propanol (99:1), flow 0.8 mL min–1] of
the crude product (11-syn/11-anti = 96:4). The crude product was
subjected to flash chromatography on silica gel [petroleum ether/
ethyl acetate (5:1); Rf(11-syn) = 0.16, Rf(11-anti) = 0.09, KMnO4] to
give 11-syn (35.0 mg, 0.12 mmol, 60 %, 97 % ee) as a colorless oil
and 11-anti (1.1 mg, 3.8 μmol, 2 %) as a colorless solid (m.p. 118–
122 °C, ref.[30] 100–102 °C).
This work was supported by the Deutsche Forschungsgemein-
schaft (DFG) (SFB 623) and the Dr. Rainer Wild-Stiftung. The
authors are grateful to Prof. M. T. Reetz, Mülheim and Marburg,
for sharing experience on the title reaction. Dr. M. Jäkel is
thanked for samples of the catalysts and Prof. K. Ditrich (BASF
SE) for enantiomerically pure 1-arylethylamines.
Keywords: Synthetic methods · Asymmetric synthesis ·
Homogeneous catalysis · Iridium · Allylation · Amination ·
Ozonolysis · Amino alcohols
[1] a) S. C. Bergmeier, Tetrahedron 2000, 56, 2561–2576, and references cited
therein; b) D. H. Rich, J. Med. Chem. 1985, 28, 263–273; c) Chloram-
phenicol: Merck Index, 10th ed., Merck and Co., Rahway, NJ (USA) 1983,
p. 298.
[2] W. C. Still, J. H. McDonald, Tetrahedron Lett. 1980, 21, 1031–1034.
[3] Review: M. T. Reetz, Chem. Rev. 1999, 99, 1121–1162. For selected exam-
ples see: a) K. Rölfing, PhD Dissertation, Ruhr-Universität Bochum, Ger-
many, 1995; b) M. T. Reetz, K. Rölfing, N. Griebenow, Tetrahedron Lett.
1994, 35, 1969–1972; c) M. T. Reetz, M. W. Drewes, A. Schmitz, Angew.
Chem. Int. Ed. Engl. 1987, 26, 1141–1143; Angew. Chem. 1987, 99, 1186–
1188.
Compound 11-syn: [α]D20 (95 % ee) = +6.6 [c = 1.02, CHCl3, (1S,2S)].
HPLC (Chiralcel OD-H, n-hexane/2-propanol 97:3, flow 0.8 mL min–1,
λ = 210 nm), tR[(+)-(1S,2S)-11] = 11.2 min, tR[(–)-(1R,2R)-11] =
1
12.9 min. H NMR (CDCl3, 300 MHz): δ = 1.42 (s, 9 H), 1.54–1.73 (m,
2 H), 1.94 (br. s, 1 H), 2.12–2.31 (m, 2 H), 3.84 (br. s, 1 H), 4.66 (br. s,
1 H), 4.96–5.06 (m, 2 H), 5.37 (d, J = 8.5 Hz, 1 H), 5.81 (tdd, J = 16.9,
10.2, 6.7 Hz, 1 H), 7.25–7.37 (m, 5 H) ppm. 13C NMR (CDCl3, 75 MHz):
δ = 28.5, 30.2, 33.1, 58.7, 74.8, 79.9, 115.3, 126.6, 127.6, 128.9, 138.2,
141.0, 156.2 ppm. HRMS (ESI+) calcd. for C17H26NO3 [M + H]+
292.1913; found 292.1909.
[4] O. V. Singh, H. Han, Org. Lett. 2007, 9, 2801–2804.
[5] a) Q.-L. Xu, L.-X. Dai, S.-L. You, Adv. Synth. Catal. 2012, 354, 2275–2282;
b) S. Guduguntla, M. Fananas-Mastral, B. L. Feringa, J. Org. Chem. 2013,
78, 8274–8280.
[6] a) For previous investigations with nucleophiles HNBoc(COR), see: R. Wei-
hofen, O. Tverskoy, G. Helmchen, Angew. Chem. Int. Ed. 2006, 45, 5546–
5549; Angew. Chem. 2006, 118, 5673–5676; b) S. Spiess, C. Berthold, R.
Weihofen, G. Helmchen, Org. Biomol. Chem. 2007, 5, 2357–2360; c) O. V.
Singh, H. Han, Tetrahedron Lett. 2007, 48, 7094–7098; d) C. Gnamm, G.
Franck, N. Miller, T. Stork, K. Brödner, G. Helmchen, Synthesis 2008, 3331–
3350.
Compound 11-anti: [α]D20 (95 % ee) = +10.0 [c = 0.35, CHCl3, (1S,2R)].
The analytical data were in agreement with the literature.[30]
(+)-(2S,3S)-2-Phenylpiperidin-3-ol
(12):
A
solution
of
K2OsO4·2 H2O (0.7 mg, 1.9 μmol) and NMO (50 wt.-% in H2O, 46 μL,
0.22 mmol) in water (160 μL) was added dropwise to a solution of
11-syn (29.3 mg, 0.10 mmol) in acetone (1.4 mL). Complete conver-
sion was reached after 4 h at room temperature [petroleum ether/
Eur. J. Org. Chem. 2016, 493–501
www.eurjoc.org
500
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
[7] a) D. Polet, A. Alexakis, Org. Lett. 2005, 7, 1621–1624; b) D. Polet, A.
Alexakis, K. Tissot-Croset, C. Corminboeuf, K. Ditrich, Chem. Eur. J. 2006,
12, 3596–3609.
[8] Review: J. F. Teichert, B. L. Feringa, Angew. Chem. Int. Ed. 2010, 49, 2486–
2528; Angew. Chem. 2010, 122, 2538–2582.
[17]
T. Moriwake, S. Hamano, S. Saito, S. Torii, S. Kashino, J. Org. Chem. 1989,
54, 4114–4120.
A. Farwick, G. Helmchen, Org. Lett. 2010, 12, 1108–1111.
M. Alcón, M. Canas, M. Poch, A. Moyano, M. A. Pericàs, A. Riera, Tetrahe-
dron Lett. 1994, 35, 1589–1592.
[18]
[19]
[9] For preparation see a) S. Spiess, J. A. Raskatov, C. Gnamm, K. Brödner, G.
Helmchen, Chem. Eur. J. 2009, 15, 11087–11090; b) J. A. Raskatov, S.
Spiess, C. Gnamm, K. Brödner, F. Rominger, G. Helmchen, Chem. Eur. J.
2010, 16, 6601–6615; c) S. T. Madrahimov, D. Markovic, J. F. Hartwig, J.
Am. Chem. Soc. 2009, 131, 7228–7229; d) M. Gärtner, S. Mader, K. Seeha-
fer, G. Helmchen, J. Am. Chem. Soc. 2011, 132, 2072–2075.
[10] For direct allylic amination with carbamates, see: a) D. J. Weix, D. Mark-
ović, M. Ueda, J. F. Hartwig, Org. Lett. 2009, 11, 2944–2947; b) S.-C.
Zheng, M. Zhang, X.-M. Zhao, Chem. Eur. J. 2014, 20, 7216–7221.
[11] To the best of our knowledge, only one example of an Ir-catalyzed allylic
substitution has been reported so far, see: H. Miyabe, A. Matsumura, K.
Moriyama, Y. Takemoto, Org. Lett. 2004, 6, 4631–4634.
[20]
J. M. Concellón, P. L. Bernad, J. A. Pérez-Andrés, J. Org. Chem. 1997, 62,
8902–8906.
[21]
[22]
[23]
[24]
T. Nishikata, B. H. Lipshutz, Org. Lett. 2009, 11, 2377–2379.
C. C. Malakar, G. Helmchen, Chem. Eur. J. 2015, 21, 7127–7134.
H. Bao, X. Qi, U. K. Tambar, J. Am. Chem. Soc. 2011, 133, 1206–1208.
J. M. Concellón, E. Riego, H. Rodríguez-Solla, A. M. Plutín, J. Org. Chem.
2001, 66, 8661–8665.
[25] a) A. E. Wróblewski, D. G. Piotrowska, Tetrahedron: Asymmetry 2002, 13,
2509–2512; b) E. P. Johnson, M. P. Hubieki, A. P. Combs, C. A. Teleha,
Synthesis 2011, 24, 4023–4026.
[26] R. B. Lettan II, K. A. Scheidt, Org. Lett. 2005, 7, 3227–3230.
[27] T. S. Cooper, A. S. Larigo, P. Laurent, C. J. Moody, A. K. Takle, Org. Biomol.
Chem. 2005, 3, 1252–1262.
[28] R. Sakae, K. Hirano, M. Miura, J. Am. Chem. Soc. 2015, 137, 6460–6463.
[29] G. M. Nicholas, T. F. Molinski, J. Am. Chem. Soc. 2000, 122, 4011–4019.
[30] M. K. Ghorai, A. Kumar, D. P. Tiwari, J. Org. Chem. 2010, 75, 137–151.
[12] For a review on substance P and neurokinin receptors see: S. Harrison,
P. Geppetti, Int. J. Biochem. Cell Biol. 2001, 33, 555–576.
[13] For recent syntheses of (+)-L-733060, see: S. V. Pansare, E. K. Paul, Org.
Biomol. Chem. 2012, 10, 2119–2125, and references cited therein.
[14] M. Gärtner, R. Weihofen, G. Helmchen, Chem. Eur. J. 2011, 17, 7605–7622.
[15] R. D. Connell, T. Rein, B. Åkermark, P. Helquist, J. Org. Chem. 1988, 53,
3845–3849.
[16] L. M. Stanley, C. Bai, M. Ueda, J. F. Hartwig, J. Am. Chem. Soc. 2010, 132,
8918–8920.
Received: October 16, 2015
Published Online: December 10, 2015
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© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim