Synthesis of an enantioenriched α-carbamoyloxy-crotylboronate and its homoaldol reaction with aldehydes

Article abstract of DOI:10.1055/s-2004-834921

Enantioenriched α-carbamoyloxy-crotylboronate 5 was prepared via the corresponding γ-stannylated carbamate. This boronate was then subjected to homoaldol reactions with aromatic and aliphatic aldehydes furnishing (Z)-anti-homoallylic alcohols in high diastereoselectivity and with complete chirality transfer.

Full text of DOI:10.1055/s-2004-834921

PAPER
217
Synthesis of an Enantioenriched a-Carbamoyloxy-crotylboronate and Its
Homoaldol Reaction with Aldehydes
S
ynthesis of an
d
Enantioenric
i
hed
a
-
C
t
arbam
h
oyloxy-crotylbor
oB
Westfälische Wilhelms-Universität Münster, Organisch-Chemisches Institut, Corrensstr. 40, 48149 Münster, Germany
Fax +49(251)8336531; E-mail: dhoppe@uni-muenster.de
Received 10 August 2004; revised 17 September 2004
Abstract: Enantioenriched a-carbamoyloxy-crotylboronate 5 was
O
B
O
prepared via the corresponding g-stannylated carbamate. This bor-
CH3OLi, THF
B
onate was then subjected to homoaldol reactions with aromatic and
aliphatic aldehydes furnishing (Z)-anti-homoallylic alcohols in high
diastereoselectivity and with complete chirality transfer.
O
O
1
2
OCH3
Cl
Scheme 1
Key words: boron, aldehydes, chirality, organometallic reagents,
asymmetric synthesis
pounds 15 (Scheme 1) but with some loss of enantioen-
richment due to partial racemization of the starting
material 1, induced by the co-product lithium chloride.6
Allylboronates are valuable building blocks in organic
synthesis as they represent allylic carbanion equivalents.
They have been mainly explored by R. W. Hoffmann, W.
R. Roush and D. S. Matteson.1 Simple allylic boronates,
however, are very moisture sensitive,2 and some of them
tend to decompose at higher temperatures.3 Therefore
they are often prepared in situ.
For the same reason the synthesis of highly enantioen-
riched a-chloroallylboronates via a chain extension of pi-
nanediol vinylboronate6,7 with dichloromethyllithium is
difficult. To obtain 1 in high enantiomeric purity, Hoff-
mann et al. had to use an indirect approach starting from
enantiomerically pure 1-butyn-3-ol.8
These features change drastically when a carbamoyloxy
group is installed at a-position to the boronate functional-
ity. a-Carbamoyloxy-allylboronates can be purified by
chromatography and they are considerably stable against
oxidation and hydrolysis.4 They can be stored and used in
exactly scaleable, small amounts for the synthesis of a se-
ries of similar structures, as it is required in combinatorial
synthesis.
a-Ethoxyalkylboronic esters can be obtained by a zinc
chloride assisted reaction of (diethoxymethyl)lithium
with the corresponding alkylboronic esters, as reported re-
cently.9 However, it is not clear whether this method is
also applicable for the synthesis of allylic derivatives.
Herein we report the synthesis of a-carbamoyloxy-crotyl-
boronate 5 in high enantiomeric excess. Based on a n-bu-
tyllithium/(–)-sparteine mediated deprotonation of crotyl
carbamate 3, the lithiated intermediates 4 and epi-4 were
prepared (Scheme 2). In solution, these lithiated species
are configurationally labile and in a dynamic equilibrium.
The (S)-configured lithium species 4 is formed exclusive-
ly via crystallization-induced asymmetric transforma-
tion.10 The solvent system pentane–cyclohexane is crucial
for the crystallization.11
The unusual stability of a-carbamoyloxy boronates can be
explained by intramolecular complexation of the boron
atom to the vicinal carbamoyloxy moiety, which reduces
the electron deficiency of the boron atom (Figure 1).
Enantioenriched allylic boronic esters containing an oxy-
gen substituent are often difficult to obtain. It is possible
to synthesize enantioenriched a-alkoxy-crotylboronates 2
from the corresponding enantioenriched a-chloro com-
Direct reaction of the crystalline lithium intermediate 4
(Scheme 2, Pathway A) with trialkyl borates yielded the
boronate 5 in low enantiomeric excess. Triisopropyl bo-
rate (Table 1, entry 1) reacted only upon warming to –50
°C resulting in a nearly racemic product. This was attrib-
uted to the fact that triisopropyl borate is a solid at –78 °C
(mp = –59 °C). Warming up the reaction mixture im-
proves the reactivity of the boron electrophile on one
hand, but on the other hand the crystalline lithium species
4 also dissolves at this temperature, which causes epimer-
ization.
O
B
N
R
O
O
O
OCb
R = allyl, alkyl
Figure 1
We also reacted the crystalline lithium species 4 with tri-
ethyl boronate (mp = –84.5 °C). In this case the boronate
5 was formed at –78 °C, but still in low enantiomeric ex-
cess (Table 1, entry 2). The reaction was monitored by
SYNTHESIS 2005, No. 2, pp 0217–0222
Advanced online publication: 24.11.2004
DOI: 10.1055/s-2004-834921; Art ID: T09504SS
x
x
.
x
x
.2
0
0
4
© Georg Thieme Verlag Stuttgart · New York

218
E. Beckmann, D. Hoppe
PAPER
ArO2S
Ph
Ar
N
Br
ArO2S
CH2Cl2, 0 °C
B
N
N
SO2Ar
N
n-BuLi,
8
N
B
Bu3Sn
(−)-sparteine
Ph
OCb
Li
+
epi-4
R
ArO2S
N
R
7
pentane/
cyclohexane
–78 °C
3
O
O
4
Ph
9
crystallization
NiPr2
Scheme 3
1) Ti(OiPr)4
2) Bu3SnCl
pathway
A
boron
electrophile
Thus, stannane 6 was reacted with in situ generated 2-
pathway
chloro-1,3-bis(toluenesulfonyl)-1,3,2-diazaborolidine
B
13
(10) in CH2Cl2 to furnish a-carbamoyloxy-diazaboroli-
O
dine 11, which could not be isolated. Hydrolysis and es-
terification with pinacol finally furnished the desired (S)-
crotylboronate 5 in 85% ee (Scheme 4).
B
Bu3Sn
OCb
O
6
80%, 88% ee
OCb
5
Scheme 2
Ts
N
B
Cl
TLC and was found to proceed very slowly. This fact sug-
gests that the boron electrophile does not react with the
crystalline lithium species but with its solution so that the
precipitate slowly dissolves again. As the lithium species
4 is configurationally labile in solution, a considerable
amount of its epimer epi-4 is formed, which also reacts
with triethyl boronate resulting in a low enantioenrich-
ment of the product 5.
, CH2Cl2, 0 °C
N
10
Ts
Bu3Sn
OCb
anti-SE′
6
88% ee
Ts
1) HCl/H2O
2) pinacol, p-TsOH·H2O
MgSO4, CH2Cl2
N
O
B
B
More reactive boron reagents such as 2-chloro-1,3-
bis(toluenesulfonyl)-1,3,2-diazaborolidine (10) or 2-chlo-
ro-4,4,5,5-tetramethyl-1,3,2-dioxaborolane12 are not solu-
ble in the solvent mixture pentane–cyclohexane, which is
required for the crystallization of lithium species 4.11
N
O
Ts
OCb
OCb
80%, 85% ee
11
5
Scheme 4
Table 1 Reaction of 4 with Boron Electrophiles
This crotylboronate was subjected to homoaldol reactions
to form a variety of homoaldol adducts 13 (Scheme 5,
Table 2). The anti-homoaldol products were formed ex-
clusively in a Z:E-ratio of 94:6 and with an enantiomeric
excess of 84–85% (Table 2). In the six-membered Zim-
Entry
Boron
Reaction
Yield
% eea
<5
electrophile
temperature
5 (%)
1
2
B(Oi-Pr)3
–78 °C →
81
–50 °C
B(OEt)3
–78 °C
78
20
O
a Enantiomeric excesses were determined by 1H NMR shift experi-
ment with 50 mol% Pr(hfc)3.
B
O
toluene
O
O
+
RCHO
5
Allyltin reagents provide an alternative way to synthesize
allylboron compounds. Corey et al. found a possibility to
prepare 2-allyl-1,3,2-diazaborolidines 9 by reaction of the
corresponding allyltributyltin compounds 7 with 2-bro-
mo-1,3,2-diazaborolidines 8 (Scheme 3).13
60 °C, 48–72 h
N
85% ee
The (R)-configured g-stannylated carbamate 6 can be eas-
ily synthesized from the lithiated species 4.11 For this pur-
pose the lithiated species was transmetallated to titanium
with tetraisopropyl titanate and subsequently reacted with
tributyltin chloride (Scheme 2, Pathway B). This route ex-
clusively led to the g-stannylated product 6,11 which is re-
quired as the following conversion to the boron species 11
(Scheme 4) proceeds in an anti-SE′-fashion.
O
B
H
OH
O
R
H3C
O
R
CH3 OCb
OCb
13
12
Scheme 5
Synthesis 2005, No. 2, 217–222 © Thieme Stuttgart · New York

PAPER
Synthesis of an Enantioenriched a-Carbamoyloxy-crotylboronate
219
Table 2 Homoaldol Reaction of Crotylboronate 5
Entry
1
Aldehyde
Product
Yield (%)
87
Z:Ec
95:5
% eed
Benzaldehydea
84
OH
CH3 OCb
13a
2
a-Naphthalenecarbaldehydea
67
>95:5
85
OH
CH3 OCb
13b
OH
3
4
o-Toluenecarbaldehydea
p-Bromobenzaldehydea
69
74
>95:5
>95:5
85
84
CH3 OCb
13c
OH
CH3 OCb
Br
13d
5
Anisaldehydea
66
>95:5
85
OH
CH3 OCb
H3CO
13e
6
7
Furfurala
60
71
>95:5
94:6
85
84
OH
O
CH3 OCb
13f
2-Methyl-propanalb
OH
CH3 OCb
13g
8
9
Propanalb
58
69
>95:5
>95:5
85
85
3-Methyl-butanalb
OH
CH3 OCb
13i
a Reaction time: 48 h.
b Reaction time: 72 h.
c E/Z-ratios were determined by 1H NMR of the crude product.
d Enantiomeric excesses were determined by chiral HPLC (column: chiragrom 1, 60 × 2 mm; solvent: i-PrOH–hexane = 1:50).
merman–Traxler transition state14 (12) the carbamoyloxy Since the complexation of the boron by the carbamoyloxy
moiety adopts a pseudoaxial position as the allylboron group boronate 5 is less reactive towards aldehydes than
compound prefers an endo-conformation.15
its titanium analogues, the homoaldol reaction was per-
formed in toluene, which allowed heating the mixture to
60 °C for a longer period of time (48–72 h). The non-acti-
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220
E. Beckmann, D. Hoppe
PAPER
1
83%) as a colorless viscous liquid in 85% ee [determined by H
vated aliphatic aldehydes (Table 2, entries 7–9) need
longer reaction times than the aromatic and heteroaromat-
ic aldehydes (Table 2, entries 1–6).
NMR shift experiment with 50 mol% Pr(hfc)3]; Rf 0.26 (Et2O–pen-
tane, 1:1); [a]D20 –27.6 (c = 0.91, CHCl3).
IR (film): 2971, 2933 (m, CH, CH3); 1632 (s, C=O, C=C); 1371 (s,
In summary, we have prepared a storable butenyl homo-
enolate equivalent in good yield and high enantiomeric
excess. This precursor can be subjected to homoaldol re-
actions with a wide variety of aldehydes in a simple pro-
cess to obtain homoallylic alcohols in good yields and
high diastereoselectivities. All reactions proceed under
complete chirality transfer with high enantiomeric excess-
es.
C-O), 1159, 1117 [m, (E)-C=C)] cm–1.
1H NMR (300 MHz, CDCl3): d = 1.11, 1.14 [s, 12 H, CH3(pinacol)],
1.14–1.25 [m, 12 H, CH3(Cb)], 1.68 (dd, 3J = 5.9 Hz, 4J = 1.3 Hz, 3
H, CH3), 3.86, 3.89 [sep, J = 6.8 Hz, 2 H, CH(Cb)], 4.19 [d, 3J =
3
3
3
7.8 Hz, 1 H, CH(B)], 5.55 [dq, J = 5.9 Hz, J = 15.5 Hz, 1 H,
(CH3)CH], 5.62 (ddq, 3J = 7.8 Hz, 3J = 15.5 Hz, 4J = 1.3 Hz, 1 H,
CH).
13C NMR (100 MHz, CDCl3): d = 15.2, 17.8 [CH3(pinacol)], 24.7,
24.8 [CH3(Cb)], 26.9 (CH3), 46.9, 48.1 [CH(Cb)], 79.7 [CH(B)],
126.3 (CH), 129.2 (CH), 130.0 [Cq(pinacol)], 162.1 [C=O(Cb)].
In principle the opposite enantiomers can be synthesized
from lithium species 4 by reacting it directly with trimeth-
yltin chloride.11 This leads to the g-stannylated carbamate
ent-6 together with the corresponding a-product in a 2:1
mixture. The g-product has the opposite configuration
compared to that obtained via the titanation-stannylation
sequence as the transmetallation to titanium proceeds un-
der inversion. By the reaction sequence described above,
the g-stannylcarbamate ent-6 can be converted to the bor-
onate ent-5, which upon reaction with aldehydes forms
the anti-homoaldol products ent-13.
Anal. Calcd for C17H32BNO4 (325.24): C, 62.78; H, 9.92; N, 4.31.
Found: C, 62.89; H, 10.19; N, 4.49.
Preparation of the Homoaldol Products 13; General Procedure
Crotylboronate 5 (163 mg, 0.5 mmol, 1.0 equiv) was dissolved in
anhyd toluene (4 mL) and the aldehyde (1.0 mmol, 2.0 equiv) was
added in toluene (1 mL). The reaction mixture was warmed to 60 °C
for 48 h (aromatic aldehydes) or 72 h (aliphatic aldehydes). After re-
moval of toluene the residue was dissolved in Et2O (5 mL) and tri-
ethanolamine (90 mg, 0.6 mmol, 1.2 equiv) was added. The
precipitate was filtered off, the solution was concentrated, and the
crude product was purified by flash column chromatography (SiO2,
Et2O–pentane) to give the homoaldol products 13.
All reactions were carried out under Ar atmosphere in flame-dried
flasks. Solvents were refluxed over calcium hydride (CH2Cl2) or so-
dium (toluene) and freshly distilled before use. The aldehydes are
commercially available and were distilled before use (except a-
naphthalenecarbaldehyde). Boron trichloride is commercially avail-
able as a 1 M solution in CH2Cl2. 2-Chloro-1,3-bis(toluenesulfo-
1
The E/Z-ratios were determined from the H NMR spectra of the
crude products. The enantiomeric excesses were determined by
chiral HPLC on a column chiragrom 1, 60 × 2 mm (Grom, Herren-
berg, Germany); solvent: i-PrOH–hexane (1:50).
13a11
nyl)-1,3,2-diazaborolidine
was
prepared
from
N,N¢-
bis(toluenesulfonyl)ethylenediamine16 according to literature.13
Yield: 132 mg (0.44 mmol, 67%); colorless oil; E:Z = 95:5; Rf 0.31
(Et2O–pentane, 1:1); [a]D20 +29.1 (c = 1.25, MeOH); 84% ee.
The IR spectra were recorded on a FT-IR spectrometer 5DCX
(Nicolet Instrument Corp., Offenbach am Main). The NMR spectra
were taken on a ARX 300 or AMX 400 spectrometer (Bruker, Ana-
lytische Messtechnik, Karlsruhe). Optical rotations were measured
on a polarimeter 341 (Perkin-Elmer & Co GmbH, Überlingen). The
enantiomeric excesses were determined by NMR shift experiment
or by HPLC using a Waters instrument consisting of: Waters 717
plus Autosampler, Waters 600 Controller, Waters 996 Photodiode
Array Detector, Waters In-Line Degasser, chiral column: chira-
grom 1, 60 × 2 mm (Grom, Herrenberg, Germany).
13b
Yield: 118 mg (0,33 mmol, 67%); colorless oil; E:Z > 95:5; Rf 0.27
(Et2O–pentane, 1:1); [a]D20 –24.3 (c = 0.86, CHCl3); 85% ee.
IR (film): 3462 (m, OH), 2970, 2932, 2872 (s, CH, CH3), 1698,
1653 (s, C=O, C=C), 799, 782, 761 [w, CH(Ar)] cm–1.
1H NMR (400 MHz, CDCl3): d = 0.99 (d, 3J = 6.9 Hz, 3 H, CH3),
1.02–1.24 [m, 12 H, CH3(Cb)], 2.20 (br s, 1 H, OH), 3.33 [ddq, 3J =
6.9 Hz, 3J = 6.4 Hz, 3J = 10.1 Hz, 1 H, CH(CH3)], 3.52, 3.95 [2 × br
s, 2 H, CH(Cb)], 4.83 (dd, 3J = 6.6 Hz, 3J = 10.1 Hz, 1 H, CH), 5.22
[d, 3J = 6.4 Hz, 1 H, CH(OH)], 7.09 (d, 3J = 6.6 Hz, 1 H, CH), 7.46–
8.20 [m, 7 H, CH(Ar)].
13C NMR (75 MHz, CDCl3): d = 15.2 (CH3), 20.5, 20.6 [CH3(Cb)],
37.7 [CH(CH3)], 46.3 [CH(Cb)], 75.5 [CH(OH)], 112.2 (CH),
123.6, 124.4, 125.7, 128.0, 128.9, 130.9, 133.9, 136.6, 138.5
[CH(Ar) + CH(OCb)], 152.6 [C=O(Cb)].
Preparation of 5; Typical Procedure
N,N′-Bis(toluenesulfonyl)ethylenediamine (4.49 g, 11.4 mmol, 2.0
equiv) was suspended in CH2Cl2 (20 mL) and BCl3 (1.0 M in
CH2Cl2, 11.4 mL, 11.4 mmol, 2.0 equiv) was added dropwise at 0
°C. The mixture was allowed to warm to r.t. and was stirred with
formation of HCl until it became a brown solution (1–2 h). The sol-
vent and the HCl were removed into a cool trap at 20 mbar. The res-
idue was dissolved in CH2Cl2 (10 mL) and added dropwise to a
solution of 611 (2.80 g, 5.7 mmol, 1.0 equiv) in CH2Cl2 (5 mL) at 0
°C. The mixture was warmed to r.t. and stirred for additional 12 h.
HCl (2 M, 10 mL) was added and the layers were separated. The
aqueous phase was extracted with Et2O (3 × 10 mL) and the com-
bined organic layers were dried over MgSO4. After removal of the
solvent in vacuum the crude product was dissolved in CH2Cl2 (10
mL) and added to a flask equipped with pinacol (1.35 g, 11.4 mmol,
2.0 equiv), p-toluenesulfonic acid monohydrate (0.05 g) and
MgSO4. This reaction mixture was stirred for 24 h and subsequently
the solid material was filtered off. After removal of the solvent in
vacuum the crude product was purified by flash column chromatog-
raphy (SiO2, EtOAc–cyclohexane) to furnish 5 (1.54 g, 4.7 mmol,
Anal. Calcd for C22H29NO3 (355.21): C, 74.33; H, 8.22; N, 3.94.
Found: C, 74.44; H, 8.18; N, 4.18.
13c
Yield: 110 mg (0.34 mmol, 69%); colorless oil; E:Z > 95:5; Rf 0.31
(Et2O–pentane, 1:1); [a]D20 –46.8 (c = 0.68, CHCl3); 85% ee.
IR (film): 3463 (m, OH), 2968, 2931 (s, CH, CH3), 1700 (s, C=O,
C=C), 761 [m, CH(Ar)] cm–1.
1H NMR (400 MHz, CDCl3): d = 0.91 (d, 3J = 6.7 Hz, 3 H, CH3),
1.21, 1.23 [br s, 12 H, CH3(Cb)], 2.06 (br s, 1 H, OH), 2.35 [s, 3 H,
CH3(Tol)], 3.06 [ddq, 3J = 6.7 Hz, 3J = 7.5 Hz, 3J = 10.0 Hz, 1 H,
CH(CH3)], 3.75, 4.05 [br s, 2 H, CH(Cb)], 4.68 [d, 3J = 7.5 Hz, 1 H,
Synthesis 2005, No. 2, 217–222 © Thieme Stuttgart · New York

PAPER
Synthesis of an Enantioenriched a-Carbamoyloxy-crotylboronate
221
CH(OH)], 4.76 (dd, 3J = 6.5 Hz, 3J = 10.0 Hz, 1 H, CH), 7.08–7.21,
13g10a
7.40 [m, 5 H, CH (Ar) + CH].
Yield: 96 mg (0.36 mmol, 71%); colorless oil; E:Z = 94:6; Rf 0.27
(Et2O–pentane, 1:1); [a]D20 +14.7 (c = 1.45, MeOH); 84% ee.
13C NMR (75 MHz, CDCl3): d = 17.5 (CH3), 19.5 [CH3(Tol)], 19.8,
20.5 [CH3(Cb)], 38.2 [CH(CH3)], 46.3, 47.7 [CH(Cb)], 74.3
[CH(OH)], 112.6 (CH), 126.1, 126.3, 127.2, 130.0, 130.2, 135.2,
136.8, 140.8 [CH (Ar) + C(Ar) + CH(OCb)], 152.7 [C=O(Cb)].
13h
Yield: 75 mg (0.29 mmol, 58%; colorless oil; E:Z > 95:5; Rf 0.25
(Et2O–pentane, 1:1); [a]D20 +6.0 (c = 0.87, CHCl3); 85% ee.
Anal. Calcd for C19H29NO3 (319.44): C, 71.44; H, 9.15; N, 4.38.
Found: C, 71.18; H, 9.23; N, 4.23.
IR (film): 3481 (m, OH), 2969, 2933, 2875 (s, CH, CH3), 1700 (s,
C=O, C=C), 1437, 1370 (w, CH2, CH3) cm–1.
13d
1H NMR (400 MHz, CDCl3): d = 0.89 (t, 3J = 7.4 Hz, 3 H, CH2CH3),
0.97 (d, 3J = 6.9 Hz, 3 H, CH3), 1.19 [br s, 12 H, CH3(Cb)], 1.37 [m,
1 H, CH(CH3)], 1.50 (m, 2 H, CH2CH3), 2.70 [m, 1 H, CH(OH)],
3.30 (br s, 1 H, OH), 3.74, 4.03 [br s, 2 H, CH(Cb)], 4.60 (dd, 3J =
6.5 Hz, 3J = 10.0 Hz, 1 H, CH), 7.04 (d, 3J = 6.5 Hz, 1 H, CH).
13C NMR (100 MHz, CDCl3): d = 10.1 (CH2CH3), 18.1 (CH3), 20.8,
20.9 [CH3(Cb)], 27.5 (CH2CH3), 36.1 [CH(CH3)], 46.1, 46.6
[CH(Cb)], 77.6 [CH(OH)], 112.6 (CH), 136.5 [CH(OCb)], 153.2
[C=O(Cb)].
Yield: 141 mg, (0.37 mmol, 74%); colorless oil; E:Z > 95:5; Rf 0.32
(Et2O–pentane, 1:1); [a]D20 –27.7 (c = 0.70, CHCl3); 84% ee.
IR (film): 3442 (m, OH), 2971, 2932, 2874 (m, CH, CH3), 1700 (s,
C=O, C=C), 761 [w, CH(Ar)] cm–1.
1H NMR (400 MHz, CDCl3): d = 0.88 (d, 3J = 6.9 Hz, 3 H, CH3),
1.24 [br s, 12 H, CH3(Cb)], 2.34 (br s, 1 H, OH), 2.92 [ddq, 3J = 6.9
Hz, 3J = 7.6 Hz, 3J = 9.9 Hz, 1 H, CH(CH3)], 3.75, 4.08 [br s, 2 H,
CH(Cb)], 4.34 [d, 1 H, CH(OH], 4.66 (dd, 3J = 6.5 Hz, 3J = 9.9 Hz,
1 H, CH), 7.14 (d, 3J = 6.5 Hz, 1 H, CH), 7.20, 7.44 [d, 3J = 8.3 Hz,
4 H, CH(Ar)].
Anal. Calcd for C14H27NO3 (257.20): C, 65.33; H, 10.57; N, 5.44.
Found: C, 65.13; H, 10.78; N, 5.16.
13C NMR (75 MHz, CDCl3): d = 17.2 (CH3), 20.5, 21.5 [CH3(Cb)],
38.7 [CH(CH3)], 46.3, 47.8 [CH(Cb)], 77.7 [CH(OH)], 112.2 (CH),
121.4, 128.5, 131.2, 137.1, 141.6 [C(Ar) + CH(Ar) + CH(OCb)],
152.7 [C=O(Cb)].
13i
Yield: 98 mg, (0.35 mmol, 69%); colorless oil; E:Z > 95:5; Rf 0.31
(Et2O–pentane, 1:1); [a]D20 +31.3 (c = 1.15, CHCl3); 85% ee.
IR (film): 3471 (m, OH), 2960, 2932, 2871 (m, CH, CH3), 1699 (s,
C=O, C=C), 1437, 1306 (w, CH2, CH3) cm–1.
Anal. Calcd for C18H26BrNO3 (383.11): C, 56.26; H, 6.82; N, 3.64.
Found: C, 56.25; H, 6.86; N, 3.62.
3
1H NMR (300 MHz, CDCl3): d = 0.84, 0.86 [d, J = 6.5 Hz, 6 H,
3
13e
(CH3)2CH], 0.98 (d, J = 6.9 Hz, 3 H, CH3), 1.19 [br s, 12 H,
Yield: 111 mg (0.33 mmol, 66%); colorless oil; E:Z > 95:5; Rf 0.21
CH3(Cb)], 1.31 [m, 3 H, CH(CH3)2 + CH2], 1.74 [m, 1 H,
CH(CH3)], 2.62 [m, 1 H, CH(OH)], 3.46 (br s, 1 H, OH), 3.76, 4.02
(Et2O–pentane, 1:1); [a]D20 –50.6 (c = 0.79, CHCl3); 85% ee.
3
[br s, 2 H, CH(Cb)], 4.60 (dd, 3J = 6.5 Hz, J = 9.9 Hz, 1 H, CH),
IR (film): 3465 (m, OH), 2979, 2933, 2873 (m, CH, CH3), 1700 (s,
C=O, C=C), 758 [w, CH(Ar)] cm–1.
7.03 (d, 3J = 6.5 Hz, 1 H, CH).
13C NMR (100 MHz, CDCl3): d = 15.2 (CH3), 17.4, 20.4, 21.4, 21.8,
23.7, 24.5 [(CH3)2CH + CH(CH3)2 + CH3(Cb)], 36.7 [CH(CH3)],
44.0 (CH2), 45.7, 46.8 [CH(Cb)], 73.2 [CH(OH)], 112.1 [CH],
136.1 [CH(OCb)], 152.8 [C=O(Cb)].
1H NMR (400 MHz, CDCl3): d = 0.80 (d, 3J = 6.8 Hz, 3 H, CH3),
1.19 [br s, 12 H, CH3(Cb)], 2.08 (br s, 1 H, OH), 2.91 [ddq, 3J = 6.8
Hz, 3J = 8.0 Hz, 3J = 10.0 Hz, 1 H, CH(CH3)], 3.73, 4.05 [br s, 2 H,
CH(Cb)], 3.74 (s, 3 H, OCH3), 4.26 [d, 3J = 8.0 Hz, 1 H, CH(OH)],
4.63 (dd, 3J = 6.6 Hz, 3J = 10.0 Hz, 1 H, CH), 6.81, 7.19 [m, 4 H,
CH(Ar)], 7.11 (d, 3J = 6.6 Hz, 1 H, CH).
Anal. Calcd for C16H31NO3 (285.23): C, 67.33; H, 10.95; N, 4.91.
Found: C, 67.22; H, 11.09; N, 4.68.
13C NMR (100 MHz, CDCl3): d = 17.2 (CH3), 20.5, 21.5 [CH3(Cb)],
38.8 [CH(CH3)], 46.9 [CH(Cb)], 55.2 (OCH3), 78.0 [CH(OH)],
112.5, 112.9, 113.6 [CH + CH(Ar)], 127.9, 134.7, 136.8 [CH(OCb)
+ Cq(Ar)], 152.8 [C=O(Cb)], 159.1 [C(OCH3)].
Acknowledgment
This work was supported by the Deutsche Forschungsgemeinschaft
(SFB 424) and by the Fonds der Chemischen Industrie.
Anal. Calcd for C19H29NO4 (335.21): C, 68.03; H, 8.71; N, 4.18.
Found: C, 67.69, H, 8.76; N, 3.89.
References
13f
Yield: 89 mg (0.30 mmol, 60%); colorless oil; E:Z > 95:5; Rf 0.33
(1) (a) Hoffmann, R. W. Pure Appl. Chem. 1988, 60, 123.
(b) Matteson, D. S. Stereodirected Synthesis with
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(c) Formation of C–C Bonds by Addition of Allyl-Type
Organometallic Compounds to Carbonyl Compounds:
Allylboron Reagents, In Houben-Weyl, Methods of Organic
Chemistry, 4th Ed., E21b; Roush, W. R., Ed.; Thieme:
Stuttgart, 1995, 1410.
(Et2O–pentane, 1:1); [a]D20 –24.2 (c = 0.51, CHCl3); 85% ee.
IR (film): 3470 (s, OH), 2981, 2935, (m, CH, CH3), 1698 (s, C=O,
C=C), 762, 745 [w, CH(Ar)] cm–1.
1H NMR (300 MHz, CDCl3): d = 0.94 (d, 3J = 6.9 Hz, 3 H, CH3),
1.24 [br s, 12 H, CH3(Cb)], 2.20 (br s, 1 H, OH), 3.18 (ddq, 3J = 6.9
Hz, 3J = 7.5 Hz, 3J = 9.8 Hz, 1 H, CH(CH3)], 3.81, 4.03 [br s, 2 H,
CH(Cb)], 4.43 [d, 3J = 7.5 Hz, 1 H, CH(OH)], 4.69 (dd, 3J = 6.5 Hz,
3J = 9.8 Hz, 1 H, CH), 6.21–6.31 [m, 2 H, CH(Ar)], 7.10 (d, 3J = 6.5
Hz, 1 H, CH), 7.33 [m, 1 H, CH(Ar)].
13C NMR (75 MHz, CDCl3): d = 17.1 (CH3), 20.5, 21.5 [CH3(Cb)],
36.2 [CH(CH3)], 46.3 [CH(Cb)], 71.7 [CH(OH)], 107.0, 110.1,
112.2 [2 × CH(Ar) + CH], 136.8 [CH(OCb)], 141.8 [CH(Ar)],
152.7, 155.2 [C=O(Cb) + Cq(Ar)].
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Anal. Calcd for C16H25NO4 (295.37): C, 65.06; H, 8.53; N, 4.74.
Found: C, 64.78; H, 8.66; N, 4.80.
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Synthesis 2005, No. 2, 217–222 © Thieme Stuttgart · New York