(N,N-Diisopropylcarbamoyloxy)-methyl p-tolyl sulfone: Preparation and application for the syntheses of 1,2-diols

Article abstract of DOI:10.1016/j.tet.2012.08.025

1-(N,N-Diisopropylcarbamoyloxy)-1-tosyl-methane (CbOCH₂Ts, Cb=N,N-diisopropylcarbamoyl) was readily prepared from p-TolSH, paraformaldehyde and CbCl. With the dual activation of CbO- and Ts-substitutions, deprotonation of CbOCH₂Ts co

Full text of DOI:10.1016/j.tet.2012.08.025

Tetrahedron 68 (2012) 8704e8711
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
(N,N-Diisopropylcarbamoyloxy)-methyl p-tolyl sulfone: preparation
and application for the syntheses of 1,2-diols
,
,
a,
*
Lu Ma a b, Dongmei Zhao b, Lin Chen a, Xin Wang a, Yue-Lei Chen a , Jingkang Shen
*
a Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, PR China
b Shenyang Pharmaceutical University, 103 Wenhua Lu, Shenyang 110016, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 10 June 2012
Received in revised form 20 July 2012
Accepted 10 August 2012
Available online 16 August 2012
1-(N,N-Diisopropylcarbamoyloxy)-1-tosyl-methane (CbOCH2Ts, Cb¼N,N-diisopropylcarbamoyl) was
readily prepared from p-TolSH, paraformaldehyde and CbCl. With the dual activation of CbO- and Ts-
substitutions, deprotonation of CbOCH2Ts could be effected not only by n-BuLi, but also by Grignard
reagents. Upon deprotonation, the title compound adds to various carbonyl structures. By choosing
proper organometallic reagents for consecutive steps, the addition intermediate undergoes in situ
conversions to efficiently yield regioselectively O-Cb protected and unprotected 1,2-diols.
Ó 2012 Elsevier Ltd. All rights reserved.
Dedicated to Professor Qi-Zhuo Wang on
the occasion of his 90th birthday
Keywords:
Nucleophilic addition
Aldehydes
N,N-Diisopropylcarbamoyl
Regioselective protection
1,2-Diols
1. Introduction
sulfinyl) carbamoyloxy bisubstitution will significantly increase the
CeH acidity, thus broaden the scope of organometallic reagents
1,2-Diols are ubiquitous in natural products and bioactive
structures. Regioselectively protected 1,2-diols are frequently en-
countered intermediates for organic synthesis.1 For preparation of
these structures, many useful methods starting from olefin or car-
bonyl structures have been devised.2 These methods generally re-
quire laborious multistep conversion, often with compromised
overall yield.
On the other side, O-carbamoyl protected alcohols proved their
directing capability in stereoselective lithiation chemistry.3 Nev-
ertheless, this chemistry has to be mediated by strong base such as
BuLi, thus limited scope of substrates could be applied for this
useful methodology. Besides, preparations of some O-carbamoyl
protected alcohols often fail to give satisfying yields, largely due to
the low reactivity and instability of carbamoyl chlorides. Efficient
syntheses of O-carbamoyl protected alcohols with higher structure
diversity are of particular interest.
used for O-carbamoyl directed metalation and the subsequent
nucleophilic reactions. Structures containing gem-sulfonyl carba-
moyloxy bisubstitutions were first prepared by Hoppe et al.4
However, their behavior upon metalation, and the following nu-
cleophilic reactions of the resulting carbanion were not systemat-
ically investigated. Hereby, we propose carbamoyloxymethyl
sulfone or sulfoxide (1) as a new building block. It is hoped that this
type of structure could be metalated under milder conditions.
While maintaining the usefulness of carbamoyloxy substitution in
the subsequent nucleophilic reactions, the additional sulfone or
sulfoxide will open possibilities for further transformations. Also, as
a surrogate of carbamoyl chloride, building block (1) could be used
to append carbamoyloxy group to complex structures.
Encouraged by early works from Hoppe et al.,4 we further
envisioned a preliminary application of structure (1): metalated
structure (1) will be added to carbonyl group, and the resulting oxy
anion will abstract the O-carbamoyl protection with the driving
force of subsequent elimination of the sulfonyl (or sulfinyl) group.
Compared to carbamoyloxy substitution, sulfonyl or sulfinyl
group is stronger activating factor for CeH bond upon metalation
(deprotonation). It is reasonable to propose that gem-sulfonyl (or
The useful intermediate, O-carbamoyl protected a-hydroxyl alde-
hyde (4), should be readily reduced to 1,2-diol structures (5) with
known methods (Scheme 1). In our lab, this proposal was realized
by experiments with unexpected findings, which led to highly
* Corresponding authors. Tel.: þ86 21 50806600 5407; e-mail addresses:
chenyl@mail.shcnc.ac.cn, chenyuelei@gmail.com (Y.-L. Chen).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.08.025

L. Ma et al. / Tetrahedron 68 (2012) 8704e8711
8705
efficient one-pot preparation of three types of 1,2-diols, including
both possible regioselectively O-carbamoyl protected and un-
protected 1,2-diols, from readily available starting materials. This
work provides a new solution for the problems described in the
beginning, and it will be elaborated in the following.
In realizing the plan in Scheme 1, preliminary experiments in-
dicated that: with n-BuLi, the addition of deprotonated 7 to simple
aldehydes generally gave slightly higher yield of structure 3 than
with i-PrMgCl. To make the results comparable with previous
reports,4a,b,c,e we kept n-BuLi as base in this part. According to early
experiments,4a,b,c,e structure 3 (often bearing more substituents on
C-2 than our compounds) should decompose to structure 4 in situ.
However, it was found difficult to initiate the Cb migration and Ts
elimination on our compounds of structure 3: protonated 3 can
always be separated in good yields. After screening numbers of
conditions, it was eventually discovered that sodium containing
base, such as NaHMDS, NaH or NaOMe, is crucial for the desired
migration and elimination from structure 3. We therefore reasoned
that the early working examples are probably due to: (1) more
substituents on C-2 of structure 3 facilitates migration and elimi-
nation for steric reasons and (2) Li metal used for preparing BuLi
often contains variable amount of sodium,9 which might accelerate
the O-Cb migration. As illustrated in Scheme 3, compound 7 was
deprotonated with n-BuLi, and then mixed with benzaldehyde to
give diastereomers 8a (53%) and 8b (45%) after separation. Com-
pounds 8a,b (as a 1.2:1 diastereomeric mixture) were then treated
with NaOMe (30% in methanol) to give an unstable aldehyde 9,
which was reduced immediately by addition of NaBH4 in situ. Un-
expectedly again, compound 11 was separated as a major product
(78%), along with 21% of desired product 12. The conversion from
compound 9 to 11 should proceed through structure 10: the steric
repulsion on C-2 of structure 10, coupled with the alcoholysis
condition of methanolated NaOMe, repels the Cb group10 from O-2
back to O-1.11 Of particular note is the stability of the O-Cb pro-
tection: compound 13 was never observed under above reaction
conditions (Scheme 3).
Scheme 1. Proposed 1,2-diol synthesis from general structure (1).
2. Results and discussion
Various compounds of structure 1 were screened against the
deprotonation step. It was found, for example, that when
R1¼sulfinyl, structure 1 is not particularly stable upon deprotona-
tion, and did not give high yield of structure 3. On the other hand,
when R¼2,2,4,4-tetramethyl-1,3-oxazolidine-3-carbonyl (Cby),5
structure 1 was identified as a difficult synthetic target, hence not
further pursued. Eventually we discovered that TsCH2OCb (7,
Cb¼N,N-diisopropylcarbamoyloxy) serves our purpose.
Similar to literature, compound 7 might be prepared by mixing
lithiated MeOCb6 and TsF.4a,c,e However lithiation of this simplest
carbamate7 may not be the best method for our purpose. Benneche
et al. prepared PhSCH2OTMS from PhSCH2OH and TMSCl.8 We
found that p-TolSCH2OH was readily formed from p-TolSH and
paraformaldehyde, however the reaction between p-TolSCH2OH
and CbCl was rather sluggish. Bases play important role in this
reaction, and they have to be carefully scrutinized to shift the re-
action to compound 6, but not decompose p-TolSCH2OH back to
thiol and formaldehyde. N,N-Dimethylaniline was recognized par-
ticularly good for this aim. Subsequent oxidation of sulfide with m-
CPBA readily gave the sulfone 7 with good yield. Thus, we are able
to prepare compound 7 in large scale from inexpensive starting
materials, avoiding using s-BuLi (Scheme 2).
Scheme 3. Migration of Cb and elimination of Ts should give compound 12, while the
second migration of Cb leads to 11 as a major product instead. (a) n-BuLi, then PhCHO,
THF, ꢁ78 ꢀC, 50 min , 53% for 8a, 45% for 8b; (b) NaOMe in MeOH, then NaBH4, THF,
0 ꢀC to rt, 2 h.
Next, we turned our attention to one-pot reactions using com-
pound 7 as starting material for the syntheses of regioselectively
protected and unprotected 1,2-diols, due to the following reasons:
(1) In view of the reaction conditions in Scheme 3, it is not only
intriguing, but also possible to combine all steps for the conversion
from 7 to 11 into one pot. (2) At this stage, however, we were still
not able to produce compound 12 (as a major product) from sep-
arated compound 8. It was felt that a one-pot reaction directly from
compound 7 may yield compound 12 (or compounds of general
structure 5), analogously to the literature conditions.4a,b,c,e (3) On
the other hand, previous experiments also demonstrated reduction
of gem-carbamoyloxy-tosyl structure with DIBAH12 to carbinol.4e
After compound 8 (or compounds of general structure 3) being
formed from compound 7, this reduction might also be carried out
in situ to yield unprotected 1,2-diol. The ideas are combined and
illustrated in Scheme 4.
Scheme 2. Preparation of the starting material 7. (a) (i) Neat, 110 ꢀC, 0.5 h; (ii) N,N-
dimethylaniline, CbCl, DCM, reflux, overnight, 76%; (b) m-CPBA, DCM, 0 ꢀC, 0.5 h, 60%.
As expected, compound 7 was readily deprotonated with n-BuLi
or Grignard reagents (preferably with i-PrMgCl). According to hy-
drogen/deuterium exchange experiments, NaHMDS and t-BuOK are
capable to partially deprotonate compound 7, too. To the best of our
knowledge, this is the first time that O-carbamoyl protected alcohol
is deprotontated with bases much weaker than BuLi. In the fol-
lowing works, both n-BuLi and i-PrMgCl were used to deprotonate
compound 7, and the results demonstrated their own advantages,
respectively.

8706
L. Ma et al. / Tetrahedron 68 (2012) 8704e8711
Table 1
Examples for one-pot syntheses described in Scheme 4
HO
1
OH
Entry (route)a
R1R2C]O
R
2
16
R
R1
R2
1 (A)
2 (A)
3 (A)
n-Pentyl
Ph
H
H
H
14a, 12%
11, 67%
14b, 59%
15a, n.d.b
12, 26%
15b, 27%
16a, n.d.
13, n.d.
16b, n.d.
4 (A)
5 (A)
6 (A)
H
H
H
14c, 80%
14d, 54%
14e, 56%
15c, 9%
16c, n.d.
16d, n.d.
16e, n.d.
Scheme 4. One-pot syntheses of regioselectively O-protected and unprotected 1,2-
diols. Conditions for route A: (a) n-BuLi, then R1R2C]O, ꢁ78 ꢀC, 50 min; (b) NaOMe
in MeOH, NaBH4, 0 ꢀC to rt, 2 h. Conditions for route B: (c) n-BuLi, then R1R2C]O,
ꢁ78 ꢀC, 50 min; (d) NaBH4, 0 ꢀC to rt, 2 h. Conditions for route C: (e) i-PrMgCl, then
R1R2C]O, 0 ꢀC, 2 h; (f) DIBAH, ꢁ78 ꢀC to rt, overnight.
15d, 16%
15e, 22%
For route A in Scheme 4, it was straightforward to combine two
operation steps in Scheme 3. Initial deprotonation (Scheme 4, step
a) was done preferably with n-BuLi than i-PrMgCl due to higher
yields, and the later migration/elimination/reduction/migration
sequence (Scheme 4, step b) was carried out in situ by simultaneous
addition of NaBH4 and methanolic NaOMe to give structure 14.
Sometimes structure 15 was isolated from this route as a minor
product, too. Structure 16 was never observed from this route. For
route B, the initial deprotonation (Scheme 4, step c) was done with
n-BuLi as well. Treatment in situ with methanolic or absolute
NaOMe along with NaBH4 invariably gave structure 14 as a major
product; changing the reducing reagent from NaBH4 to LiBH4 or
several Selectrides seemed not affecting the reaction direction, too.
We therefore used NaBH4 as a base and a reducing reagent to create
a strict aprotic condition, and structure 15 was then isolated as
a major product, with excellent selectivity for most examples
(Scheme 4, step d). Interestingly, to use this reduction condition for
step d, the initial step c has to be done with n-BuLi. When i-PrMgCl
was applied, the same NaBH4 condition for step d failed to give
either structure 15, or structure 14. We have not detected the for-
mation of structure 16 from route B. For route C in Scheme 4, ad-
dition intermediate from step e with n-BuLi could not react with
DIBAH in situ. However, when i-PrMgCl was used for deprotona-
tion, DIBAH readily reduced the intermediate to desired product 16,
without any detectable formation of structures 14 and 15.
7 (A)
8 (A)
9 (A)
H
H
H
14f, 71%
14g, 57%
14h, 60%
15f, n.d.
15g, n.d.
15h, 11%
16f, n.d.
16g, n.d.
16h, n.d.
10 (A)
11 (B)
Me
Ph
Me
H
14i, 64%
11, n.d.
15i, n.d.
12, 49%
16i, n.d.
13, n.d.
12 (B)
13 (B)
H
H
14j, n.d.
14b, 6%
15j, 57%
15b, 50%
16j, n.d.
16b,n.d.
14 (B)
15 (B)
H
H
14c, n.d.
14k, n.d.
15c, 51%
15k, 68%
16c, n.d.
16k, n.d.
16 (B)
H
14l, n.d.
15l, 68%
16l, n.d.
Itisobviousthattheorganometallic reagents used foreverysingle
step interfere with the subsequent conversions, and the reaction
direction can therefore be tuned by matching reagents used for
consecutive steps. Examples for Scheme 4 are showcased in Table 1.
As demonstrated in Table 1, route A (entries 1e10, Table 1) is
compatible with common substituted benzaldehydes. The yields of
desired products 11 and 14aei are moderate to good, and not sig-
nificantly altered by the substitutions on the phenyl ring. Pyridine
carboxaldehydes13 gave complex products in the reaction se-
quence. The selectivities of route A to structure 14 are moderate to
good. Minor product 15 was removed readily by chromatography,
while structure 16 was never observed. However the purification of
structure 14 was occasionally disturbed by the presence of benzyl
alcohols from reduction of unreacted benzaldehydes. In such cases,
stepwise alternative of route A is recommended. It is noteworthy
that acetone gave the desired product as well with excellent se-
lectivity. Although it is difficult to understand the selectivity pat-
tern according to present data, products 11 and 14aei with 1-OCb
group remain useful for synthesis, particularly with well-
established Cb directed lithiation chemistry.3
17 (B)
18 (B)
H
H
14d, 11%
14e, n.d.
15d, 49%
15e, 70%
16d, n.d.
16e, n.d.
19 (B)
20 (C)
21 (C)
H
H
H
14g, n.d.
11, n.d.
15g, 49%
12, n.d.
16g, n.d.
13, 57%
16d, 62%
Ph
14d, n.d.
15d, n.d.
22 (C)
23 (C)
H
14e, n.d.
15e, n.d.
16e, 62%
H
14g, n.d.
15g, n.d.
16g, 61%
24 (C)
Ph
Ph
14m, n.d.
15m, n.d.
16m, 57%
Similar to route A, route B (entries 11e19, Table 1) is compatible
with common substituted benzaldehydes, but not with pyridine car-
boxaldehydes.13 Yields of structure 15 are consistently moderate to
good, and selectivities to structure 15 are good to excellent. Structure
a
Reaction routes are described in Scheme 4.
n.d.: not detected by NMR. After workup, the reaction mixture was inspected by
b
proton NMR to identify the presence of substance in question. Flash chromatogra-
phy was then used to determine the yield.

L. Ma et al. / Tetrahedron 68 (2012) 8704e8711
8707
14 was rarely (entries 14 and 18, Table 1), and structure 16 was never
observed from this route. 2-O-Protected 1,2-diols 12, 15bee, 15g, and
15jel generally have to be prepared via multistep conversion accord-
ing to established 1,2-diols synthesis and protective group chemistry.
Moreover, installations of O-Cb protection on such secondary alcohols
are often difficult. However, they could now be prepared in one pot,
from readily available aldehydes and building block 7.
Route C invariably gives moderate yields of the desired un-
protected diols 13, 16dee, 16g, and 16m (entries 21e24, Table 1)
with excellent selectivity to structure 16, even when very hindered
diphenyl ketone was used (entry 24, Table 1). This route offers
a quick access to many useful 1,2-diol target molecules.
mixed and heated at 110 ꢀC for 30 min under nitrogen. The mixture
was then cooled to rt to give crude p-TolSCH2OH as a colorless oil,
which was directly dissolved in DCM (150 mL), treated with CbCl
(24.5 g, 150 mmol, 1.5 equiv) and N,N-dimethylaniline (13.3 g,
110 mmol, 1.1 equiv), and refluxed overnight. The resulting brown
mixture was then cooled to rt, washed with 2 N aq HCl, satd aq
NaHCO3, and brine. The organic phase was then separated and
concentrated to give an oil, which was purified with flash chro-
matography (on silica gel with 60e90 ꢀC petroleum ether and
EtOAc) to give product 6 (light yellow oil, 21.4 g, 80 mmol, 76%).
Compound 6: Rf 0.39 (ethyl acetate/60e90 ꢀC petroleum ether,
1:20); HPLC tR 3.8 min; 1H NMR (400 MHz, CDCl3)
d 7.38e7.35 (m,
2H, Ar), 7.13e7.11 (m, 2H, Ar), 5.44 (s, 2H, CH2OCb), 4.01 (br s, 1H,
Cb), 3.78 (br s, 1H, Cb), 2.33 (s, 3H, Ar-CH3), 1.19 (d, J¼5.8 Hz, 12H,
3. Conclusion
Cb); 13C NMR (100 MHz, CDCl3)
d 154.4 (C]O), 137.2 (Arq),
In summary, we have proposed and efficiently synthesized
a new building block 7, which was found to be readily deprotonated
with n-BuLi and Grignard reagents. Thanks to this finding, the
following one-pot 1,2-diol syntheses became possible: By carefully
choosing organometallic reagents for consecutive steps, from 7,
readily available carbonyl compounds, and inexpensive reagents,
we developed highly telescoped one-pot syntheses for three types
of 1,2-diols, including both possible regioselectively O-Cb protected
and unprotected 1,2-diols, which generally require multistep syn-
thesis according to known methods. Based on the importance of
1,2-diols and well-established carbamoyloxy-directed lithiation
chemistry, it is possible for building block 7, above described one-
pot syntheses of 1,2-diols, and various Cb-protected alcohol prod-
ucts to find more applications in organic synthesis. Further use of
building block 7 is under active exploration in our group.
131.5(Arq), 131.0 (2C, Ar), 129.7 (2C, Ar), 69.0 (SCH2OCb), 46.5 (Cb),
45.5 (Cb), 21.3 (2C, Cb), 21.0 (Ar-CH3), 20.6 (2C, Cb); HRMS (ESIþ)
calcd for C15H23NO2SNaþ 304.1347, found 304.1336.
4.2.2. (N,N-Diisopropylcarbamoyloxy)methyl
p-tolyl
sulfone
(7). Compound 6 (20.0 g, 71.07 mmol, 1 equiv) was dissolved in
DCM (300 mL). To this solution at 0 ꢀC, a solution of m-CPBA (75%,
49.1 g, 213.21 mmol, 3 equiv) in DCM (200 mL) was added drop-
wise. Monitored by TLC, the resulting slurry was stirred for further
30 min at 0 ꢀC, and then treated with satd aq Na2S2O3 and satd aq
NaHCO3. The organic phase was separated and the aqueous phase
was washed with DCM. Combined organic phases were washed
with brine, concentrated, and purified with flash chromatography
(on silica gel with 60e90 ꢀC petroleum ether and EtOAc) to give
product 7 (white solid, 13.4 g, 42.76 mmol, 60%). Compound 7: Rf
0.43 (ethyl acetate/60e90 ꢀC petroleum ether, 1:4); mp 68e69 ꢀC;
4. Experimental section
4.1. General
HPLC tR 3.8 min; 1H NMR (400 MHz, CDCl3)
d 7.83e7.77 (m, 2H, Ar),
7.37e7.32 (m, 2H, Ar), 5.19 (s, 2H, TsCH2OCb), 3.92 (br s, 1H, Cb),
3.71 (br s, 1H, Cb), 2.44 (s, 3H, Ar-CH3), 1.16 (d, J¼6.4 Hz, 6H, Cb),
1.09 (d, J¼6.4 Hz, 6H, Cb); 13C NMR (100 MHz, CDCl3)
d 151.7 (C]O),
All solvents were dried and purified prior to use: Toluene was
distilled from sodium, Et2O and THF were distilled from potassium,
and CH2Cl2 was distilled from CaH2. All other commerciallyavailable
reagents were used as received. Reactions at ꢁ78 ꢀC were performed
in a dry ice/acetone bath. All moisture sensitive reactions were
performed under N2 (ca. þ1.1 bar) in heating-gun (500e600 ꢀC)/
vacuum dried glassware sealed with rubber septa. Flash chroma-
tography was performed on silica gel (300e400 mesh ASTM), and
monitored by thin layer chromatography (TLC) on HSGF-254
145.3 (Arq), 133.8 (Arq), 129.7 (2C, Ar), 129.0 (2C, Ar), 76.7
(TsCH2OCb), 46.5 (Cb), 46.4 (Cb), 21.6 (AreCH3), 21.0 (2C, Cb), 20.0
(2C, Cb); HRMS (ESIþ) calcd for C15H23NO4SNaþ 336.1245, found
336.1250. Anal. Calcd for C15H23NO4S (313.13): C, 57.48; H, 7.40; N,
4.47; S, 10.23. Found: C, 57.54; H, 7.50; N, 4.46; S, 10.29.
4.2.3. 1-(N,N-Diisopropylcarbamoyloxy)-2-hydroxyl-2-phenylethyl
p-tolyl sulfones (8a,b). Compound 7 (300 mg, 0.96 mmol, 1 equiv)
was dissolved in anhydrous Et2O (9 mL), cooled to ꢁ78 ꢀC, and
treated with n-BuLi (1.6 M in hexanes, 0.8 mL, 1.25 mmol,
1.3 equiv). The mixture was stirred at this temperature for 45 min,
treated with benzaldehyde (112 mg, 1.06 mmol, 1.1 equiv), and
again stirred at ꢁ78 ꢀC for 1 h. TLC indicated the reaction has been
completed. The resulting clear solution was quenched by satd aq
NH4Cl. The organic layer was separated, and the aqueous phase was
washed with ether for several times. Combined organic phases
were washed with brine, concentrated, and purified with flash
chromatography (on silica gel with 60e90 ꢀC petroleum ether and
EtOAc) to give products 8a (colorless oil, 215 mg, 0.51 mmol, 53%)
and 8b (colorless oil, 180 mg, 0.43 mmol, 45%). Compound 8a: Rf
0.29 (ethyl acetate/60e90 ꢀC petroleum ether, 1:4); HPLC tR
(10e40 mm) TLC plates. NMR data were collected on a Varian
Mercury-300 High Performance Digital FT-NMR, a Varian Mercury-
400 High Performance Digital FT-NMR, or a Bruker Ultrashield 500
NMR. Spectra from solutions in CDCl3 (dC¼77.0 ppm) are calibrated
relative to SiMe4
(
dH¼0.00 ppm). HRMS were carried out on
a Thermo Finnigan MAT-95 spectrometer (for EI), or on a Waters, Q-
Tof Ultima Global spectrometer (for ESI). Melting points were
measured on an uncorrected SGW X-4 micro melting point appa-
ratus. HPLC analysis was performed on a Gilson HPLC system (306
pump, UV/vis-156 Detector, 215 liquid handle) with an YMC-ODS
column (4.6ꢂ50 mm, 5 m). HPLC conditions: solvent A¼H2O con-
m
taining 0.1% (v/v) TEA, solvent B¼MeCN containing 0.1% (v/v) TEA;
flow rate¼2.5 mL/min; gradient (B%): 0e5 min (4%e95%); peaks
were identified at 254 nm and 214 nm. An Elementar Vario EL Cube
analyzer was used for elemental analysis.
3.8 min; 1H NMR (400 MHz, CDCl3)
d 7.83e7.78 (m, 2H, Ar),
7.42e7.36 (m, 2H, Ar), 7.35e7.20 (m, 5H, Ar), 5.92 (d, J¼1.4 Hz, 1H,
CHOH), 5.76 (pseudo-s, 1H, CHOCb), 4.18e4.02 (m, 1H, Cb), 3.70 (d,
J¼1.4 Hz, 1H, OH), 3.46e3.31 (m, 1H, Cb), 2.41 (s, 3H, AreCH3), 1.15
(d, J¼6.9 Hz, 3H, Cb), 1.13 (d, J¼6.9 Hz, 3H, Cb), 0.87 (d, J¼6.9 Hz, 3H,
4.2. Preparation of substrates and initial explorations de-
scribed in Schemes 2 and 3
Cb), 0.82 (d, J¼6.9 Hz, 3H, Cb); 13C NMR (100 MHz, CDCl3)
d 150.2
(C]O), 145.2 (Arq), 137.5 (Arq), 132.5 (Arq), 129.2 (2C, Ar), 129.1 (2C,
Ar), 127.8 (2C, Ar), 127.7 (Ar), 125.8 (2C, Ar), 86.1 (CHOCb), 69.6
(CHOH), 46.1 (Cb), 45.5 (Cb), 21.2 (CH3), 20.5 (Cb), 20.3 (Cb), 19.3
(Cb), 19.2 (Cb); HRMS (ESIþ) calcd for C22H29NO5SNaþ 442.1664,
4.2.1. p-Tolyl-(N,N-diisopropylcarbamoyloxy)-methyl sulfide (6). p-
TolSH (11.4 g, 0.10 mol, 1 equiv), paraformaldehyde (3.0 g, 0.10 mol,
1 equiv), and methanolic NaOMe (30%, 0.03 mL, 0.0017 equiv) were

8708
L. Ma et al. / Tetrahedron 68 (2012) 8704e8711
found 442.1663. Compound 8b: Rf 0.19 (ethyl acetate/60e90 ꢀC
petroleum ether, 1:4); HPLC tR 3.8 min; 1H NMR (400 MHz, CDCl3)
solution was stirred at ꢁ78 ꢀC for 45 min, treated with corre-
sponding carbonyl compound (neat, 0.35 mmol, 1.1 equiv), stirred
at ꢁ78 ꢀC for further 50 min, and treated with NaBH4 (121 mg,
3.2 mmol, 10 equiv). The resulting suspension was gradually
warmed to rt and stirred at rt until completion (ca. 2 h) indicated by
TLC. The reaction was quenched with satd aq NH4Cl. The organic
layer was separated, and the aqueous phase was washed with ether
for several times. Combined organic phases were washed with
brine, concentrated, and purified with flash chromatography (on
silica gel with 60e90 ꢀC petroleum ether and EtOAc) to give
products 12, 15bee, 15g, and 15jel.
d
7.86e7.79 (m, 2H, Ar), 7.42e7.36 (m, 2H, Ar), 7.35e7.23 (m, 5H,
Ar), 6.02 (d, J¼8.9 Hz, 1H, CHOCb), 5.34 (dd, J¼8.9, 2.4 Hz, 1H,
CHOH), 3.92e3.79 (m, 1H, Cb), 3.62 (d, J¼2.4 Hz, 1H, OH), 3.31e3.15
(m, 1H, Cb), 2.42 (s, 3H, AreCH3), 0.96e0.77 (m, 12H, Cb); 13C NMR
(100 MHz, CDCl3) d 149.4 (C]O), 145.0 (Arq), 137.3 (Arq), 133.2 (Arq),
129.2 (2C, Ar), 128.9 (2C, Ar), 128.1 (Ar), 127.8 (2C, Ar), 127.2 (2C, Ar),
86.0 (CHOCb), 71.4 (CHOH), 46.1 (Cb), 45.0 (Cb), 21.2 (Ar-CH3), 20.0
(Cb), 19.9 (Cb), 19.3 (2C, Cb); HRMS (ESIþ) calcd for C22H29NO5SNaþ
442.1664, found 442.1651.
4.2.4. 1-Phenyl-2-O-(N,N-diisopropylcarbamoyl)-1,2-ethanediol (11)
and 1-O-(N,N-diisopropylcarbamoyl)-1-phenyl-1,2-ethanediol
(12). Compounds 8a,b (as 1.2:1 diastereomeric mixture, 100 mg,
0.24 mmol, 1 equiv) were dissolved in dry THF (3 mL) and cooled to
0 ꢀC. To this solution, NaBH4 (72 mg, 1.92 mmol, 8 equiv) and
methanolic NaOMe (30% w/v, 0.17 mL, 0.96 mmol, 4 equiv) were
added. The resulting suspension were stirred at this temperature for
30 min, slowly warmed to rt, and stirred at rt for 2 h with frequent
TLC inspection. Upon completion (indicated by TLC), the reaction
was quenched with satd aq NH4Cl. The organic layer was separated,
and the aqueous phase was washed with ether for several times.
Combined organic phases were washed with brine, concentrated,
and purified with flash chromatography (on silica gel with 60e90 ꢀC
petroleum ether and EtOAc) to give products 1114 (colorless oil,
49 mg, 0.18 mmol, 78%) and 12 (colorless oil, 13 mg, 0.05 mmol,
21%). Compound 11: Rf 0.35 (ethyl acetate/60e90 ꢀC petroleum
4.5. General procedure for route C
Compound 7 (100 mg, 0.32 mmol, 1 equiv) was dissolved in dry
THF (2 mL), and cooled to 0 ꢀC. To this solution, i-PrMgCl (2.0 M in
THF, 0.22 mL, 0.44 mmol, 1.4 equiv) was added. The clear solution
was stirred at 0 ꢀC for 2 h, treated with corresponding carbonyl
compound (neat, 0.38 mmol, 1.2 equiv), stirred at 0 ꢀC for further
50 min, cooled to ꢁ78 ꢀC, and treated with DIBAH (1.0 M in hex-
anes, 3.8 mL, 3.8 mmol, 12 equiv). The resulting mixture was
gradually warmed to rt and stirred overnight. Upon completion
(indicated by TLC), the reaction was quenched with satd aq NH4Cl,
and stirred with satd aq Rochelle salt. The organic layer was sep-
arated, and the aqueous phase was washed with ether for several
times. Combined organic phases were washed with brine, con-
centrated, and purified with flash chromatography (on silica gel
with 60e90 ꢀC petroleum ether and EtOAc) to give products 13,
16dee, 16g, and 16m.
ether, 1:4); HPLC tR 3.4 min; 1H NMR (400 MHz, CDCl3)
d 7.55e7.01
(m, 5H, Ph), 4.97 (dt, J¼7.0, 3.5 Hz, 1H, CHOH), 4.26 (d, J¼3.7 Hz, 1H,
CH2OCb), 4.28 (d, J¼7.0 Hz, 1H, CH2OCb), 4.02 (br s, 1H, Cb), 3.81 (d,
J¼3.5 Hz, 1H, OH), 3.77 (br s, 1H, Cb), 1.19 (br s, 12H, Cb); 13C NMR
4.6. Experiments described in Scheme 4 and Table 1
(125 MHz, CDCl3)
d
156.4 (C]O), 140.6 (Phq), 128.4 (2C, Ph), 127.8
4.6.1. 1-O-(N,N-Diisopropylcarbamoyl)-1,2-heptanediol
(Ph),126.2 (2C, Ph), 73.5 (CHOH), 70.4 (CH2OCb), 46.6 (Cb), 45.7 (Cb),
21.2 (2C, Cb), 20.5 (2C, Cb); HRMS (ESIþ) calcd for C15H23NO3Naþ
288.1576, found 288.1587. Compound 12: Rf 0.40 (ethyl acetate/
60e90 ꢀC petroleum ether,1:3); HPLC tR 3.2 min; 1H NMR (400 MHz,
(14a). According to route A, from compound 7 (100 mg,
0.32 mmol), compound 14a (colorless oil, 10 mg, 0.04 mmol, 12%)
was obtained. Compound 14a: Rf 0.29 (ethyl acetate/60e90 ꢀC pe-
troleum ether, 1:4); HPLC tR 3.8 min; 1H NMR (400 MHz, CDCl3)
CDCl3)
4.07 (s, 1H, Cb), 3.92e3.80 (m, 3H, Cb, CH2OH), 3.08 (br s, 1H, OH),
1.22 (m, 12H, Cb); 13C NMR (100 MHz, CDCl3)
155.4 (C]O), 137.3
(Phq), 128.1 (2C, Ph), 127.7 (Ph), 126.2 (2C, Ph), 77.9 (CHOCb), 66.9
(CH2OH), 46.3 (Cb), 45.2 (Cb), 21.0 (2C, Cb), 20.0 (2C, Cb); HRMS
(ESIþ) calcd for C15H23NO3Naþ 288.1576, found 288.1589.
d
7.44e7.27 (m, 5H, Ph), 5.84 (dd, J¼7.8, 3.6 Hz, 1H, CHOCb),
d 4.83 (m, 1H, CHOH), 4.05 (br s, 1H, Cb),3.79 (br s, 1H, Cb),
3.74e3.62 (m, 2H, CH2OCb), 3.18 (br s, 1H, OH), 1.70e1.48 (m, 2H,
CH2(CH2)3CH3), 1.44e1.25 (m, 6H, CH2(CH2)3CH3), 1.22 (d, J¼6.8 Hz,
12H, Cb), 0.88 (m, 3H, CH2(CH2)3CH3); 13C NMR (125 MHz, CDCl3)
d
d
156.7 (C]O), 77.2 (CHOH), 66.3 (CH2OCb), 46.5 (Cb), 45.5 (Cb),
31.7 (CH2), 31.1 (CH2), 25.2 (CH2), 22.5 (CH2), 21.5 (2C, Cb), 20.6 (2C,
Cb), 14.0 (CH2(CH2)3CH3); HRMS (ESIþ) calcd for C14H29NO3Naþ
282.2045, found 282.2050.
4.3. General procedure for route A
Compound 7 (100 mg, 0.32 mmol, 1 equiv) was dissolved in dry
THF (2 mL), and cooled to ꢁ78 ꢀC. To this solution, n-BuLi (1.6 M in
hexanes, 0.26 mL, 0.42 mmol, 1.3 equiv) was added. The yellow so-
lution was stirred at ꢁ78 ꢀC for 45 min, treated with corresponding
carbonyl compound (neat, 0.35 mmol, 1.1 equiv), stirred at ꢁ78 ꢀC
for further 50 min, and treated with NaBH4 (121 mg, 3.2 mmol,
10 equiv) and methanolic NaOMe (30% w/v, 0.34 mL, 1.92 mmol,
6 equiv). The resulting mixture was gradually warmed to rt and
stirred at rt until completion (ca. 2 h, indicated by TLC). The reaction
was quenched with satd aq NH4Cl. The organic layer was separated,
and the aqueous phase was washed with ether for several times.
Combined organic phases were washed with brine, concentrated,
and purified with flash chromatography (on silica gel with 60e90 ꢀC
petroleum ether and EtOAc) to give products 11 and 14aei.
4.6.2. 1-Phenyl-2-O-(N,N-diisopropylcarbamoyl)-1,2-ethanediol (11)
and 1-O-(N,N-diisopropylcarbamoyl)-1-phenyl-1,2-ethanediol
(12). According to route A, from compound 7 (100 mg, 0.32 mmol),
compounds 11 (colorless oil, 57 mg, 0.21 mmol, 67%) and 12 (color-
less oil, 22 mg, 0.08 mmol, 26%) were obtained. Their NMR data are
identical with the products obtained from compound 8.
4.6.3. 1-(2,4-Dimethylphenyl)-2-O-(N,N-diisopropylcarbamoyl)-1,2-
ethanediol (14b) and 1-O-(N,N-diisopropylcarbamoyl)-1-(2,4-
dimethylphenyl)-1,2-ethanediol (15b). According to route A, from
compound 7 (100 mg, 0.32 mmol), compounds 14b (white solid,
55 mg, 0.19 mmol, 59%) and 15b (colorless oil, 25 mg, 0.09 mmol,
27%) were obtained. Compound 14b: Rf 0.43 (ethyl acetate/
60e90 ꢀC petroleum ether, 1:4); mp 109e110 ꢀC; HPLC tR 3.8 min;
1H NMR (300 MHz, CDCl3)
d
7.42 (d, J¼7.9 Hz, 1H, Ar), 7.04 (d,
4.4. General procedure for route B
J¼7.9 Hz, 1H, Ar), 6.96 (s, 1H, Ar), 5.22e5.11 (m, 1H, CHOH),
4.28e4.13 (m, 2H, CH2OCb), 4.01 (br s, 1H, Cb), 3.82 (br s, 1H, Cb),
3.47 (s, 1H, OH), 2.34 (s, 3H, Ar-CH3), 2.30 (s, 3H, Ar-CH3), 1.35e1.15
Compound 7 (100 mg, 0.32 mmol, 1 equiv) was dissolved in dry
THF (2 mL), and cooled to ꢁ78 ꢀC. To this solution, n-BuLi (1.6 M in
hexanes, 0.26 mL, 0.42 mmol, 1.3 equiv) was added. The yellow
(m, 12H, Cb); 13C NMR (100 MHz, CDCl3)
d
156.3 (C]O), 137.2 (Arq),
135.3 (Arq), 134.5 (Arq), 131.1 (Ar), 126.8 (Ar), 126.0 (Ar), 70.2

L. Ma et al. / Tetrahedron 68 (2012) 8704e8711
8709
(CHOH), 69.3 (CH2OCb), 46.4 (Cb), 45.6 (Cb), 21.2 (2C, Cb), 21.0
(AreCH3), 20.5 (2C, Cb), 19.0 (AreCH3); HRMS (ESIþ) calcd for
C17H27NO3Naþ 316.1889, found 316.1889. Compound 15b: Rf 0.48
(ethyl acetate/60e90 ꢀC petroleum ether, 1:3); HPLC tR 3.6 min; 1H
58 mg, 0.18 mmol, 56%) and 15e (colorless oil, 23 mg, 0.07 mmol,
22%) were obtained. Compound 14e: Rf 0.47 (ethyl acetate/
60e90 ꢀC petroleum ether, 1:2); HPLC tR 3.4 min; 1H NMR
(400 MHz, CDCl3)
d
7.34 (d, J¼8.4 Hz,1H, Ar), 6.49 (dd, J¼8.4, 2.4 Hz,
NMR (400 MHz, CDCl3)
d
7.25 (d, J¼7.8 Hz, 1H, Ar), 7.02 (d, J¼7.8 Hz,
1H, Ar), 6.44 (d, J¼2.4 Hz, 1H, Ar), 5.16e5.07 (m, 1H, CHOH), 4.30 (d,
J¼2.4 Hz, 1H, CH2OCb), 4.29 (s, 1H, CH2OCb), 4.13e3.91 (br s, 1H,
Cb), 3.86e3.74 (m, 2H, Cb, OH),3.82 (s, 3H, OCH3), 3.80 (s, 3H,
1H, Ar), 6.99 (s, 1H, Ar), 6.03 (dd, J¼8.1, 3.2 Hz, 1H, CHOCb), 4.05 (br
s, 1H, Cb), 3.95e3.61 (m, 3H, Cb, CH2OH), 3.17 (br s, 1H, OH), 2.38 (s,
3H, AreCH3), 2.29 (s, 3H, AreCH3), 1.42e1.04 (m, 12H, Cb); 13C NMR
OCH3), 1.19 (m, 12H, Cb). 13C NMR (100 MHz, CDCl3)
d 160.3 (Arq),
(100 MHz, CDCl3)
d
155.6 (C]O), 137.0 (Arq), 134.6 (Arq), 132.6 (Arq),
157.3 (Arq), 156.5 (C]O), 128.1 (Ar), 121.0 (Arq), 104.0 (Ar), 98.3 (Ar),
69.2 (CHOH), 68.9 (CH2OCb), 55.3 (2C, OCH3), 46.4 (Cb), 45.6 (Cb),
21.1 (2C, Cb), 20.5 (2C, Cb); HRMS (ESIþ) calcd for C17H27NO5Naþ
348.1787, found 348.1775. Compound 15e: Rf 0.34 (ethyl acetate/
60e90 ꢀC petroleum ether, 1:2); HPLC tR 3.3 min; 1H NMR
130.9 (Ar), 126.3 (Ar), 125.7 (Ar), 74.7 (CHOCb), 66.2 (CH2OH), 46.1
(Cb), 45.3 (Cb), 21.1 (2C, Cb), 20.5 (Ar-CH3), 20.0 (2C, Cb), 18.7
(AreCH3); HRMS (ESIþ) calcd for C17H27NO3Naþ 316.1889, found
316.1886.
(400 MHz, CDCl3)
d
7.34 (d, J¼8.4 Hz,1H, Ar), 6.49 (dd, J¼8.4, 2.4 Hz,
4.6.4. 1-(3-Chlorophenyl)-2-O-(N,N-diisopropylcarbamoyl)-1,2-
ethanediol (14c) and 1-O-(N,N-diisopropylcarbamoyl)-1-(3-
chlorophenyl)-1,2-ethanediol (15c). According to route A, from
compound 7 (100 mg, 0.32 mmol), compounds 14c (colorless oil,
77 mg, 0.26 mmol, 80%) and 15c (colorless oil, 9 mg, 0.03 mmol, 9%)
were obtained. Compound 14c: Rf 0.39 (ethyl acetate/60e90 ꢀC
petroleum ether, 1:4); HPLC tR 3.7 min; 1H NMR (400 MHz, CDCl3)
1H, Ar), 6.45 (d, J¼2.4 Hz, 1H, Ar), 6.15 (dd, J¼6.6, 4.0 Hz, 1H,
CHOCb), 4.15e4.00 (br s, 1H, Cb), 3.90e3.75 (m, 3H, Cb, CH2OH),
3.81 (s, 3H, OCH3), 3.80(s, 3H, OCH3), 3.12 (br s, 1H, OH), 1.22 (m,
12H, Cb); 13C NMR (125 MHz, CDCl3)
d 160.6 (Arq), 157.3 (Arq), 156.2
(C]O), 128.0 (Ar), 118.6 (Arq), 104.2 (Ar), 98.4 (Ar), 73.5 (CHOCb),
66.6 (CH2OH), 55.4 (2C, OCH3), 46.6 (Cb), 45.6 (Cb), 21.5 (2C, Cb),
20.5 (2C, Cb); HRMS (ESIþ) calcd for C17H27NO5Naþ 348.1787, found
348.1773.
d
7.46e7.38 (m,1H, Ar), 7.30e7.22 (m, 3H, Ar), 4.94 (dt, J¼6.6, 3.1 Hz,
1H, CHOH), 4.35e4.20 (m, 3H, CH2OCb, OH), 4.00 (br s, 1H, Cb), 3.74
(br s, 1H, Cb), 1.19 (s, 12H, Cb); 13C NMR (100 MHz, CDCl3)
156.4
d
4.6.7. 1-(4-Fluorophenyl)-2-O-(N,N-diisopropylcarbamoyl)-1,2-
ethanediol (14f). According to route A, from compound 7 (100 mg,
0.32 mmol), compound 14f (colorless oil, 64 mg, 0.23 mmol, 71%)
was obtained. Compound 14f: Rf 0.36 (ethyl acetate/60e90 ꢀC pe-
troleum ether, 1:4); HPLC tR 3.4 min; 1H NMR (400 MHz, CDCl3)
(C]O), 142.9 (Arq), 134.3 (Arq), 129.6 (Ar), 127.8 (Ar), 126.4 (Ar),
124.3 (Ar), 72.8 (CHOH), 70.2 (CH2OCb), 46.6 (Cb), 45.8 (Cb), 21.0
(2C, Cb), 20.4 (2C, Cb); HRMS (ESIþ) calcd for C15H22NO3ClNaþ
322.1186, found 322.1187. Compound 15c: Rf 0.35 (ethyl acetate/
60e90 ꢀC petroleum ether, 1:3); HPLC tR 3.5 min; 1H NMR
d
7.40e7.32 (m, 2H, Ar), 7.09e6.97 (m, 2H, Ar), 4.98e4.92 (m, 1H,
CHOH), 4.32e4.18 (m, 2H, CH2OCb), 4.00 (br s, 2H, OH, Cb), 3.76 (br
s, 1H, Cb), 1.19 (br s, 12H, Cb); 13C NMR (100 MHz, CDCl3)
162.3 (d,
(400 MHz, CDCl3)
1H, CHOCb), 4.05 (br s, 1H, Cb), 3.95e3.75 (m, 3H, Cb, CH2OH), 2.85
(br s, 1H, OH), 1.23 (s, 12H, Cb); 13C NMR (100 MHz, CDCl3)
154.9
d
7.38e7.20 (m, 4H, Ar), 5.78 (dd, J¼7.4, 3.8 Hz,
d
d
J¼245.5 Hz, Arq), 156.3 (C]O), 136.4 (d, J¼2.9 Hz, Arq), 127.9 (Ar),
127.8 (Ar), 115.3 (Ar), 115.1 (Ar), 72.8 (CHOH), 70.3 (CH2OCb), 46.6
(Cb), 45.7 (Cb), 21.2 (2C, Cb), 20.4 (2C, Cb); HRMS (ESIþ) calcd for
C15H22NO3FNaþ 306.1481, found 306.1485.
(C]O), 139.5 (Arq), 134.0 (Arq), 129.4 (Ar), 127.8 (Ar), 126.3 (Ar),
124.4 (Ar), 76.9 (CHOCb), 66.4 (CH2OH), 46.3 (Cb), 45.2 (Cb), 21.1
(2C, Cb), 20.0 (2C, Cb); HRMS (ESIþ) calcd for C15H22NO3ClNaþ
322.1186, found 322.1179.
4.6.8. 1-(3,4-Difluorophenyl)-2-O-(N,N-diisopropylcarbamoyl)-1,2-
ethanediol (14g). According to route A, from compound 7 (100 mg,
0.32 mmol), compound 14g (colorless oil, 55 mg, 0.18 mmol, 57%)
was obtained. Compound 14g: Rf 0.27 (ethyl acetate/60e90 ꢀC pe-
troleum ether, 1:4); HPLC tR 3.5 min; 1H NMR (300 MHz, CDCl3)
4.6.5. 1-(4-Methoxyphenyl)-2-O-(N,N-diisopropylcarbamoyl)-1,2-
ethanediol (14d) and 1-O-(N,N-diisopropylcarbamoyl)-1-(4-
methoxyphenyl)-1,2-ethanediol (15d). According to route A, from
compound 7 (100 mg, 0.32 mmol), compounds 14d (colorless oil,
51 mg, 0.17 mmol, 54%) and 15d (colorless oil, 15 mg, 0.05 mmol,
16%) were obtained. Compound 14d: Rf 0.53 (ethyl acetate/
60e90 ꢀC petroleum ether, 1:2); HPLC tR 3.3 min; 1H NMR
d
7.30e7.20 (m,1H, Ar), 7.19e7.06 (m, 2H, Ar), 4.93 (dt, J¼6.5, 3.1 Hz,
1H, CHOH), 4.34e4.17 (m, 3H, CH2OCb, OH), 4.00 (br s, 1H, Cb), 3.76
(br s, 1H, Cb), 1.18 (br s, 12H, Cb); 13C NMR (125 MHz, CDCl3)
156.4
d
(400 MHz, CDCl3)
d
7.37e7.28 (m, 2H, Ar), 6.97e6.81 (m, 2H, Ar),
(C]O), 151.0 (dd, J¼75.4, 12.7 Hz, Arq), 149.1 (dd, J¼74.8, 12.7 Hz,
Arq), 137.1e136.9 (m, Arq), 122.0 (dd, J¼6.2, 3.6 Hz, Ar), 117.1 (d,
J¼17.3 Hz, Ar), 115.3 (d, J¼17.9 Hz, Ar), 72.5 (CHOH), 70.2 (CH2OCb),
46.7 (Cb), 45.8 (Cb), 21.1 (2C, Cb), 20.4 (2C, Cb); HRMS (ESIþ) calcd
for C15H21NO3F2Naþ 324.1387, found 324.1368.
4.92 (t, J¼5.5 Hz, 1H, CHOH), 4.25 (d, J¼0.6 Hz, 1H, CH2OCb), 4.23 (s,
1H, CH2OCb), 4.02 (br s, 1H, Cb), 3.80 (s, 3H, OCH3), 3.78 (br s, 1H,
Cb), 3.62 (br s, 1H, OH), 1.20 (m, 12H, Cb); 13C NMR (100 MHz,
CDCl3)
d 159.2 (Arq), 156.3 (C]O), 132.7 (Arq), 127.4 (2C, Ar), 113.8
(2C, Ar), 72.9 (CHOH), 70.3 (CH2OCb), 55.2 (OCH3), 46.5 (Cb), 45.7
(Cb), 21.1 (2C, Cb), 20.5 (2C, Cb); HRMS (ESIþ) calcd for
C16H25NO4Naþ 318.1681, found 318.1664. Compound 15d: Rf 0.25
(ethyl acetate/60e90 ꢀC petroleum ether, 1:3); HPLC tR 3.2 min; 1H
4.6.9. 1-(4-Trifluoromethylphenyl)-2-O-(N,N-diisopropylcarbamoyl)-
1,2-ethanediol (14h) and 1-O-(N,N-diisopropylcarbamoyl)-1-(4-
trifluoromethylphenyl)-1,2-ethanediol (15h). According to route A,
from compound 7 (100 mg, 0.32 mmol), compounds 14h (colorless
oil, 64 mg, 0.19 mmol, 60%) and 15h (colorless oil, 12 mg,
0.04 mmol, 11%) were obtained. Compound 14h: Rf 0.33 (ethyl ac-
etate/60e90 ꢀC petroleum ether, 1:4); mp 53e54 ꢀC; HPLC tR
NMR (400 MHz, CDCl3)
d 7.32e7.27 (m, 2H, Ar), 7.06e6.65 (m, 2H,
Ar), 5.78 (dd, J¼7.9, 3.6 Hz, 1H, CHOCb), 4.09 (br s, 1H, Cb),
3.92e3.86 (m, 1H, CH2OH), 3.81e3.76 (m, 5H, Cb, CH2OH, OCH3),
3.02 (m, 1H, OH), 1.20 (m, 12H, Cb); 13C NMR (125 MHz, CDCl3)
d
159.4 (Arq), 156.0 (C]O), 129.9 (Arq), 128.1 (2C, Ar), 114.0 (2C, Ar),
3.8 min; 1H NMR (400 MHz, CDCl3)
d
7.61 (d, J¼8.2 Hz, 2H, Ar), 7.53
78.0 (CHOCb), 67.3 (CH2OH), 55.2 (OCH3), 46.8 (Cb), 45.5 (Cb), 21.6
(2C, Cb), 20.5 (2C, Cb); HRMS (ESIþ) calcd for C16H25NO4Naþ
318.1681, found 318.1685.
(d, J¼8.2 Hz, 2H, Ar), 5.03 (dd, J¼7.1, 2.5 Hz, 1H, CHOH), 4.37e4.24
(m, 3H, CH2OCb, OH), 4.00 (br s, 1H, Cb), 3.74 (br s, 1H, Cb),1.19 (br s,
12H, Cb); 13C NMR (100 MHz, CDCl3)
d 156.4 (C]O), 144.7 (Arq),
129.9 (q, J¼32.5 Hz, CF3), 126.4 (2C, Ar), 125.2 (m, 2C, Ar), 122.7
(Arq), 73.0 (CHOH), 70.2 (CH2OCb), 46.6 (Cb), 45.8 (Cb), 21.0 (2C, Cb),
20.4 (2C, Cb); HRMS (ESIþ) calcd for C16H22NO3F3Naþ 356.1449,
found 356.1467. Compound 15h: Rf 0.30 (ethyl acetate:petroleum
4.6.6. 1-(2,4-Dimethoxyphenyl)-2-O-(N,N-diisopropylcarbamoyl)-
1,2-ethanediol (14e) and 1-O-(N,N-diisopropylcarbamoyl)-1-(2,4-
dimethoxyphenyl)-1,2-ethanediol (15e). According to route A, from
compound 7 (100 mg, 0.32 mmol), compounds 14e (colorless oil,
ether,1:3); tR 3.7 min; 1H NMR (400 MHz, CDCl3)
d
7.64 (d, J¼8.1 Hz,

8710
L. Ma et al. / Tetrahedron 68 (2012) 8704e8711
2H, Ar), 7.48 (d, J¼8.1 Hz, 2H, Ar), 5.86 (dd, J¼7.2, 3.8 Hz, 1H,
CHOCb), 4.05 (br s, 1H, Cb), 3.96e3.79 (m, 3H, Cb, CH2OH), 2.68 (br
s, 1H, CH2OH), 1.41e1.16 (m, 12H, Cb); 13C NMR (125 MHz, CDCl3)
was obtained. Compound 15l: Rf 0.34 (ethyl acetate/60e90 ꢀC pe-
troleum ether, 1:3); mp 83e84 ꢀC; HPLC tR 3.3 min; 1H NMR
(400 MHz, CDCl3)
d
7.35 (dd, J¼7.5, 1.7 Hz, 1H, Ar), 7.28 (ddd, J¼8.2,
d
155.3 (C]O), 142.0 (Arq), 130.3 (q, J¼32.6 Hz, CF3), 127.0 (2C, Ar),
7.5, 1.7 Hz, 1H, Ar), 6.96 (td, J¼7.5, 1.0 Hz, 1H, Ar), 6.88 (dd, J¼8.2,
1.0 Hz, 1H, Ar), 6.24 (dd, J¼6.7, 3.7 Hz, 1H, CHOCb), 4.05 (br s, 1H,
Cb), 3.96e3.76 (m, 3H, Cb, CH2OH), 3.84 (s, 3H, OCH3), 3.06 (dd,
J¼6.7, 5.1 Hz, 1H, OH), 1.23 (m, 12H, Cb); 13C NMR (100 MHz, CDCl3)
125.6 (m, 2C, Ar), 122.9 (Ar), 77.5 (CHOCb), 67.0 (CH2OH), 46.9 (Cb),
45.8 (Cb), 21.6 (2C, Cb), 20.4 (2C, Cb); HRMS (ESIþ) calcd for
C16H22NO3F3Naþ 356.1449, found 356.1467.
d
155.6 (C]O), 128.5 (Arq), 126.6 (2C, Ar), 125.6 (Arq), 120.0 (Ar),
4.6.10. 1-Methyl-2-O-(N,N-diisopropylcarbamoyl)-1,2-propanediol
110.0 (Ar), 73.0 (CHOCb), 66.0 (CH2OH), 54.9 (OCH3), 46.1 (Cb), 45.2
(Cb), 21.0 (2C, Cb), 20.0 (2C, Cb); HRMS (ESIþ) calcd for
C16H25NO4Naþ 318.1681, found 318.1684.
(14i). According to route A, from compound
7
(100 mg,
0.32 mmol), compound 14i (colorless oil, 45 mg, 0.20 mmol, 64%)
was obtained. Compound 14i: Rf 0.23 (ethyl acetate/60e90 ꢀC pe-
troleum ether, 1:4); HPLC tR 2.8 min; 1H NMR (400 MHz, CDCl3)
4.6.17. 1-(4-Methoxyphenyl)-2-O-(N,N-diisopropylcarbamoyl)-1,2-
ethanediol (14d) and 1-O-(N,N-diisopropylcarbamoyl)-1-(4-
methoxyphenyl)-1,2-ethanediol (15d). According to route B, from
compound 7 (100 mg, 0.32 mmol), compounds 14d (colorless oil,
10 mg, 0.04 mmol, 11%) and 15d (colorless oil, 46 mg, 0.16 mmol,
49%) were obtained. Their NMR data are identical with the products
obtained via route A.
d
4.06 (br s, 1H, Cb), 4.02 (s, 2H, CH2OCb), 3.83 (br s, 1H, Cb), 2.79 (br
s, 1H, OH), 1.23 (d, J¼6.8 Hz, 12H, Cb); 13C NMR (125 MHz, CDCl3)
d
156.2 (C]O), 73.0 (C(CH3)2OH), 70.2 (CH2OCb), 46.6 (Cb), 45.6
(Cb), 26.5 (2C, C(CH3)2OH), 21.5 (2C, Cb), 20.5 (2C, Cb); HRMS (EIþ)
calcd for C11H23NO3 217.1678, found 217.1679.
4.6.11. 1-O-(N,N-Diisopropylcarbamoyl)-1-phenyl-1,2-ethanediol
(12). According to route B, from compound 7 (100 mg, 0.32 mmol),
compound 12 (colorless oil, 42 mg, 0.16 mmol, 49%) was obtained. Its
NMR data are identical with the products obtained from compound 8.
4.6.18. 1-O-(N,N-Diisopropylcarbamoyl)-1-(2,4-dimethoxyphenyl)-
1,2-ethanediol (15e). According to route B, from compound 7
(100 mg, 0.32 mmol), compound 15e (colorless oil, 73 mg,
0.22 mmol, 70%) was obtained. Its NMR data are identical with the
products obtained via route A.
4.6.12. 1-O-(N,N-Diisopropylcarbamoyl)-1-(naphthalen-2-yl)-1,2-
ethanediol (15j). According to route B, from compound 7 (100 mg,
0.32 mmol), compound 15j (colorless oil, 58 mg, 0.18 mmol, 57%)
was obtained. Compound 15j: Rf 0.40 (ethyl acetate/60e90 ꢀC pe-
troleum ether, 1:3); HPLC tR 3.6 min; 1H NMR (400 MHz, CDCl3)
4.6.19. 1-O-(N,N-Diisopropylcarbamoyl)-1-(3,4-difluorophenyl)-1,2-
ethanediol (15g). According to route B, from compound 7 (200 mg,
0.64 mmol), product 15g (colorless oil, 94 mg, 0.31 mmol, 49%) was
obtained. Compound 15g: Rf 0.29 (ethyl acetate/60e90 ꢀC petro-
leum ether, 1:3); HPLC tR 3.4 min; 1H NMR (400 MHz, CDCl3)
d
8.14 (d, J¼8.5 Hz, 1H, Ar), 7.90e7.79 (m, 2H, Ar), 7.63e7.45 (m, 4H,
Ar), 6.64 (dd, J¼7.2, 3.3 Hz, 1H, CHOCb), 4.16e3.83 (m, 4H, Cb,
CH2OH), 3.27 (br s, 1H, OH), 1.24 (m, 12H, Cb); 13C NMR (125 MHz,
d
7.24e7.03 (m, 3H, Ar), 5.76 (dd, J¼7.3, 4.0 Hz, 1H, CHOCb), 4.05 (br
s,1H, Cb), 3.94e3.75 (m, 3H, Cb, CH2OH), 2.92 (br s,1H, OH), 1.22 (br
s, 12H, Cb); 13C NMR (100 MHz, CDCl3)
154.7 (C]O), 150.9 (dd,
CDCl3) d 156.0 (C]O),133.8 (Arq), 133.5 (Arq), 130.3 (Arq), 128.9 (Ar),
128.7 (Ar),126.6 (Ar),125.9 (Ar),125.2 (Ar),124.2 (Ar),123.1 (Ar), 75.8
(CHOCb), 67.3 (CH2OH), 46.7 (Cb), 46.0 (Cb), 21.4 (2C, Cb), 20.6 (2C,
Cb); HRMS (ESIþ) calcd for C19H25NO3Naþ 338.1732, found 338.1732.
d
J¼26.9, 12.6 Hz, Arq), 148.4 (dd, J¼26.9, 12.6 Hz, Arq), 134.7 (t,
J¼4.5 Hz, Arq), 122.4 (dd, J¼6.3, 3.6 Hz, Ar), 116.9 (d, J¼17.4 Hz, Ar),
115.3 (d, J¼17.9 Hz, Ar), 76.2 (CHOCb), 66.1 (CH2OH), 46.3 (Cb), 45.2
(Cb), 21.1 (2C, Cb), 19.9 (2C, Cb); HRMS (ESIþ) calcd for
C15H21NO3F2Naþ 324.1387, found 324.1375.
4.6.13. 1-(2,4-Dimethylphenyl)-2-O-(N,N-diisopropylcarbamoyl)-1,2-
ethanediol (14b) and 1-O-(N,N-diisopropylcarbamoyl)-1-(2,4-
dimethylphenyl)-1,2-ethanediol (15b). According to route B, from
compound 7 (100 mg, 0.32 mmol), compounds 14b (white solid,
6 mg, 0.02 mmol, 6%) and 15b (colorless oil, 47 mg, 0.16 mmol, 50%)
were obtained. Their NMR data are identical with the products
obtained via route A.
4.6.20. 1-Phenyl-1,2-ethanediol (13). According to route C, from
compound 7 (100 mg, 0.32 mmol), compound 13 (white solid,
25 mg, 0.18 mmol, 57%) was obtained. Compound 13: 1H NMR
(300 MHz, CDCl3)
1H, CHOH), 3.73e3.58 (m, 2H, CH2OH), 3.49 (br s,1H, OH), 3.13 (br s,
1H, OH); 13C NMR (125 MHz, CDCl3)
140.5 (Phq), 128.5 (2C, Ph),
d
7.36e7.25 (m, 5H, Ph), 4.77 (dd, J¼8.2, 3.5 Hz,
4.6.14. 1-O-(N,N-Diisopropylcarbamoyl)-1-(3-chlorophenyl)-1,2-
ethanediol (15c). According to route B, from compound 7 (100 mg,
0.32 mmol), compound 15c (colorless oil, 49 mg, 0.16 mmol, 51%)
was obtained. Its NMR data are identical with the products ob-
tained via route A.
d
128.0 (Ph), 126.1 (2C, Ph), 74.7 (CHOH), 68.0 (CH2OH). NMR of data
of compound 13 are consistent with the literature.15
4.6.21. 1-(4-Methoxyphenyl)-1,2-ethanediol (16d). According to
route C, from compound 7 (100 mg, 0.32 mmol), compound 16d
(white solid, 33 mg, 0.20 mmol, 62%) was obtained. Compound
4.6.15. 1-O-(N,N-Diisopropylcarbamoyl)-1-(4-bromophenyl)-1,2-
ethanediol (15k). According to route B, from compound 7 (100 mg,
0.32 mmol), compound 15k (colorless oil, 75 mg, 0.22 mmol, 68%) was
obtained. Compound 15k: Rf 0.37 (ethyl acetate/60e90 ꢀC petroleum
16d: 1H NMR (400 MHz, CDCl3)
d
7.25 (d, J¼8.7 Hz, 2H, Ar), 6.87 (d,
J¼8.7 Hz, 2H, Ar), 4.72 (dd, J¼8.2, 3.5 Hz, 1H, CHOH), 3.79 (s, 3H,
OCH3), 3.68e3.58 (m, 2H, CH2OH), 3.35 (br s, 1H, OH), 3.02 (br s, 1H,
ether,1:3); HPLC tR 3.6 min; 1H NMR (400 MHz, CDCl3)
d
7.52e7.47 (m,
OH); 13C NMR (125 MHz, CDCl3)
d 159.3 (Arq), 132.6 (Arq), 127.4 (2C,
2H, Ar), 7.27e7.22 (m, 2H, Ar), 5.76 (dd, J¼7.5, 3.8 Hz,1H, CHOCb), 4.06
Ar), 113.9 (2C, Ar), 74.3 (CHOH), 68.0 (CH2OH), 55.3 (OCH3). NMR of
(br s,1H, Cb), 3.94e3.72 (m, 3H, Cb, CH2OH), 2.91 (br s,1H, OH),1.21 (m,
data of compound 16d are consistent with the literature.16
12H, Cb); 13C NMR (100 MHz, CDCl3)
d 155.0 (C]O), 136.5 (Arq), 131.2
(2C, Ar), 127.9 (2C, Ar), 121.6 (Arq), 77.0 (CHOCb), 66.4 (CH2OH), 46.3
(Cb), 45.2 (Cb), 21.1 (2C, Cb), 20.0 (2C, Cb); HRMS (ESIþ) calcd for
C15H22NO3BrNaþ 366.0681, found 366.0689.
4.6.22. 1-(2,4-Dimethoxyphenyl)-1,2-ethanediol (16e). According to
route C, from compound 7 (100 mg, 0.32 mmol), compound 16e
(white solid, 39 mg, 0.20 mmol, 62%) was obtained. Compound 16e:
Rf 0.17 (ethyl acetate/60e90 ꢀC petroleum ether, 1:1); mp
4.6.16. 1-O-(N,N-Diisopropylcarbamoyl)-1-(2-methoxyphenyl)-1,2-
ethanediol (15l). According to route B, from compound 7 (100 mg,
0.32 mmol), compound 15l (white solid, 64 mg, 0.22 mmol, 68%)
112e113 ꢀC; HPLC tR 2.0 min; 1H NMR (400 MHz, CDCl3)
d 7.27 (d,
J¼8.3 Hz, 1H, Ar), 6.49 (dd, J¼8.3, 2.3 Hz, 1H, Ar), 6.45 (d, J¼2.3 Hz,
1H, Ar), 4.97 (dd, J¼8.0, 3.5 Hz, 1H, CHOH), 3.81 (s, 3H, OCH3), 3.80

L. Ma et al. / Tetrahedron 68 (2012) 8704e8711
8711
1412e1415; (c) Park, C. P.; Lee, J. H.; Yoo, K. S.; Jung, K. W. Org. Lett. 2010, 12,
2450e2452; (d) Griffith, J. C.; Jones, K. M.; Picon, S.; Rawling, M. J.; Kariuki, B.
M.; Campbell, M.; Tomkinson, N. C. O. J. Am. Chem. Soc. 2010, 132, 14409e14411;
(e) Giglio, B. C.; Schmidt, V. A.; Alexanian, E. J. J. Am. Chem. Soc. 2011, 133,
13320e13322.
(s, 3H, OCH3), 3.78e3.64 (m, 2H, CH2OH), 2.98 (br s, 1H, OH), 2.38
(br s, 1H, OH); 13C NMR (125 MHz, CDCl3)
160.5 (Arq), 157.6 (Arq),
128.0 (Ar), 120.9 (Arq), 104.2 (Ar), 98.6 (Ar), 71.0 (CHOH), 66.6
(CH2OH), 55.4 (CH3), 55.3 (CH3); HRMS (EIþ) calcd for C10H14O4
198.0892, found 198.0887.
d
2. For a survey of established 1,2-diol synthesis and protection methodology, see,
for example: (a) Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem. Rev.
1994, 94, 2483e2547; (b) Smith, M. B.; March, J. March’s Advanced Organic
Chemistry: Reactions, Mechanisms, and Structure, 6th ed.; John Wiley & Sons:
Hoboken, NJ, 2007; (c) Larock, R. C. Comprehensive Organic Transformations: A
Guide to Functional Group Preparations, 2nd ed.; John Wiley & Sons: New York,
NY, 1999, pp 961e1196; (d) Greene, T. W.; Wuts, P. G. M. Protective Groups in
Organic Synthesis, 3rd ed.; John Wiley & Sons: New York, NY, 1999, pp 17e245.
3. For reviews, see for example: (a) Organolithiums in Enantioselective Synthesis;
Hodgson, G. M., Ed.Topics in Organometallic Chemistry; Springer: Berlin/Hei-
delberg, Germany, 2003; (b) Hoppe, D.; Hense, T. Angew. Chem., Int. Ed. 1997, 36,
2282e2316; (c) Beak, P.; Basu, A.; Gallagher, D. J.; Park, Y. S.; Thayumanavan, S.
Acc. Chem. Res. 1996, 29, 552e560; (d) Hoppe, D. Synthesis 2009, 43e55; For
recent applications of carbamoyloxy directed stereoselective lithiation, see for
example: (e) Sonawane, R. P.; Jheengut, V.; Rabalakos, C.; Larouche-Gauthier, R.;
Scott, H. K.; Aggarwal, V. K. Angew. Chem., Int. Ed. 2011, 50, 3760e3763; (f) Nave,
S.; Sonawane, R. P.; Elford, T. G.; Aggarwal, V. K. J. Am. Chem. Soc. 2010, 132,
17096e17098; (g) Stymiest, J. L.; Bagutski, V.; French, R. M.; Aggarwal, V. K.
Nature 2008, 456, 778e782.
4.6.23. 1-(3,4-Difluorophenyl)-1,2-ethanediol (16g). According to
route C, from compound 7 (100 mg, 0.32 mmol), compound 16g
(colorless oil, 34 mg, 0.20 mmol, 62%) was obtained. Compound
16g: Rf 0.21 (ethyl acetate/60e90 ꢀC petroleum ether, 1:1); HPLC tR
2.1 min; 1H NMR (400 MHz, CDCl3)
d 7.25e7.10 (m, 2H, Ar), 7.07 (m,
1H, Ar), 4.78 (dd, J¼8.1, 3.1 Hz, 1H, CHOH), 3.78e3.54 (m, 2H,
CH2OH), 3.21 (br s, 1H, OH), 2.65 (br s, 1H, OH); 13C NMR (100 MHz,
CDCl3)
d
150.8 (dd, J¼38.9, 24.0 Hz, Arq), 148.2 (dd, J¼75.8, 42.9 Hz,
Arq), 138.3e135.2 (m, Arq), 121.5 (dd, J¼6.3, 3.6 Hz, Ar), 116.8 (d,
J¼17.3 Hz, Ar), 114.6 (d, J¼17.8 Hz, Ar), 73.0 (CHOH), 67.3 (CH2OH);
HRMS (EIþ) calcd for C8H8F2O2 174.0492, found 174.0494.
4.6.24. 1,1-Diphenyl-1,2-ethanediol (16m). According to route C,
from compound 7 (100 mg, 0.32 mmol), compound 16m (white
solid, 39 mg, 0.18 mmol, 57%) was obtained. Compound 16m: 1H
4. (a) Reggelin, M.; Tebben, P.; Hoppe, D. Tetrahedron Lett. 1989, 30, 2915e2918;
(b) Tebben, P.; Reggelin, M.; Hoppe, D. Tetrahedron Lett. 1989, 30, 2919e2922;
(c) Hoppe, D.; Tebben, P.; Reggelin, M.; Bolte, M. Synthesis 1997, 183e190; (d)
Hoppe, D.; Kraemer, T.; Schwark, J.-R.; Zschage, O. Pure Appl. Chem. 1990, 62,
1999e2006; (e) Chen, Y.-L.; Hoppe, D. J. Org. Chem. 2009, 74, 4188e4194; (f)
Chen, Y.-L.; Hoppe, D. Tetrahedron: Asymmetry 2009, 20, 1561e1567.
5. Hintze, F.; Hoppe, D. Synthesis 1992, 12, 1216e1218.
NMR (400 MHz, CDCl3)
d 7.44e7.40 (m, 4H, Ph), 7.37e7.30 (m, 4H,
Ph), 7.28e7.24 (m, 2H, Ph), 4.13 (d, J¼6.4 Hz, 2H, CH2OH), 3.27 (s,1H,
CHOH), 2.03 (t, J¼6.4 Hz, 1H, CH2OH); 13C NMR (125 MHz, CDCl3)
6. Cravey, M. J.; Kohn, H. J. Am. Chem. Soc. 1980, 102, 3928e3939.
d
143.8 (2C, Phq), 128.4 (4C, Ph), 127.5 (2C, Ph), 126.4 (4C, Ph), 78.6
7. (a) Boche, G.; Bosold, F.; Lohrenz, J. C. W.; Opel, A.; Zulauf, P. Chem. Ber. 1993,
€
€
€
(CHOH), 69.4 (CH2OH). NMR of data of compound 16m are con-
126, 1873e1885; (b) Ozlugedik, M.; Kristensen, J.; Wibbeling, B.; Frohlich, R.;
sistent with the literature.17
Hoppe, D. Eur. J. Org. Chem. 2002, 414e427.
8. Gundersen, L.-L.; Benneche, T. Acta Chem. Scand. 1991, 45, 975e977.
9. Aside from accelerating the reaction between lithium metal and n-butyl ha-
lides, sodium impurity in lithium plays certain role in other reactions, too. See
for example: Walborsky, H. M.; Banks, R. B. Bull. Soc. Chim. Belg. 1980, 89,
849e868.
10. The migration of OCb protection is unexpected since it is known to be quite
stable under such conditions: see for example Chen, Y. L.; Frohlich, R.; Hoppe,
D. Tetrahedron: Asymmetry 2009, 20, 1144e1149.
11. Undesired O-acyl migrations are frequently encountered problem in organic
synthesis, while some of them could be useful. See for example: (a) Vares, L.;
Rein, T. J. Org. Chem. 2002, 67, 7226e7237; (b) Kraehenbuehl, K.; Picasso, S.;
Vogel, P. Helv. Chim. Acta 1998, 81, 1439e1479; (c) Martin, J. B. J. Am. Chem. Soc.
1953, 75, 5483e5486.
Acknowledgements
This work was supported by the National Natural Science
Foundation of China (81102306).
Supplementary data
Copies of the 1H NMR and 13C NMR spectra of new intermediates
and products are provided. Supplementary data associated with
this article can be found in the online version, at http://dx.doi.org/
10.1016/j.tet.2012.08.025.
12. We have not used LAH condition due to functional group tolerance issue and
workup difficulties in larger reactions.
13. Ma, L.; Chen, Y. -L., unpublished results in this lab.
14. Kapeller, D.; Barth, R.; Mereiter, K.; Hammerschmidt, F. J. Am. Chem. Soc. 2007,
129, 914e923.
References and notes
15. Plietker, B.; Niggemann, M.; Pollrich, A. Org. Biomol. Chem. 2004, 2, 1116e1124.
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Chem.dEur. J. 2004, 10, 5581e5606.
1. For examples of recently reported 1,2-diol synthesis methodologies: (a) Trost,
B. M.; Malhotra, S.; Koschker, P.; Ellerbrock, P. J. Am. Chem. Soc. 2011, 134,
2075e2084; (b) Seayad, J.; Seayad, A. M.; Chai, C. L. L. Org. Lett. 2010, 12,
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