Exploiting π shielding interactions of η6 arene chromium (0) complexes: New auxiliaries derived from the biogenic chiral pool

Article abstract of DOI:10.1016/j.jorganchem.2007.09.005

A family of highly selective chiral auxiliaries containing arene chromium (0) complexes has been prepared using biogenic precursors from the chiral pool. The systems, derived from isomannide, prolinol, and xylofuranose were applied to the asymmetric Diels-Alder reaction of derived acrylate esters. Factors influencing stereoselectivity with the auxiliaries have been investigated and delineated including the impact of mixed ligands on the chromium (0) complex. Under optimal conditions, the auxiliaries give >95% e.e. and 98:2 exo:endo ratio in cycloaddition with cyclopentadiene.

Full text of DOI:10.1016/j.jorganchem.2007.09.005

Available online at www.sciencedirect.com
Journal of Organometallic Chemistry 692 (2007) 5459–5473
www.elsevier.com/locate/jorganchem
Exploiting p shielding interactions of g6 arene chromium (0)
complexes: New auxiliaries derived from the biogenic chiral pool
a
a
a
b
a
Jane Li , Longfei Xie , Mustafa Guzel , Steven B. Heaton , Dong Ma ,
a
a,
*
Amy E. Kallmerten , Graham B. Jones
a
Bioorganic and Medicinal Chemistry Laboratories, Department of Chemistry and Chemical Biology, Northeastern University,
Boston, MA 02115, United States
b
Roche Carolina Inc., 6173 East Old Marion Highway, Florence, SC 29502, United States
Received 26 July 2007; received in revised form 4 September 2007; accepted 5 September 2007
Available online 12 September 2007
Abstract
A family of highly selective chiral auxiliaries containing arene chromium (0) complexes has been prepared using biogenic precursors
from the chiral pool. The systems, derived from isomannide, prolinol, and xylofuranose were applied to the asymmetric Diels–Alder
reaction of derived acrylate esters. Factors influencing stereoselectivity with the auxiliaries have been investigated and delineated includ-
ing the impact of mixed ligands on the chromium (0) complex. Under optimal conditions, the auxiliaries give >95% e.e. and 98:2 exo:endo
ratio in cycloaddition with cyclopentadiene.
ꢀ 2007 Elsevier B.V. All rights reserved.
Keywords: Chiral auxiliary; Chiral pool; Chromium (0) arene complexes
1. Introduction
vide access to a range of p basic through p acidic char-
acteristics 2 [4]. The criteria for two entities to engage in
a p stack are satisfied when p clouds interact through
Of the many tactics employed to achieve facial selec-
tivity in asymmetric cycloadditions, p shielding of one
face of the dienophile to attack has become a common
and effective strategy [1]. Examples include both chiral
catalysts and auxiliaries, where the interaction of the chi-
ral controller and dienophile range from passive (steric
shielding) through active (p–p stacking) [1]. We have
been engaged in the design of auxiliaries and catalysts
where pendant aryl substituents interact with a proximal
acrylate to establish a high degree of facial selectivity in
cycloaddition viz. 1. Interactions between the two entities
can be modulated via the corresponding arene chromium
carbonyl complexes [2,3], mixed ligand derivatives pro-
˚
space at a distance of between 3 and 3.5 A, with optimal
˚
overlap at approximately 3.4 A [5]. Based on this crite-
rion we wished to investigate the concept of face selec-
tion in a series of readily available auxiliaries derived
from the chiral pool, and surveyed a variety of inexpen-
sive building blocks. We ultimately decided to pursue
monobenzylated derivatives of xylofuranose 3, isoman-
nide 4 and N-benzyl prolinol 5 based on the fact that:
(a) molecular modeling analysis suggested that derived
acrylate esters could position at p-stacking distance from
the aryl, (b) the ligands themselves are commercially
available and also easily accessible from other feedstocks
[6], (c) the electronics of the benzyl group could be mod-
ulated at ease via arene chromium (0) complexation, and
(d) in the case of 5 both enantiomeric forms are
available.
*
Corresponding author. Tel.: +1 617 373 2822; fax: +1 617 373 8795.
E-mail address: gr.jones@neu.edu (G.B. Jones).
0022-328X/$ - see front matter ꢀ 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2007.09.005

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J. Li et al. / Journal of Organometallic Chemistry 692 (2007) 5459–5473
X
OC
CO
Cr
O
O
HO
Y
X
O
Z
H
HO
H
O
O
O
O
Z
1
2
H
3
H
H
O
O
HO
H
OH
OH
N
H
4
5
H
[STRUCTURES 1-5]
2. Results and discussion
erate yield, allowing us to immediately probe cycloaddition
to cyclopentadiene under the influence of various Lewis
acids. To aid in determination of facial- and diastereoselec-
tivity, samples of authentic adducts 9 (R = H or alkyl) were
also prepared from 10 and 7 [7]. Initial results with alkyl
aluminum species were disappointing, though clear prefer-
ence for endo addition were evident (Table 1, entry 3). With
the exception of zinc, other metal derivatives yielded little
benefit, and additional aluminum species were investigated.
Aluminum chloride proved most effective, giving apprecia-
ble diastereoselectivity and endo preference when multiple
equivalents were employed (Table 1, entry 17).
Our initial goal was to prepare acrylate ester derivatives
of each building block that would allow assessment of ste-
reocontrol imparted the by benzyl chromium (0) com-
plexed appendages in cycloaddition reactions. This would
subsequently allow us to modulate and refine steric and
electronic parameters of the arene group and delineate fac-
tors contributing to selectivity.
2.1. Xylofuranoses
Xylofuranonse 3 is a commercially available acetonide
and the primary and secondary alcohols permit a wide
range of derivatives to be produced. Conversion to the
mono TBS ether (TBSCl, imidazole, DMF) proceeded in
quantitative yield, and the ether 6 could then be trans-
formed to benzyl derivative 7 via selective deprotection
(Scheme 1). Conversion to the acrylate 8 proceeded in mod-
With results in hand, we sought to quantitate the impact
of the corresponding arene chromium (0) derivatives, and
their synthesis was investigated from ligand 7 (Scheme 2).
Direct complexation was effective and in addition to tricar-
bonyl derivative 11, representative mixed ligand phos-
phines and phosphites 12 were produced by photolytic
ligand exchange. The family of derivatives was converted
to analogous acrylates 13 without incident, and the sub-
strates subjected to cycloadditions using the optimized con-
ditions for 8.
O
OH
O
O
1. NaH, PhCH2Br
THF, 66%
O
TBSO
O
HO
O
Though some improvement was evident using the bulky
derivative 13c (Table 1, entry 20), the poor result for 13a
and, particularly 13b were surprising, and may be a conse-
quence of (observed) in situ decomplexation under the con-
ditions of cycloaddition and workup. Molecular modeling
studies (PM3) suggested however that sufficient overlap
between the acrylate and benzyl entities was present to
establish p shielding [2], and since the benzyl group of
13b is approximately isoelectronic with that of 8, points
to an undesirable steric realignment. Possibly compound-
ing these geometric constraints is the need for multiple
equivalents of Lewis acid in the process, a presumed conse-
quence of the abundance of metal chelating sites (ether
groups) in the auxiliary. Accordingly, we elected to investi-
gate an alternate oxygenated auxiliary to determine if mul-
tiple Lewis acid chelation sites were the barrier, and
initiated studies on isomannide derivatives.
2. TBAF, THF, 97%
O
6
7
H
Et3N, CH2Cl2, 74%
10
O
COCl
Et3N, CH Cl2, 87%
2
Cl
O
O
O
O
O
H
Cyclopentadiene,
Lewis acid, -78 oC
O
CO R
2
8
9
R=auxiliary
Scheme 1. Preparation and cycloaddition of benzyloxy xylofuranose
acrylates.

J. Li et al. / Journal of Organometallic Chemistry 692 (2007) 5459–5473
5461
%de
Table 1
Cycloaddition of acrylates 8/13 with cyclopentadiene
Entry
Substrate
Lewis acid (eq.)
% 9
Temp. (Time)
Endo/Exo
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
8
8
Et2AlCl (1.2)
Et2AlCl (1.2)
EtAlCl2 (1.2)
EtAlCl2 (1.2)
EtAlCl2 (1.2)
TiCl4 (1.2)
BF3 Æ OEt2 (1.2)
SnCl4 (1.2)
SnCl4 (1.2)
SnCl4 (1.2)
ZnBr2 (1.2)
AlCl3 (1.2)
AlCl3 (3.0)
AlCl3 (3.5)
AlCl3 (4.5)
AlCl3 (5.0)
AlCl3 (4.0)
AlCl3 (4.0)
AlCl3 (4.0)
AlCl3 (4.0)
–
ꢀ78 ꢁC (16h)
ꢀ25 ꢁC (16 h)
ꢀ78 ꢁC (16 h)
ꢀ25 ꢁC (16 h)
0 ꢁC (4 h)
–
–
0
23
3
0
–
–
–
–
15
25
30
30
<1
<1
–
75:25
99:1
89:11
92:8
–
–
–
–
95:5
90:10
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
8
8
8
8
ꢀ78 ꢁC (16 h)
ꢀ78 ꢁC (16 h)
ꢀ78 ꢁC (16 h)
ꢀ50 ꢁC (16 h)
ꢀ25 ꢁC (2 h)
+25 ꢁC (16 h)
ꢀ78 ꢁC (4 h)
ꢀ78 ꢁC (16 h)
ꢀ78 ꢁC (16 h)
ꢀ78 ꢁC (16 h)
ꢀ78 ꢁC (16 h)
ꢀ78 ꢁC (12 h)
ꢀ78 ꢁC (48 h)
ꢀ78 ꢁC (48 h)
ꢀ78 ꢁC (48 h)
8
8
8
–
8
18
98
90
85
75
71
70
71
64
65
70
40
3
8
8
45
63
60
59
38
77
33
50
83
8
8
8
8
8
13a
13b
13c
All cycloaddition conducted in CH2Cl2. Cycloadducts derived from 13 were decomplexed in Et2O, then analyzed by chiral HPLC (Chiracel OD, 10% 2-
propanol:90% hexanes eluent, 1 mL/min flow rate) using a racemic endo product as both an internal and external control (tR endoS = 18.9 min
endoR = 20.2 min).
O
OH
O
Cr(CO) 6,
n
-Bu2O,
O
THF Δ, 15h
O
7
11
45%
OC Cr
OC
CO
acryloyl chloride
PPh3, P(OPh)3
Et3N, CH2Cl2, 55%
PhH, hν, 5h
70-79%
O
O
O
HO
O
O
O
O
O
acryloyl chloride
O
Et3N, CH2Cl2, 42-50%
O
12
13
a X = CO
b X= P(OPh)3
c X = PPh3
b X= P(OPh)3
c X = PPh3
OC Cr
X
OC Cr
X
CO
CO
Scheme 2. Preparation of g6 arene complexed xylofuranose acrylates.
2.2. Isomannides
late may be influenced by p-stacking interactions, helping
to account for the good levels of asymmetric induction
observed [8]. To investigate this system further, and
attempt modulation of the p–p interactions, ligand 4 was
transformed into a monobenzylated common precursor,
Isomannide is a commercially available building block
which has already seen use as an auxiliary for cycloaddi-
tions. Loupy has reported that cycloaddition to this acry-

5462
J. Li et al. / Journal of Organometallic Chemistry 692 (2007) 5459–5473
H
1. BnCl,
O
O
1. BnCl,
TMSO
LiH, DMF
Ph
LiH, DMF
H
O
O
O
4
2. TMSCl
Ph
2. ClCOCH=CH2
lutidine 40%
imidazole 70%
O
O
H
O
H
15
14
1. Cr(CO)6, nBu2O,
THF 125 oC 16h 95%
2. hν, PhH, X 75-90%
3. K2CO3 MeOH 90-95%
CO
CO
O
Cr
X
Cr
X
H
H
O
O
O
HO
CO
CO
ClCOCH=CH2
lutidine 30-40%
a X=CO
b X=P(OMe)3
c X=P(OEt)3
d X=P(OPh)3
O
O
O
H
O
H
17
16
Scheme 3. Preparation of control and g6 arene isomannide acrylates.
which could be converted to arene complexes or control
substrate 14 as desired (Scheme 3). For the complexes,
bis protected ether 15 was subjected to g6 complexation
followed by ligand substitution to give ligand precursors
which were deprotected to give alcohols 16 and converted
to give a family of acrylates 17. Surprisingly, though acry-
lates 17a–c were stable, the bulkier triphenylphosphite ana-
log 17d was not isolable, resulting in decomplexation (to
14) even under a variety of conditions. Cycloaddition of
the acrylates 14 and 17 was then conducted using cyclo-
pentadiene, and various Lewis acid combinations.
Following decomplexation, the d.e. of the cycloadduct 9
was assessed using chiral HPLC (OD column), yielding
some important findings (Table 2). Aluminum trichloride
proved ineffective (entries 1–2) but appreciable d.e. is
obtained using chloroalkyl aluminums with 14, confirming
prior reports [8], and revealing a consistent and marked
benefit of complexation (viz. entries 3–4, 7–8, and 12–13).
Additional improvements were possible using the dichloro-
ethyl aluminum, a trend observed in both g6 complexed
and uncomplexed series. In all cases examined the endo R
enantiomeric cycloaddition product predominated. Since
p–p interactions were reasoned to contribute to diastereo-
control in substrate 14, it was surprising to find that in
the case of the p deficient 17a, diastereocontrol is enhanced
over 14 (entries 7–8), contrary to that observed in the anal-
ogous 8-phenylmethyl acrylate complexes [9]. The more
electron rich mixed ligand systems performed even better,
the trend seemingly reflecting a mix of steric and electronic
factors (entries 9–10). Lower temperatures led to even
higher selectivity, ultimately giving a system with extremely
high facial and diastereocontrol (entry 14). In an attempt
to rationalize these findings, a number of spectroscopic
studies were undertaken using ligands 14 and 17.
Assuming an s-trans enoate geometry is adopted in the
Lewis acid catalyzed cycloaddition, a p–p stacked model
Table 2
Cycloaddition of acrylates 14/17 with cyclopentadiene
Entry
Substrate
Lewis acid (eq.)
%9
Temp. (Time)
Endo/Exo
%de
1
2
3
4
5
6
7
8
9
10
11
12
13
14
14
14
AlCl3 (1.0)
AlCl3 (3.0)
55
69
42
72
39
66
42
81
53
71
55
74
22
73
ꢀ78 ꢁC (12 h)
ꢀ78 ꢁC (2 h)
ꢀ78 ꢁC (2 h)
ꢀ78 ꢁC (2 h)
ꢀ10 ꢁC to r.t. (6 h)
ꢀ40 ꢁC (2 h)
ꢀ78 ꢁC (2 h)
ꢀ78 ꢁC (2 h)
ꢀ78 ꢁC (2 h)
ꢀ78 ꢁC (2 h)
ꢀ78 ꢁC (2 h)
ꢀ78 ꢁC (2 h)
ꢀ78 ꢁC (2 h)
ꢀ90 ꢁC (2 h)
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
36
31
70
80
67
84
88
95
97
97
86
88
94
99
14
Et2AlCl (1.0)
Et2AlCl (1.0)
EtAlCl2 (1.0)
EtAlCl2 (1.0)
EtAlCl2 (1.0)
EtAlCl2 (1.0)
EtAlCl2 (1.0)
EtAlCl2 (1.0)
EtAlCl2 (0.5)
EtAlCl2 (2.0)
EtAlCl2 (2.0)
EtAlCl2 (1.0)
17a
14
14
14
17a
17b
17c
14
14
17a
17c
All cycloaddition conducted in CH2 Cl2. Cycloadducts derived from 17 were decomplexed in Et2O, then analyzed by chiral HPLC (Chiracel OD, 10% 2-
propanol:90% hexanes eluent, 1 mL/min flow rate) using a racemic endo adduct prepared by alternate methods as both an internal and external control.

J. Li et al. / Journal of Organometallic Chemistry 692 (2007) 5459–5473
5463
(A) does not account for the observed endo R cycloadduct,
which would require addition to the (p shielded) upper
face, and which also imposes unfavorable geometry on
the ester function. Fluorescence quenching studies indi-
cated a concentration dependent interaction between the
acrylate and aryl moieties of 14 in the absence of Lewis
acid [2]. No quenching was observed with the analogous
arene complexes 17 (or control alkane analogs of 14), either
in the presence or absence of Lewis acid, which may indi-
detected by fluorescence quenching, or the participation
of the metal carbonyl tripod itself in binding to the Lewis
acid. From these results, though the precise origins of ste-
reoselectivity remain to be defined, it is clear that the iso-
mannide template is an effective building block for use in
asymmetric cycloaddition chemistry. Additionally, the
per-oxygenated skeleton does not share the requirement
for multiple equivalents of Lewis acid observed with the
xylofuranoses.
X
OC
CO
H4
Hb
H
Hc
Cr
H
O
O
O
Hb
O
O
Hc
O
H
O
Ha
O
O
O
O
Hb
Hc
O
Ha
Al
O
H
O
H
Ha
H
O
C
A
B
Al
[STRUCTURES A-C]
cate the metal carbonyl tripod either imparts a conforma-
tional bias to the benzyl group, or electronically insulates
the arene. Chemical shift analysis of the acrylate protons
in 14 and 17 (CDCl3, 25 ꢁC) did not reveal a trend for
upfield shift consistent with p stacking with the phenyl ring,
instead giving near uniform values for the entire series,
even in the presence of Lewis acid (Table 3). More reveal-
ing were nOe studies, which failed to show any nOe
between the vinyl group protons and either the aryl moiety
or benzylic hydrogens, in both 14 and 17. However, in the
presence of EtAlCl2, nOe’s were observed between the phenyl
H4 and the acrylate Hb (5%) and Hc (2%), suggesting that a
conformational change ensues when Lewis acid coordinates
to the enoate. Taken together, the data suggest conforma-
tion B, where approach of the diene is directed to the
underside of the enoate, leading to the observed endo R
cycloadduct. The correlation of steric bulk with d.e. in
the case of derivatives 17, can be satisfied with structure
C, the metal carbonyl group serving to amplify p shielding
of the upper face of the enoate. Other possibilities include
interaction of (the metal complexed) arene with the acry-
late by some form of charge transfer process that is not
2.3. N-benzyl prolinols
Proline derivatives have seen widespread use in catalysts
and auxiliaries, and N-benzyl prolinol is now commercially
available [10]. To initiate our studies L-proline was con-
verted to its prolinol derivative and a variety of benzyl
chlorides 18 were used to assemble the N-benzyl prolinols
19 (Scheme 4). Conversion to the corresponding acrylates
20 allowed us to probe the efficiency and stereoselectivity
of cycloaddition on the basic template, using a series of
Lewis acids with cyclopentadiene. Initial results (Table 4)
confirmed the viability of the design criteria with moderate
to good endo selectivity achieved and appreciable diastero-
control. Through a survey of various Lewis acids, boron
trifluoride performed best, with reproducible success under
a variety of conditions. Product chemical yields ranged
from poor to excellent, and the auxiliary could be recov-
ered in good (ꢁ90%) yield by reduction of the ester linkage.
In all cases, the major product obtained was the endo R iso-
mer, confirmed by comparison with authentic material [11].
The most striking results were observed with 4-substituted
derivatives 20b–d, where a strong correlation between dia-
stereoselectivity and electron donor ability of the substitu-
ent X emerged. As the same trends were not reflected in
endo:exo ratios, we became especially interested in the
(mixed ligand) arene chromium complexes, with their
unique potential to modulate through-space electronics.
Thus, commencing with 19a, high yielding direct complex-
ation was achieved to give alcohol 21, presumably via intra-
molecular delivery of the Cr(CO)3 tripod from an
intermediate oxo-Cr complex (Scheme 4) [12]. Ligand
exchange was effective without need for masking of the
Table 3
1H NMR analysis of isomannide acrylates (d)a
Entry
Substrate
Ha
Hb
Hc
1
2
3
4
5
a
14
14 (+EtAlCl2)
17a
17b
17c
6.18
6.10
6.12
6.22
6.24
5.87
5.85
5.82
5.87
5.88
6.46
6.43
6.40
6.54
6.57
Designation of Ha, Hb, Hc as shown in structures A–C.

5464
J. Li et al. / Journal of Organometallic Chemistry 692 (2007) 5459–5473
H
1. LiAlH4, THF (54%)
2. K2CO 3, THF
OH
a X = H 69%
N
b X = OCH 3 77%
c X= CH 3 91%
d X = NO2 90%
COOH
N
H
Cl
X
18
X
19
O
Cr(CO) 6,
Bu2O, THF
n
Et3N,
THF
Cl
H
OH
Δ 12h 78%
N
a X = H 51%
H
b X = OCH 3 72%
c X=CH3 90%
O
N
d X = NO2 90%
O
OC
Cr
CO
21
20
X
OC
Et3 N,
THF
O
PPh3 or
P(OPh)3
Cl
PhH hν
H
H
O
OH
O
N
N
O
Cl
OC
Cr
CO
OC
Cr
CO
Et3 N,
THF
23
22
X
X
a X= PPh3 73%
b X=P(OPh)3 76%
c X=CO 48%
a X= PPh3 69%
b X=P(OPh)3 63%
Scheme 4. Synthesis and Cycloaddition to N-benzyl prolinol acrylates.
Table 4
Cycloaddition of acrylates 20/23 with cyclopentadiene
Entry
Substrate
Lewis acid (eq.)
% 9
Temp. (Time)
Endo/Exo
%de
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
20a
20a
20a
20a
20a
20a
20a
20a
20a
20a
20b
20c
20d
23a
23b
23c
BF3 Æ OEt2 (1.2)
BF3 Æ OEt2 (1.2)
BF3 Æ OEt2 (1.2)
BF3 Æ OEt2 (2.0)
SnCl4 (1.2)
SnCl4 (1.2)
TiCl4 (1.2)
TiCl2(OiPr)2 (1.2)
AlEt2Cl (1.2)
AlEtCl2 (1.2)
BF3 Æ OEt2 (1.2)
BF3 Æ OEt2 (1.2)
BF3 Æ OEt2 (1.2)
BF3 Æ OEt2 (1.2)
BF3 Æ OEt2 (1.2)
BF3 Æ OEt2 (1.2)
<1
6
ꢀ78 ꢁC (48 h)
ꢀ50 ꢁC (12 h)
ꢀ25 ꢁC (6 h)
ꢀ25 ꢁC (6 h)
ꢀ25 ꢁC (6 h)
ꢀ50 ꢁC (12 h)
ꢀ25 ꢁC (6 h)
ꢀ25 ꢁC (6 h)
ꢀ25 ꢁC (6 h)
ꢀ25 ꢁC (6 h)
ꢀ25 ꢁC (12 h)
ꢀ25 ꢁC (12 h)
ꢀ25 ꢁC (12 h)
ꢀ25 ꢁC (24 h)
ꢀ25 ꢁC (24 h)
ꢀ25 ꢁC (24 h)
–
–
20:1
8.8:1
5.8:1
1.5:1
3.7:1
–
95
55
81
21
81
–
57
24
23
10
<1
<1
10
5
90
65
77
99
86
77
–
–
10:1
1:40
39:1
22:1
20:1
35:1
32:1
28:1
93
80
83
68
22
98
97
96
All cycloadditions conducted in CH2 Cl2. Cycloadducts derived from 23 were decomplexed in Et2O, then analyzed. Exo:endo ratios determined by GC–MS
(HP-5, evap. temp. 220 ꢁC; operating temp. 60 ꢁC 5 min then 4 ꢁC/min ramp rate to 145 ꢁC); endo 18.32 min. exo 18.58 min; de determined by HPLC
(Chiracel OD, 3% 2-propanol:97% hexanes eluent, 1 mL/min flow rate) in comparison to reference standards (tRexoS = 4.84 min exoR = 5.48 min, tR
endoS = 5.95 min endoR = 6.97min).
alcohol group, allowing 22a and 22b to be expeditiously
converted to the corresponding acrylates 23.
Cycloaddition was efficient with all three substrates
(Table 4) and expected correlations between p donor ability
and endo preference/diastereoselectivity were observed
within the series. Clearly, substrate 23c presents a more
electron deficient p face than 20a suggesting that the steric
bulk of the metal carbonyl tripod contributes substantively
to diastereoselectivity. Substantial diastereoselectivity was
obtained in the case of 23a, suggesting the platform to be

J. Li et al. / Journal of Organometallic Chemistry 692 (2007) 5459–5473
5465
H
1. BF3.OEt2
O
1.
H
H
N
PPh
2
O
O
N
21
PhH, hν
O
Ph
OC
2. hν, THF
Cr
2. acryloyl chloride
Et3N, THF
55%
24
P
>99:1
CO
25
Ph
2
78%
Scheme 5. Preparation and cycloaddition of polymer supported derivative.
suitable for application in other areas, and confirming the
fact that a high degree of electronic control can be achieved
by ligand substitution on Cr (entries 14–16), consistent
with arene p basicity.
ularly useful in applications involving electrostatic
interactions.
LA
One such avenue of interest to us lies in preparation of
solid-supported variants of this system. Prompted by origi-
nal reports from the Semmelhack et al. [13], and Thomas
groups [14], we have prior experience of the so-called
‘traceless linker’ approach for solid-supported synthesis.
Specifically we have used polystyrene bound mixed ligand
phosphine–chromium arene complexes to conduct polymer
supported synthesis of a library of steroid derivatives [15].
Given the ease of uncoupling of products from the solid
support following synthesis (UV release) we thus sought
application of the technology in this series of auxiliaries.
Accordingly, irradiation of 21 in the presence of polysyt-
rene–diphenylphosphine complex resulted in formation of
the mixed ligand derivative, which was converted to acry-
late ester 24 without incident (Scheme 5). Cycloaddition
proceeded with essentially complete diastereoselectivity,
and the adduct 25 could be uncoupled from the support
merely by exposure to light.
In an attempt to rationalize these findings, spectroscopic
studies were undertaken using ligands 20 & 23. Assuming
an s-trans enoate geometry is adopted in the Lewis acid
catalyzed cycloaddition, a p–p stacked/shielded model is
consistent with the observed endo R cycloadduct, which
implies approach of diene with the methylene group anti
to the (mobile) benzyl substituent Structures D–E. How-
ever, chemical shift analysis of the acrylate protons in 20
and 23 (CDCl3, 25 ꢁC) revealed only minor perturbations
in the presence of Lewis acid. If pronounced p stacking
effects were operational, upfield shift of these protons
would be expected (viz. structure D) [1]. Additional nOe
experiments were conducted on substrates and in the case
of 20c irradiation of the aryl methyl group resulted in
<2% enhancement of the acrylate vinyl protons. Based
on these data, a face-to-edge arrangement (structure E)
seems most plausible and must contribute to the remark-
able selectivity and high degree of control observed at
ꢀ25 ꢁC. The effectiveness of 23 and especially solid sup-
ported variant 24 as chiral auxiliaries is encouraging partic-
ularly given their efficient syntheses. Further, given the
clear facial preference observed it can be expected that a
number of applications beyond cycloaddition to acrylate
derivatives will be forthcoming, and it may become partic-
O
H
N
H
O
LA
O
O
Ha
N
Hb
Cr
Hb
Ha
OC
Hc
X
Hc
CO
R
D
E
[STRUCTURES D-E]
3. Conclusion
The goal of the investigation was to highlight the use of
electronically tunable chiral auxiliaries derived from the
biogenic chiral pool as templates for asymmetric p-facial
cycloaddition chemistry. Derived acrylates show apprecia-
ble endo- and diastereoselectivity in cycloadditions, and the
selectivity can clearly be enhanced by introduction of pen-
dant g6 arene chromium carbonyl complexes. The metal
carbonyl complexed ligands can be recycled with ease by
ester reduction (LAH) of the product adducts. Spectro-
scopic studies suggest that a form of vinyl-face p shielding
determines stereochemical bias in the cycloaddition reac-
tions, features which will find applications in a variety of
related asymmetric processes and in the design of new cat-
alysts and auxiliaries. Though all three ligands studied are
amenable to formation of benzyl g6 arene complexes and
show some degree of stereoselectivity, the isomannide
and proline derived systems proved most versatile. In the
latter case the affordability of the building block coupled
with high degree of control at ꢀ25 ꢁC suggest this as a can-
didate for further development in asymmetric reactions
where p shielding of an enophile is desirable, and in the
case of 24 for application in parallel screening methodol-
ogy. More significantly, studies confirm that a very tight
degree of electronic control can be afforded by mixed
ligand arene Cr (0) derivatives, and applications in the
design of electronic and charge activated materials may
be forthcoming.

5466
J. Li et al. / Journal of Organometallic Chemistry 692 (2007) 5459–5473
4. Experimental
cooled to 0 ꢁC and a suspension of NaH (1.266 g of 60%,
31.647 mmol) in THF (5 mL) was added dropwise. The
resulting solution was stirred for 10 min at 0 ꢁC, after
which the solution was warmed to room temperature and
benzyl bromide (3.47 mL, 4.962 g, 29.009 mmol) and of
tetra-n-butyl-ammonium iodide (25 mg, 0.04 mmol) added.
The resulting mixture was stirred at room temperature for
3 h, heated to 50 ꢁC for an additional 2 h, then condensed
in vacuo. The residue was dissolved in CH2Cl2, and the
solution washed with water (1 · 20 mL), and brine
(1 · 10 mL). The solution was dried over MgSO4, then con-
centrated in vacuo. The crude oil was subjected to SGC
(2:98 to 5:95 EtOAc:hexanes) to afford the title compound
(6.868 g, 66%) as a colorless oil [17]; 1H NMR (d) 7.24–7.29
(m, 5H), 5.85 (d, J = 3.9 Hz, 1H), 4.61 (d, J = 12 Hz, 1H),
4.52 (d, J = 12 Hz, 1H), 4.53 (d, J = 3.9 Hz, 1H), 4.21–4.15
(m, 1H), 3.93 (d, J = 3.3 Hz, 1H), 3.88–3.67 (m, 2H), 1.42
(s, 3H), 1.25 (s, 3H), 0.83 (s, 9H), 0.00 (s, 6H); 13C NMR
(d) 138.0, 128.6, 128.0, 127.8, 111.2, 105.3, 82.8, 81.6,
81.1, 72.5, 61.6, 27.1, 26.5, 26.1, 18.5, ꢀ5.07, ꢀ5.19.
General methods for the preparation, handling and fluo-
rescence quenching studies of chromium complexes have
been published [2]. Ether, THF and n-Butyl ether were dis-
tilled from sodium benzophenone ketyl. Hexanes and ben-
zene were distilled from calcium hydride. Dichloromethane
was distilled from P2O5 before use. DMF was dried stirring
with BaO for 12 h at room temperature, followed by distilla-
tion from alumina at reduced pressure. Solvents used for
complexations were deoxygenated by three cycles of freezing
under vacuum, purging with nitrogen gas and thawing.
Acroleins were distilled from calcium hydride immediately
prior to use. Hexacarbonyl chromium was purchased from
Strem Chemicals Inc. and used as supplied. All other chem-
icals were purchased from Aldrich and used as supplied. Sil-
ica gel chromatography (SGC) was conducted using Merck
silica gel under standard flash chromatographic conditions.
Photo-irradiations were conducted using a Hanovia 450W
medium pressure Hg lamp enclosed in a light box. Ultrasoni-
cations were performed using a Branson 450 unit. Unless
otherwise noted, NMR were recorded in CDCl3 solution
4.3. 3-O-benzyl-xylofuranose-2,3-acetonide (7)
1
on a Varian Unity Innova instrument at 300 MHz for H
and 75 MHz for 13C spectra. Peaks are listed parts per mil-
lion downfield from TMS and coupling constants expressed
in Hertz. Structural assignments of complexes were addi-
tionally supported by induced (hm, Et2O, 12h) decomplex-
ation and comparison to authentic uncomplexed ligands.
A 100 mL round bottom flask was charged with 4-O-
TBDMS-3-O-benzyl-xylofuranose-2,3-acetonide (1.410 g,
3.570 mmol) in THF (50 mL) and the solution cooled to
0 ꢁC. Tetra-n-butyl ammonium fluoride (5.354 mmol,
5.354 mL of 1 M in THF) was added dropwise and the
reaction was stirred for an additional 10 min at 0 ꢁC and
then 1 h at room temperature. The solvent was evaporated,
and residue dissolved in EtOAc (40 mL) and the solution
was washed with water (3 · 100 mL) and brine
(1 · 100 mL) then dried over MgSO4. The solution was fil-
tered, and the filtrate condensed in vacuo, and the residue
was purified by SGC (40:60 EtOAc:hexanes) to give the
4.1. 4-O-t-butyldimethylsilyl-xylofuranose-2,3-acetonide (6)
A 100 mL round bottom flask was charged with a solution
of 1, 2-O-isopropylidene-xylofuranose (5 g, 26.29 mmol) and
imidazole (5.369 g, 78.86 mmol) in dry DMF (25 mL). The
solution was cooled to 0 ꢁC and a solution of TBDMSCl
(4.359 g, 28.917 mmol) in dry DMF (25 mL) was added
dropwise. The resulting mixture was warmed to room tem-
perature and stirred for 16 h. DMF was removed by distil-
lation under reduced pressure and the residue was taken up
in CH2 Cl2(30 mL), and successively washed with water
(1 · 40 mL), then brine (1 · 20 mL). The organic phase
was dried over MgSO4 and concentrated in vacuo. The
residual oil was subjected to SGC (13:87 EtOAc:hexanes)
to afford the title compound (7.987 g, 99.8%) as a colorless
1
title compound (968 mg, 97%) as a colorless oil [7]; H
NMR (d) 7.39–7.31 (m, 5H), 5.99 (d, J = 2.1 Hz, 1H),
4.73 (d, J = 7.2 Hz, 1H), 4.64 (d, J = 2.4 Hz, 1H), 4.49
(d, J = 7.2 Hz, 1H), 4.30–4.27 (m, 1H), 4.02 (d,
J = 2.1 Hz, 1H), 3.97–3.83 (m, 2H), 1.6 (br.s, OH), 1.49
(s, 3H), 1.34 (s, 3H); 13C NMR (d) 137.3, 128.9, 128.4,
127.9, 112.0, 105.3, 83.0, 82.7, 80.3, 72.1, 61.2, 27.0, 26.5.
4.4. 3-O-benzyl-xylofuranose-2,3-acetonide-acrylate (8)
1
oil [16]; H NMR (d) 5.96 (d, J = 3.6 Hz, 1H), 4.51 (d,
J = 3.3 Hz, 1H), 4.40 (d, J = 3.3 Hz, 1H), 4.33 (t,
J = 3.3 Hz, 1H), 4.15–4.11 (m, 2H), 1.49 (s, 3H), 1.32 (s,
3H), 0.89 (s, 9H), 0.11 (s, 6H); 13C NMR (d) 111.4,
105.0, 85.6, 80.7, 74.8, 61.7, 26.8, 26.3, 25.9(3C), 18.3,
ꢀ5.3(2C).
A 10 mL round bottom flask was charged with 3-O-ben-
zyl-xylofuranose-2,3-acetonide (45 mg, 0.161 mmol), trieth-
ylamine (0.11 mL, 0.805 mmol), and CH2Cl2 (2 mL). The
solution was cooled to ꢀ10 ꢁC with the aid of an ice-salt
bath and acryloyl chloride (0.401 mmol, 0.033 mL) was
added dropwise over 10 min. The reaction mixture was stir-
red at ꢀ10 ꢁC for 10 min, then the resulting light brown
slurry warmed to room temperature. The residue was dis-
solved in CH2Cl2 (5 mL) and the solution washed with
water (3 · 5 mL) and brine (1 · 10 mL), then dried over
MgSO4, and concentrated in vacuo. The crude residue
was purified via SGC (15:85, EtOAc:hexanes) to yield the
4.2. 4-O-t-butyldimethylsilyl-3-O-benzyl-xylofuranose2,3-
acetonide
A 25 mL round bottom flask was charged with a solu-
tion of 4-O-t-butyldimethylsilyl-xylofuranose-2,3-acetonide
(8.029 g, 26.372 mmol) in THF (10 mL). The flask was

J. Li et al. / Journal of Organometallic Chemistry 692 (2007) 5459–5473
5467
title compound (40 mg, 74%) as a colorless oil [7]; 1H NMR
(d) 7.34–7.31 (m), 6.41 (dd, J = 17.1 Hz and J = 1.2 Hz,
1H), 6.12 (dd, J = 17.1 Hz, 10.5 Hz, 1H), 5.97 (d,
J = 3.6 Hz, 1H), 5.83 (dd, J = 10.5, 1.2 Hz, 1H), 4.69 (d,
J = 12.3 Hz, 1H), 4.64 (d, J = 3.9 Hz, 1H), 4.51–4.32 (m,
3H), 3.97 (d, J = 2.7 Hz, 1H), 1.60 (br.s, OH) 1.49 (s,
3H), 1.33 (s, 3H); 13C NMR (d) 166.1, 137.3, 131.4,
128.8, 128.3, 128.2, 127.9, 112.1, 105.5, 82.3, 81.8, 78.3,
72.1, 62.5, 27.0, 26.5.
ylphosphine (2.337 g, 8.922 mmol) in benzene (5.0 mL) was
then added via cannula. The resulting mixture was irradi-
ated (medium pressure Hg lamp) for 6 h, then the solvent
removed in vacuo. The crude residue was purified by
SGC (30:70 EtOAc:Hexanes) to give the title compound
(580 mg, 79%) as a red oil; 1H NMR (Acetone-d6, d)
7.80–7.12 (m, 20H), 5.91 (bs, 1H), 5.00–3.60 (m, 7H),
1.45 (s, 3H), 1.30 (s, 3H); 13C NMR (Acetone-d6, d)
205.5, 140.1, 139.8, 133.2, 133.1, 129.3, 128.5, 128.1,
127.8, 111.2, 105.2, 102.1, 90.4, 82.4, 81.2, 71.4, 59.6,
26.6, and 25.8; C35H35O7CrP requires: C, 64.61; H, 5.42.
Found: C, 64.88; H, 5.63.
4.5. 3-O-benzyl-xylofuranose-2,3-acetonide: arene chromium
tricarbonyl complex (11)
A 200 mL round bottom flask was charged with 3-O-
benzyl-xylofuranose-2,3-acetonide (1.875 g, 6.689 mmol),
chromium hexacarbonyl (2.944 g, 13.378 mmol) and a mix-
ture of n-Bu2O/THF (96 mL of 6:1 n-Bu2O:THF). The
resulting mixture was degassed using the triple cycle
freeze-thaw procedure and then refluxed for 16 h. The mix-
ture was cooled to room temperature, filtered through a
plug of silica and then the solvent was removed in vacuo.
The crude yellow oil was purified by SGC (20:80 to 33:67
EtOAc:hexanes) to yield the title compound (631.7 mg,
4.8. 3-O-benzyl-xylofuranose-2,3-acetonide: acrylate arene
chromium tricarbonyl complex (13a)
A 50 mL round bottom flask was charged with 3-O-ben-
zyl-xylofuranose-2,3-acetonide arene chromium carbonyl
complex (1.496 g, 3.587 mmol) and degassed CH2Cl2
(22 mL). The resulting solution was cooled to ꢀ10 ꢁC
and degassed Et3N (17.938 mmol, 2.52 mL) and degassed
acryloyl chloride (0.729 mL, 8.969 mmol) were added,
respectively. After 10 min the reaction mixture was warmed
to room temperature and after 1 h the solvent was removed
in vacuo. The crude residue was purified by SGC (30:70,
Et2O:hexanes) to yield the title compound (927 mg, 55%)
as a yellow oil; 1H NMR (Acetone-d6, d) 6.43 (dd,
J = 17.4 Hz, J = 1.8 Hz, 1H), 6.17 (dd, J = 17.4 Hz,
J = 9.9 Hz, 1H), 6.00–5.88 (m, 2H), 5.70–5.50 (m, 5H),
4.84 (d, J = 3.9 Hz, 1H), 4.57–4.25 (m, 6H), 4.16(d,
J = 3.3 Hz, 1H), 1.43 (s, 3H), 1.29 (s, 3H). 13C NMR (Ace-
tone-d6, d) 233.6, 205.6, 165.4, 130.9, 128.5, 111.5, 108.9,
105.5, 94.5, 93.4, 82.9, 82.0, 78.0, 69.9, 62.2, 26.4, 25.7;
IR (neat) 3089 (br), 3051, 1953, 1859, 1830, 1715, 1481,
and 1036 cmꢀ1; C21H22O9Cr requires: C, 53.62; H, 4.71.
Found: C, 53.81; H, 4.95.
1
45%) as a yellow oil; H NMR (Acetone-d6, d) 5.86 (d,
J = 3.6 Hz, 1H), 5.70–5.50 (m, 5H), 4.80–4.30 (m, 3H),
4.30–4.75 (m, 1H), 3.97 (d, J = 3.3 Hz, 1H), 3.94–3.68
(m, 2H), 1.41 (s, 3H), 1.27 (s, 3H); 13C NMR (Acetone-
d6, d) 233.6, 205.6, 111.5, 109.5, 105.2, 94.5, 93.4, 82.9,
81.2.0, 69.9, 59.5, 26.5, 25.9; IR (neat) 3021 (br), 3045,
2942, 1978, 1905, 1896, 1450, and 1025 cmꢀ1; C18H20O8Cr
requires: C, 51. 93; H, 4.84. Found: C, 52.17; H, 5.09.
4.6. Benzyloxy xylofuranose-2,3-acetonide: arene chromium
dicarbonyl triphenylphosphite complex (12b)
3-O-benzyl-xylofuranose-2,3-acetonide: arene chromium
tricarbonyl complex (785 mg, 1.885 mmol) was dissolved in
degassed benzene (20.0 mL, triple freeze pump thaw
4.9. Benzyl xylofuranose-2,3-acetonide acrylate ester:
dicarbonyl phosphite complex (13b)
cycles).
Degassed
triphenylphosphite
(4.94 mL,
18.854 mmol) was then added via cannula. The resulting
mixture was irradiated (Hg lamp) for 6 h, then the solvent
removedin vacuo. The crude residue was purified by SGC
(15:75 EtOAc:hexanes) to yield the title compound
A 25 mL round bottom flask was charged with 3-O-ben-
zyl-xylofuranose-2,3-acetonide: arene chromium carbonyl
complex (296 g, 0.423 mmol) and degassed CH2 Cl2
(10 mL). The resulting solution was cooled to ꢀ10 ꢁC
and degassed Et3N (2.115 mmol, 0.297 mL) and degassed
acryloyl chloride (0.086 mL, 1.057 mmol) were added
respectively. After 10 min the reaction mixture was warmed
to room temperature and after 1 h the solvent was removed
in vacuo. The crude residue was purified by SGC (15:85
Et2O:hexanes) to yield the title compound (133 mg, 42%)
1
(823 mg, 70%) as a yellow solid. m.p. 36–40 ꢁC; H NMR
(Acetone-d6, d) 7.75–7.00 (m, 20H), 5.85 (m, 1H), 5.00–
3.20 (m, 7H), 1.41 (s, 3H), 1.25 (s, 3H); 13C NMR (Ace-
tone-d6, d) 205.5, 136.0, 130.1, 129.7, 129.5, 124.4, 122.0,
121.9, 120.9, 111.0, 105.1, 91.8, 89.3, 88.8, 79.7, 68.7,
26.5, and 25.7; C35H35O10CrP requires: C, 60.17; H, 5.05.
Found: C, 60.36; H, 5.21.
1
as a yellow oil; H NMR (Acetone-d6, d) 7.38–7.10 (m,
4.7. Benzyloxy xylofuranose-2,3-acetonide: arene chromium
dicarbonyl triphenylphosphine complex (12c)
20H), 6.34 (ddd, J = 9.9 Hz, J = 2.1 Hz, J = 17.1 Hz,
1H), 6.12 (dd, J = 4.5 Hz, J = 17.1 Hz, 1H), 5.93 (ddd,
J = 4.5 Hz, J = 9.9 Hz, J = 1.8 Hz, 1H), 5.80 (d,
J = 3.9 Hz, 1H), 4.88–4.76 (m, 2H), 4.43 (d, J = 3.9 Hz,
1H), 4.20–4.00 (m, 1H), 3.72 (d, J = 3 Hz, 1H), 3.63–3.30
(m, 2H), 1.42 (s, 3H), 1.34 (s, 3H). 13C NMR (Acetone-d6,
3-O-benzyl-xylofuranose-2,3-acetonide: arene chromium
tricarbonyl complex (371 mg, 0.892 mmol) was dissolved in
degassed benzene (5.0 mL). A degassed solution of triphen-

5468
J. Li et al. / Journal of Organometallic Chemistry 692 (2007) 5459–5473
d) 205.5, 152.5, 130.9, 129.8, 129.5, 128.4, 124.5, 122.0,
121.9, 119.4, 115.3, 111.4, 105.4, 91.5, 89.6, 89.3, 77.9,
62.2, 26.4, and 25.8; C38H37O11CrP requires: C, 60.64; H,
4.95. Found: C, 60.91; H, 5.18.
oxy)perhydro[3,2-b]furan-3-ol (2.19 g, 9.28 mmol) and
imidazole (6.3 g, 92.8 mmol) in dry DMF (30 mL). The
reaction mixture was stirred at r.t. for 24 h then poured
over iced HCl (1% (v/v), 2 · 100 mL), washed with satu-
rated NaHCO3 (2 · 100 mL), then water (2 · 100 mL),
and then extracted with EtOAc (3 · 100 mL). The organic
extracts were combined, condensed in vacuo, and the resid-
ual oil purified by SGC (95:5 through 50:50 hexanes/
EtOAc) to give the title compound (2.85 g, 99%) as a color-
less oil; 1H NMR (d) 7.33–7.24 (m, 5H), 4.70 (d,
J = 11.9 Hz, 1H), 4.61 (t, J = 8.0 Hz, 2H), 4.48 (t,
J = 4.3 Hz, 1H), 4.34 (t, J = 3.9 Hz, 1H), 4.07–4.00 (m,
1H), 3.96–3.92 (q, J = 4.7 Hz, 2H), 3.72 (d, J = 8.3 Hz,
1H), 3.68–3.60 (q, J = 7.8 Hz, 1H), and 0.14 (s, 9H); 13C
NMR (d) 137.6, 128.4, 128.2, 127.7, 81.8, 80.1, 79.3, 73.6,
72.2, 70.9, and ꢀ0.24; IR (neat) 3500–3330 (br), 3045,
2238, 1556, 1442, and 1022 cmꢀ1; MS (m/e) 307 (M ꢀ 1,
46.8%), 309 (M + 1, 72.1); [a]D = +149.5 (c = 0.33,
CHCl3); Anal. Calc. for C16H24O4Si: C, 62.30; H, 7.84.
Found: C, 62.76; H, 8.02%.
4.10. Benzyl xylofuranose-2,3-acetonide acrylate ester:
dicarbonyl phosphine complex (13c)
A 25 mL round bottom flask was charged with 3-O-ben-
zyl-xylofuranose-2,3-acetonide: arene chromium dicar-
bonyl triphenylphosphine complex (105 mg, 0.161 mmol)
and degassed CH2Cl2(10 mL). The resulting solution was
cooled to ꢀ10 ꢁC and degassed Et3N (0.805 mmol,
0.113 mL) and degassed acryloyl chloride (0.033 mL,
0.402 mmol) were added, respectively. After 10 min the
reaction mixture was warmed to room temperature and
after 1 h the solvent was removed in vacuo. The crude res-
idue was purified by SGC (15:85, Et2O:hexanes) to yield
1
the title compound (48 mg, 42%) as a red oil; H NMR
(Acetone-d6, d) 7.60–7.20 (m, 20H), 6.39–6.33 (m, 1H),
6.24–6.05 (m, 1H), 5.98–5.52 (m, 2H), 5.00–3.60 (m, 7H),
1.45 (s, 3H), 1.30 (s, 3H);13C NMR (Acetone-d6, d) 205.5,
140.1, 139.8, 133.2, 133.1, 129.3, 128.5, 128.1, 127.8,
111.2, 105.2, 102.1, 90.4, 82.4, 81.2, 71.4, 59.6, 26.6, 25.8;
C38H37O8CrP requires: C, 64.77; H, 5.29. Found: C,
64.93; H, 5.51.
4.13. {[(3R,3aS,6R,6aR)-6-(benzyloxy)perhydro-
[3,2-b]furan-3-yl]oxy}trimethyl silane chromium (0)
tricarbonyl (16a)
A mixture of {[(3R,3aS,6R,6aR)-6-(benzyloxy)perhy-
dro[3,2-b]furan-3-yl]oxy} trimethyl silane (1.6 g, 5.3 mmol)
and chromium hexacarbonyl (2.3 g, 10.6 mmol) in
nBu2O:THF (60:10, 70 mL) was heated using standard
complexation conditions for 16 h. On cooling the mixture
was filtered and the solution condensed in vacuo. The resid-
ual oil was purified by SGC (95:5 through 70:30 hexanes/
EtOAc) to give the title compound (1.04 g, 44%) as yellow
4.11. (3R,3aS,6R,6aR)-6-(benzyloxy)perhydro-
[3,2-b]furan-3-ol
A 250 mL round bottom flask was charged with isoman-
nide (11.0 g, 75.0 mmol), lithium hydride (0.6 g, 75.0 mmol)
and dry DMF (50 mL). The mixture stirred at r.t. for
15 min then freshly distilled benzyl chloride (8.6 mL,
75.0 mmol) cannulated into the solution. The mixture was
then sonicated for 24 h. The mixture was then washed with
water (3 · 200 mL) extracted with EtOAc (3 · 200 mL), and
the organic solution condensed in vacuo. The residue was
purified by SGC (hexanes:EtOAc to 50:50 to 10:90 eluent)
to give the title compound (12.01 g, 68%) as white powder
1
oil; H NMR (d) 6.92 (s, 1H), 5.23 (m, 4H), 5.12 (m, 1H),
4.43–4.30 (m, 2H), 4.20–4.02 (m, 3H), 3.92–3.80 (m, 2H),
3.64–3.48 (m, 2H), 2.75 (d, J = 10.2 Hz, 1H) and 0.001
(s, 9H); 13C NMR (d) 232.5, 107.2, 92.6, 92.3, 91.7, 81.8,
80.3, 80.0, 73.1, 71.9, 71.3, 70.4, and ꢀ0.33; IR (neat)
3025, 2940, 1976, 1901, 1889, 1454, and 1023 cmꢀ1; MS
(m/e) 445 (M + 1, 11.8%), 372 (M-TMS, 34.6);
[a]D = +85.12 (c = 0.46, CHCl3). Anal. Calc. for
C19H24CrO7Si: C, 51.34; H, 5.44. Found: C, 51.48; H,
5.51%.
1
m.p. 89–90.5 ꢁC (dec); H NMR (d) 7.36–7.28 (m, 5H),
4.77 (d, J = 11.8 Hz, 1H), 4.55 (t, J = 8.1 Hz, 2H), 4.48 (t,
J = 5.1 Hz, 1H), 4.28 (br, 1H), 4.09–4.05 (q, J = 5.9 Hz,
1H), 4.03–3.96 (q, J = 7.1 Hz, 2H), 3.74 (d, J = 6.6 Hz,
1H), 3.72–3.69 (t, J = 4.5 Hz, 1H) and 2.88–2.83 (t,
J = 7.5 Hz, 1H); 13C NMR (d) 137.5, 128.5, 127.9, 81.7,
80.6, 79.0, 74.8, 72.6, 72.2 and 71.4; IR (neat) 3500–3330
(br), 2988, 1445, and 987 cmꢀ1; MS (m/e) 237 (M + 1,
35.1%), 236 (M+, 9.0), 235 (M ꢀ 1, 73.7); [a]D = +112.72
(c = 0.4, CHCl3). Anal. Calc. for C13H16O4: C, 66.09; H,
6.83. Found: C, 66.13; H, 6.89%.
4.14. (3R,3aS,6R,6aR)-6-(benzyloxy)perhydro[3,2-
b]furan-3-ol mono (trimethyl phosphite) chromium (0)
dicarbonyl (16b)
Protected arene complex, {[(3R,3aS,6R,6aR)-6-(benzyl-
oxy)perhydro[3,2-b]furan-3-yl]oxy} trimethyl silane chro-
mium (0) tricarbonyl (0.18 g, 0.40 mmol), was dissolved in
dry benzene (5 mL) in a quartz test tube, then trim-
ethylphosphite (0.24 mL, 2.00 mmol) added to the tube,
and the solution degassed using a slow stream of Argon
gas. The vessel was capped and the mixture irradiated (Han-
ovia 450W Hg lamp) for 8h, following which the solvent
was condensed in vacuo. The residue was dissolved in
4.12. {[(3R,3aS,6R,6aR)-6-(benzyloxy)perhydro-
[3,2-b]furan-3-yl]oxy}trimethylsilane (15)
TMSCl (5.9 mL, 46.4 mmol) was cannulated into a pre-
cooled (ꢀ10 ꢁC) solution of (3R,3aS,6R,6aR)-6-(benzyl-

J. Li et al. / Journal of Organometallic Chemistry 692 (2007) 5459–5473
5469
MeOH (10 mL) and potassium carbonate (0.28 g,
2.00 mmol) added. After stirring at r.t. for 12 h, the mixture
was filtered through a plug of silica gel (EtOAc, 50 mL), the
filtrate condensed in vacuo, and the resulting oil purified by
SGC (40:60 through 10:90 hexanes:EtOAc) to give the title
55.4%), 291 (M + 1, 17.5), 293 (M+3, 67.2); [a]D =
+26.59 (c = 0.19, CHCl3). Anal. Calc. for C16H18O5: C,
66.19; H, 6.25. Found: C, 66.28; H, 6.32%.
4.15. (3R,3aS,6R,6aR)-6-(benzyloxy)perhydro-
[3,2-b]furan-3-yl acrylate chromium tricarbonyl (17a)
1
compound (0.12 g, 78%) as yellow oil; H NMR (CD3OD,
d) 4.69 (m, 1H), 4.21 (m, 2H), 4.07 (d, J = 11.5 Hz, 1H),
3.94–3.87 (t, J = 11.2 Hz, 2H), 3.77 (m, 1H), 3.59 (m,
1H), 3.48 (m, 1H), 3.31 (d, J = 5.7 Hz, 2H), 3.06 (m, 1H),
3.00 (q, J = 6.3 Hz, 1H), 2.88 (d, J = 10.8 Hz, 2H) and
2.71 (s, 9H); 13C NMR (d) 240.5, 240.1, 105.0, 92.8, 92.6,
92.2, 91.9, 84.7, 83.1, 82.9, 82.4, 75.2, 74.7, 74.3, 73.5, and
52.9; IR (neat) 3450 (br), 3120, 2966, 2286, 1920, 1852,
1434, and 967 cmꢀ1; [a]D = +74.16 (c = 0.25, CHCl3).
Anal. Calc. for C18H25CrO9P: C, 46.16; H, 5.38. Found:
C, 46.34; H, 5.47%.
Acryloyl chloride (2.59 mL, 31.84 mmol) was added at
ꢀ40 ꢁC to a solution of (3R,3aS,6R,6aR)-6-(benzyloxy)per-
hydro[3, 2-b]furan-3-ol acrylate chromium tricarbonyl
(2.37 g, 6.37 mmol) and triethylamine (3.55 mL,
25.47 mmol) in CH2Cl2 (40 mL). After stirring at r.t. for
6 h, the reaction was quenched by addition of water
(50 mL), then extracted with CH2 Cl2 (3 · 150 mL), and
the extracts dried over Na2SO4. The solution was filtered,
condensed in vacuo and the residue purified by SGC
(80:20 through 50:50 hexanes/EtOAc) to give the title com-
1
4.14.1. (3R,3aS,6R,6aR)-6-(benzyloxy)perhydro-
[3,2-b]furan-3-ol mono (triethyl phosphite) chromium (0)
dicarbonyl (16c)
pound (1.64 g, 60%) as yellow oil; H NMR (d) 6.40 (d,
J = 8.4 Hz, 1H), 6.16–6.08 (dd, J = 17.2 Hz, 6.9 Hz, 1H),
5.82 (d, J = 10.3 Hz, 1H), 5.38 (m, 4H), 5.33 (d,
J = 6.3 Hz, 1H), 5.26 (d, J = 5.6 Hz, 1H), 5.15 (d,
J = 5.6 Hz, 1H), 4.74 (t, J = 5.7 Hz, 1H), 4.56 (d,
J = 4.7 Hz, 1H), 4.45 (d, J = 11.4 Hz, 1H), 4.16–4.06 (m,
4H) and 3.66 (t, J = 8.2 Hz, 1H); 13C NMR (d) 232.5,
165.4, 131.6, 127.5, 106.8, 92.7, 92.6, 92.5, 92.4, 91.8,
80.7, 80.1, 79.8, 73.9, 70.8, 70.7, and 68.8; IR (neat) 3088,
Using identical procedure to that used for 16b,
{[(3R,3aS,6R,6aR)-6-(benzyloxy)perhydro [3, 2-b]furan-3-
yl]oxy} trimethyl silane chromium (0) tricarbonyl (0.13 g,
0.29 mmol) and triethylphosphite (0.25 mL, 1.45 mmol)
1
gave the title compound (0.14 g, 97%) as a yellow oil; H
NMR (d) 4.95 (m, 4H), 4.63 (m, 1H), 4.36 (d, J = 8.4 Hz,
2H), 4.16 (m, 1H), 4.00 (m, 3H), 3.88 (m, 2H), 3.79 (q,
J = 9.3 Hz, 6H), 3.60 (m, 1H), 3.19 (m, 1H), 2.80–2.63 (br,
1H) and 1.17 (t, J = 7.2 Hz, 9H); 13C NMR (d) 237.5,
237.1, 100.7, 89.4, 89.3, 88.9, 81.4, 80.0, 79.3, 73.8, 71.9,
71.6, 70.9, 70.6, 63.1, 59.2 and 15.7; IR (neat) 3464 (br),
3038, 2919, 1915, 1838, 1506, 1396, 1268, 1038, and
766 cmꢀ1; [a]D = +27.98 (c = 0.28, CHCl3). Anal. Calc.
for C21H31CrO9P: C, 49.41; H, 6.12. Found: C, 49.55; H,
6.18%.
3042, 1945, 1866, 1834, 1712, 1488 and 1039 cmꢀ1
;
[a]D = +54.25 (c = 0.4, CHCl3). Anal. Calc. for
C19H20CrO8: C, 53.53; H, 4.26. Found: C, 53.48; H, 4.17%.
4.16. (3R,3aS,6R,6aR)-6-(benzyloxy)perhydro-
[3,2-b]furan-3-yl acrylate mono(trimethyl
phosphite)chromium (0) dicarbonyl (17b)
Using similar procedure for 17a, acryloyl chloride
(0.09 mL, 1.10 mmol), (3R,3aS,6R,6aR)-6-(benzyloxy)per-
hydro[3,2-b]furan-3-ol acrylate mono trimethylphoshite
chromium (0) dicarbonyl (0.17 g, 0.38 mmol) and 2,6-luti-
dine (0.17 mL, 1.47 mmol) gave the title compound
(0.067 g, 35%) as yellow oil; 1H NMR (d) 6.54 (d,
J = 8.7 Hz, 1H), 6.24–6.18 (dd, J = 12.3 Hz, 6.9 Hz, 1H),
5.87 (d, J = 10.4 Hz, 1H), 5.28 (m, 4H), 5.15 (q,
J = 5.7 Hz, 1H), 4.76–4.72 (m, 2H), 4.54–4.48 (m, 2H),
4.13–3.88 (m, 5H), 3.74 (s, 9H) and 3.63 (t, J = 8.7 Hz,
1H); 13C NMR (d) 237.2, 236.5, 165.8, 137.2, 132.1,
104.9, 93.1, 92.8, 92.2, 91.8, 90.3, 80.7, 80.2, 78.7, 74.3,
72.5, 71.0, 70.4, and 31.5; IR (neat) 3085, 2987, 1844,
4.14.2. (3R,3aS,6R,6aR)-6-(benzyloxy)perhydro-
[3,2-b]furan-3-yl acrylate (14)
Acryloyl chloride (1.62 mL, 20 mmol) was added at
ꢀ40 ꢁC to a solution of (3R,3aS,6R,6aR)-6-(benzyloxy)per-
hydro[3,2-b]furan-3-ol (1.2 g, 5.0 mmol) and triethylamine
(2.0 mL, 15.0 mmol) in CH2Cl2 (40 mL). After stirring
6 h. at r.t., the reaction was quenched by addition of water
(50 mL), then extracted with CH2Cl2 (3 · 100 mL). The
extracts were dried over Na2SO4 then the solution filtered,
condensed in vacuo and the residue purified by SGC (50: 50
hexanes:CH2Cl2) to give the title compound (1.44 g, 99%)
1
as pale yellow oil; H NMR (d) 7.36 (d, J = 5.7 Hz, 4H),
1812, 1698, 1415, and 965 cmꢀ1
;
[a]D = +102.71
7.31 (m, 1H), 6.49–6.43 (dd, J = 15.9 Hz, 1.2 Hz, 1H),
6.21–6.12 (dd, J = 13.8 Hz, 4.8 Hz, 1H), 5.87 (d,
J = 9.9 Hz, 1H), 5.20 (q, J = 6.3 Hz, 1H), 4.76 (d,
J = 4.2 Hz, 1H), 4.73, (m, 1H), 4.57 (d, J = 012 Hz, 1H),
4.51 (t, J = 4.8 Hz, 1H), 4.06–4.00 (m, 3H), 3.93 (t,
J = 7.6 Hz, 1H) and 3.65 (t, J = 8.4 Hz, 1H); 13C NMR
(d) 165.4, 137.4, 131.6, 128.4, 127.9, 127.6, 127.4, 80.6,
80.1, 78.7, 74.2, 72.4, 70.9 and 70.4; IR (neat) 3092, 2375,
1698, 1446, 1123, and 781 cmꢀ1; MS (m/e) 290 (M+,
(c = 0.14, CHCl3). Anal. Calc. for C21H27CrO10P: C,
48.28; H, 5.21. Found: C, 48.71; H, 5.54%.
4.17. (3R,3aS,6R,6aR)-6-(benzyloxy)perhydro-
[3,2-b]furan-3-yl acrylate mono (triethyl phosphite)
chromium (0) dicarbonyl (17c)
Using similar procedure for 17a, acryloyl chloride
(0.05 mL, 0.61 mmol), (3R,3aS,6R,6aR)-6-(benzyloxy)-

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J. Li et al. / Journal of Organometallic Chemistry 692 (2007) 5459–5473
perhydro[3,2-b]furan-3-ol acrylate mono triethylphoshite
chromium (0) dicarbonyl (0.104 g, 0.367 mmol) and 2,6-
lutidine (0.095 mL, 0.815 mmol) gave the title compound
(0.029 g, 25%) as yellow oil; 1H NMR (d) 6.57 (d,
J = 9.0 Hz, 1H), 6.26–6.20 (dd, J = 11.7 Hz, 6.0 Hz, 1H),
5.88 (d, J = 10.2 Hz, 1H), 5.24 (m, 4H), 5.13 (q,
J = 5.1 Hz, 1H), 4.72–4.68 (m, 2H), 4.56–4.51 (m, 2H),
4.15–3.91 (m, 5H), 3.58 (q, J = 8.7 Hz, 6H), 3.45 (t,
J = 7.2 Hz, 1H) and 2.25 (t, J = 6.3 Hz, 9H); 13C NMR
(d) 236.2, 234.9, 165.1, 137.1, 132.3, 101.8, 92.9, 92.6,
92.1, 91.6, 90.9, 80.8, 80.2, 79.2, 74.4, 72.6, 70.9, 70.1,
58.7, and 28.5; IR (neat) 3132, 3076, 1832, 1805, 1702,
1427, and 986 cmꢀ1; [a]D = +168.59 (c = 0.14, CHCl3).
Anal. Calc. for C24 H33CrO10P: C, 51.07; H, 5.89. Found:
C, 51.12; H, 5.92%.
1H), 2.72–2.77 (m, 1H), 2.60 (s, 1H), 2.19–2.28 (m, 1H),
1.66–1.97 (m, 4H); 13C NMR (d) 147.6, 147.3, 129.4,
123.8, 64.9, 62.4, 58.4, 54.8, 27.8, 23.7.
4.21. N-benzyl prolinol acrylate (20 X = H)
To solution of N-benzyl prolinol (777 mg, 4.068 mmol)
in THF (10 mL) was added acryloyl chloride (0.8 mL,
10.170 mmol) and Et3N (3 mL, 20.340 mmol) at 0 ꢁC.
The solution was warmed to r.t. and stirred for 6 h. The
solution was washed with brine (1 · 5 mL) and to the
organic layer was added 5 N HCl solution at 0 ꢁC to bring
the pH 1. The aqueous layer was neutralized with ammo-
nium hydroxide solution to bring the pH 9, then extracted
with ethyl acetate (3 · 20 mL) and the combined extracts
dried over Na2SO4. The mixture was filtered and then con-
densed in vacuo and the residue purified by SGC (hex-
anes:ethyl acetate = 80:20) to give the title compound
4.18. 4-Methoxy N-benzyl prolinol (19b)
1
A solution of L-prolinol (1.16 g, 11.49 mmol) and 4-
methyloxybenzylchloride (1.83 g, 11.71 mmol) in THF
(40 mL) was stirred with anhydrous K2CO3 (6 g) for 16 h
at r.t. Dilute HCl was added to acidify the aqueous layer
to pH 1. The aqueous layer was separated, extracted with
EtOAc (1 · 20 mL), cooled to 0 ꢁC, basified with ammo-
nium hydroxide, and extracted with CH2Cl2 (4 · 20 mL).
The combined extracts were dried (Na2SO4) concentrated
in vacuo, then the residue purified by SGC (EtOAc:hex-
anes = 66:34) to yield the title compound (1.95 g, 77%) as
(509.5 mg, 51%) as a colorless oil; H NMR (d) 7.22–7.36
(m, 5H), 6.42 (dd, 1H, J = 17.5 Hz, 1.5 Hz), 6.15 (dd,
1H, J = 11 Hz, 17.5 Hz), 5.82 (dd, 1H, J = 11 Hz,
1.5 Hz), 4.08–4.22 (m, 3H), 3.43 (d, 1H, J = 13.5 Hz),
2.84–2.98 (m, 2H), 2.22–2.30 (m, 1H), 1.92–2.02 (m, 1H),
1.64–1.80 (m, 3H); 13C NMR (d) 166.2, 139.7, 131.0,
129.1, 128.8, 128.5, 127.1, 67.5, 62.1, 59.7, 54.7, 28.7, 23.2.
4.22. 4-Methoxy N-benzyl prolinol acrylate (20b)
1
a viscous oil; H NMR (d) 7.20 (d, 2H, J = 8.4 Hz), 6.85
Using similar procedure to 20a, compound 19b (580 mg,
(d, 2H, J = 8.4 Hz), 3.88 (d, 1H, J = 12.9 Hz), 3.80 (s,
3H), 3.61 (dd, 1H, J = 3.3 Hz, 10.5 Hz), 3.41 (dd, 1H,
J = 10.5 Hz, 1.8 Hz), 3.30 (d, 1H, J = 12.9 Hz), 2.90–3.00
(m, 1H), 2.64–2.76 (m, 1H), 2.33 (s, 3H), 2.22–2.32 (m,
1H), 1.60–2.00 (m, 4H); 13C NMR (d) 159.2, 131.6,
130.0, 113.9, 64.3, 62.0, 58.0, 55.4, 54.6, 28.1, 23.6.
2.62 mmol) and acryloyl chloride (0.5 mL, 6.56 mmol) gave
the title compound (520 mg, 72%) as a colorless oil; H
1
NMR (d) 7.22 (d, 2H, J = 8.1 Hz), 6.88 (d, 2H,
J = 8.7 Hz), 6.40 (d, 1H, J = 17.4 Hz), 6.14 (dd, 1H,
J = 10.5 Hz, 17.1 Hz), 5.82 (dd, 1H, J = 10.5 Hz, 1.2 Hz),
3.72–4.2 (m, 6H), 3.36 (d, 1H, J = 12.3 Hz), 2.67–2.93
(m, 2H), 2.24 (dd, 1H, J = 17.1 Hz, 9 Hz), 1.87 (m, 1H),
1.59–1.74 (m, 3H); 13C NMR (d) 166.4, 158.8, 131.7,
130.9, 130.2, 128.7, 113.8, 67.5, 61.9, 59.0, 55.5, 54.5,
28.7, 23.1.
4.19. 4-Methyl N-benzyl prolinol (19c)
Similar procedure to 19b, L-prolinol (1.17 g,
11.58 mmol) and a-bromo-p-xylene (2.2 g, 11.88 mmol)
gave the title compound (1.673 g, 71%) as a viscous oil;
1H NMR (d) 7.18 (d, 2H, J = 7.5 Hz), 7.12 (d, 2H,
J = 8.1 Hz), 3.91 (d, 1H, J = 12.9 Hz), 3.64 (dd, 1H,
J = 3.3 Hz, 10.5 Hz), 3.42 (dd, 1H, J = 10.5 Hz, 1.8 Hz),
3.32 (d, 1H, J = 13.2 Hz), 2.80–3.00 (m, 2H), 2.60–2.80
(m, 1H), 2.33 (s, 3H), 2.20–2.30 (m, 1H), 1.50–2.00 (m,
4H); 13C NMR (d) 138.8, 136.5, 129.2, 128.9, 64.4, 62.0,
58.4, 54.6, 28.1, 23.6.
4.23. 4-Methyl N-benzyl prolinol acrylate (20c)
Using similar procedure to 20a, compound 19c (2 g,
8.24 mmol) and acryloyl chloride (1.6 mL, 20.6 mmol) gave
the title compound (1.92 g, 91%) as a colorless oil; 1H
NMR (d) 7.20 (d, 2H, J = 7.8 Hz), 7.11 (d, 2H,
J = 7.5 Hz), 6.41 (dd, 1H, J = 17.1 Hz, 1.5 ), 6.14 (dd,
1H, J = 10.5 Hz, 17.7 Hz), 5.82 (dd, 1H, J = 10.5 Hz,
1.5 Hz), 4.02–4.23 (m, 3H), 3.40 (d, 1H, J = 12.9 Hz),
2.83–2.96 (m, 2H), 2.23 (s, 3H), 2.20–2.30 (m, 1H), 1.92–
2.00 (m, 1H), 1.63–1.78 (m, 3H).
4.20. 4-Nitro N-benzyl prolinol (19d)
Using similar procedure to 19b, L-prolinol (1.34 g,
13.27 mmol)
and
4-nitrobenzyl
chloride
(2.5 g,
4.24. 4-Nitro N-benzyl prolinol acrylate (20d)
14.59 mmol) yielded the title compound (1.64 g, 52%) as
1
a viscous oil; H NMR (d) 8.13 (d, 2H, J = 8.1 Hz), 7.45
Using similar procedure to 20a, compound 19d (936 mg,
3.965 mmol) and acryloyl chloride (0.4 mL, 4.758 mmol)
gave the title compound (1.05 g, 91%) as a colorless oil;
(d, 2H, J = 8.4 Hz), 4.02–4.09 (m, 1H), 3.62 (dd, 1H,
J = 3.3 Hz, 10.8 Hz), 3.44 (d, J = 13.8 Hz), 2.88–2.95 (m,

J. Li et al. / Journal of Organometallic Chemistry 692 (2007) 5459–5473
5471
1H NMR (d) 8.12 (dd, 2H, J = 8.7 Hz, 6.6 Hz), 7.46 (dd,
2H, J = 9 Hz, 2.4 Hz), 6.36 (dd, 1H, J = 17.1 Hz, 1.5 Hz),
6.08 (dd, 1H, J = 10.5 Hz, 17.1 Hz), 5.79 (dd, 1H,
J = 10.5 Hz, 1.5 Hz), 3.60–3.65 (m, 2H), 3.42–3.65 (m,
2H), 2.72–2.95 (m, 2H), 2.16–2.28 (m, 1H), 1.62–1.72 (m,
4H).
photolysis chamber and irradiated (Hanovia 450W Hg
lamp) for 6 h. The solution was condensed in vacuo and
the residue purified by SGC (gradient of hexanes, through
hexanes:ethyl acetate = 95:5 to hexanes:ethyl acetate = 1:1)
to give the corresponding monotriphenylphosphine com-
plex compound 22a (923.9 mg, yield: 69%) as a yellow oil
which was used immediately in the next step. To this crude
4.25. N-benzyl prolinol chromium tricarbonyl complex (21)
residue was added a solution of acryloyl chloride
(0.306 mL, 4.113 mmol) in THF (60 mL) then Et3N
(1.224 mL, 8.23 mmol). The mixture was degassed at 0 ꢁC
then warmed to r.t. and stirred for 6 h. The solution was
filtered through a plug of silica gel then concentrated in
vacuo and the residue purified by SGC (hex-
anes:EtOAc = 50:50) to give the title compound (734 mg,
A mixture of Cr(CO)6 (2.3 g, 10.47 mmol), N-benzyl
prolinol (1 g, 5.236 mmol), THF (20 mL), and n-butyl ether
(140 mL) was subjected to triple freeze-pump-thaw cycles
then heated at 125–130 ꢁC in the dark for 20 h. The solu-
tion was concentrated to 20 mL then filtered through a
plug of silica gel and evaporated to dryness. The residue
was purified by SGC (hexanes:EtOAc = 50:50) to give the
1
73%) as a yellow oil; H NMR (Acetone-d6,d) 7.20–7.80
(m, 20H), 6.37 (dd, 1H, J = 1.5 Hz, 17.1 Hz), 6.16 (dd,
1H, J = 10.2 Hz, 17.1 Hz), 5.87 (dd, 1H, J = 1.5 Hz,
10.2 Hz), 4.60–5.00 (m, 2H), 4.00–4.20 (m, 2H), 3.85 (d,
1H, J = 12.9 Hz), 3.12 (d, 1H, J = 12.9 Hz), 2.90–3.00
(m, 1H), 2.20–2.40 (m, 1H), 1.60–1.80 (m, 3H); 13C
NMR (Acetone-d6,d) 205.7, 166.0, 140.4, 139.9, 133.2,
133.1, 130.6, 129.2, 128.8, 128.1, 128.0, 104.2, 92.2, 91.6,
90.4, 90.2, 89.8, 67.1, 61.8, 59.0, 54.3, 28.3, and 23.1; IR
(neat) 3080, 3041, 1940, 1871, 1826, 1705, 1502, and
1029 cmꢀ1; C35H34NO4CrP requires: C, 68.29; H, 5.57.
Found: C, 68.50; H, 5.71.
1
title compound (1 g, 78%) as a pale yellow oil; H NMR
(Acetone-d6, d) 5.52–5.70 (m, 5H), 3.98 (d, 1H,
J = 13.2 Hz), 3.50–3.60 (m, 2H), 3.05–3.28 (m, 2H), 2.74
(s, 1H), 2.31–2.37 (m, 1H), 1.49–2.10 (m, 4H); 13C NMR
(Acetone-d6, d) 234.1, 205.5, 112.1, 95.1, 94.9, 94.6, 92.9,
66.8, 64.8, 58.3, 54.7, 28.0, 23.2; IR (neat) 3020, 2945,
1979, 1903, 1885, 1450, and 1020 cmꢀ1; C15H17NO4Cr
requires: C, 55.05; H, 5.23. Found: C, 55.36; H, 5.41.
4.26. N-benzyl prolinol chromium tricarbonyl complex-
acrylate ester (23c)
4.28. N-benzyl prolinol chromium dicarbonyl monophosphite
complex-acrylate ester (23b)
A solution 21 (50 mg 1.53 mmol) in THF (20 mL) was
degassed (triple freeze-pump-thaw cycle) then acryloyl
chloride (0.3 mL, 3.83 mmol) and Et3
N
(1.1 mL,
Using similar procedures employed for 23a, trip-
henylphosphite (4.27 g, 13.76 mmol) and complex 21
(450 mg, 1.376 mmol) gave crude 22b (527 mg, 63%) which
was reacted directly with acryloyl chloride (0.297 mL,
3.792 mmol) and Et3N (1.17 mL, 7.585 mmol) to yield the
7.65 mmol) added at 0 ꢁC. The solution was warmed to
r.t. and stirred for 6 h. Silica gel (1 g) was added and the
resulting slurry concentrated in vacuo then transferred to
a flash column and the mixture purified by SGC (hex-
anes:EtOAc = 80:20) under a positive pressure of argon.
The title compound (368 mg, 63%) was isolated as a pale
yellow oil; 1H NMR (Acetone-d6,d) 6.36 (dd, 1H,
J = 2.1 Hz, 17.1 Hz), 6.16 (dd, 1H, J = 10.5 Hz, 17.1 Hz),
5.89(dd, 1H, J = 1.5 Hz, 10.5 Hz), 5.60–5.80 (m, 4H),
5.50–5.60 (m, 1H), 4.02–4.24 (m, 2H), 3.92 (d, 1H,
J = 13.8 Hz), 3.24 (d, 1H, J = 13.8 Hz), 3.02–3.16 (m,
1H), 2.86–3.02 (m, 1H), 2.34–2.46 (m, 1H), 1.90–2.10 (m,
1H), 1.60–1.80 (m, 3H); 13C NMR (Acetone-d6,d) 233.0,
205.3, 165.9, 130.5, 128.8, 95.1, 94.8, 94.6, 93.0, 66.9,
62.2, 58.1, 54.4, 28.1, and 23.3; IR (neat) 3091, 3008,
1851, 1696, 1405 and 967 cmꢀ1 C18H19NO5Cr requires:
C, 56.69; H, 5.02. Found: C, 56.84; H, 5.33.
1
title compound (433 mg, 76%) as a yellow oil; H NMR
(Acetone-d6,d) 7.00–7.80 (m, 20H), 6.39 (dd, 1H,
J = 0.9 Hz, 17.1 Hz), 6.17 (dd, 1H, J = 10.2 Hz, 17.1 Hz),
5.88 (dd, 1H, J = 10.2 Hz, 0.9 Hz), 4.80–5.00 (m, 1H),
4.61 (s, 1H), 4.00–4.20 (m, 2H), 3.47 (d, 1H,
J = 12.9 Hz), 2.77 (d, 2H, J = 12.9 Hz), 1.40–2.36 (m,
4H); 13C NMR (Acetone-d6, d) 205.6, 165.7, 152.8, 152.7,
130.7, 130.2, 129.8, 128.8, 124.5, 122.1, 122.0, 107.7, 92.5,
92.1, 90.7, 90.4, 88.5, 67.0, 61.9, 58.4, 54.1, 28.3, and
23.1; IR (neat) 3136, 3071, 1829, 1810, 1715, 1421, and
989 cmꢀ1; C35H34N O7CrP requires: C, 63.34; H, 5.16.
Found: C, 63.59; H, 5.41.
4.29. Preparation of polymer bound complex (24)
4.27. N-benzyl prolinol chromium dicarbonyl monophosphine
complex-acrylate ester (23a)
Degassed (triple freeze-pump-thaw cycles) anhydrous
THF (10 mL) was cannulated to a mixture of compound
21 (651.6 mg, 1.99 mmol) and polymer-supported triphen-
ylphosphine (331 mg, 1 mmol). The mixture was again
degassed (double freeze-pump-thaw cycles) then placed in
a photolysis chamber and irradiated (Hanovia 450W Hg
lamp) for 48 h. The mixture was filtered and the residue
A solution of triphenylphosphine (6.3 g, 23.85 mmol) in
benzene (5 mL) was degassed (triple freeze-pump-thaw
cycles) then cannulated into a flask containing complex
21 (780 mg, 2.385 mmol). The mixture was again degassed
(double freeze-pump-thaw cycles) and then placed in a

5472
J. Li et al. / Journal of Organometallic Chemistry 692 (2007) 5459–5473
washed with anhydrous THF (10 mL) then anhydrous
ether (10 mL). The residue was suspended in THF
(20 mL) then acryloyl chloride (0.254 mL, 3.239 mmol) fol-
lowed by Et3N (1 mL, 6.477 mmol) was added at 0 ꢁC. The
solution was warmed to r.t. then stirred for 24 h, filtered,
then washed with water (10 mL), THF (10 mL) ether
(10 mL) and acetone (10 mL) then dried in vacuo to yield
the title compound (533 mg, 78%) as a yellow solid which
used immediately for cycloaddition reactions; 31P NMR
(121 MHz, Acetone-d6, d) 91.87 ppm.
isommanoyl) (0.094 g, 81%) as colorless oil; 1H NMR
(300 MHz, CDCl3) d 7.34–7.27 (m, 4H), 7.27–7.24 (dd,
J = 5.1 Hz, 2.4 Hz, 1H), 6.15–6.12 (dd, J = 5.7 Hz,
3.0 Hz, 1H), 5.95–5.92 (dd, J = 5.7 Hz, 2.7 Hz, 1H), 5.01–
4.97 (q, J = 6.0 Hz, 1H), 4.72–4.68 (d, J = 12.0 Hz, 1H),
4.61 (t, J = 5.1 Hz, 1H), 4.41 (t, J = 5.1 Hz, 1H), 4.00–
3.86 (m, 4H), 3.63 (t, J = 8.2 Hz, 1H), 3.18 (s, 1H), 2.96–
2.93 (m, 1H), 2.84 (s, 1H), 1.87–1.79 (m, 2H), 1.39–1.36
(dd, J = 10.5 Hz, 3.9 Hz, 2H) and 1.23–1.20 (dd,
J = 8.1 Hz, 0.9 Hz, 1H); 13C NMR (75 MHz, CDCl3) d
173.8, 137.4, 137.1, 132.2, 128.1, 127.6, 80.3, 79.8, 78.5,
73.5, 72.1, 71.0, 69.9, 49.3, 45.8, 42.5, 42.2, and 28.8; IR
(neat) 3123, 2978, 1723, 1475, and 1056 cmꢀ1; MS (m/e)
354 (M ꢀ 2, 17.9%), 355 (M ꢀ 1, 11.9), 356 (M+, 25.5),
357(M+1, 12.8); [a]D = +134.91 (c = 0.22,CHCl3); HPLC
(Daicel OD, 90:10 hexanes:IPA as eluent, 1 mL/min,
k = 254 nm) tR 18.13 min minor(S), tR 19.80 min major
(R); Anal. Calc. for C21H24 O5: C, 70.77; H, 6.79. Found:
C, 70.82; H, 6.82%. Alternatively, reductive cleavage of
adducts could be conducted [LiAlH4, 0 ꢁC, 2 h] to liberate
the corresponding endo R norbornene-2-methanol [11];
1H NMR (300 MHz, CDCl3) 6.10–6.14(m, 1H), 5.92–
5.96(m, 1H), 3.19–3.4(m, 2H), 2.91(s. 1H), 2.79(s, 1H),
2.22–2.32(m, 1H), 1.76–1.84(m, 2H), 1.23–1.45(m, 2H),
0.47–0.54(m, 1H); 13C NMR (75 MHz, CDCl3) 137.6,
132.4, 66.7, 49.7, 43.8, 42.4, 41.9, 29.0; [a]D = +95ꢁ
(c = 0.6, 95% EtOH).
4.30. Authentic endo adduct (9) via acyl chloride 10
SOCl2 (1.59 mL, 21.776 mmol) was added to a solution
of 5-norbonene-2-carboxylic acid (2.006 g, 14.517 mmol) in
dry CH2Cl2(8 mL) and the resulting mixture stirred for
12 h. The solvent was removed in vacuo and the residual
oil was distilled under reduced pressure to give 10
(1.759 g, 77%) as a colorless liquid [7]. To a solution of
3-O-benzyl-xylofuranose-2,3-acetonide (200 mg, 0.713
mmol) in CH2Cl2 (5 mL) at ꢀ10 ꢁC, was added 10
(279.34 mg, 1.784 mmol) and Et3N (0.5 mL, 3.567 mL).
The resulting mixture was warmed to r.t. and stirred for
2 h then washed with water (20 mL), brine (20 mL), dried
over MgSO4 and concentrated in vacuo. The crude product
was purified by SGC (10:90 EtOAc:hexanes) to yield 9
(248 mg, 87%) as a pale yellow oil [7]; 1H NMR
(500 MHz, CDCl3) 7.40–7.26 (m, 5H, Ph), 6.20–6.14 (m,
1H, endo-R, S-H-50), 6.14–6.06 (m, 2H, exo-H-50and 60),
5.95 (d, J = 2.1 Hz, 1H), 5.94–5.88 (m, 1H, endo-R, S-H-
60), 4.67 (d, J = 12 Hz, 1H, OCH2Ph), 4.62 (d,
J = 3.6 Hz, 1H, CH), 4.50 (dd, J = 12 Hz and J = 2.7 Hz,
1H, OCH2Ph), 4.38–4.18 (m, 3H, CH, and CH2O), 3.95
(t, J = 2.7 Hz, 1H), 3.22 (s, 1H, endo-R-H-40), 3.17 (s, 1H,
endo-S-H-40), 3.02 (s, 1H, exo-H-40), 3.00–2.88 (m, 1H,
H-10), 2.27–2.20 (m, 1H, exo-H-70), 1.94–1.86 (m, 1H,
endo-H-70and exo-H-70) 1.49 (s, 3H, CH3), 1.43–1.38 (m,
2H) 1.32 (s, 3H, CH3), 1.30–1.24 (m, 2H); 13C NMR
(300 MHz, CDCl3, DEPT) 175.4, 138.0, 132.5, 132.4,
128.8, 128.4, 127.9, 112.0, 105.4, 82.3, 81.9, 81.8, 78.4,
72.1, 49.8, 46.0, 42.3, 42.7, 29.9, 27.0, 26.4.
Acknowledgements
We thank the PRF (Administered by the American
Chemical Society) for financial support of this work
(33920-AC1).
References
[1] For general references to asymmetric Diels–Alder cycloadditions
using chiral auxiliaries see: (a) J. Seyden-Penne, Chiral Auxiliaries
and Ligands in Asymmetric Synthesis, Wiley, New York, 1995;
(b) R.E. Gawley, J. Aube, Principles of Asymmetric Synthesis,
Pergamon, 1996;
(c) H. Kunz, M. Weymann, M. Follmann, P. Allef, K. Oertel, M.
Schultz-Kukula, A. Hofmeister, Polish J. Chem. 73 (1999) 15.
[2] G.B. Jones, B.J. Chapman, J.E. Mathews, J. Org. Chem. 63 (1998)
2928.
[3] (a) S.G. Nelson, M.A. Hilfiker, Org. Lett. 9 (1999) 1379;
(b) C. Bolm, K. Muniz, Chem. Soc. Rev. 28 (1999) 51;
(c) U. Englert, R. Haerter, D. Vasen, A. Salzer, E.B. Eggeling, D.
Vogt, Organometallics 18 (1999) 4390;
4.31. Specimen procedure for cycloaddition reactions with
17a
EtAlCl2 (0.33 mL, 0.33 mmol) was added to a solution
of 17a (0.14 g, 0.34 mmol) in dry (5 mL) and the solution
stirred at ꢀ78 ꢁC for 1 h. Freshly distilled cyclopentadiene
(0.06 mL, 0.82 mmol) was added to the solution via syringe,
and the mixture stirred at ꢀ78 ꢁC for a further 2 h. The
reaction was quenched with water (10 mL) and the mixture
extracted with ether (3 · 50 mL). The ethereal extracts were
condensed in vacuo, the residue resuspended in CH2Cl2
(10 mL) and exposed to direct sunlight for 2 h. The solution
was then filtered through a plug of silica gel, condensed in
vacuo and the residue purified by SGC (95:5 through 60:40
hexanes:EtOAc) to give decomplexed adduct 9 (R = benzyl
(d) S.U. Son, H.-Y. Jang, I.S. Lee, Y.K. Chung, Organometallics 17
(1998) 3236;
(e) S.U. Son, H.-Y. Jang, J.W. Han, I.S. Lee, Y.K. Chung,
Tetrahedron: Asymmetry 10 (1999) 347;
(f) S. Top, G. Jaouen, J. Org. Chem. 46 (1981) 78;
(g) C.A. Merlic, J.C. Walsh, Tetrahedron Lett. 39 (1998) 2083;
(h) C. Pasquier, S. Naili, L. Pelinski, J. Brocard, A. Mortreux, F.
Agbossou, Tetrahedron: Asymmetry 9 (1998) 193;
(i) U. Englert, A. Salzer, D. Vasen, Tetrahedron: Asymmetry 9
(1998) 1867;
(j) N. Taniguchi, M. Uemura, Tetrahedron Lett. 38 (1997) 7199;
(k) A. Ariffin, A.J. Blake, W.-S. Li, N.S. Simpkins, Synlett (1997) 1453;

J. Li et al. / Journal of Organometallic Chemistry 692 (2007) 5459–5473
5473
(l) E.L.M. Cowton, S.E. Gibson, M.J. Schneider, M.H. Smith, J.
Chem. Soc., Chem. Commun. (1996) 839;
(c) T. Yamashita, H. Yasueda, N. Nakamura, Chem. Lett. (1974)
585.
(m) Y. Hayashi, H. Sakai, N. Kaneta, M. Uemura, J. Organometal.
Chem. 503 (1995) 143;
[11] (a) A.M. Janseen, A.H. Klunder, B. Zwanenburg, Tetrahedron Lett.
31 (1990) 7219;
(n) M. Uemura, Y. Hayashi, Y. Hayashi, Tetrahedron: Asymmetry 4
(1993) 2291.
[4] L. Xie, G.B. Jones, Tetrahedron Lett. 46 (2005) 3579.
[5] G.B. Jones, B.J. Chapman, Synthesis (1995) 475.
[6] (S)-N-benzylprolinol: Fluka cat. #13839; Isomannide: Aldrich cat. #
32, 926-6; xylofuranose: Fluka cat. #59545.
(b) J.A. Berson, J.S. Walia, A. Remanick, S. Suzuki, P. Reynolds-
Warnhoff, D. Willner, J. Am. Chem. Soc. 83 (1961) 3986.
[12] S. Top, G. Jaouen, J. Org. Chem. 46 (1981) 78.
[13] M.F. Semmelhack, G. Hilt, J.H. Colley, Tetrahedron Lett. 39 (1998)
7683.
[14] S.E. Gibson, N.J. Hales, M.A. Peplow, Tetrahedron Lett. 40 (1999)
1417.
[15] G.B. Jones, J.M. Wright, G. Hynd, J.K. Wyatt, M. Yancisin, M.A.
Brown, Org. Lett. 2 (2000) 1863.
[16] P. Radha Krishua, V. Kannan, A. Ilangovan, G.V. M Sharma,
Tetrahedron: Asymmetry 12 (2001) 829.
[17] J.R. Bearder, M.L. Dewis, D.A. Whiting, J. Chem. Soc., Perkin
Trans. 1 (1995) 227.
[7] V.F. Ferreira, S. Pinheiro, C.C. Perrone, P.R.R. Costa, J. Braz.
Chem. Soc. 11 (2000) 266.
[8] A. Loupy, D. Monteux, Tetrahedron Lett. 37 (1996) 7023.
[9] G.B. Jones, B.J. Chapman, Synlett (1997) 439.
[10] For applications see (a) H. Waldmann, J. Org. Chem. 53 (1988) 6133;
(b) S. Itsuno, K. Ito, A. Hirao, S. Nakahama, J. Chem. Soc., Perkin
Trans. 1 (1984) 2887;