N-(α-chloroalkyloxycarbonyl)pyrrolidines as a source of oxygenated d1- reagents

Article abstract of DOI:10.1002/(SICI)1099-0690(199911)1999:11<3005::AID-EJOC3005>3.0.CO;2-7

Reaction of the N-(α-chloroalkyloxycarbonyl)pyrrolidines 1 with lithium powder and a catalytic amount of 4,4'-di-tertbutylbiphenyl (DTBB, 2.5 mol-%) in the presence of different electrophiles [iBuCHO, tBuCHO, PhCHO, Et₂CO, (CH₂)₅CO, PhCOMe, Ph₂CO, MeaSiCl], in THF at temperatures ranging between -78 and -60°C leads after hydrolysis with water, to the expected functionalized carbamates 2. Deprotection of compounds 2, derived from carbonyl compounds, with lithium hydroxide in a mixture of ethanol and water at 80°C affords the corresponding 1,2-diols 3.

Full text of DOI:10.1002/(SICI)1099-0690(199911)1999:11<3005::AID-EJOC3005>3.0.CO;2-7

FULL PAPER
N-(␣-Chloroalkyloxycarbonyl)pyrrolidines as a Source of Oxygenated
d1-Reagents
Javier Ortiz,[a] Albert Guijarro,[a] and Miguel Yus*[a]
´
Dedicated to Prof. Dr. Jose Elguero on the occasion of his 65th birthday
Keywords: Organolithium compounds / d1-Reagents / Lithiation / Carbamates / 1,2-Diols
Reaction of the N-(α-chloroalkyloxycarbonyl)pyrrolidines 1
between –78 and –60°C leads, after hydrolysis with water, to
with lithium powder and a catalytic amount of 4,4Ј-di-tert- the expected functionalized carbamates 2. Deprotection of
butylbiphenyl (DTBB, 2.5 mol-%) in the presence of different
compounds 2, derived from carbonyl compounds, with lithium
electrophiles [iBuCHO, tBuCHO, PhCHO, Et2CO, (CH2)5CO, hydroxide in a mixture of ethanol and water at 80°C affords the
PhCOMe, Ph2CO, Me3SiCl], in THF at temperatures ranging correponding 1,2-diols 3.
working under Barbier-type reaction conditions.[17] In this
paper we apply this methodology to the transformation of
O-chloroalkyl carbamates into the corresponding α-func-
Introduction
Functionalized organolithium compounds[1] are interest-
ing intermediates in synthetic organic chemistry because, in
a reaction with electrophiles, they are able to transfer their
functionality to the other reagent giving polyfunctionalized
molecules in only one reaction step. Among these lithium
compounds, the α-oxygenated alkyl derivatives of type I
(R ϭ alkyl: α-alkoxy carbanionic building blocks of the
type ROϪCϪ) belong to the family of so-called d1-reagents,
following SeebachЈs nomenclature,[2] and can be prepared
by four different routes: (1) Direct deprotonation of ethers
of type II (only in special cases e.g. alkyl benzyl ethers[3a]
or tert-butyl methyl ether[3b]) with an alkyllithium and a
coreagent [tetrametylethylenediamine (TMEDA) or potass-
ium tert-butoxide]; (2) Tin-lithium transmetallation of com-
pounds of type III with n-butyllithium;[4] (3) Sulfur-lithium
exchange in compounds of type IV with activated lithium
(e.g. lithium naphthalenide);[5] (4) Chlorine-lithium ex-
change in chloroethers of type V with lithium and either
a stoichiometric[6] or a catalytic[7][8] amount of an arene,
naphthalene or 4,4Ј-di-tert-butylbiphenyl (DTBB) being the
most commonly used[9] (Scheme 1). To the best of our
knowledge the alcohol derivatives of type I (R ϭ H, Me
or COX: α-hydroxy carbanion building blocks of the type
HOϪCϪ)have only been prepared following routes (1)[10]
and (2)[11] with, in the first case, very hindered arylic es-
ters[10a] or O-benzyl carbamates.[10b,10c,11] In the last few
years we have applied the above-mentioned arene-catalyzed
lithiation[8] (route 4) for the generation of organolithium
reagents starting from nonhalogenated materials,[13] very
reactive functionalized organolithium compounds from
chlorinated precursors[14] and heterocycles[15] or polylithi-
ated building blocks[16] from polychlorinated materials and
tionalized organolithium compounds, which have been
trapped in situ with different electrophilic reagents.[18]
Scheme 1. Preparation of d1-reagents I
Results and Discussion
The reaction of O-(α-chloroalkyl) carbamates 1a؊c with
an excess of lithium powder (ca. 1:7 molar ratio) and a cata-
lytic amount of DTBB (1:0.05 molar ratio; 2.5 mol-%) in
the presence of different electrophiles [iBuCHO, tBuCHO,
PhCHO, Et2CO, (CH2)5CO, PhCOMe, Ph2CO, Me3SiCl] in
THF, under the reaction conditions (temperature and reac-
tion time) given in Table 1 gave, after hydrolysis, the corre-
sponding reaction products 2aa؊cf (Scheme 2 and Table 1).
It should be noted that the process shown in Scheme 1
has to be performed under Barbier-type reaction conditions
[a]
´
´
Departamento de Quımica Organica, Facultad de Ciencias,
Universidad de Alicante,
Apdo. 99, E-03080 Alicante, Spain
Fax: (internat.) ϩ34-96/5903549
E-mail: yus@ua.es
Scheme 2. a: Li, DTBB cat. (2.5 mol%), Eϩ ϭ iBuCHO, tBuCHO,
PhCHO, Et2CO, (CH2)5CO, PhCOMe, Ph2CO, Me3SiCl, THF; b:
H2O
Eur. J. Org. Chem. 1999, 3005Ϫ3012
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
1434Ϫ193X/99/1111Ϫ3005 $ 17.50ϩ.50/0
3005

J. Ortiz, A. Grujarro, M. Yus
FULL PAPER
Table 1. Preparation of carbamates 2
in order to avoid decomposition of the intermediate of type
In the last part of this study we performed the deprotec-
VI, generated in situ, even at low temperature. This inter- tion of carbamates 2 derived from carbonyl compounds. Al-
mediate, which can decompose either by reaction with the though this process could be carried out by reduction with
excess lithium or by nucleophilic addition to the amide moi- DIBAL in refluxing THF for 6 h (Table 2, entry 6 and foot-
ety, is stabilized by intramolecular coordination of the lith- note [c]),[18] we found that hydrolysis with lithium hydroxide
ium atom to the carbonylic oxygen, through the so-called at 80°C for 1.5 h worked just as well, so we used this meth-
CIPE (”complex-induced polarity effect”).[19] Once the in- odology to obtain the corresponding 1,2-diols 3 (Scheme 3
termediates VI are formed, they react mainly with the elec- and Table 2). After this deprotection it is apparent that we
trophile present in the reaction medium to give the expected can use the methodology described in this paper to intro-
reaction products. As a confirmation of the low stability duce the nucleophilic HOCH(R)Ϫ unit into carbonyl com-
of this type of intermediate, we performed the step-by-step pounds, which act as electrophilic components.
process starting from the chlorocarbamate 1b and carrying
out the DTBB-catalyzed lithiation at Ϫ90°C followed by
deuterolysis with deuterium oxide, obtaining a very poor
yield (<10%) of the expected product 2a (R ϭ Me, E ϭ
D) with a very low deuterium content (<5%, from mass
spectrometry). Unexpectedly, when the same two-step pro-
cess was carried out with the starting material 1c, the corre-
Scheme 3. a: LiOH, EtOH/H2O, 80°C, 1.5 h
sponding product 2c (R ϭ c-C6H11, E ϭ D) was isolated
in 81% yield and with 70% deuterium incorporation (mass
spectrometry). The starting chlorocarbamates 1 were pre-
pared from the corresponding chlorinated chloroformates
and pyrrolidine in the presence of pyridine.
Conclusions
From the results described in this paper we can conclude
that this methodology is a new and versatile way to generate
a synthetic equivalent of α-lithiated alcohols. They readily
trap electrophiles in situ to give functionalized alcohols,
mainly 1,2-diols.
3006
Eur. J. Org. Chem. 1999, 3005Ϫ3012

N-(α-Chloroalkyloxycarbonyl)pyrrolidines as a Source of Oxygenated d1-Reagents
Table 2. Preparation of diols 3
FULL PAPER
for 15 min at 0°C under an argon atmosphere. The resulting mix-
ture was allowed to warm to room temperature (2 h for 1a,b and
40 min for 1c) and then dichloromethane (100 mL) was added. The
Experimental Section
General: All reactions were performed in oven-dried glassware un-
der an argon atmosphere. Ϫ Melting points: Reichert Thermovar
Apparatus. Ϫ 1H- and 13C-NMR spectroscopy: Bruker AC-300
with CDCl3 as a solvent; chemical shifts are quoted relative to
TMS as internal standard; δ in ppm, J in Hz. Ϫ FTIR: Nicolet
Impact 400D spectrophotometer recorded on films between NaCl
plates and reported in cmϪ1. Ϫ GC-LRMS: Shimazu QP-5000
Mass Spectrometer at 70 eV using electronic impact; relative inten-
sities for signals Ն10% in parentheses. Ϫ GC: Hewlett Packard HP-
5890 instrument equipped with a flame ionization detector and a
12 m HP-1 capillary column (0.2 mm diam., 0.33 mm film thick-
ness), with nitrogen (2 mL/min) as the carrier gas, Tinjector ϭ 275°C,
Tdetector ϭ 300°C, Tcolumn ϭ 60°C (3 min) and 60Ϫ270°C (15°C/
min). Ϫ TLC: Schleicher & Schuell F1400/LS 254 plates coated
with a 0.2 mm layer of silica gel; Rf values are given under these
conditions. Ϫ Column chromatography: Merk silica gel 60 of
63Ϫ200 mesh. Ϫ HRMS: Finigan MAT 955. Ϫ Microanalysis:
Microanalysis Service at the University of Alicante. Ϫ Commer-
cially available reagents were purchased (Aldrich, Acros) of the
highest grade and used without further purification. Chloromethyl
(Fluka) and α-chloroethyl (Aldrich) chloroformates are commer-
cially available. α-Chloro-α-cyclohexylmethyl chloroformate was
prepared from cyclohexanecarboxaldehyde and triphosgene follow-
ing the literature procedure.[20] [CAUTION: αϪChloroalkyl chloro-
formates are toxic and should be handled carefully]. Solvents were
dried by standard procedures.[21]
resulting solution was sucessively washed with 0.2
 HCl
(3 ϫ 10 mL), water (3 ϫ 10 mL) and brine (2 ϫ 10 mL). The or-
ganic layer was dried with Na2SO4, the solvent evaporated, and
the resulting residue distilled at reduced pressure to give the title
compounds 1b (65% yield; b.p. 50°C/0.1 Torr) and 1c (60% yield;
b.p. 140°C/0.1 Torr). Compound 1a was used without purification
for the lithiation reaction (ഠ 100% crude yield).
N-(Chloromethyloxycarbonyl)pyrrolidine (1a): oil. Ϫ IR (film): ν˜ ϭ
1
1732 (CϭO), 1121, 1093 (CO) cmϪ1. Ϫ H NMR: δ ϭ 1.85Ϫ1.95
(m, 4 H, CH2CH2CH2N), 3.40Ϫ3.50 (m, 4 H, CH2NCH2), 5.79 (s,
2 H, CH2Cl). Ϫ 13C NMR: δ ϭ 24.7, 25.55 (CH2CH2CH2N), 46.4,
46.9 (CH2NCH2), 70.55 (CH2Cl), 152.0 (CO2). Ϫ GC-LRMS: m/z
(%) ϭ 165 (Mϩ ϩ 2, 8), 163 (Mϩ, 24), 114 (80), 98 (10), 70 (50),
69 (10), 56 (56), 55 (70), 43 (32), 42 (100). Ϫ HRMS: m/z ϭ
163.0399 (Mϩ); calcd. for C6H10ClNO2: 163.0400.
N-[(1-Chloro)ethyloxycarbonyl]pyrrolidine (1b): oil. Ϫ IR (film): ν˜ ϭ
1731 (CϭO), 1100, 1071 (CO) cmϪ1. Ϫ 1H NMR: δ ϭ 1.81 (d, J ϭ
5.8 Hz, 3 H, CH3), 1.85Ϫ1.95 (m, 4 H, CH2CH2CH2N), 3.40Ϫ3.50
(m, 4 H, CH2NCH2), 6.61 (q, J ϭ 5.8 Hz, 1 H, CH). Ϫ 13C NMR:
δ
ϭ 24.7, 25.5 (CH2CH2CH2N), 25.45 (CH3), 45.8, 46.25
(CH2NCH2), 82.8 (CH), 151.85 (CO2). Ϫ GC-LRMS: m/z (%) ϭ
179 (Mϩ ϩ 2, 1.4), 177 (Mϩ, 4.2), 114 (39), 98 (61), 87 (11), 70
(55), 65 (35), 63 (100), 56 (53), 55 (68), 44 (18), 43 (71), 42 (53), 41
(62). Ϫ HRMS: m/z ϭ 177.0537 (Mϩ); calcd. for C7H12ClNO2:
177.0556.
Preparation of the Chlorocarbamates 1: To a stirred solution of pyr-
rolidine (1.42 g, 20 mmol), and pyridine (1.58 g, 20 mmol), in di-
chloromethane (15 mL) was added dropwise a solution of the cor-
responding chloroformate (20 mmol) in dichloromethane (5 mL)
N-[(Chlorocyclohexyl)methyloxycarbonyl]pyrrolidine (1c): oil. Ϫ IR
1
(film): ν˜ ϭ 1728 (CϭO), 1100, 1080 (CO) cmϪ1. Ϫ H NMR: δ ϭ
1.10Ϫ1.35 (m, 4 H, 4 ϫ CH cyclohexyl ring), 1.63Ϫ2.05 (m, 11
Eur. J. Org. Chem. 1999, 3005Ϫ3012
3007

J. Ortiz, A. Grujarro, M. Yus
FULL PAPER
H, 7 ϫ CH cyclohexyl ring, CH2CH2CH2N), 3.30Ϫ3.50 (m, 4 H,
(CϭO), 1182, 1130, 1110 (CO) cmϪ1. Ϫ 1H NMR: δ ϭ 0.90 (t, J ϭ
CH2NCH2), 6.32 (d, J ϭ 4.8 Hz, 1 H, CHCl). Ϫ 13C NMR: δ ϭ 7.4 Hz,
6 H, 2 ϫ CH3CH2), 1.53 (q, J ϭ 7.4 Hz, 4 H,
24.8, 25.6 (3C), 26.1 (5 ϫ CH2 cyclohexyl ring), 27.85, 28.25 2 ϫ CH3CH2), 1.80Ϫ1.95 (m, 4 H, CH2CH2CH2N), 2.50 (s, 1 H,
(CH2CH2CH2N), 44.95 (CHCH2), 45.85, 46.3 (CH2NCH2), 90.25 OH), 3.35Ϫ3.45 (m, 4 H, CH2NCH2), 4.03 (s, 2 H, CH2O). Ϫ 13C
(CHCl), 152.2 (CO2). Ϫ GC-LRMS: m/z (%) ϭ 209 (Mϩ Ϫ HCl,
NMR: δ ϭ 7.57 (2 ϫ CH3CH2), 24.85, 25.65 (CH2CH2CH2N),
6), 99 (5), 98 (100), 56 (23), 55 (76). Ϫ HRMS: m/z ϭ 209.1404 28.5 (2 ϫ CH3CH2), 45.75, 46.2 (CH2NCH2), 69.75 (CH2O), 73.85
(Mϩ Ϫ HCl); calcd. for C12H19NO2: 209.1416.
(COH), 155.35 (CO2). Ϫ GC-LRMS: m/z (%) ϭ 186 (Mϩ
Ϫ
CH3CH2, 8), 129 (21), 114 (100), 98 (82), 71 (10), 70 (33), 57 (14),
56 (37), 55 (71), 45 (29), 44 (12), 43 (36).
Preparation of Compounds 2 by DTBB-Catalyzed Lithiation of
Chlorocarbamates 1 under Barbier Conditions: To a blue suspension
of lithium powder (100 mg, 14 mmol) and DTBB (26 mg, N-[(1-Hydroxycyclohexyl)methyloxycarbonyl]pyrrolidine (2ae): oil,
0.1 mmol) in THF (6 mL) was slowly added (ca. 15 min) a solution
of the starting material 2 (2 mmol) and the corresponding elec-
trophile (2 mmol) in THF (4 mL) at Ϫ78°C under an argon atmos-
Rf ϭ 0.24 (hexane/ethyl acetate, 1:1). Ϫ IR (film): ν˜ ϭ 3421 (OH),
1683 (CϭO), 1130, 1107, 1071 (CO) cmϪ1. Ϫ 1H NMR: δ ϭ
1.40Ϫ1.70 (m, 10 H, 5 ϫ CH2 cyclohexyl ring), 1.83Ϫ1.95 (m, 4 H,
phere. The reaction mixture was stirred for 40 min or 2 h (see Table CH2CH2CH2N), 2.53 (br s, 1 H, OH), 3.35Ϫ3.45 (m, 4 H,
1) at temperatures ranging between Ϫ78 and Ϫ60°C (see Table 1),
and was then hydrolyzed with water (10 mL). After warming to
room temperature the crude mixture was extracted with diethyl
ether (3 ϫ 20 mL), the organic layer was dried with Na2SO4 and
the solvents evaporated. The residue was purified by column chro-
CH2NCH2), 4.01 (s, 2 H, CH2O). Ϫ 13C NMR: δ ϭ 21.6, 25.7 (2
C), 34.25 (2 C) (5 ϫ CH2 cyclohexyl ring), 24.8 (CH2CH2CH2N),
45.7, 46.15 (CH2NCH2), 70.6 (CH2O) 72.15 (COH), 155.25 (CO2).
Ϫ GC-LRMS: m/z (%) ϭ 227 (Mϩ, 0.7), 130 (13), 129 (31), 114
(100), 98 (48), 81 (13), 70 (29), 56 (22), 55 (52), 44 (10), 43 (52), 42
matography [silica gel (flash chromatography for compounds 2bb, (20), 41 (40). Ϫ HRMS: m/z ϭ 227.1512 (Mϩ); calcd. for
bf, cf), hexane/ethyl acetate] to give pure compounds 2. Yields are
C12H21NO3: 227.1521.
reported in Table 1.
N-[(2-Hydroxy-2-phenyl)propyloxycarbonyl]pyrrolidine (2af): oil,
N-[(2-Hydroxy-4-methyl)pentyloxycarbonyl]pyrrolidine (2aa): oil,
Rf ϭ 0.36 (hexane/ethyl acetate, 1:1). Ϫ IR (film): ν˜ ϭ 3427 (OH),
1
Rf ϭ 0.31 (hexane/ethyl acetate, 1:1). Ϫ IR (film): ν˜ ϭ 3430 (OH), 1683 (CϭO), 1181, 1129, 1108 (CO) cmϪ1. Ϫ H NMR: δ ϭ 1.56
1
1683 (CϭO), 1181, 1130, 1101 (CO) cmϪ1. Ϫ H NMR: δ ϭ 0.86 (s, 3 H, CH3), 1.80Ϫ1.90 (m, 4 H, CH2CH2CH2N), 3.22Ϫ3.38 (m,
(t, J ϭ 6.7 Hz, 6 H, 2 ϫ CH3), 1.70Ϫ1.79 [m, 5 H, CH2CH2CH2N,
4 H, CH2NCH2), 3.53 (s, 1 H, OH), 4.22, 4.30 (2 d, J ϭ 11.6 Hz,
(CH3)2CH], 2.90 (br s, 1 H, OH), 3.26- 3.40 (m, 4 H, CH2NCH2), 2 H, CH2O), 7.20Ϫ7.50 (m, 5 H, ArH). Ϫ 13C NMR: δ ϭ 24.85,
3.78Ϫ3.88 (m, 1 H, CHOH), 3.92 (dd, J ϭ 11.3, 7.0 Hz, 1 H,
CHHO), 4.07 (dd, J ϭ 11.3, 3.1 Hz, CHHO). Ϫ 13C NMR: δ ϭ
25.6 (CH2CH2CH2N), 26.35 (CH3), 45.7, 46.2 (CH2NCH2), 72.85
(CH2O), 74.0 (COH), 125.15, 126.95, 128.1, 144.8 (4 ϫ ArC),
21.9, 23.2 (2 ϫ CH3), 24.2 [CH(CH3)2], 24.8, 25.55 155.35 (CO2). Ϫ GC-LRMS; m/z (%): ϭ 234 (Mϩ Ϫ CH3, 0.2),
(CH2CH2CH2N), 42.2 [CH2CH(CH3)2], 45.7, 46.15 (CH2NCH2), 129 (32), 121 (20), 115 (10), 114 (100), 98 (30), 77 (16), 71 (11), 70
68.5 (CHOH), 69.8 (CH2O), 155.35 (CO2). Ϫ GC- LRMS: m/z
(%) ϭ 215 (Mϩ, 0.2), 158 (12), 129 (16), 116 (65), 114 (100), 98
(75), 70 (33), 56 (33), 55 (80). Ϫ HRMS: m/z ϭ 215.1534 (Mϩ);
calcd. for C11H21NO3: 215.1521.
(36), 56 (31), 55 (48), 44 (17), 43 (68). Ϫ HRMS: m/z ϭ 234.1146
(Mϩ Ϫ CH3); calcd. for C13H16NO3: 234.1130.
N-[(2,2-Diphenyl-2-hydroxy)ethyloxycarbonyl]pyrrolidine
(2ag):
white solid (m.p. 153Ϫ155°C, hexane), Rf ϭ 0.48 (hexane/ethyl
acetate, 1:1). Ϫ IR (KBr): ν˜ ϭ 3486 (OH), 1683 (CϭO), 1216, 1185,
N-[(3,3-Dimethyl-2-hydroxy)butyloxycarbonyl]pyrrolidine (2ab): oil,
Rf ϭ 0.44 (hexane/ethyl acetate, 1:1). Ϫ IR (film): ν˜ ϭ 3447 (OH),
1129 (CO) cmϪ1
.
Ϫ
1H NMR:
δ
ϭ
1.75Ϫ1.85 (m,
4 H,
1
1684 (CϭO), 1132, 1113, 1095 (CO) cmϪ1. Ϫ H NMR: δ ϭ 0.96
CH2CH2CH2N), 3.10Ϫ3.20, 3.30Ϫ3.40 (2 m, 4 H, CH2NCH2),
[s, 9 H, (CH3)3C], 1.80Ϫ1.95 [m, 4 H, CH2CH2CH2N], 2.84 (br d, 3.90 (s, 1 H, OH), 4.69 (s, 2 H, CH2O), 7.20Ϫ7.50 (m, 10 H, ArH).
J ϭ 3 Hz, 1 H, OH), 3.22Ϫ3.35 (m, 4 H, CH2NCH2), 3.45 (m, 1
H, CHOH), 4.08 (dd, J ϭ 11.6, 8.5 Hz, 1 H, CHHCH), 4.28 (dd,
Ϫ
13C NMR: δ ϭ 24.8, 25.5 (CH2CH2CH2N), 45.7, 46.25
(CH2NCH2), 70.9 (CH2O), 77.95 (COH), 126.55, 127.25, 128.1,
J ϭ 11.6, 2.0 Hz, CHHCH). Ϫ 13C NMR: δ ϭ 24.9, 25.7 143.95 (4 ϫ ArC), 155.15 (CO2). Ϫ GC-LRMS: m/z (%) ϭ 294
(CH2CH2CH2N), 25.85 [(CH3)3C], 33.9 [(CH3)3C], 45.8, 46.25 (Mϩ Ϫ H2O, 1.4), 196 (25), 184 (11), 183 (74), 165 (14), 114 (50),
(CH2NCH2), 67.3 (CH2O), 78.0 (CH), 155.65 (CO2). Ϫ GC-
105 (70), 98 (98), 77 (44), 72 (10), 70 (16), 56 (44), 55 (100). Ϫ
LRMS: m/z (%) ϭ 158 [Mϩ Ϫ (CH3)3C, 27], 116 (53), 114 (67), 98 C19H21NO3 (311.38): calcd. C 73.29, H 6.80, N 4.50; found C
(100), 70 (31), 57 (32), 56 (40), 55 (70), 44 (21). Ϫ HRMS: m/z ϭ
73.05, H 6.84, N 4.46.
215.1532 (Mϩ); calcd. for C11H21NO3: 215.1521.
N-(Trimethylsilylmethyloxycarbonyl)pyrrolidine (2ah): oil, Rf ϭ 0.68
(hexane/ethyl acetate, 1:1). Ϫ IR (KBr): ν˜ ϭ 1705 (CϭO), 1178,
N-[(2-Hydroxy-2-phenyl)ethyloxycarbonyl]pyrrolidine (2ac): white
solid (m.p. 79Ϫ80°C, toluene), Rf ϭ 0.29 (hexane/ethyl acetate,
1:1). Ϫ IR (KBr): ν˜ ϭ 3411 (OH), 1681 (CϭO), 1131, 1111, 1066,
1128, 1102 (CO), 857 (CSi) cmϪ1. Ϫ H NMR: δ ϭ 0.04 [s, 9 H,
1
(CH3)3Si], 1.75Ϫ1.85 (m, 4 H, CH2CH2CH2N), 3.25Ϫ3.40 (m, 4
1028 (CO) cmϪ1
. Ϫ δ ϭ 1.70Ϫ1.93 [m, 4
1H NMR: H, H, CH2NCH2), 3.68 (s, 2 H, CH2Si). Ϫ 13C NMR: δ ϭ Ϫ3.2
CH2CH2CH2N], 3.20Ϫ3.33 (m, 4 H, CH2NCH2), 3.70 (br s, 1 H, [(CH3)3Si], 24.95, 25.7 (CH2CH2CH2N), 46.2, 45.6 (CH2NCH2),
OH), 4.10Ϫ4.16 (m, 2 H, CH2CH), 4.85 (dd, J ϭ 6.5, 4.4 Hz, 1 H,
57.9 (CH2O), 156.35 (CO2). Ϫ GC-LRMS: m/z (%) ϭ 201 (Mϩ,
0.2), 186 (40), 142 (10), 114 (50), 98 (30), 73 (100), 56 (45), 55 (78),
CHOH), 7.18Ϫ7.30 (m, 5 H, ArH). Ϫ 13C NMR: δ ϭ 24.8, 25.55
(CH2CH2CH2N), 45.75, 46.15 (CH2NCH2), 70.35 (CH2O), 73.0 45 (27). Ϫ HRMS: m/z ϭ 201.1188 (Mϩ); calcd. for C9H19NO2Si:
(CHO), 126.1, 127.7, 128.25, 140.35 (4 ϫ ArC), 155.45 (CO2). Ϫ 201.1185.
GC-LRMS: m/z (%) ϭ 217 [Mϩ Ϫ H2O, 3], 129 (21), 116 (23), 114
(56), 98 (80), 91 (35), 79 (12), 77 (27), 71 (10), 70 (28), 65 (14), 56
N-[(2-Hydroxy-1,3,3-trimethyl)butyloxycarbonyl]pyrrolidine
(2bb), First diastereomer: white solid (m.p. 65Ϫ66°C, hexane), Rf ϭ
(45), 55 (100). Ϫ C13H17NO3 (235.28): calcd. C 66.36, H 7.28, N
0.38 (hexane/ethyl acetate, 1:1). Ϫ IR (KBr): ν˜ ϭ 3455 (OH), 1678
5.95; found C 66.43, H 7.35, N 5.79.
(CϭO), 1129, 1106 (CO) cmϪ1. Ϫ 1H NMR: δ ϭ 0.98 [s, 9 H,
N-[(2-Ethyl-2-hydroxy)butyloxycarbonyl]pyrrolidine (2ad): oil, Rf ϭ
0.36 (hexane/ethyl acetate, 1:1). Ϫ IR (film): ν˜ ϭ 3435 (OH), 1684
(CH3)3C], 1.29 (d, J ϭ 6.5 Hz, 3 H, CH3CH), 1.75Ϫ1.92 (m, 4 H,
CH2CH2CH2N), 2.15 (s, H, OH), 3.25Ϫ3.40 (m, H,
1
4
3008
Eur. J. Org. Chem. 1999, 3005Ϫ3012

N-(α-Chloroalkyloxycarbonyl)pyrrolidines as a Source of Oxygenated d1-Reagents
FULL PAPER
CH2NCH2), 3.47 (d, J ϭ 3.1 Hz, 1 H, CHOH), 4.97 (qd, J ϭ 6.5,
3.1 Hz, 1 H, CH3CH). Ϫ 13C NMR: δ ϭ 16.0 (CH3CH), 25.55, 1.75Ϫ1.90 (m,
25.65 (CH2CH2CH2N), 26.6 [(CH3)3C], 34.3 [(CH3)3C], 45.95, 46.1
NMR: δ ϭ 1.16 (d, J ϭ 6.1 Hz, 3 H, CH3CH), 1.55 (s, 3 H, CH3C),
H, CH2CH2CH2N), 3.10Ϫ3.35 [m, H,
CH2NCH2, OH], 5.05 (q, J ϭ 6.1 Hz, 1 H, CH), 7.18Ϫ7.57 (m, 5
4
5
(CH2NCH2), 72.75 (CH3CH), 80.75 (CHOH), 154.5 (CO2). Ϫ GC- H, ArH). Ϫ 13C NMR: δ ϭ 15.4 (CH3CH), 24.1 (CH3C), 24.7,
LRMS: m/z (%) ϭ 172 [Mϩ Ϫ (CH3)3C, 8], 143 (11), 116 (52), 114 25.5 (CH2CH2CH2N), 45.55, 46.0 (CH2NCH2), 76.2 (COH), 77.3
(70), 99 (20), 98 (100), 71 (11), 70 (18), 57 (50), 56 (25), 55 (51), 44 (CH3CH), 125.5, 126.8, 127.85, 145.2 (4 ϫ ArC), 154.7 (CO2). Ϫ
(20), 43 (36). Ϫ C12H23NO3 (229.32): calcd. C 62.85, H 10.11, N
6.11; found C 62.53, H 9.86, N 5.98. Second diastereomer: IR
GC-LRMS: m/z (%) ϭ 246 (Mϩ Ϫ OH, 0.2), 143 (47), 121 (42),
115 (13), 114 (99), 99 (20), 98 (90), 77 (24), 72 (12), 70 (45), 56 (57),
55 (95), 44 (20), 43 (100), 42 (24), 41 (29). Ϫ C15H21NO3 (263.34):
(KBr): ν˜ ϭ 3486 (OH), 1678 (CϭO), 1180, 1132, 1109 (CO) cmϪ1
.
Ϫ 1H NMR: δ ϭ 0.94 [s, 9 H, (CH3)3C], 1.34 (d, J ϭ 6.4 Hz, 3 H, calcd. C 68.42, H 8.04, N 5.32; found C 68.75, H 8.22, N 5.26.
CH3CH), 1.80Ϫ1.95 (m, 4 H, CH2CH2CH2N), 2.12 (br s, 1 H,
N-[(Deuterocyclohexyl)methyloxycarbonyl]pyrrolidine (2c, E ؍ D):
OH), 3.23Ϫ3.45 (m, 5 H, CH2NCH2, CHOH), 5.10 (qd, J ϭ 6.4,
oil, Rf ϭ 0.63 (hexane/ethyl acetate, 1:1). Ϫ IR (film): ν˜ ϭ 1703
1.2 Hz, 1H, CH3CH). Ϫ 13C NMR: δ ϭ 19.5 (CH3CH), 24.75,
24.8 (CH2CH2CH2N), 26.25 [(CH3)3C], 35.0 [(CH3)3C], 45.5, 45.6
1
(CϭO), 1132, 1115, 1099 (CO) cmϪ1. Ϫ H NMR: δ ϭ 0.80Ϫ2.00
[m, 15 H, 11 H cyclohexyl ring, CH2CH2CH2N], 3.32Ϫ3.42 (m, 4
(CH2NCH2), 69.75 (CH3CH), 81.15 (CHOH), 153.8 (CO2). Ϫ GC-
H, CH2NCH2), 3.89 (d, J ϭ 6.4 Hz, 1 H, CHD). Ϫ 13C NMR:
LRMS: m/z (%) ϭ 172 [Mϩ Ϫ (CH3)3C, 16], 116 (15), 114 (37), 98
δ ϭ 24.9, 25.7 (3 C), 26.45 (5 ϫ CH2 cyclohexyl ring), 29.65 (2 C,
CH2CH2CH2N), 37.4 (CHCH2), 45.65, 46.0 (CH2NCH2), 69.75 (t,
(175), 70 (26), 57 (100), 56 (21), 55 (47), 44 (40), 43 (56).
J ϭ 22 Hz, 1 C, CHD), 155.35 (CO2). Ϫ GC-LRMS: m/z (%) ϭ
212 (Mϩ, 0.1), 116, (90), 98 (12), 70 (23), 68 (13), 67 (16), 56 (58),
55 (100), 54 (12).
N-[(2-Ethyl-2-hydroxy-1-methyl)butyloxycarbonyl]pyrrolidine
(2bd): white solid (m.p. 85Ϫ86°C, hexane), Rf ϭ 0.40 (hexane/ethyl
acetate, 1:1). Ϫ IR (KBr): ν˜ ϭ 3475 (OH), 1675 (CϭO), 1131, 1100
(CO) cmϪ1. Ϫ 1H NMR: δ ϭ 0.91 (t, J ϭ 7.5 Hz, 6 H,
2 ϫ CH3CH2), 1.23 (d, J ϭ 6.4 Hz, 3 H, CH3CH), 1.35Ϫ1.68 (m,
4 H, 2 ϫ CH3CH2), 1.80Ϫ1.95 (m, 4 H, CH2CH2CH2N), 1.98 (s,
1 H, OH), 3.30Ϫ3.45 (m, 4 H, CH2NCH2), 4.84 (q, J ϭ 6.4 Hz, 1
H, CH). Ϫ 13C NMR: δ ϭ 7.45, 7.5 (2 ϫ CH3CH2), 14.95
N-[(1-Cyclohexyl-2-ethyl-2-hydroxy)butyloxycarbonyl]pyrrolidine
(2cd): white solid (m.p. 96Ϫ98°C, hexane), Rf ϭ 0.49 (hexane/ethyl
acetate, 1:1). Ϫ IR (KBr): ν˜ ϭ 3462 (OH), 1676 (CϭO), 1130, 1127,
1115 (CO) cmϪ1. Ϫ 1H NMR: δ ϭ 0.88, 0.90 (2 t, J ϭ 7.5, 7.5
Hz, 6 H, 2 ϫ CH3), 1.05Ϫ2.10 (m, 20 H, 11 H cyclohexyl ring,
(CH3CH), 24.85,
25.65
(CH2CH2CH2N), 26.65, 28.1
2 ϫ CH2CH3, CH2CH2CH2N, OH), 3.35- 3.50 (m,
4 H,
(2 ϫ CH3CH2), 45.75, 46.2 (CH2NCH2), 75.1 (CH), 75.8 (COH),
154.85 (CO2). Ϫ GC-LRMS: m/z (%) ϭ 200 (Mϩ Ϫ CH3CH2, 4),
143 (19), 116 (16), 114 (10), 98 (70), 71 (14), 70 (23), 57 (27), 56
(28), 55 (50), 45 (29), 44 (12), 43 (36). Ϫ C12H23NO3 (229.32):
calcd. C 62.85, H 10.11, N 6.11; found C 63.26, H 10.34, N 6.04.
CH2NCH2), 4.64 (d, J ϭ 2.4 Hz, 1 H, CHO). Ϫ 13C NMR: δ ϭ
7.65 (2 C, 2 ϫ CH3), 24.85, 25.65 (CH2CH2CH2N), 26.2, 26.3, 26.6,
26.85, 27.7, 28.8, 32.25 (5 ϫ CH2 cyclohexyl ring, 2 ϫ CH2CH3),
38.45 (CHCH2), 45.7, 46.25 (CH2NCH2), 76.95 (COH), 80.95
(CHO), 155.2 (CO2). Ϫ GC-LRMS: m/z (%) ϭ 268 (Mϩ
Ϫ
CH3CH2, 1), 211 (11), 116 (63), 115 (21), 114 (100), 98 (55), 71
(16), 70 (14), 57 (24), 56 (18), 55 (58), 45 (14), 43 (18). Ϫ
C17H31NO3 (297.44): calcd. C 68.65, H 10.51, N 4.71; found C
68.30, H 10.57, N 4.55.
N-[1-(1Ј-Hydroxycyclohexyl)ethyloxycarbonyl]pyrrolidine
(2be):
white solid (m.p. 72Ϫ74°C, hexane), Rf ϭ 0.38 (hexane/ethyl acet-
ate, 1:1). Ϫ IR (KBr): ν˜ ϭ 3448 (OH), 1681 (CϭO), 1129, 1104
(CO) cmϪ1. Ϫ 1H NMR: δ ϭ 1.23 (d, J ϭ 6.1 Hz, 3 H, CH3),
1.16Ϫ1.78 (m, 11 H, 5 ϫ CH2 cyclohexyl ring, OH), 1.82Ϫ1.94 (m,
4 H, CH2CH2CH2N), 3.30Ϫ3.45 (m, 4 H, CH2NCH2), 4.71 (q, J ϭ
6.1 Hz, 1 H, CH). Ϫ 13C NMR: δ ϭ 14.4 (CH3), 21.25, 21.4, 25.7,
N-[Cyclohexyl-(1Ј-hydroxycyclohexyl)methyloxycarbonyl]-
pyrrolidine (2ce): white solid (m.p. 113Ϫ115°C, hexane), Rf ϭ 0.51
(hexane/ethyl acetate, 1:1). Ϫ IR (KBr): ν˜ ϭ 3505 (OH), 1682 (Cϭ
1
O), 1177, 1134, 1107 (CO) cmϪ1. Ϫ H NMR: δ ϭ 1.02Ϫ2.05 (m,
32.5,
34.05 (5 ϫ CH2
cyclohexyl
ring), 24.8,
25.55
(CH2CH2CH2N), 45.6, 46.05 (CH2NCH2), 72.6 (COH), 76.8 (CH),
154.7 (CO2). Ϫ GC-LRMS: m/z (%) ϭ 212 (Mϩ Ϫ CH3CH2, 0.1),
143 (22), 115 (11), 114 (100), 99 (15), 98 (52), 81 (17), 71 (26), 70
(41), 69 (10), 57 (12), 56 (42), 55 (83), 53 (11), 45 (25), 44 (18), 43
(52), 42 (26), 41 (56). Ϫ C13H23NO3 (241.33): calcd. C 64.70, H
9.61, N 5.80; found C 64.67, H 9.79, N 5.72.
26 H, 10 ϫ CH2 cyclohexyl ring, CH2CH2CH2N, CHCHO, OH),
3.30- 3.50 (m, 4 H, CH2NCH2), 4.53 (d, J ϭ 3.0 Hz, 1 H,
CHCHO). Ϫ 13C NMR: δ ϭ 21.5 (2 C), 24.85, 25.7 (2 C), 26.2,
26.3, 26.55, 27.55, 32.3, 33.25, 35.5 (12 C, CH2CH2CH2N,
10 ϫ CH2 cyclohexyl rings), 38.4 (CHCHO), 45.65, 46.25
(CH2NCH2), 73.8 (COH), 82.85 (CHCHO), 155.2 (CO2). Ϫ GC-
LRMS: m/z (%) ϭ 211 [Mϩ Ϫ (CH2)5CO, 20], 116 (63), 115 (27),
115 (27), 114 (100), 99 (18), 98 (51), 71 (20), 70 (17), 56 (20), 55
(62).
N-[(2-Hydroxy-1-methyl-2-phenyl)propyloxycarbonyl]pyrrolidine
(2bf), First diastereomer: white solid (m.p. 123Ϫ125°C, hexane),
Rf ϭ 0.40 (hexane/ethyl acetate, 1:1). Ϫ IR (KBr): ν˜ ϭ 3436 (OH),
1667 (CϭO), 1198, 1095 (CO) cmϪ1. Ϫ 1H NMR: δ ϭ 1.04 (d, J ϭ
N-[(1-Cyclohexyl-2-hydroxy-2-phenyl)propyloxycarbonyl]-
6.4 Hz, 3 H, CH3CH), 1.58 (s, 3 H, CH3C), 1.80Ϫ1.93 (m, 4 H, pyrrolidine (2cf), First diastereomer: white solid (m.p. 160Ϫ162°C,
CH2CH2CH2N), 2.62 (s,
CH2NCH2), 5.05 (q, J ϭ 6.4 Hz, 1 H, CH), 7.15Ϫ7.47 (m, 5 H,
ArH). δ ϭ 15.1 (CH3CH), 24.9, 25.65 NMR: δ ϭ 0.97Ϫ1.93 [m, 16 H, 11 H cyclohexyl ring,
13C NMR:
1
H, OH), 3.30Ϫ3.45 (m,
4
H, hexane), Rf ϭ 0.42 (hexane/ethyl acetate, 1:1). Ϫ IR (KBr): ν˜ ϭ
3443, 3129 (OH), 1685 (CϭO), 1128, 1108, 1067 (CO) cmϪ1. Ϫ 1H
Ϫ
(CH2CH2CH2N), 27.55 (CH3C), 45.75, 46.25 (CH2NCH2), 76.0 CH2CH2CH2N, OH], 1.51 (s, 3 H, CH3), 3.40Ϫ3.55 (m, 4H,
(COH), 77.4 (CH3CH), 125.35, 126.8, 127.95, 144.2 (4 ϫ ArC), CH2NCH2), 4.91 (d, J ϭ 3.3 Hz, 1 H, CHO), 7.24Ϫ7.51 (m, 5 H,
154.7 (CO2). Ϫ GC-LRMS: m/z (%) ϭ 246 (Mϩ Ϫ OH, 0.1), 143
ArH). Ϫ 13C NMR: δ ϭ 24.9, 25.75 (CH2CH2CH2N), 26.1 (2 C),
(37), 121 (28), 115 (10), 114 (88), 99 (14), 98 (72), 77 (18), 71 (38), 26.3, 27.65, 31.95 (5 ϫ CH2 cyclohexyl ring), 29.4 (CH3), 38.45
70 (33), 56 (44), 55 (77), 44 (15), 43 (100), 42 (14), 41 (23). Ϫ (CHCH2), 45.8, 46.4 (CH2NCH2), 77.1 (COH), 83.25 (CHO),
C15H21NO3 (263.34): calcd. C 68.42, H 8.04, N 5.32; found C
125.15, 126.7, 128.0, 144.55 (4 ϫ ArC), 155.15 (CO2). Ϫ GC-
68.63, H 8.15, N 5.28. Second diastereomer: white solid (m.p. LRMS: m/z (%) ϭ 211 (Mϩ Ϫ CH3COPh, 15), 121 (30), 116 (31),
96Ϫ98°C, hexane), Rf ϭ 0.36 (hexane/ethyl acetate, 1:1). Ϫ IR 115 (15), 144 (60), 99 (13), 98 (97), 71 (23), 70 (14), 56 (27), 55
(KBr): ν˜ ϭ 3427 (OH), 1678 (CϭO), 1129, 1104 (CO) cmϪ1. Ϫ 1H (76), 43 (100). Ϫ C20H29NO3 (331.46): calcd. C 72.47, H 8.82, N
Eur. J. Org. Chem. 1999, 3005Ϫ3012
3009

J. Ortiz, A. Grujarro, M. Yus
FULL PAPER
4.23; found C 72.40, H 8.91, N 4.34. Second diastereomer: white
1-Hydroxymethylcyclohexanol (3ae):[11a] white solid (m.p. 75°C,
solid (m.p. 143Ϫ145°C, hexane), Rf ϭ 0.34 (hexane/ethyl acetate, toluene), Rf ϭ 0.25 (hexane/ethyl acetate, 3:7). Ϫ IR (KBr): ν˜ ϭ
1:1). Ϫ IR (KBr): ν˜ ϭ 3410 (OH), 1678 (CϭO), 1139, 1120, 1111,
3287 (OH), 1081, 1044 (CO) cmϪ1. Ϫ 1H NMR: δ ϭ 1.20Ϫ1.70
(m, 10 H, 5 ϫ CH2 cyclohexyl ring), 1.95, 2.15 (2 ϫ br s, 2 H,
(CO) cmϪ1. Ϫ 1H NMR: δ ϭ 1.07Ϫ1.90 [m, 15 H, 11 H cyclohexyl
ring, CH2CH2CH2N], 1.58 (s, 3 H, CH3), 2.99 (s, 1 H, OH), 2 ϫ OH), 3.45 (s, 2 H, CH2O). Ϫ 13C NMR: δ ϭ 21.8 (2 C), 25.85,
3.35Ϫ3.50 (m, 4 H, CH2NCH2), 4.85 (d, J ϭ 4.0 Hz, 1 H, CHO), 34.0 (2 C) (5 ϫ CH2 cyclohexyl ring), 70.0 (CH2OH), 71.9 (COH).
7.26Ϫ7.51 (m, 5 H, ArH). Ϫ 13C NMR: δ ϭ 24.8, 25.65 Ϫ GC-LRMS: m/z (%) ϭ 130 (Mϩ, 0.4), 99 (100), 87 (10), 81(79),
(CH2CH2CH2N), 25.05 (CH3), 26.1, 26.2, 26.3, 27.85, 32.3
(5 ϫ CH2 cyclohexyl ring), 38.5 (CHCH2), 45.65, 46.25
(CH2NCH2), 76.9 (COH), 84.05 (CHO), 125.6, 126.9, 127.9, 145.35
79 (17), 69 (10), 57 (16), 55 (40), 53 (11), 43 (44).
2-Phenyl-1,2-propanediol (3af):[24] white solid (m.p. 106Ϫ108°C,
toluene), Rf ϭ 0.30 (hexane/ethyl acetate, 3:7). Ϫ IR (KBr): ν˜ ϭ
3398 (OH), 1603, 1493 (Ph), 1069, 1044, 1027 (CO) cmϪ1. Ϫ 1H
NMR: δ ϭ 1.42 (s, 3 H, CH3C), 1.96, 2.68 (2 s, 2 H, 2 ϫ OH), 3.51
(d, J ϭ 11.3 Hz, 1 H, CHHO), 3.67 (d, J ϭ 11.3 Hz, 1 H, CHHO),
7.15Ϫ7.40 (5 H, m, ArH). Ϫ 13C NMR: δ ϭ 25.95 (CH3), 70.95
(CH2), 74.8 (COH), 125.05, 127.05, 128.15, 145.05 (4 ϫ ArC). Ϫ
GC-LRMS: m/z (%) ϭ 152 (Mϩ, 0.4), 121 (47), 105 (21), 77 (14),
51 (12), 43 (100).
(4 ϫ ArC), 155.35 (CO2). Ϫ GC-LRMS: m/z (%) ϭ 211 (Mϩ
Ϫ
CH3COPh, 13), 121 (27), 116 (28), 115 (13), 99(12), 98 (90), 71
(21), 70 (13), 56 (24), 55 (74), 43 (100). Ϫ C20H29NO3 (331.46):
calcd. C 72.47, H 8.82, N 4.23; found C 72.82, H 8.84, N 4.31.
Preparation of 1,2-Diols 3 by Hydrolysis of Carbamates 2: A mix-
ture of the corresponding compound 2 (0.5 mmol) in ethanol
(5 mL) and 3  LiOH aqueous solution (2.5 mL) was warmed at
80°C for 1.5 h. The resulting mixture was cooled to room tempera-
ture, acidified with 2  hydrochloric acid and extracted with ethyl
acetate (4 ϫ 10 mL). The organic layer was neutralized with satu-
rated aqueous NaHCO3, dried with Na2SO4 and the solvents eva-
porated. The resulting residue contained essentially pure (>95%
from NMR spectroscopy) 3. For analytical purposes they were dis-
tilled (kugelrohr) at reduced pressure (0.1 Torr). Yields are reported
in Table 2.
1,1-Diphenyl-1,2-ethanediol (3ag):[25] white solid (m.p.
120Ϫ121°C, toluene), Rf ϭ 0.55 (hexane/ethyl acetate, 3:7). Ϫ IR
(KBr): ν˜ ϭ 3377, 3311 (OH), 3083, 3057, 3023 (Ph), 1104, 1070,
1
1044 (CO) cmϪ1. Ϫ H NMR: δ (CD3OD) ϭ 4.14 (s, 2 H, CH2),
7.23Ϫ7.48 (m, 10 H, ArH). Ϫ 13C NMR: δ ϭ 70.75 (CH2), 80.35
(COH), 128.65, 128.7, 129.75, 147.3 (8 ϫ ArC). Ϫ GC-LRMS: m/z
(%) ϭ 196 (Mϩ Ϫ H2O, 3.2), 168 (77), 167 (15), 166 (36), 165 (43),
152 (27), 82 (15), 82 (11), 51 (10).
4-Methyl-1,2-pentanediol (3aa):[22] oil, Rf ϭ 0.29 (hexane/ethyl acet-
ate, 3:7). Ϫ IR (film): ν˜ ϭ 3385 (OH), 1076, 1025 (CO) cmϪ1. Ϫ
1H NMR: δ ϭ 0.91, 0.93 [2 d, J ϭ 5.5, 5.5 Hz, 6 H, (CH3)2CH],
1.16Ϫ1.37, 1.70Ϫ1.84 [2 m, 2 H, CH2CHC(CH3)2], 1.71Ϫ1.84 [m,
1 H, (CH3)2CH], 2.50, 3.28 (2 ϫ br s, 2 H, 2 ϫ OH), 3.39 (dd, J ϭ
11.6, 7.9 Hz, 1 H, CHHOH), 3.61 (dd, J ϭ 11.6, 2.4 Hz, 1 H,
CHHOH), 3.77 (m, 1 H, CHOH). Ϫ 13C NMR: δ ϭ 22.05, 23.3
[(CH3)2CH], 24.4 [(CH3)2CH], 41.95 [(CH3)2CHCH2], 67.1
(CH2OH), 70.4 (CHOH). Ϫ GC-LRMS: m/z (%) ϭ 118 (Mϩ, 0.4),
87 (30), 69 (82), 61 (28), 57 (14), 45 (67), 43 (100), 41 (69).
4,4-Dimethyl-2,3-pentanediol (3bb).[26] First diastereomer: white
solid (m.p. 71Ϫ72°C, hexane), Rf ϭ 0.34 (hexane/ethyl acetate, 1:1).
Ϫ IR (KBr): ν˜ ϭ 3381 (OH), 1073, 1040, 1013, 1001 (CO) cmϪ1
.
Ϫ 1H NMR: δ ϭ 0.97 [s, 9 H, (CH3)3C], 1.23 (d, J ϭ 6.1 Hz, 3 H,
CH3CH), 1.96, 2.10 (2 br s, 2 H, 2 ϫ OH), 3.40 [d, J ϭ 3.1 Hz, 1
H, CHC(CH3)3], 3.95 (qd, J ϭ 6.1, 3.1 Hz, 1 H, CHCH3). Ϫ 13C
NMR: δ ϭ 18.55 (CH3CH), 26.65 [(CH3)3C], 34.0 [(CH3)3C], 68.5
[CHC(CH3)3], 82.55 (CHCH3). Ϫ GC-LRMS: m/z (%) ϭ 114 (Mϩ
Ϫ H2O, 0.15), 87 (40), 75 (16), 73 (13), 69 (41), 57 (100), 45 (37),
43 (42), 41 (60). Second diastereomer: oil, Rf 0.31 (hexane/ethyl
acetate, 1:1). Ϫ IR (film): ν˜ ϭ 3416 (OH), 1132, 1067, 1016 (CO)
cmϪ1. Ϫ 1H NMR: δ ϭ 0.95 [s, 9 H, (CH3)3C], 1.25 (d, J ϭ 6.1
Hz, 3 H, CH3CH), 2.50Ϫ2.90 (br s, 2 H, 2 ϫ OH), 2.98 [d, J ϭ 1.2
Hz, 1 H, CHC(CH3)3], 3.98 (qd, J ϭ 6.1, 1.2 Hz, 1 H, CHCH3).
3,3-Dimethyl-1,2-butanediol (3ab):[11b] oil, Rf ϭ 0.26 (hexane/ethyl
acetate, 3:7). Ϫ IR (film): ν˜ ϭ 3404 (OH), 1090, 1044, 1020 (CO)
cmϪ1. Ϫ 1H NMR: δ ϭ 0.92 [s, 9 H, (CH3)3C], 3.36 (dd, J ϭ 10.0,
2.4 Hz, 1 H, CHHOH), 3.44 (br s, 1 H, OH), 3.48 (t, J ϭ 10.0 Hz,
1 H, CHHOH), 3.73 (dd, J ϭ 10.0, 2.4 Hz, 1 H, CHHOH). Ϫ 13C
NMR: δ ϭ 25.9 [(CH3)3C], 33.5 [(CH3)3C], 63.1 (CH2OH), 79.7
(CHOH). Ϫ GC-LRMS: m/z (%) ϭ 100 (Mϩ Ϫ H2O, 0.9), 87 (67),
69 (33), 61 (11), 57 (85), 56 (27), 55 (13), 44 (27), 43 (50).
Ϫ
13C NMR: δ ϭ 22.55 (CH3CH), 25.8 [(CH3)3C], 33.5 [(CH3)3C],
65.2 [CHC(CH3)3], 80.9 (CHCH3). Ϫ GC-LRMS: m/z (%) ϭ 114
(Mϩ Ϫ H2O, 0.2), 87 (36), 75 (26), 73 (14), 69 (37), 57 (100), 45
(55).
3-Ethyl-2,3-pentanediol (3bd):[27] oil, Rf ϭ 0.33 (hexane/ethyl acet-
ate, 1:1). Ϫ IR (film): ν˜ ϭ 3486 (OH), 1100, 1086 (CO) cmϪ1. Ϫ
1H NMR: δ ϭ 0.88 (t, J ϭ 7.6 Hz, 6 H, 2 ϫ CH3CH2), 1.15 (d,
J ϭ 6.1 Hz, 3 H, CH3CH), 1.31Ϫ1.69 (m, 4 H, 2 ϫ CH2), 2.44 (br
s, 2 H, 2 ϫ OH), 3.73 (q, J ϭ 6.1 Hz, 1 H, CH3CH). Ϫ 13C NMR:
δ ϭ 7.5, 7.6 (2 ϫ CH3CH2), 17.1 (CH3CH), 25.95, 27.5 (2 ϫ CH2),
1-Phenyl-1,2-ethanediol (3ac):[11a] white solid (m.p. 64°C, toluene),
Rf ϭ 0.26 (hexane/ethyl acetate, 3:7). Ϫ IR (KBr): ν˜ ϭ 3315 (OH),
1110, 1088, 1077, 1054, 1026 (CO) cmϪ1. Ϫ 1H NMR: δ ϭ 3.36
(br s, 2 H, 2 ϫ OH), 3.55Ϫ3.76 (m, 2 H, CH2O), 4.72Ϫ4.78 (m, 1
H, CHO), 7.20Ϫ7.30 (m, 5 H, ArH). Ϫ 13C NMR: δ ϭ 67.95
(CH2OH), 74.65 (CHOH), 126.0, 127.85, 128.45, 140.45 (4 ϫ ArC).
Ϫ GC-LRMS: m/z (%) ϭ 138 (Mϩ, 6.5), 107 (100), 79 (80), 77
(54), 51 (20).
70.95 (CH), 76.25 (COH). Ϫ GC-LRMS: m/z (%) ϭ 117 (Mϩ
Ϫ
CH3, 0.16), 103 (15), 87 (57), 85 (13), 69 (31), 57 (75), 55 (15), 45
(100), 43 (99), 41 (61).
2-Ethyl-1,2-butanediol (3ad):[23] white solid (m.p. 42Ϫ43°C, tolu-
ene), Rf ϭ 0.29 (hexane/ethyl acetate, 3:7). Ϫ IR (KBr): ν˜ ϭ 3404
1-(1Ј-Hydroxyethyl)-1-cyclohexanol (3be):[28] oil, Rf ϭ 0.29 (hexane/
ethyl acetate, 1:1). Ϫ IR (film): ν˜ ϭ 3404 (OH), 1097, 1075, 1048
(OH), 1073, 1055 (CO) cmϪ1. Ϫ 1H NMR: δ ϭ 0.87 (t, J ϭ 7.6 (CO) cmϪ1. Ϫ 1H NMR: δ ϭ 1.16 (d, J ϭ 6.7 Hz, 3 H, CH3),
Hz, 6 H, 2 ϫ CH3CH2), 1.51 (2 q, J ϭ 7.3 Hz, 4 H, 2 ϫ CH2CH3),
2.17, 2.35 (s, br s, 2 H, 2 ϫ OH), 3.46 (s, 2 H, CH2O). Ϫ 13C NMR: 3.57 (q, J ϭ 6.7 Hz, 1 H, CH). Ϫ 13C NMR: δ ϭ 16.95 (CH3),
δ ϭ 7.6 (2 ϫ CH3CH2), 27.55 (2 ϫ CH2CH3), 67.3 (CH2OH), 75.05 21.4, 21.6, 25.85, 31.25, 34.15 (5 ϫ CH2), 73.4 (COH), 73.75 (CH).
(COH). Ϫ GC-LRMS: m/z (%) ϭ 101 (Mϩ Ϫ OH, 0.3), 87 (45), Ϫ GC-LRMS: m/z (%) ϭ 126 (Mϩ Ϫ H2O, 0.2), 99 (77), 81 (100),
1.20Ϫ1.70 (m, 10 H, 5 ϫ CH2), 2.00Ϫ2.45 (2 ϫ br s, 2 H, 2 ϫ OH),
71 (125), 69 (13), 57 (15), 45 (100), 43 (83), 41 (60).
79 (15), 57 (20), 55 (65), 45 (19), 43 (70), 42 (18), 41 (39).
3010
Eur. J. Org. Chem. 1999, 3005Ϫ3012

N-(α-Chloroalkyloxycarbonyl)pyrrolidines as a Source of Oxygenated d1-Reagents
2-Phenyl-2,3-butanediol (3bf):[26] white solid (m.p. 46°C, hexane),
FULL PAPER
Acknowledgments
Rf ϭ 0.30 (hexane/ethyl acetate, 1:1). Ϫ IR (KBr): ν˜ ϭ 3416 (OH),
1602, 1493, 1447 (Ph), 1080, 1067, 1058, 1050 (CO) cmϪ1. Ϫ 1H
NMR: δ ϭ 0.94 (d, J ϭ 6.1 Hz, 3 H, CH3CH), 1.59 (s, 3 H, CH3C),
2.50 (s, 2 H, 2 ϫ OH), 3.87 (q, J ϭ 6.1 Hz, 1 H, CH), 7.21Ϫ7.44
(m, 5H, ArH). Ϫ 13C NMR: δ ϭ 17.6 (CH3CH), 26.6 (CH3C),
74.25 (CH), 76.45 (COH), 125.35, 126.8, 128.05, 144.54 (4 ϫ ArC).
Ϫ GC-LRMS: m/z (%) ϭ 148 (Mϩ Ϫ H2O, 0.25), 122 (18), 121
(43), 104 (12), 77 (23), 51 (19), 45 (11), 43 (100).
This work was supported by the DGICYT (nos. PB94Ϫ1514 and
PB97Ϫ0133) from the Spanish Ministerio de Educacion y Cultura
(MEC). A. G. thanks the MEC for a grant.
´
[1]
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[1a]
´
C. Najera, M. Yus, Trends Org. Chem. 1991, 2,
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´
C. Najera, M. Yus, Recent Res. Devel. Org.
155Ϫ181. Ϫ
Chem. 1997, 1, 67Ϫ96.
2-Phenyl-2,3-butanediol (3bfЈ):[26] oil, Rf ϭ 0.36 (hexane/ethyl acet-
ate, 1:1). Ϫ IR (film): ν˜ ϭ 3420 (OH), 1606, 1499 (Ph), 1034, 1112
D. Seebach, Angew. Chem. 1979, 91, 259Ϫ278; Angew. Chem.
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M. K. Yeh, J. Chem. Soc., Chem. Commun. 1981,
1
(CO) cmϪ1. Ϫ H NMR: δ ϭ 1.09 (d, J ϭ 6.1 Hz, 3 H, CH3CH),
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1983, 24, 3165Ϫ3168.
1.48 (s, 3 H, CH3C), 2.74, 3.25 (2 s, 2 H, 2 ϫ OH), 3.93 (q, J ϭ
6.1 Hz, 1 H, CH), 7.21Ϫ7.44 (m, 5 H, ArH). Ϫ 13C NMR: δ ϭ
16.6 (CH3CH), 22.75 (CH3C), 74.05 (CH), 76.55 (COH), 125.55,
126.85, 128.05, 146.0 (4 ϫ ArC). Ϫ GC-LRMS: m/z (%) ϭ 148
(Mϩ Ϫ H2O, 0.3), 121 (18), 105 (6), 77 (8), 43 (100).
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Leading references: [4a] W. C. Still, J. Am. Chem. Soc. 1978, 100,
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W. C. Still, A. Mitra, J. Am. Chem. Soc.
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[4e]
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D. K. Hutchison, P. L. Fuchs J. Am. Chem.
1-Cyclohexyl-2-ethyl-1,2-butanediol (3cd):[29] white solid (m.p.
144Ϫ150°C, hexane), Rf ϭ 0.70 (hexane/ethyl acetate, 1:1). Ϫ IR
[4f]
Soc. 1987, 109, 4930Ϫ4939. Ϫ
C. A. Broka, W. J. Lee, T.
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1
(KBr): ν˜ ϭ 3421, 3345 (OH), 1134, 11095, 1086 (CO) cmϪ1. Ϫ H
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1.10Ϫ2.02 (m, 17 H, 7 ϫ CH2, CHCHO, 2 ϫ OH), 3.26 (d, J ϭ 4.3
Hz, 1 H, CHCHO). Ϫ 13C NMR: δ ϭ 7.75, 7.9 (2 ϫ CH3), 26.3 (2
C), 26.6 (2 C), 26.85 (5 ϫ CH2 cyclohexyl ring), 28.5, 32.1
(2 ϫ CH2CH3), 39.0 (CHCHO), 77.1 (COH), 77.95 (CHCHO). Ϫ
GC-LRMS: m/z (%) ϭ 171 (Mϩ Ϫ CH2CH3, 1), 87 (100), 86 (18),
69 (14), 57 (45), 55 (28), 45 (78).
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6305Ϫ6306. Ϫ
K. Tomooka, T. Igarashi, M. Watanabe, T.
[4m]
Nakai, Tetrahedron Lett. 1992, 33, 5795Ϫ5798. Ϫ
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M. Hoffmann, V. Wittmann, H. Kessler, P. Uhlmann, A. Va-
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1-(Cyclohexylhydroxymethyl)cyclohexanol (3ce): white solid (m.p.
90Ϫ92°C, hexane), Rf ϭ 0.58 (hexane/ethyl acetate, 1:1). Ϫ IR
[4o]
Ϫ
O. Frey, M. Hoffmann, H. Kessler, Angew. Chem. 1995,
107, 2194Ϫ2195; Angew. Chem. Int. Ed. Engl. 1995, 34,
[4p]
1
(KBr): ν˜ ϭ 3415 (OH), 1098, 1085 (CO) cmϪ1. Ϫ H NMR: δ ϭ
2026Ϫ2028. Ϫ
M. Hoffmann, F. Burkhart, G. Hessler, H.
Kessler, Helv. Chim. Acta. 1996, 79, 1519Ϫ1532.
1.05Ϫ1.95 (m, 22 H, 10 ϫ CH2, CHCHO, OH), 2.04 (d, J ϭ 6.7
Hz, 1 H, OH) 3.26 (dd, J ϭ 6.7, 1.8 Hz, 1 H, CHCHO). Ϫ 13C
NMR: δ ϭ 21.8, 21.85, 25.75, 26.2, 26.3, 26.55, 26.8, 32.25, 33.0,
36.0 (10 ϫ CH2), 38.75 (CHCHO), 74.0 (COH), 80.6 (CHCHO).
Ϫ GC-LRMS: m/z (%) ϭ 212 (Mϩ, 0.1), 99 (100), 98 (66), 83 (13),
81 (76), 67 (16), 57 (16), 55 (51), 53 (11), 43 (36). Ϫ HRMS: m/z ϭ
212.1774 (Mϩ); calcd. for C13H24O2: 212.1776.
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T. Cohen, J. R. Matz, J. Am. Chem. Soc. 1980, 102,
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B. Kruse, R. Brükner, Tetra-
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A. Guijarro, M. Yus, Tetrahedron Lett. 1993, 34,
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3484Ϫ3490. Ϫ
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A. Guijarro, B. Manchen˜o, J. Ortiz, M. Yus,
1-Cyclohexyl-2-phenyl-1,2-propanediol (3cf): white solid (m.p.
113Ϫ115°C, hexane), Rf ϭ 0.65 (hexane/ethyl acetate, 1:1). Ϫ IR
(KBr): ν˜ ϭ 3462, 3341 (OH), 1603, 1494 (Ph), 1120, 1098, 1063
(CO) cmϪ1. Ϫ 1H NMR: δ ϭ 0.95Ϫ1.80 (m, 11 H, 5 ϫ CH2,
CHCHO), 1.62 (s, 3 H, CH3) 2.07 (d, J ϭ 5.8 Hz, 1 H, OH) 2.37
(s, 1 H, OH), 3.52 (d, J ϭ 5.8 Hz, 1 H, CHCHO), 7.20Ϫ7.45 (m,
5 H, ArH). Ϫ 13C NMR: δ ϭ 25.95, 26.15 (2 C), 26.5, 32.1
(5 ϫ CH2), 29.1 (CH3), 39.15 (CHCHO), 77.4 (COH), 81.6
(CHCHO), 124.9, 126.65, 128.1, 145.35 (4 ϫ ArC). Ϫ GC-LRMS:
m/z (%) ϭ 216 (Mϩ ϪH2O, 1.5), 111 (25), 105 (20), 83 (100), 55
(52), 41 (26). Ϫ HRMS: m/z ϭ 216.1517 (Mϩ Ϫ H2O); calcd. for
C15H20O: 216.1514. Ϫ C15H22O2 (234.33): calcd. C 76.88, H 9.46;
found C, 77.19, H 9.56.
[7c]
J. Ortiz, A. Guijarro,
[8] [8a]
´
First account: M. Yus, D. J. Ramon, J. Chem. Soc., Chem.
[8b]
Commun. 1991, 398Ϫ400. Ϫ
Rev. 1996, 155Ϫ161.
Review: M. Yus, Chem. Soc.
[9]
For a comparative study on the use of different arenes as elec-
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1980, 45, 1924Ϫ1930.
[10] [10a]
P. Beak, L. G. Carter, J. Org. Chem. 1981, 46, 2363Ϫ2373.
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Ϫ
B. A. Barner, R. S. Mani, Tetrahedron Lett. 1989, 30,
[10c]
5413Ϫ5416. Ϫ
W. Guarnieri, M. Grehl, D. Hoppe, Angew.
Chem. 1994, 106, 1815Ϫ1818; Angew. Chem. Int. Ed. Engl.
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1-Cyclohexyl-2-phenyl-1,2-propanediol (3cfЈ): white solid (m.p.
90Ϫ91°C, hexane), Rf ϭ 0.66 (hexane/ethyl acetate, 1:1). Ϫ IR
(KBr): ν˜ ϭ 3345 (OH), 1600, 1493 (Ph), 1082, 1074, 1045 (CO)
[12]
Indirect routes involving α-lithiated boranes[12a] or silyl deriva-
tives[12b]
:
A. Pelter, L. Williams, J. W. Wilson, Tetrahedron
[12a]
1
cmϪ1. Ϫ H NMR: δ ϭ 1.10Ϫ1.78 (m, 10 H, 5 ϫ CH2), 1.54 (s, 3
Lett. 1983, 24, 627Ϫ630. Ϫ [12b] K. Tamao, N. Ishida, M. Kum-
ada, J. Org. Chem. 1983, 48, 2120Ϫ2122.
H, CH3), 1.79 (d, J ϭ 4.2 Hz, 1 H, OH), 1.96 (m, 1 H, CHCHO),
2.71 (s, 1 H, OH), 3.61 (t, J ϭ 3.9 Hz, 1 H, CHCHO), 7.20Ϫ7.50
(m, 5 H, ArH). Ϫ 13C NMR: δ ϭ 24.35 (CH3), 26.2 (2 C), 26.6,
26.8, 32.05 (5 ϫ CH2), 38.9 (CHCHO), 76.9 (COH), 81.55
(CHCHO), 125.35, 126.85, 128.1, 147.05 (4 ϫ ArC). Ϫ GC-LRMS:
m/z (%) ϭ 216 (Mϩ Ϫ H2O, 0.5), 187 (24), 134 (34), 105 (100), 91
[13] [13a]
Review: D. Guijarro, M. Yus, Recent Res. Devel. Org.
[13b]
Chem. 1998, 2, 713Ϫ744. Ϫ
Last paper on this topic from
our laboratory: A. Bachki, F. Foubelo, M. Yus, Tetrahedron
Lett. 1998, 39, 7759Ϫ7762.
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[14b]
Review: ref.[1]
Ϫ
Last paper on this topic from our
laboratory: F. Foubelo, M. Yus, Tetrahedron Lett. 1999, 40,
743Ϫ746.
(25), 77 (12), 55 (23), 41 (29). Ϫ HRMS: m/z ϭ 216.1536 (Mϩ
Ϫ
[15] [15a]
Review: M. Yus, F. Foubelo, Rev. Heteroatom Chem. 1997,
[15b]
H2O); calcd. for C15H20O: 216.1514.
17, 73Ϫ107. Ϫ
Last paper on this topic from our labora-
Eur. J. Org. Chem. 1999, 3005Ϫ3012
3011

J. Ortiz, A. Grujarro, M. Yus
FULL PAPER
[22]
[23]
tory: T. Soler, A. Bachki, L. R. Falvello, F. Foubelo, M. Yus,
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Review: F. Foubelo, M. Yus, Trends Org. Chem. 1998, 7,
[16b]
1Ϫ26. Ϫ
Last paper on this topic from our laboratory: C.
[24]
[25]
´
Gomez, F. F. Huerta, M. Yus, Tetrahedron 1998, 54,
1853Ϫ1866.
[17] [17a]
Monograph: C. Blomberg in The Barbier Reaction and Re-
lated One-Step Processes (Eds.: K. Hafner, C. W. Rees, B. M.
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[27]
[28]
[29]
Trost, J.-M. Lehn, P. von R. Schleyer, R. Zahvadnik), Springer-
[17b]
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Review: F. Alonso, M. Yus, Recent
D. P. G. Hamon, R. A. Massy-Westrop, T. Pipithakul, Aust. J.
Chem. 1974, 27, 2199; Chem. Abstr. 1975, 82, 31397 g.
K. Tanino, T. Shimizu, M. Kuwahara, I. Kuwajima, J. Org.
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Res. Devel. Org. Chem. 1997, 1, 397Ϫ436. Ϫ [17c] Last paper on
´
this topic from our laboratory: C. Gomez, F. F. Huerta, M. Yus,
Tetrahedron 1998, 54, 6177Ϫ6184.
[18]
[19]
[20]
[21]
Preliminary communication: A. Guijarro, M. Yus, Tetrahedron
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R. M. Kislovets, N. A. Kararanov, I. I. Lapkin, Izv. Vyssh.
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3012
Eur. J. Org. Chem. 1999, 3005Ϫ3012