Titanium-catalyzed Reformatsky-type reaction

Article abstract of DOI:10.1016/j.jorganchem.2007.02.037

A catalytic titanium mediated Reformatsky reaction is presented. The technique employs cyclopentadienyltitaniumdichloride(IV) (10 mol%) in conjunction with Mn (2 equiv.), as the stoichiometric reductant, and (CF₃CO)₂O (1.5 equiv.), a

Full text of DOI:10.1016/j.jorganchem.2007.02.037

Journal of Organometallic Chemistry 692 (2007) 3191–3197
www.elsevier.com/locate/jorganchem
Titanium-catalyzed Reformatsky-type reaction
Laura Sgreccia, Marco Bandini, Stefano Morganti, Arianna Quintavalla,
*
Achille Umani-Ronchi, Pier Giorgio Cozzi
`
Dipartimento di Chimica ‘‘G. Ciamician’’, Universita di Bologna, Via Selmi, 2 40126 Bologna, Italy
Received 14 December 2006; received in revised form 7 February 2007; accepted 7 February 2007
Available online 1 March 2007
Abstract
A catalytic titanium mediated Reformatsky reaction is presented. The technique employs cyclopentadienyltitaniumdichloride(IV)
(10 mol%) in conjunction with Mn (2 equiv.), as the stoichiometric reductant, and (CF3CO)2O (1.5 equiv.), as the scavenger, and it is
based on the formation of titanocene(III) chloride as a mild and homogeneous single-electron reductant. The reaction gives moderate
yields of the desired Reformatsky adduct, and it works well with aromatic and aliphatic aldehydes.
ꢀ 2007 Elsevier B.V. All rights reserved.
Keywords: Reformatsky reaction; Titanium; Mn; Catalysis
1. Introduction
reaction promoted by ClMn(Salen) [7], and a catalytic
imino Reformatsky reaction in the presence of 20 mol%
of N-methylephedrine [8]. Our methodologies employed
the rather expensive Me2Zn as reducing agent. Although
Et2Zn and Me2Zn could be readily prepared [9], from a
practical standpoint the employment of manganese or zinc
dust as reductants in the presence of a suitable chiral metal
complex will be advantageous.
The Reformatsky reaction [1], discovered more than 115
years ago, is still a well established method widely used in
synthesis allowing the straightforward addition of zinc eno-
lates to aldehydes, ketones, or imines through the direct
insertion of zinc into a-halogenated ketones, or esters.
Unfortunately, the reaction is sensitive to several reaction
parameters, and in particular, quality of the zinc dust can
strongly halter the performance of the processes, being
the reaction initiated by insertion of zinc into the car-
bon–halogen bond. In this context, several attempts have
been addressed toward this issue with particular concern
to sources and quality of activated zinc [2].
Recently, a new type of Reformatsky reaction in which
ZnR02 (R02 ¼ Me; Et) was used as a zinc source and
RhCl(PPh)3 [3] or Ni(PPh3)2Cl2 [4] as catalysts, were
described. The new homogeneous variants of the Refor-
matsky reaction have been used in developing asymmetric
versions, with the introduction of chiral auxiliaries [5], or
ligands [6]. We have successfully developed an enantiose-
lective catalytic version of the homogeneous Reformatsky
Furstner has introduced the use of Zn and Mn, in com-
¨
bination with a scavenger, in catalytic redox reactions
[10]. A catalytic McMurry type reaction was realized by
the employment of catalytic amount of titanium, in the
presence of stoichiometric amount of Zn and Me3SiCl as
scavenger [10a], while the catalytic version of the Nozaki–
Hiyama–Kishi–Takai reaction [10b] was described with
the employment of CrCl3 in catalytic amount. Both these
protocols were used in the presence of chiral ligands permit-
ting the carbon–carbon bond formation in a catalytic asym-
metric fashion [11]. On the other hand, interesting
Reformatsky-type reaction based on chromium were
described by Wessjohann [12]. Although toxic Cr(VI) is
not involved in these stoichiometric or catalytic processes,
stringent environmental issue asks about the development
of ‘‘greener’’ processes. Titanium complexes are considered
environmental friendly compounds of practical use and
*
Corresponding author. Tel.: +39 051 2099511; fax: +39 051 2099456.
E-mail address: piergiorgio.cozzi@unibo.it (P.G. Cozzi).
0022-328X/$ - see front matter ꢀ 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2007.02.037

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L. Sgreccia et al. / Journal of Organometallic Chemistry 692 (2007) 3191–3197
titanium(III) complexes are active and mild reducing agents
[13]. In this paper we disclose our preliminary results
towards the development of a unprecedented catalytic Ti/
Mn redox cycle for Reformatsky reaction with aliphatic
and aromatic aldehydes.
In order to study a truly catalytic titanium-mediated
Reformatsky reaction, we selected benzaldehyde 1a and
tertbutyl bromoacetate as reaction partners. The reaction
was performed in CH3CN using catalytic amount of
Cp2TiCl2 (10 mol%) in the presence of stoichiometric
amount of Mn as the reducing agent. A range of scaveng-
ers, able to cleave the oxo-titanium intermediate liberating
the organic products from the titanium complex, were
tested (Scheme 2). Frequently, the pinacol product 3 was
isolated as the major product, while no traces of desired
4 were obtained. Quite interestingly, when the reaction
was performed in the presence of trifluoroacetic anhydride
as the scavenger, we were able to observe the formation of
the desired adduct in modest amount.
2. Result and discussion
Titanocene(III) chloride (Cp2TiCl ‘‘Nugent’s reagents’’)
is a mild and useful reductant that was used in the single-
electron opening epoxides and subsequent trapping of the
resulting b-titanoxy radicals [14,15]. It found also applica-
tion in the reduction of aromatic aldehydes [16], vicinal
dihalides [17], sulfoxides [18], nitroarene [18], a-halo car-
bonyl species [19], and in living radical polymerization
[20]. Based on these observations, Little recently reported
a Reformatsky reaction in which stoichiometric amount
of Cp2TiCl was used [21]. This method affords high yields
in the range of 88–92% with aliphatic aldehydes. Although
the catalytic use of titanocene in the presence of Zn in
Reformatsky reactions was reported by Ding [22], it was
unclear which species (i.e. zinc or titanium (III)) was the
active reductant [23]. Major drawback of the chemistry
described by Little consists in the use of the stoichiometric
amount of titanocene along with the limitation to aliphatic
aldehydes. In fact, it is well known that aromatic aldehydes
easily undergo pinacol coupling if treated with titano-
cene(III) in stoichiometric [24] or catalytic amount [25]
(Scheme 1).
The reaction was optimized by varying different reaction
parameters, and Table 1 reports selected experiments.
Among the different reaction solvents examined, CH3CN
gave the better yield, while the best catalyst was Cp2TiCl2.
Other titanocenes were examined as well, namely CpTiCl3,
CpꢀTiCl2, Cp*TiCl3, CpSiTiCl2, Cp2Ti(OTf)2, CpMeTiCl2,
2
2
2
but they were not able to improve the yield of the reaction.
The product was isolated after basic hydrolysis of the triflu-
oroacetate derivatives. Experiments conduced with differ-
ent bromoacetates showed that tertbutyl bromoacetate
gives better yields (entry 4).
A key point of this Reformatsky reaction is the depro-
tection step, that is realized by treating the crude reaction
mixture with bases. Unfortunately, the trifluoroacetyl
derivatives are unstable and their purification on silica gel
R
R
Me3SiO
Me3SiO
CHO
Cp2TiCl2 3 mol%
+
Zn (or Mn), Me3SiCl
R
OSiMe3
OSiMe3
2 equiv.
R
R
yield 90%
de 82%
Scheme 1. Pinacol coupling of aromatic aldehydes promoted by low-valent titanium complexes.
OR
O
OR
CHO
Cp2TiCl2 10 mol%
Mn, scavenger
3: 40-75%
OtBu
+
O
OR
Br
2
1a
Ot
Bu
4: 0-20%
Scavengers
ClMe2Si
R = R1CO, CF3CO, BOC, R2Me2Si
NC
Me
SiMe2Cl
SiMe2Cl
O
O
O
Cl
BOC2O
BnO
Cl
Ph
Cl
O
O
F3C
O
CF3
Scheme 2. Titanium-catalyzed Reformatsky reaction in the presence of different titanium metal complexes and scavengers.

L. Sgreccia et al. / Journal of Organometallic Chemistry 692 (2007) 3191–3197
3193
Table 1
Optimization of the Reformatsky reaction catalytic in titanium
i) Cp2TiCl2 cat.
Mn, (CF3CO)2O
O
OH
O
CHO
OtBu
OtBu
+
Br
ii) NaOH, THF-H2O
4a
Entrya
Solvent
Catalyst (mol%)
Yieldb (%)
1
2
3
4c
5
CH3CN
THF
DMF
10
10
10
10
5
20
30
10
10
10
10
60
45
0
30
22
0
0
10
0
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
6
7
8d
9e
10f
11g
a
30
0
All the reactions were conduced at room temperature for 24 h using 1 equiv. of benzaldehyde, 1.5 equiv. of ester, 3 equiv. of Mn and 1.5 equiv. of
(CF3CO)2O. The Cp2TiCl2 was used in 10 mol% in a concentration of 0.2 M with respect the reaction solvent.
b
Isolated yield of the hydrolyzed product after chromatographic purification.
Ethyl bromoacetate was used as reaction partner.
Concentration of the titanium catalyst was 0.1 M.
Concentration of the titanium catalyst was 0.4 M.
1 equiv. of (CF3CO)2O was used as scavenger.
3 equiv. of (CF3CO)2O were used as scavengers.
c
d
e
f
g
caused extensive decomposition. On the other hand the
deprotection is quite sensitive to hindrance of the ester,
and in the case of tertbutyl, higher isolated yields were
always observed.
after deprotection, showing a probable retroaldol mecha-
nism that was reducing the yield. Unfortunately all the
attempts to use different deprotection schemes (i.e. LiOH,
LiOOH) in order to improve yield failed.
The reaction is quite sensitive to concentration and
quantity of the catalyst (Table 1, entries 8–10). In fact, per-
forming the model reaction in the presence of more than
20 mol% of the titanium catalyst, and maintaining unal-
tered the other variables, no product was isolated. This
was determined by the fast pinacol coupling occurring
under these conditions. The concentration of the reaction
is, on this respect, important. High concentration fur-
nished the desired product in very low yield, while in
diluted conditions, no reaction occurred. In Table 1 the
effect of varying the equivalent of (CF3CO)2O is also
reported. Optimal yields were obtained when 1.5 equiv.
of the reagent were employed. Lower quantities decreased
the yield while an excess of anhydride promoted the pina-
col coupling. The effect of the temperature of the reaction
was also evaluated. Performing the reaction of benzalde-
hyde with different esters at 0 ꢁC considerably reduced
the isolated yield, sign of incomplete reaction. The general
scope of the method was evaluated with a variety of ali-
phatic and aromatic aldehydes, and in Table 2 a collection
of results is reported.
Tentatively, we propose for this Reformatsky reaction
the catalytic cycle depicted in Fig. 1.
We believe that manganese enolates are not involved in
our reaction. In fact, Rieke showed that activated Mn(0),
prepared through the reduction of anhydrous Mn salts
with lithium and naphthalene [26], was giving good yield
in the corresponding Mn-mediated Reformatsky reaction.
However, non activated Mn is reacting sluggishly with
bromohalides.
Moreover, to exclude the intermediacy of Mn enolates
in our process we have studied the model reaction in
absence of titanium, using Me3SiCl or (CF3CO)2O as scav-
engers. Only in the presence of additive such as NaI and
using Me3SiCl, the desired product was isolated in 41%
yield. In addition, Durandetti has reported that activated
Mn can form enolate with bromoesters only with long reac-
tion time (3–4 days), carrying out the reaction at 50 ꢁC [27].
We can reasonably conclude that our process is controlled
by titanium and the formation of titanium enolates is
involved. In an attempt to develop stereocontrolled tita-
nium catalyzed Reformatsky reaction, we have tested dif-
ferent chiral titanium complexes 5–7 (Scheme 3). The
Duthaler–Hafner [28] titanium complex 5 is commercially
available, the titanium catalyst 6 was prepared by the reac-
tion conditions described by Joshi [29]. Finally, the tita-
nium catalyst 7 was obtained in situ by addition of
The aldehydes were completely consumed during the
reactions, however, the isolated yields are showing that
the concomitant pinacol coupling was reduced but not
completely eliminated under the optimal reaction condi-
tions. Moreover, a certain amount of aldehyde was present

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L. Sgreccia et al. / Journal of Organometallic Chemistry 692 (2007) 3191–3197
Table 2
metallation from the Duthaler–Hafner reagent afford
good facial selectivity with aldehydes in diethyl ether as
the reaction solvent [31]. Quite interestingly, the stereose-
lection was independent by the reaction temperature in
the limit of the isobutyraldehyde investigated. The Joshi’s
catalyst 6 is stable in the presence of Mn and scavengers,
and it is able to give good stereoselection in the pinacol
coupling, while the system 7 is stable in the presence of
metal alcohoxydes.
The titanium-catalyzed Reformatsky reaction with aromatic and aliphatic
aldehydes
i) Cp2TiCl2 (10 mol%)
O
O
OH
Mn, (CF3CO)2O
RCHO
OtBu
+
R
OtBu
ii) NaOH, THF-H2O
1a-l
Br
4a-l
Yieldb (%)
Aldehydea
CHO
Product
4a
60
The three chiral titanium catalysts promoted the tita-
nium Reformatsky reaction with benzaldehyde, affording
the desired product 4a in 45%, 42% and 70% yield, respec-
tively. Unfortunately, no enantiomeric excess was detected
[32]. Titanium enolates formed in the reaction conditions
can react through open transition state, in which a metal
complex, acting as a Lewis acid, is activating the aldehyde,
or they react through cyclic transition state, in which the
4b
32
CHO
MeO
Cl
4c
4d
4e
50
40
30
CHO
CHO
O
X: Cl, CO2CF3
F3C
O
O
R
OtBu
Br
F
Mn
2 Cp2TiX2
(CF3CO)2O
CHO
MnX2
Cp2TiBrX
Cp
X
Ti
R
Cp
2 Cp2TiX
O
O
OtBu
4f
40
50
CHO
CHO
OTiCp2X
Bu
O
Br
O
t
OtBu
4g
RCHO
Fig. 1. Proposed catalytic cycle for the titanium-mediated Reformatsky
reaction.
4h
40
CHO
4i
4j
48
32
CHO
H
H
O
Cl
O
Cl
O
O
N
N
O
Ti
O
O
O
O
Ti
Ti
O
O
Cl
O
O
CHO
O
Ph
a
N
O
O
All the reactions were conduced at room temperature for 24–48 h using
1 equiv. of aldehyde, 1.5 equiv. of ester, 3 equiv. of Mn and 1.5 equiv. of
(CF3CO)2O. The Cp2TiCl2 was used in 10 mol% in a concentration of
0.2 M to respect the reaction solvent.
O
O
7
5
6
b
Isolated yield of the hydrolyzed product after chromatographic
OH
O
O
i) Mn, (CF3CO)2O
ii) NaOH, THF/H2O
CHO
+
purification.
OtBu
OtBu
Br
1a
4a
Ti(OiPr)4 to the free ligand [30]. The systems 5–7 were cho-
sen on the basis of the following considerations. The three
titanium complexes are quite different in terms of coordina-
tion properties. The titanium enolates prepared by trans-
yield 45%, with 6
yield 70%, with 7
yield 42%, with 8
Scheme 3. Reformatsky reaction promoted by chiral titanium catalysts.

L. Sgreccia et al. / Journal of Organometallic Chemistry 692 (2007) 3191–3197
3195
aldehyde and titanium enolate are coordinated by the same
4.2. General procedure for the titanium-mediated
Reformatsky reaction
titanium atom. In addition, when cyclic transition states
are possible, boat and chair transition state could be ener-
getically available. Our Reformatsky reaction is probably
occurring through the formation of a titanium enolate at
room temperature. The presence of additive and Lewis acid
salts, formed during the reaction course, open the access to
many concomitant transition states making the Reformat-
sky reaction unselective. A more effective catalyst design in
order to control the process with chiral titanium complex
will be the object of further investigations.
In a two necked flask Cp2TiCl2 (0.05 mmol) was dis-
solved in CH3CN (1.8 mL) then Mn (1.5 mmol) was added.
The mixture was stirred 5–15 min. until the titanium com-
plex was reduced (color turned into green). To the reaction
mixture tertbutyl bromoacetate (0.75 mmol) was added
and the mixture was stirred for 1 h at room temperature,
then the aldehyde (0.5 mmol) and trifluoroacetic anhydride
(1.5 mmol) were added. The reaction mixture was stirred
24–36 h, then the mixture was quenched by water. The
reaction mixture was filtered over celiteꢀ and extracted
three times with Et2O. The collect organic phases were
evaporated under reduced pressure to give a dark yellow
oil containing the crude trifluoroacetate esters. The oil
was dissolved in THF (2 mL) and NaOH 1 M (1 mL)
was added. The reaction mixture was stirred few minutes
then diluted with H2O. The aqueous mixture was extracted
with Et2O (3 · 4 mL) then the organic phases were
reunited, dried over Na2SO4 and then evaporated under
reduced pressure to give an oil purified by flash chromatog-
raphy (eluant: c-Hex:Et2O 9:1–8:2).
3. Conclusion
In summary, we have described a truly catalytic tita-
nium mediated Reformatsky reaction promoted by cata-
lytic amount of Cp2TiCl2 or other titanium complexes.
The combined use of stoichiometric amount of Mn as
reductant, and of (CF3CO)2O as a scavenger allowed mod-
erate yields of the corresponding Reformatsky adducts to
be obtained with aliphatic and aromatic aldehydes. First
attempts to promote a catalytic enantioselective Reformat-
sky reaction with chiral titanium complexes were unsuc-
cessful, but we are confident that the conditions described
in this paper can guide we or other groups to reach this
goal in a near future.
4.2.1. tertButyl-3-hydroxy-3-phenyl-propionate (4a)
1H NMR (CDCl3, 200 MHz) d: 1.13 (s, 9H); 2.64–2.68
(m, 2H); 3.47 (d, 1H, J = 3.4 Hz); 5.09 (m, 1H); 7.38–
7.35 (m, 5H).
4. Experimental
13C NMR (CDCl3, 50 MHz) d: 171.6; 142.6; 128.3 (·2);
127.5; 125.6 (·2); 81.3; 70.3; 44.3; 28.0.
4.1. General details
IR (neat): 3447, 2979, 2931, 1727, 1150 (cmꢁ1).
GC–MS: 165 (22); 147 (8); 230 (6); 79 (54); 57 (88); 167
(7); 51 (22) (m/z).
1H NMR spectra were recorded on Varian 200 MHz or
Varian 300 MHz spectrometers. chemical shifts are
reported in ppm from tetramethylsilane with the solvent
resonance as the internal standard (deuterochloroform: d
7.27 ppm). Data are reported as follows: chemical shifts,
multiplicity (s = singlet, d = dublet, t = triplet, q = quar-
tet, br = broad, m = multiplet), coupling constants (Hz).
13C NMR spectra were recorded on a Varian 50 MHz
and Varian 75 MHz spectrometers with complete proton
decoupling. Mass spectra were performed at an ionizing
voltage of 70 eV. Chromatographic purification was made
with 240–400 mesh silica gel. Analytical gas chromatogra-
phy (GC) was performed on a Hewlett-Packard HP 6890
gas chromatograph, with a flame ionization detector and
split-mode capillary injection system, using a Crosslinked
5% PH ME Siloxane (30 m) column or a Megadex5 chiral
(25 m) column. IR analysis were performed with an FT-IR
spectrophotometer. IR spectra are expressed by wavenum-
bers (cmꢁ1). Analytical high performance liquid chroma-
tography was performed on a liquid chromatograph
equipped with a variable wave-length UV detector (deute-
rium lamp 100–600 nm), using a Daicel OD (0.46 cm
ID · 25 cm) (Daicel Inc.). Anhydrous CH3CN was pur-
chased by Fluka. Mn, (CF3CO)2O were used as received
(Fluka, Aldrich). All aldehydes were freshly distilled by
Kulgerorh apparatus before their use.
(R)-tertButyl-3-hydroxy-3-phenyl-propionate,
+39.0ꢁ (c 1.24, CHCl3) [32,33].
[a]D =
4.2.2. tertButyl-3-hydroxy-3-(4-methoxyphenyl)-propionate
(4b)
1H NMR (CDCl3, 200 MHz): d: 1.46 (s, 9H); 2.60–2.73
(m, 2H); 3.31–3.40 (br, 1H); 3.81 (s, 3H); 5.01–5.10 (m,
1H); 6.87–6.92 (m, 2H); 7.29–7.34 (m, 2H).
13C NMR (CDCl3, 50 MHz) d: 171.7; 158.9; 134.7;
126.9; 113.71; 81.4; 70.0; 52.2; 44.3; 28.1.
IR (neat) 3196, 2976, 2873, 1727, 1150 (cmꢁ1).
GC–MS: 234 (11); 178 (100); 161 (44); 133 (15); 77 (15);
57 (20) (m/z).
4.2.3. tertButyl-3-hydroxy-3-(4-fluorophenyl)-propionate
(4c)
1H NMR (CDCl3, 300 MHz) d: 1.45 (s, 9H); 2.61–2.65
(d, 2H, J = 6.3 Hz); 3.55–3.53(d, 1H, J = 3.2 Hz); 5.51–
5.01 (m, 1H); 7.04 (t, 2H, J = 8.6 Hz); 7.34 (dd, 2H,
J = 8.2, 8.1 Hz).
13C NMR (CDCl3, 75 MHz) d: 171.6; 164.5; 159.6; 138.3
(d, J = 12 Hz); 127.4 (d, J = 31 Hz); 115.0 (d, J = 85 Hz):
81.5; 69.7; 44.3; 28.0.

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L. Sgreccia et al. / Journal of Organometallic Chemistry 692 (2007) 3191–3197
IR (neat): 3439, 2980, 1725, 1153 (cmꢁ1).
GC–MS: 183 (27); 165 (9); 125 (100); 97 (30); 77 (13); 57
(95) (m/z).
13C NMR (CDCl3, 75 MHz) d: 171.8; 148.2; 139.9;
126.4; 125.6; 81.3; 70.3; 44.2; 33.1; 30.9; 28.1; 23.9.
IR (neat): 3447, 2979, 2931, 1727, 1150 (cmꢁ1).
GC–MS: 165 (22); 147 (8); 230 (6); 79 (54); 57 (88); 167
(7); 51 (22) (m/z).
4.2.4. tertButyl-3-hydroxy-3-(4-chlorophenyl)-propionate
(4d)
4.2.9. tertButyl-3-hydroxy-3-cyclohexyl-propionate (4i)
1H NMR (CDCl3, 200 MHz) d: 1.50–1.00 (m, 7H); 1.48
(s, 9H); 2.55–2.20 (m, 2H); 3.10 (d, 1H, J = 3.2 Hz); 3.82
(m, 1H).
1H NMR (CDCl3, 200 MHz) d: 1.45 (s, 9H); 2.64–2.68
(m, 2H); 3.47 (d, 1H, J = 3.4 Hz); 5.09 (m, 1H); 7.320–
7.348 (m, 4H).
13C NMR (CDCl3, 50 MHz) d: 171.4; 141.1; 133.1;
128.4; 126.9; 81.6; 69.6; 44.1; 28.0.
13C NMR (CDCl3, 50 MHz) d: 172.9; 81.1; 72.18; 43.0;
36.5; 28.7; 28.3; 28.1; 28.5; 27.0; 26.2.
IR (neat): 3447, 2979, 2931, 1727, 1150 (cmꢁ1).
GC–MS: 165 (22); 147 (8); 230 (6); 79 (54); 57 (88); 167
(7); 51 (22) (m/z).
IR (neat) 3447, 2979, 2931, 1727, 1150 (cmꢁ1).
GC–MS: 165 (22); 147 (8); 230 (6); 79 (54); 57 (88); 167
(7); 51 (22) (m/z).
4.2.5. tertButyl-3-hydroxy-3-(4-bromophenyl)-propionate
(4e)
4.2.10. tertButyl-3-hydroxy-3-nhexyl-propionate (4j)
1H NMR (CDCl3, 200 MHz) d: 0.92 (t, 3H, J = 7.2 Hz);
1.80–1.10 (m, 10H); 1.42 (s, 9H); 2.35 (dd, 1H, J = 6.0,
11.0 Hz); 2.42 (dd, 1H, J = 2.2, 11.0 Hz); 3.1 (br s, 1H);
4.09–3.94 (m, 1H).
1H NMR (CDCl3, 200 MHz) d: 1.45 (s, 9H); 2.63–2.58
(m, 2H); 3.47 (d, 1H, J = 3.2 Hz); 5.09 (m, 1H); 7.27–
7.23 (m, 2H); 7.49–7.45 (m, 2H).
13C NMR (CDCl3, 50 MHz) d: 171.6; 141.5; 131.3;
127.3; 121.2; 81.6; 69.6; 44.1; 28.0.
13C NMR (CDCl3, 50 MHz) d: 172.3; 81.0; 68.0; 42.3;
36.4; 31.7; 28.1; 25.1; 22.6; 14.0.
IR (neat): 3447, 2979, 2931, 1727, 1150 (cmꢁ1).
GC–MS: 165 (22); 147 (8); 230 (6); 79 (54); 57 (88); 167
(7); 51 (22) (m/z).
IR (neat): 3447, 2979, 2931, 1727, 1150 (cmꢁ1).
GC–MS: 165 (22); 147 (8); 230 (6); 79 (54); 57 (88); 167
(7); 51 (22) (m/z).
4.2.6. tertButyl-3-hydroxy-3-(2-fluorophenyl)-propionate
(4f)
4.2.11. tertButyl-3-hydroxy-3-(3-phenylpropyl) propionate
(4k)
1H NMR (CDCl3, 300 MHz) d: 1.46 (s, 9H); 2.71–2.65
(m, 2H); 3.70 (d, 1H, J = 3.6 Hz); 5.40 (dd, 1H, J = 3.6,
8.4 Hz); 7.03 (t, 1H, J = 8.7 Hz); 7.16 (t, 1H, J = 7.2 Hz);
7.27–7.26 (m, 1H); 7.54 (t, 1H, J = 7.5 Hz).
13C NMR (CDCl3, 75 MHz) d: 171.6; 160.9; 158.1; 129.2
(d, J = 45 Hz); 128.8 (d, J = 33 Hz); 127.1 (d, J = 17 Hz);
124.1 (d, J = 13 Hz); 115.1 (d, J = 85 Hz); 81.5; 64.5;
42.8; 28.0.
1H NMR (CDCl3, 200 MHz) d: 1.46 (s, 9H); 1.90–1.60
(m, 2H); 2.45–2.30 (m, 3H); 2.90–2.60 (m, 2H); 4.20–3.90
(m, 1H); 7.36–7.14 (m, 5H).
13C NMR (CDCl3, 50 MHz) d: 171.6; 142.6; 128.3;
127.5; 125.6; 81.3; 70.3; 44.3; 30.9; 28.0.
IR (neat): 3447, 2979, 2931, 1727, 1150 (cmꢁ1).
GC–MS: 165 (22); 147 (8); 230 (6); 79 (54); 57 (88); 167
(7); 51 (22) (m/z).
IR (neat): 3469, 2979, 2932, 1717, 1152 (cmꢁ1).
GC–MS: 184 (11); 125 (72); 97 (22); 77 (17); 57 (100); 51
(22) (m/z).
Acknowledgements
The European Commission through the project FP6-
505267-1 (LIGBANK), and PRIN 2005 (Progetto Nazio-
nale: Sintesi e Stereocontrollo di Molecole Organiche per
lo Sviluppo di Metodologie Innovative di Interesse Appli-
cativo) are acknowledged for financial support for this
research.
4.2.7. tertButyl-3-hydroxy-3-(4-tertbutylphenyl)-propionate
(4g)
1H NMR (CDCl3, 200 MHz) d: 1.30 (s, 9H); 1.44 (s,
9H); 2.63–2.65 (m, 2H); 3.27 (d, 1H, J = 3.0 Hz); 5.09
(m, 1H); 7.35–7.26 (m, 4H).
13C NMR (CDCl3, 75 MHz) d: 171.6; 150.4; 139.6;
125.4; 125.2; 81.3; 70.2; 44.3; 34.5; 31.3; 28.1.
IR (neat) 2972, 2924,1707, 1050 (cmꢁ1).
GC–MS: 221 (16); 161 (100); 147 (21); 119 (10); 105 (20);
91 (27); 77 (10); 57 (81) (m/z).
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