The stereodivergent asymmetric synthesis of a range of 2-(1′- hydroxyalkyl)phenols

Article abstract of DOI:10.1016/j.tet.2010.07.058

The use of the (S)-α-methylbenzyl group as a chiral auxiliary has allowed the diastereoselective ortho-deprotonation of a chromium tricarbonyl complexed phenoxy ring. When the resultant ortho-anion is treated with an aldehyde two diastereoisomeric complex

Full text of DOI:10.1016/j.tet.2010.07.058

Tetrahedron 66 (2010) 8076e8088
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
The stereodivergent asymmetric synthesis of a range of 2-(10-hydroxyalkyl)-
phenols
*
Stephen G. Davies , W. Ewan Hume, Paul M. Roberts, James E. Thomson
Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, OX1 3TA, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 12 May 2010
Received in revised form 2 July 2010
Accepted 20 July 2010
Available online 27 July 2010
The use of the (S)-a-methylbenzyl group as a chiral auxiliary has allowed the diastereoselective ortho-
deprotonation of a chromium tricarbonyl complexed phenoxy ring. When the resultant ortho-anion is
treated with an aldehyde two diastereoisomeric complexes are formed, in relatively poor dr, which differ
in the configuration of the newly formed benzylic stereogenic centre. However, both ortho-formylation
followed by treatment with Grignard reagents and ortho-acylation followed by reduction with Super-
HydrideÒ were found to be completely diastereoselective, giving access to either epimer of the corre-
sponding benzylic alcohol complexes in >99:1 dr. Subsequent oxidative removal of the chromium
Keywords:
Asymmetric synthesis
Arene chromium tricarbonyl
Stereoselective deprotonation
Enantiopure carbinols
tricarbonyl unit, followed by cleavage of the O-
hydroxyalkyl)phenols. Following this stereodivergent procedure, either enantiomer of the product may
be accessed from a single antipode of [( -methylbenzyloxy)benzene]Cr(CO)3.
Ó 2010 Elsevier Ltd. All rights reserved.
a
-methylbenzyl chiral auxiliary gives enantiopure 2-(10-
a
1. Introduction
2. Results and discussion
2.1. ortho-Deprotonation studies
Chromium tricarbonyl complexes of benzaldehyde and phenyl
ketoneseachpossessinganortho-substituentarechiralandhavebeen
shown to undergo a variety of diastereoselective addition reactions1
making them attractive building blocks for asymmetric synthesis.
This has led to a number of approaches being developed for their
preparation inhomochiralform. Resolutionprocedureshaveinvolved
the separation of diastereoisomers2 and kinetic resolutions via oxa-
zolidines3 and enantioselective yeast reductions.4 Asymmetric syn-
theses have been achieved via stereoselective complexation of chiral
aminals,5 and the stereoselective ortho-metallation of phenyl com-
plexes bearing homochiral side-chains,6 homochiral acetals,7 homo-
chiral aminals8 and homochiral sulphoxides.9 Homochiral lithium
amide bases have been used to enantioselectively ortho-deprotonate
prochiral substrates, such as anisole chromium tricarbonyl,10 phenyl
chromium tricarbonyl carbamates11 and benzaldehyde acetal chro-
mium tricarbonyl complexes.10,11 As part of our ongoing research
program concerning the utility of arene chromium tricarbonyl com-
plexes in synthesis,12,13 we became interested in the stereoselective
[(S)-(a-Methylbenzyloxy)benzene]Cr(CO)3 3 was produced via
treatment of the sodium salt of (S)-
a-methylbenzyl alcohol 2 with
(fluorobenzene)Cr(CO)3 1, giving (S)-3 in 90% isolated yield
(Scheme 1). It is known that treatment of (anisole)Cr(CO)3 with BuLi
results in regiospecific removal of an ortho-proton from the com-
plexed aryl ring via chelation of the base with the methoxy group,15
hence it was expected that treatment of (S)-3 with base would result
in preferential removal of one of the diastereotopic ortho-protons. It
was anticipated that the preferred conformation of 3 would involve
minimisation of syn-pentane-type interactions between the com-
plexed arene ring and the a-methylbenzyl chiral auxiliary giving rise
to two possible conformations 4A and 4B. Within 4A, unfavourable
steric interactions are experienced between the Cr(CO)3 unit and the
phenyl group of the auxiliary; therefore 4B, in which the pro-S ortho-
ortho-deprotonation of [(S)-(a-methylbenzyloxy)-benzene]Cr(CO)3
followed by alkylation with a range of electrophiles. We describe
herein the conversion of the resultant ortho-substituted complexes
into either enantiomer of the corresponding 2-(10-hydroxyalkyl)-
phenols via a stereodivergent acylation/nucleophilic addition pro-
cedure. Part of this work has been communicated previously.14
Scheme 1. Reagents and conditions: (i) NaH, THF, rt, 16 h.
* Corresponding author. E-mail address: steve.davies@chem.ox.ac.uk (S.G. Davies).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.07.058

S.G. Davies et al. / Tetrahedron 66 (2010) 8076e8088
8077
proton is shielded by the auxiliary, was expected to be the favoured
conformation (Fig. 1). In support of this hypothesis, the two dia-
stereotopic ortho-protons within 3 were found to have significantly
different chemical shifts by 1H NMR spectroscopic analysis (dH 4.86
and 5.27 ppm), consistent with one of these protons being signifi-
cantly more shielded by the phenyl ring of the auxiliary than the
other.
In order to exploit this diastereoselective ortho-deprotonation
protocol for the generation of new benzylic stereogenic centres, it
was envisaged that the ortho-anions derived from (S)-3 could be
reacted with prochiral electrophiles such as aldehydes. Thus, a so-
lution of (S)-3 in THF was added dropwise to a solution of LDA at
ꢀ78 ꢁC in THF. The resultant mixture was stirred at ꢀ78 ꢁC for 3 h
then 5.0 equiv of the requisite aldehyde (as a solution in THF) was
added and the reaction mixture was allowed to warm up to 0 ꢁC
over a period of 16 h to give mixtures of the corresponding ortho-
substituted complexes 9e18 in ꢂ65:35 dr after work-up. Purifica-
tion allowed separation of the diastereoisomers to give 9e18 in
>99:1 dr (Scheme 3). In each case 1H NMR spectroscopic analysis of
9e18 revealed diagnostic peaks at dH 4.73e4.89 ppm, correspond-
ing to the C(6)H protons, confirming that the deprotonation oc-
curred with complete diastereoselectivity. The relative
configuration within the minor product 17 was unambiguously
established by single crystal X-ray analysis of the racemate, with
the absolute configuration within (1pR,10R,
from the known configuration of the (S)-
a
S)-17 being assigned
Figure 1. Diastereoselective deprotonation of the pro-R ortho-proton within (S)-3 with
LDA. [HR¼pro-R proton. HS¼pro-S proton].
a
-methylbenzyl stereo-
centre (Fig. 2). The absolute configuration within the major
diastereoisomer 12 could therefore be unambiguously assigned and
the absolute configurations within the major products 9e11 and 13
were therefore assigned by analogy.
An ortho-deprotonation/methylation sequence was initially car-
ried out with a variety of bases in order to assess the effectiveness of
the
a-methylbenzyl chiral auxiliary in controlling the diaster-
eoselective deprotonation of (S)-3. In order to asses the extent of
enantiorecognition phenomena16 within this system, and to provide
authentic samples of the two possible diastereoisomers 7 and 8 that
could be derived from ortho-methylation of (S)-3, (RS)-5 was reacted
with (RS)-6 to give racemic 7 and 8 in approximately 50:50 dr; this
result indicates that enantiorecognition phenomena are not occur-
ring to an appreciable extent in this system. Deprotonation and
subsequent methylation of (RS)-3 was next undertaken. The requisite
base was added to a solution of (RS)-3 in THF at ꢀ78 ꢁC. After stirring
at ꢀ78 ꢁC for 3 h (during which time a colour change from yellow to
orange was observed)17 excess methyl iodide was added. The re-
action mixture was then allowed to warm up to 0 ꢁC over a period of
16 h. The ratios of 7:8 obtained from deprotonation with the alkyl
lithium bases were found to be low, presumably due to their high
reactivity. However, with the less reactive lithium amide base LDA
high levels of diastereoselectivity were obtained. Lower tempera-
tures (ꢀ100 ꢁC) and following an inverse addition procedure, where
a solution of (RS)-3 was added dropwise to a solution of the base in
THF, were both found to increase the diastereoselectivity of this
process, i.e., the deprotonation is under kinetic rather than thermo-
dynamic control (Scheme 2).
Scheme 3. Reagents and conditions: (i) LDA, THF, ꢀ78 ꢁC, 3 h, RCHO, 16 h. [aCrude;
bIsolated in >99:1 dr].
Figure 2. Chem3D representation of the single crystal X-ray structure of
(1pRS,10RS,
aSR)-17 (some H atoms have been omitted for clarity).
We have previously shown that the addition of nucleophiles to
chromium tricarbonyl complexes of ortho-anisaldehyde and ortho-
methoxyphenyl ketones occurs with very high levels of diaster-
eoselectivity.18 In each case the nucleophile adds to the carbonyl
group in the anti conformation 19A, presumably owing to lone
pairelone pair repulsions between the oxygen atoms, on the face
distal to the chromium tricarbonyl moiety (Fig. 3). We therefore en-
visaged that nucleophilic addition to a range of homochiral ortho-acyl
complexes derived from (S)-3 would lead to the diastereoselective
formation of the corresponding benzylic alcohol complexes.
Scheme 2. Reagents and conditions: (i) THF, rt, 16 h; (ii) Base then MeI (see table).
[i¼inverse addition].

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S.G. Davies et al. / Tetrahedron 66 (2010) 8076e8088
benzylic alcohols 13 and 18 was obtained in 58:42 dr; purification of
this mixture gave 18 in 54% yield and 13 in 40% yield as single di-
astereoisomers (>99:1 dr) in each case (Scheme 5).
Scheme 5. Reagents and conditions: (i) LiBHEt3, THF, ꢀ78 ꢁC, 2 h. [aCrude 42:58 dr
(13:18); 13 was also isolated in 40% yield from this reaction].
The stereochemical outcome of these reactions is consistent
with nucleophilic addition to the complexes in the anti conforma-
tion (see 19A, Fig. 3) onto the face distal to the chromium tri-
carbonyl moiety. The poor diastereoselectivity (42:58 dr) observed
for reduction of 27 is thought to arise from the fact that the car-
bonyl group of the ketone is not able to adopt a geometry which is
coplanar with the complexed aryl ring and is consistent with the
higher carbonyl absorption frequency in the infrared spectrum of
27 (1700 cmꢀl) compared to that observed in the other acyl com-
plexes 22e26 (w1670 cmꢀl), and the fact that the solution of 27 in
THF is not the diagnostic red colour which was observed for 22e26.
Figure 3. Diastereoselective nucleophilic addition to ortho-acyl substituted chromium
tricarbonyl complexed arenes.
ortho-Benzoyl 26 and ortho-pivaloyl 27 complexes were obtained
as single diastereoisomers (>99:1 dr)19 in 67 and 65% yield, re-
spectively, via direct acylation of the ortho-anion derived from (S)-3
with benzyl chloride and pivaloyl chloride. Additionally, treatment
of the ortho-anion derived from (S)-3 with DMF gave, after work-up
and chromatographic purification, ortho-formyl 22 in 82% yield and
>99:1 dr. Repeated attempts at formation of the corresponding
acetyl, propanoyl and isobutanoyl derivatives 23e25 via treatment
of the ortho-anion derived from (S)-3 with the requisite acyl chlo-
ride, chloroformate, N,N-dimethylamide or Weinreb amide reagents
failed to yield the desired products. Therefore, the crude reaction
mixtures resulting from treatment of the ortho-anion derived from
(S)-3 with acetaldehyde, propanaldehyde and isobutyraldehyde
were subjected to an oxidation protocol with Ac2O and DMSO to
give the corresponding ortho-acyl derivatives 23e25 as single di-
astereoisomers (>99:1 dr) in 62e77% yield (Scheme 4).
2.3. Grignard addition to ortho-formyl substituted complexes
The epimeric alcohols 9e13 were accessed by an analogous
procedure involving the addition of Grignard reagents to ortho-
formyl 22. Thus, treatment of 22 with the requisite Grignard re-
agents gave complexes 9e13 in >99:1 dr in each case; purification of
the crude reaction mixtures gave 9e13 in good yield and >99:1 dr.
However, the use of Grignard reagents containing a b-hydrogen also
brought about concomitant reduction of the aldehyde moiety giving
28 in 24, 28 and 10% yield upon treatment of 22 with EtMgBr,
iPrMgBrand tBuMgBr, respectively, although in each case the desired
1-(a
-methylbenzyloxy)-2-(10-hydroxyalkyl)benzene
chromium
tricarbonyl complexes were formed as the major products and were
isolated in ꢂ70% yield and >99:1 dr (Scheme 6). The stereochemical
outcome of these reactions is again consistent with nucleophilic
addition to the complexes in the anti conformation (see 19A, Fig. 3)
onto the face distal to the chromium tricarbonyl moiety.
Scheme 4. Reagents and conditions: (i) LDA, THF, ꢀ78 ꢁC, 3 h, then RCOCl, THF,
ꢀ78 ꢁC, 16 h; (ii) LDA, THF, ꢀ78 ꢁC, 3 h, then DMF, THF, ꢀ78 ꢁC, 16 h; (iii) LDA, THF,
ꢀ78 ꢁC, 3 h, RCHO, 16 h; (iv) DMSO, Ac2O, rt, 16 h. [aCombined yield after two steps].
2.2. Reduction of ortho-acyl substituted complexes
The reduction of ketone complexes 23e27 was achieved with
Super-HydrideÒ. Thus, 3.0 equiv of Super-HydrideÒ was added to
solutions of the ketone complexes 23e27 in THF at ꢀ78 ꢁC. Upon
addition, the red colour of the solution, which is diagnostic of
a conjugated ortho-acyl substituted arene chromium tricarbonyl
complex, changed to yellowexcept when R¼tBu as this complex was
yellow in colour initially.20 1H NMR spectroscopic analysis of the
crude reaction mixtures following reduction with Super-HydrideÒ
revealed that 14e17 were all formed in >99:1 dr. Purification of the
crude reaction mixtures gave 14e17 as single diastereoisomers in
ꢂ92% isolated yield. In the case of ortho-pivaloyl 27 a mixture of
Scheme 6. Reagents and conditions: (i) RMgX, THF, ꢀ78 ꢁC, 2 h. [aIsolated in 10e28%
i
yield and >99:1 dr upon reaction with EtMgBr, PrMgBr and tBuMgBr].
2.4. Deprotection and decomplexation
Having developed methodology for the synthesis of single di-
astereoisomers of 1-(
zene chromium tricarbonyl complexes, the removal of the chiral
a
-methylbenzyloxy)-2-(10-hydroxyalkyl)ben-

S.G. Davies et al. / Tetrahedron 66 (2010) 8076e8088
8079
auxiliary was investigated. However all attempts at this, while at
4. Experimental
the same time trying to retain the chromium tricarbonyl unit, were
unsuccessful. Hydrogenolysis, using 5% Pd/C under four atmo-
spheres of H2, resulted in only starting material being recovered.
Sodium/liquid ammonia reduction21 also failed, even upon the
addition of excess Na. Removal of the chromium tricarbonyl unit
was therefore carried out prior to cleavage of the auxiliary. Solu-
tions of complexes 14e18 and 9e13 in Et2O were therefore allowed
to stand in air and direct sunlight for two days to give decomplexed
arenes 29e33 and 39e43, respectively, in 67e91% yield as single
diastereoisomers in each case after chromatographic purification.
Subsequent cleavage of the auxiliary from 29e31, 33, 39e41 and 43
was achieved via hydrogenolysis to give the corresponding phe-
nolic alcohols 34e36 and 38 in ꢂ91% isolated yield.22 For substrates
32 and 42 it was decided that the auxiliary should be removed
using Na in liquid NH3, owing to the presence of two benzylic
groups in each case. Thus, liquid NH3 was added to a solution of the
requisite ether at ꢀ78 ꢁC. Sodium was subsequently added and the
solution turned from yellow to an intense blue colour. Stirring was
continued at ꢀ78 ꢁC for 15 min, after which time MeOH was
carefully added. The desired phenolic alcohols (R)-37 and (S)-37
were isolated in 52 and 56% yield, respectively, after purification by
flash column chromatography. In each case the enantiopurity of the
2-(10-hydroxyalkyl)phenols was determined to be >99:1 er
(Scheme 7).23
4.1. General experimental
All reactions involving organometallic or other moisture-sensitive
reagents were carried out under a nitrogen or argon atmosphere
using standard vacuum line techniques and glassware that was flame
dried and cooled under nitrogen before use. Solvents were dried
according to the procedure outlined by Grubbs and co-workers.24
Water was purified by a Millipore ElixÒ UV-10 system. All other sol-
vents were used as supplied (analytical or HPLC grade) without prior
purification. Organic layers were dried over MgSO4. Thin layer
chromatography was performed on aluminium plates coated with 60
F254 silica. Plates were visualised using UV light (254 nm), iodine, 1%
aq KMnO4, or 10% ethanolic phosphomolybdic acid. Flash column
chromatography was performed on Kieselgel 60 silica.
Elemental analyses were recorded by the microanalysis service
of the Inorganic Chemistry Laboratory, University of Oxford, U.K.
Melting points were recorded on a Gallenkamp Hot Stage apparatus
and are uncorrected. Optical rotations were recorded on a Per-
kineElmer 241 polarimeter with a water-jacketed 10 cm cell. Spe-
cific rotations are reported in 10ꢀ1 deg cm2 gꢀ1 and concentrations
in g/100 mL. IR spectra were recorded on a Bruker Tensor 27 FT-IR
spectrometer. Selected characteristic peaks are reported in cmꢀ1
.
NMR spectra were recorded on Bruker Avance spectrometers in the
deuterated solvent stated. The field was locked by external refer-
encing to the relevant deuteron resonance. Low-resolution mass
spectra were recorded on either a VG MassLab 20-250 or a Micro-
mass Platform 1 spectrometer. Accurate mass measurements were
run on either a Bruker MicroTOF, which was internally calibrated
with polyalanine, or a Micromass GCT instrument fitted with
a Scientific Glass Instruments BPX5 column (15 mꢃ0.25 mm) using
amyl acetate as a lock mass.
4.2. General procedure 1: diastereoselective ortho-
deprotonation and alkylation
A solution of 3 (1.0 equiv) in THF was added to a solution of LDA
(1.5 equiv) in THF at ꢀ78 ꢁC and the resultant solution was stirred at
ꢀ78 ꢁC for 3 h. A solution of the requisite electrophile (5.0 equiv) in
THF at ꢀ78 ꢁC was then added. The reaction mixture was then
allowed to warm to 0 ꢁC over a period of 16 h. After this time satd aq
NaHCO3 was added and the organic layer was concentrated in
vacuo. The residue was dissolved in CH2Cl2. The resultant solution
was filtered through Al2O3 (eluent CH2Cl2) and the filtrate was
concentrated in vacuo.
4.3. General procedure 2: oxidation of benzylic alcohols
Scheme 7. Reagents and conditions: (i) hn, O2, Et2O, rt, 48 h; (ii) H2 (4 atm), Pd/C,
EtOH, rt, 16 h; (iii) Na, NH3, ꢀ78 ꢁC, 15 min.
The mixture of diastereoisomeric benzylic alcohols was dis-
solved in DMSO and Ac2O was added slowly whilst N2 was bubbled
through the reaction mixture. The resultant solution was then
allowed to stir at rt, in the dark, for 16 h. The reaction mixture was
then diluted with benzene, cooled to 0 ꢁC, and sequentially washed
with 20% aq NaOH, water and brine, then concentrated in vacuo.
3. Conclusion
The use of the
a-methylbenzyl group as a chiral auxiliary has
allowed the diastereoselective ortho-deprotonation of [(S)-(
a
-
methylbenzyloxy)benzene]Cr(CO)3. When the resultant ortho-an-
ions are treated with aldehydes two epimeric alcohol complexes
are formed in relatively low dr. However, sequential ortho-acyla-
tion, followed by nucleophilic addition of either Super-HydrideÒ or
Grignard reagents proceeds with high levels of diastereoselectivity.
Subsequent removal of the chromium tricarbonyl unit followed by
4.4. General procedure 3: reduction of ortho-acyl complexes
with Super-HydrideÒ
LiBHEt3 (1.0 M in THF, 3.0 equiv) was added to a solution of the
requisite ortho-acyl complex (1.0 equiv) in THF at ꢀ78 ꢁC and the
resultant solution was stirred at ꢀ78 ꢁC for 2 h. After this time
MeOH was added and the reaction mixture was allowed to warm to
rt. The reaction mixture was then concentrated in vacuo and the
residue was redissolved in CH2Cl2. The resultant solution was
cleavage of the O-a-methylbenzyl group provides access to either
antipode of the corresponding the 2-(10-hydroxyalkyl)phenols in
good yield and >99:1 er.

8080
S.G. Davies et al. / Tetrahedron 66 (2010) 8076e8088
filtered through Al2O3 (eluent CH2Cl2) and the filtrate was con-
centrated in vacuo.
(207 mg, 60% dispersion in mineral oil, 5.17 mmol) in THF (20 mL)
at rt. The reaction mixture was stirred for 2 h at rt then a solution of
(fluorobenzene)tricarbonylchromium(0) (1.00 g, 4.31 mmol) in THF
(20 mL) was added and the resultant mixture was stirred at rt for
16 h before being concentrated in vacuo. The yellow residue was
then dissolved in CH2Cl2 and the resultant solution was filtered
through Al2O3 (eluent CH2Cl2) and concentrated in vacuo. Purifi-
cation via flash column chromatography (eluent 30e40 ꢁC petro-
leum ether/Et2O, 10:1) gave (S)-3 as a yellow oil (1.25 g, 87%, >99:1
4.5. General procedure 4: reaction of ortho-formyl complexes
with Grignard reagents
The requisite Grignard reagent (4.0 equiv) was added dropwise to
a solutionofortho-formyl complex 22(1.0 equiv)inTHFatꢀ78 ꢁC and
the resultant mixture was stirred at ꢀ78 ꢁC for 2 h. After this time
MeOHwasadded and the reaction mixturewasallowedtowarm tort.
The reaction mixture was then concentrated in vacuo and the residue
was redissolved in CH2Cl2. The resultant solutionwas filtered through
Al2O3 (eluent CH2Cl2) and the filtrate was concentrated in vacuo.
er); [
a
]
D
24 ꢀ305 (c 0.3 in CH2Cl2).
4.7.3. (1pRS,aSR)- and (RS,RS)-[1-(a-Methylbenzyloxy)-2-methyl-
benzene]tricarbonylchromium(0) 7 and 8.
4.6. General procedure 5: decomplexation
A solution of the requisite complex in Et2O was left open to the
air and allowed to stand in direct sunlight for 2 days. After this time
the reaction mixture was filtered through Al2O3 (eluent Et2O) and
the filtrate was concentrated in vacuo.
A solution of (RS)-a-methylbenzylalcohol 2 (55 mg, 0.45 mmol)
4.7. General procedure 6: O-deprotection via hydrogenolysis
THF(10 mL) was added dropwisetoa suspension ofNaH(20 mg, 60%
dispersion in mineral oil, 0.49 mmol) in THF (10 mL) at rt. The re-
action mixture was stirred for 2 h at rt then a solution of (RS)-(2-
Pd/C (30% w/w) was added to a solution of the requisite O-a-
methylbenzyl ether (1.0 equiv) in EtOH and the resultant mixture
was vigorously stirred under H2 (4 atm) for 16 h. After this time the
reaction mixture was filtered through Celite (eluent MeOH) and the
filtrate was concentrated in vacuo.
methyl-1-fluorobenzene)tricarbonylchromium(0)
5
(100 mg,
0.41 mmol) inTHF (10 mL) was added and the resultant mixture was
stirred at rt for 16 h before being concentrated in vacuo. The yellow
residue was dissolved in CH2Cl2 and the resultant solution was fil-
tered through Al2O3 (eluent CH2Cl2) and then concentrated in vacuo
to give a 50:50 mixture of 7 and 8. Purification via flash column
chromatography (eluent 30e40 ꢁC petroleum ether/Et2O,10:1) gave
7 as a yellow solid (69 mg, 49%) and 8 as a yellow oil (63 mg, 44%).
Data for 7: C18H16CrO4 requires C, 62.1; H, 4.6%; found C, 62.25; H,
4.6%; mp 66e67 ꢁC (from 30e40 ꢁC petroleum ether); nmax (CHCl3)
2890, 2880, 1970, 1880, 1470, 1385, 1175, 1080, 1020, 625; dH
4.7.1. (RS)-[(a-Methylbenzyloxy)benzene]tricarbonylchromium(0) 3.
(500 MHz, CDCl3) 1.66 (3H, d, J 6.5, C(
(1H, t, J 6.1, C(4)H), 4.87 (1H, d, J 6.1, C(2)H), 5.11 (1H, q, J 6.5, C(
5.20 (1H, dt, J 6.1,1.5, C(5)H), 5.50 (1H, dd, J 6.1,1.3, C(3)H), 7.30e7.41
(5H, m, Ph); dC (50 MHz, CDCl3) 16.3 (C(6)Me), 24.8 (C( )Me), 77.9 (C
)), 78.3 (C(6)), 79.8 (C(2)), 86.2 (C(4)), 93.2 (C(5)), 97.3 (C(3)),125.2,
128.2,129.3 (o,m,p-Ph),141.0 (i-Ph),142.1 (C(1)),195.7 (Cr(CO)3); m/z
(CIþ) 349 ([MþH]þ, 100%), 348 ([M]þ, 34%), 264 ([MꢀC3O3]þ, 47%).
Data for 8: C18H16CrO4 requires C, 62.1; H, 4.6%; found C, 62.2; H,
4.7%; nmax (CHCl3) 2930, 2920, 2910, 2890, 2870, 2860, 1965, 1880,
1480,1455,1385,1155,1100,1070, 620; dH (200 MHz, CDCl3) 1.63 (3H,
a
)Me), 2.27 (3H, s, C(6)Me), 4.85
A solution of (RS)-a-methylbenzylalcohol 2 (578 mg, 4.74 mmol) in
a
)H),
THF (20 mL) was added dropwise to a suspension of NaH (207 mg, 60%
dispersion in mineral oil, 5.17 mmol) in THF (20 mL) at rt. The reaction
mixture was stirred for 2 h at rt then a solution of (fluorobenzene)
tricarbonylchromium(0) (1.00 g, 4.31 mmol) inTHF (20 mL) was added
and the resultant mixture was stirred at rt for 16 h before being con-
centrated in vacuo. The yellow residue was then dissolved in CH2Cl2
and the resultant solution was filtered through Al2O3 (eluent CH2Cl2)
and concentrated in vacuo. Purification via flash column chromatog-
raphy (eluent 30e40 ꢁC petroleum ether/Et2O, 10:1) gave (RS)-3 as
a yellow oil (1.30 g, 90%); C17H14CrO4 requires C, 61.1; H, 4.2%; found C,
61.1; H, 4.5%; mp 64e66 ꢁC (pentane); nmax (CHCl3) 3090, 2960, 2930,
2870, 1990, 1840, 1470, 1465, 1455, 1440, 1375, 1155, 1090, 1080, 1075,
a
(a
d, J 6.4, C(
5.07e5.11(2H,m, C(
d, J 6.2, C(5)H), 7.33e7.44 (5H, m, Ph); dC (50 MHz, CDCl3) 16.2 (C(6)
Me), 23.7 (C( )Me), 78.5 (C( )), 79.9 (C(2)), 88.1 (C(4)), 91.5 (C(5)), 95.3
a)Me), 2.23 (3H, s, C(6)Me), 4.94 (1H, t, J 6.3, C(4)H),
a)H, C(2)H),5.22(1H,dt, J6.3,1.4, C(3)H), 5.37(1H,
a
a
1070, 610; dH (300 MHz, CDCl3) 1.63 (3H, d, J 6.4, C(
6.1, C(4)H), 4.86 (1H, dd, J 7.0, 2.1, C(6)H), 5.10 (1H, q, J 6.4, C(
(1H, ddd, J6.9, 2.5, 0.9, C(2)H), 5.37(1H, dt, J7.5,1.3, C(5)H), 5.54 (1H, dt, J
7.3,1.3, C(3)H), 7.29e7.42 (5H, m, Ph); dC (50 MHz, CDCl3)24.5(C( )Me),
77.9 (C( )), 78.0 (C(6)), 82.1 (C(2)), 85.3 (C(4)), 94.7 (C(5)), 95.8 (C(3)),
a)Me), 4.80 (1H, t, J
(C(3)), 98.7 (C(6)), 126.0, 128.5, 129.0 (o,m,p-Ph), 140.8 (i-Ph), 142.1 (C
a)H), 5.27
(1)), 198.0 (Cr(CO)3); m/z (EIþ) 348 ([M]þ, 7%), 264 ([MꢀC3O3]þ, 19%).
a
4.7.4. (1pR,10S, S)- and (1pR,10R, -Methylbenzyloxy)-2-(10-
a aS)-[1-(a
hydroxyethyl)benzene]tricarbonylchromium(0) 9 and 13.
a
125.4, 128.4,129.3 (o,m,p-Ph), 141.9 (i-Ph),142.2 (C(1)),192.3 (Cr(CO)3);
m/z (EIþ) 335 ([MþH]þ, 3%), 334 ([M]þ, 16%), 250 ([MꢀC3O3]þ, 41%).
4.7.2. (S)-[(a-Methylbenzyloxy)benzene]tricarbonylchromium(0) 3.
Following general procedure 1, treatment of (S)-3 (100 mg,
1.50 mmol) with LDA (0.6 mL, 0.60 mmol) followed by acetaldehyde
A solution of (S)-
in THF (20 mL) was added dropwise to a suspension of NaH
a-methylbenzylalcohol 2 (578 mg, 4.74 mmol)

S.G. Davies et al. / Tetrahedron 66 (2010) 8076e8088
8081
(66 mg, 1.50 mmol) gave a 70:30 mixture of 9 and 13, respectively.
Purification via flash column chromatography (eluent 30e40 ꢁC
petroleum ether/Et2O, 5:1) gave 9 as a yellow oil (70 mg, 62%, >99:1
dr) and 13 as a yellow oil (20 mg, 18%, >99:1 dr).
Data for 9: nmax (CH2Cl2) 3600, 2940, 2930, 2870, 1960, 1880,
1530, 1495, 1430, 1380, 1350, 1265, 1210, 1175, 1155, 1110, 1075,
1030, 1010, 1000, 930, 895, 640, 630; dH (200 MHz, CDCl3) 1.57 (3H,
Me), 29.5 (C(20)), 70.6 (C(10)), 76.07 (C(
a
)), 78.3 (C(6)), 83.9 (C(4)),
94.6 (C(5)), 95.0 (C(3)), 103.8 (C(2)), 124.9, 128.2, 129.2 (o,m,p-Ph),
140.1 (C(1)), 141.4 (i-Ph), 233.2 (Cr(CO)3); m/z (EIþ) 392 ([M]þ, 1%),
290 ([MꢀC8H8]þ, 10%); HRMS (CIþ) C20H20CrOþ5 ([M]þ) requires
392.0710; found 392.0710.
4.7.6. (1pR,10S, S)- and (1pR,10R, -Methylbenzyloxy)-2-(10-
a aS)-[1-(a
hydroxy-20-methylpropyl)benzene]tricarbonylchromium(0) 11 and 16.
d, J 6.4, C(20)H3), 1.70 (3H, d, J 6.3, C(
a
)Me), 2.27 (1H, br s, OH),
4.82e4.88 (2H, m, C(6)H, C(4)H), 5.13e5.17 (2H, m, C(
)H, C(10)H),
5.33e5.37 (1H, m, C(5)H), 5.96 (1H, dd, J 6.9, 1.1, C(3)H), 7.30e7.47
(5H, m, Ph); dC (50 MHz, CDCl3) 23.9 (C(20)), 24.8 (C(
)Me), 63.9 (C
(10)), 76.7 (C(
)), 78.2 (C(6)), 85.5 (C(4)), 92.4 (C(5)), 94.4 (C(3)),
a
a
a
107.3 (C(2)), 125.1, 128.4, 129.4 (o,m,p-Ph), 140.1 (C(1)), 142.0 (i-Ph),
234.1 (Cr(CO)3); m/z (CIþ) 378 ([M]þ, 5%), 361 ([MꢀOH]þ, 100%), 274
([MꢀC8H8]þ, 13%), 255 ([MꢀC8H10O]þ, 3%); HRMS (CIþ) C19H18CrOþ5
([M]þ) requires 378.0554; found 378.0550.
Data for 13: nmax (CH2Cl2) 3600, 2950, 2940, 2920, 2880, 1970,
1880, 1530, 1465, 1380, 1270, 1070, 1030, 1010, 1000, 930, 640, 635;
dH (300 MHz, CDCl3) 1.61 (3H, d, J 6.6, C(20)Me), 1.69 (3H, d, J 6.5, C
Following general procedure 1, treatment of (S)-3 (100 mg,
1.50 mmol) with LDA (0.6 mL, 0.60 mmol) followed by iso-
butyraldehyde (108 mg, 1.50 mmol) gave a 65:35 mixture of 11
and 16, respectively. Purification via flash column chromatogra-
phy (eluent 30e40 ꢁC petroleum ether/Et2O, 5:1) gave 11 as
a yellow oil (75 mg, 62%, >99:1 dr) and 16 as a yellow oil (24 mg,
20%, >99:1 dr).
Data for 11: nmax (CH2Cl2) 3620, 3580, 2960, 2930, 2280, 1965,
1880, 1530, 1430, 1265, 1070, 1030, 1010, 1000, 930, 640, 630; dH
(200 MHz, CDCl3) 1.07 (6H, t, J 7.1, C(20)Me2), 1.65 (3H, d, J 6.4, C
(a
)Me), 2.54 (1H, br d, J 4.6, OH), 4.78e4.83 (2H, m, C(6)H, C(4)H),
5.10e5.13 (1H, m, C(10)H), 5.18 (1H, q, J 6.5, C(
)H), 5.38 (1H, dt, J 5.9,
1.3, C(5)H), 5.82 (1H, dd, J 6.5, 1.3, C(3)H), 7.30e7.43 (5H, m, Ph); dC
(50 MHz, CDCl3) 21.9 (C(20)), 24.7 (C( )Me), 64.6 (C(10)), 76.0 (C(
)),
a
a
a
78.4 (C(6)), 83.9 (C(4)), 94.1 (C(5)), 94.6 (C(3)), 103.6 (C(2)), 124.9,
128.3, 129.2 (o,m,p-Ph), 140.5 (C(1)), 141.4 (i-Ph), 233.1 (Cr(CO)3);
m/z (CIþ) 378 ([M]þ, 5%), 361 ([MꢀOH]þ, 100%), 225
([MꢀC3HCrO4]þ, 7%); HRMS (CIþ) C19H18CrOþ5 ([M]þ) requires
378.0554; found 378.0556.
(
a
)Me), 1.79 (1H, d,
4.76e4.79 (1H, d, J 6.8, C(10)H), 4.86e4.89 (2H, m, C(6)H, C(4)H),
5.09 (1H, q, J 6.4, C( )H), 5.35 (1H, dt, J 6.7, 1.4, C(5)H), 5.89 (1H,
dd, J 6.2, 1.2, C(3)H), 7.27e7.45 (5H, m, Ph); dC (50 MHz, CDCl3)
14.3 (C(20)MeA), 17.1 (C(20)MeB), 25.0 (C( )Me), 34.5 (C(20)), 70.9 (C
(10)), 76.0 (C(
)), 78.5 (C(6)), 85.1 (C(4)), 93.4 (C(5)), 94.6 (C(3)),
J
3.0, OH), 1.99e2.02 (1H, m, C(20)H),
4.7.5. (1pR,10S, S)- and (1pR,10R, -Methylbenzyloxy)-2-(10-
a aS)-[1-(a
hydroxypropyl)benzene]tricarbonylchromium(0) 10 and 15.
a
a
a
106.1 (C(2)), 124.8, 128.1, 129.1 (o,m,p-Ph), 140.8 (C(1)), 141.9
(i-Ph), 233.4 (Cr(CO)3); m/z (CIþ) 389 ([MꢀOH]þ, 100%), 253
([MꢀC3HCrO4]þ, 22%), 149 ([MꢀC11H9CrO4]þ, 22%), 105
([MꢀC14H17CrO4]þ, 50%); HRMS (CIþ) C21H22CrO5þ ([M]þ) requires
406.0867; found 406.0869.
Data for 16: nmax (CH2Cl2) 3620, 3580, 2960, 2940, 2880, 1965,
1880, 1700, 1530, 1430, 1220, 1070, 1030, 650, 645, 630; dH
(200 MHz, CDCl3) 0.96 (3H, d, J 6.8, C(20)MeA), 1.19 (3H, d, J 6.6, C(20)
Following general procedure 1, treatment of (S)-3 (100 mg,
1.50 mmol) with LDA (0.6 mL, 0.60 mmol) followed by propio-
naldehyde (87 mg, 1.50 mmol) gave a 65:35 mixture of 10 and 15,
respectively. Purification via flash column chromatography (eluent
30e40 ꢁC petroleum ether/Et2O, 5:1) gave 10 as a yellow oil (73 mg,
62%, >99:1 dr) and 15 as a yellow oil (21 mg, 18%, >99:1 dr).
Data for 10: nmax (CH2Cl2) 3600, 2940, 2880, 1960, 1880, 1530,
1495, 1430, 1380, 1270, 1225, 1210, 1080, 1070, 930, 645, 630; dH
MeB), 1.69 (3H, d, J 6.4, C(
d, J 9.0, OH), 3.93 (1H, t, J 8.0, C(10)H), 4.74e4.76 (2H, m, C(6)H, C(4)
H), 5.18 (1H, q, J 6.4, C( )H), 5.35 (1H, dt, J 6.9, 1.3, C(5)H), 5.55 (1H,
dd, J 6.2, 1.2, C(3)H), 7.28e7.46 (5H, m, Ph); dC (50 MHz, CDCl3) 19.1
(C(20)MeA), 20.3 (C(20)MeB), 24.9 (C( )Me), 34.1 (C(20)), 76.1 (C(10)),
78.4 (C( )), 79.1 (C(6)), 83.6 (C(4)), 94.1 (C(5)), 97.1 (C(3)), 103.5 (C
a
)Me), 2.19e2.22 (1H, m, C(20)H), 2.99 (1H,
a
a
a
(2)), 124.8, 128.3, 129.2 (o,m,p-Ph), 139.3 (C(1)), 141.3 (i-Ph), 233.0
(Cr(CO)3); m/z (CIþ) 252 ([MꢀC3HCrO4]þ, 6%); HRMS (CIþ)
C21H22CrOþ5 ([M]þ) requires 406.0867; found 406.0886.
(200 MHz, CDCl3) 1.10 (3H, t, J 7.3, C(30)H3), 1.65 (3H, d, J 6.4, C(
a)
Me), 1.80e1.84 (2H, m, C(20)H2), 1.90 (1H, d, J 3.0, OH), 4.79 (1H, d,
J 6.6, C(6)H), 4.87 (1H, t, J 6.3, C(4)H), 4.96e5.00 (1H, m, C(10)H),
5.10 (1H, q, J 6.4, C(
dd, J 6.3, 1.3, C(3)H), 7.26e7.45 (5H, m, Ph); dC (50 MHz, CDCl3)
10.1 (C(30)), 24.8 (C( )Me), 30.8 (C(20)), 68.3 (C(10)), 74.4 (C(
)),
a)H), 5.34 (1H, dt, J 6.7, 1.4, C(5)H), 5.90 (1H,
4.7.7. (1pR,10S, S)- and (1pR,10R, -Methylbenzyloxy)-2-(10-
a aS)-[1-(a
hydroxy-10-phenylmethyl)benzene]tricarbonylchromium(0)12 and17.
a
a
78.33 (C(6)), 85.4 (C(4)), 92.8 (C(5)), 94.5 (C(3)), 106.5 (C(2)),
125.1, 128.4, 129.4 (o,m,p-Ph), 140.5 (C(1)), 142.1 (i-Ph), 234.0 (Cr
(CO)3); m/z (CIþ) 392 ([M]þ, 9%), 375 ([MꢀOH]þ, 100%), 239
([MꢀC3HCrO4]þ, 3%); HRMS (CIþ) C20H20CrOþ5 ([M]þ) requires
392.0710; found 392.0703.
Data for 15: nmax (CH2Cl2) 3600, 2950, 2940, 2930, 2880, 1965,
1880, 1530, 1430, 1225, 1070, 900, 650, 640, 630; dH (200 MHz,
CDCl3) 1.17 (3H, t, J 7.4, C(30)H3), 1.68 (3H, d, J 6.4, C(
a
)Me),
1.82e1.87 (2H, m, C(20)H2), 2.73 (1H, d, J 5.9, OH), 4.61e4.66 (1H,
m, C(10)H), 4.75e4.79 (2H, m, C(6)H, C(4)H), 5.17 (1H, q, J 6.4, C(
H), 5.38 (1H, dt, J 5.9, 1.3, C(5)H), 5.82 (1H, dd, J 6.5, 1.3, C(3)H),
7.27e7.45 (5H, m, Ph); dC (50 MHz, CDCl3) 11.3 (C(30)), 24.7 (C(
a
)
Following general procedure 1, treatment of (S)-3 (100 mg,
1.50 mmol) with LDA (0.6 mL, 0.60 mmol) followed by benzaldehyde
(159 mg, 1.50 mmol) gave a 65:35 mixture of 12 and 17, respectively.
a
)

8082
S.G. Davies et al. / Tetrahedron 66 (2010) 8076e8088
Purification via flash column chromatography (eluent 30e40 ꢁC
petroleum ether/Et2O, 5:1) gave 12 as a yellow oil (80 mg, 61%,
>99:1 dr) and 17 as a yellow oil (25 mg, 19%, >99:1 dr).
2940, 2930, 1920, 2880, 1960, 1885, 1605, 1590, 1485, 1460, 1390,
1380, 1370, 1350, 1170, 1155, 1095, 1085, 1080, 1070, 1010, 900, 645,
620; dH (300 MHz, CDCl3) 1.08 (9H, s, CMe3), 1.64 (1H, d, J 2.7, OH),
Data for 12: C24H20CrO5 requires C, 65.3; H, 4.5%; found C, 65.3; H,
4.6%; mp 127e128 ꢁC (pentane); nmax (CHCl3) 3600, 3470, 2940, 2880,
2860,1965,1885,1605,1600,1495,1490,1460,1455,1450,1445,1380,
1080, 1070, 1065, 1020, 1010, 620; dH (300 MHz, CDCl3) 1.67 (3H, d, J
1.66 (3H, d, J 6.4, C(
(10)H), 4.88 (1H, t, J 6.3, C(4)H), 5.07 (1H, q, J 6.4, C(
6.7,1.4, C(5)H), 5.88(1H, dd, J 6.3,1.3, C(3)H), 7.28e7.43 (5H, m, Ph);dC
(50 MHz, CDCl3) 25.1 (C(
)Me), 26.0 (CMe3), 36.6 (CMe3), 72.6 (C(10)),
75.6 (C( )), 79.0 (C(6)), 84.8 (C(4)), 94.6 (C(2)), 95.2 (C(5)), 106.0 (C
a
)Me), 4.73 (1H, d, J 6.6, C(6)H), 4.80 (1H, d, J 2.6, C
a)H), 5.36 (1H, dt, J
a
6.4, C(a)Me), 2.35 (1H, d, J 3.0, OH), 4.77 (1H, d, J 6.8, C(6)H), 4.87(1H, t,
a
J 6.3, C(4)H), 5.13 (1H, q, J 6.4, C(
a
)H), 5.32e5.35 (1H, m, C(5)H), 6.07
(3)),125.1,128.3,129.4 (o,m,p-Ph),142.3 (i-Ph),138.7 (C(1)), 232.7 (Cr
(1H, d, J 2.8, C(10)H), 6.11e6.14 (1H, m, C(3)H), 6.66e6.68 (2H, m, Ph),
6.94e6.97 (3H, m, Ph), 7.09e7.11 (3H, m, Ph), 7.39e7.42 (2H, m, Ph); dC
(CO)3); m/z (CIþ) 421 ([MþH]þ, 9%), 403 ([MꢀOH]þ, 100%).
Data for 18: C22H24CrO5 requires C, 62.9; H, 5.7%; found C, 62.7; H,
5.6%;mp186e190 ꢁC(dec, Et2O);nmax (CHCl3)3570,2950, 2915,2905,
2870,1965,1890,1590,1470,1460,1395,1380,1370,1175, 1095,1070,
1015, 900, 620; dH (300 MHz, CDCl3) 1.08 (9H, s, CMe3), 1.71 (3H, d, J
(50 MHz, CDCl3) 24.8 (C(a)Me), 69.5(C(6)), 75.4, 77.9(C(a
), C(10)), 84.9
(C(4)), 92.6 (C(2)), 94.5 (C(5)), 104.9 (C(3)), 125.0, 127.0, 128.3, 128.4,
128.8, 129.2 (o,m,p-Ph), 139.7 (C(1)), 141.6, 142.1 (i-Ph), 235.1 (Cr
(CO)3); m/z (CIþ) 440 ([M]þ, 4%), 423 ([MꢀOH]þ, 100%).
6.4, C(
4.78 (1H, d, J 6.8, C(6)H), 5.19 (1H, q, J 6.4, C(
(5)H), 5.47 (1H, dd, J 6.2,1.2, C(3)H), 7.31e7.45 (5H, m, Ph); dC (50 MHz,
CDCl3) 25.0 (C(
)Me), 26.8 (CMe3), 38.2 (CMe3), 73.3 (C(10)), 76.0 (C
(a)), 79.7 (C(6)), 83.9 (C(4)), 94.3 (C(2)), 98.0 (C(5)), 101.1 (C(3)), 125.1,
a
)Me), 3.85 (1H, d, J 3.4, C(10)H), 4.74 (1H, dt, J 6.2, 0.5, C(4)H),
)H), 5.32e5.34 (1H, m, C
Data for 17: C24H20CrO5 requires C, 65.3; H, 4.5%; found C, 65.35;
H, 4.5%; mp 117e121 ꢁC (dec, pentane); nmax (CHCl3) 3600, 2960,
2940, 2930, 1965, 1890, 1495, 1460, 1450, 1380, 1180, 1160, 1090,
a
a
860, 635, 625; dH (300 MHz, CDCl3) 1.74 (3H, d, J 6.5, C(
(1H, d, J 4.6, OH), 4.66 (1H, t, J 6.0, C(4)H), 4.78 (1H, d, J 6.6, C(6)H),
5.13 (1H, dd, J 6.3, 1.3, C(3)H), 5.20 (1H, q, J 6.4, C( )H), 5.34 (1H, dt, J
6.6, 1.3, C(5)H), 6.05 (1H, d, J 4.5, C(10)H), 7.22e7.48 (8H, m, Ph),
7.58e7.60 (2H, m, Ph); dC (50 MHz, CDCl3) 24.8 (C( )Me), 71.2 (C(6)),
75.8, 78.5 (C(
), C(10)), 84.1 (C(4)), 94.7 (C(2)), 95.9 (C(5)), 103.5 (C
a)Me), 3.10
128.6, 129.5 (o,m,p-Ph), 140.1 (C(1)), 141.7 (i-Ph), 233.0 (Cr(CO)3); m/z
a
(CIþ) 438 ([MþNH4]þ, 8%), 420 ([M]þ, 13%), 403 ([MꢀOH]þ, 100%).
a
4.7.9. (1pR,
aS)-[1-(a-Methylbenzyloxy)-2-formylbenzene]tricarbo-
a
nylchromium(0) 22.
(3)), 125.1, 127.1, 128.4, 128.6, 128.8, 129.4 (o,m,p-Ph), 139.6 (C(1)),
141.0, 141.6 (i-Ph), 233.3 (Cr(CO)3); m/z (CIþ) 423 ([MꢀOH]þ, 17%).
4.7.7.1. X-ray crystal structure determination for (1pRS,10RS,
17. Data were collected using an Enrafenonius CAD4 diffractom-
eter with graphite monochromated Cu K radiation using standard
aSR)-
a
procedures at 190 K. The structure was solved by direct methods
(SIR92); all non-hydrogen atoms were refined with anisotropic
thermal parameters. Hydrogen atoms were added at idealised po-
sitions. The structure was refined using CRYSTALS.25
Following general procedure 1, treatment of (S)-3 (500 mg,
1.50 mmol) with LDA (3.0 mL, 3.00 mmol) followed by DMF (548 mg,
7.50 mmol) gave, after purification by flash column chromatography
(eluent 30e40 ꢁC petroleum ether/Et2O, 2:1), 22 as a red solid
(445 mg, 82%,>99:1dr);C18H14CrO5 requiresC,59.7;H, 3.9%;foundC,
X-ray crystal structure data for (1pRS,10RS,
aSR)-17 [C24H20CrO5]:
M¼440.4, monoclinic, space group
P
21/n, a¼10.6255(7) Å,
b¼6.6609(6) Å, c¼29.424(2) Å,
b
¼95.54(1)ꢁ, V¼2072.8(1) Å3, Z¼4,
59.45; H, 3.7%; mp 89e93 ꢁC (pentane); [
a]
D
24 þ642 (c 0.8 in CH2Cl2);
yellow block, crystal dimensions¼0.20ꢃ0.20ꢃ0.20 mm3. The final
nmax (CHCl3) 2930, 2890, 2880, 1985, 1910, 1680, 1495, 1455, 1450,
1380,1175,1155,1090,1065,610;dH (300 MHz,CDCl3)1.70(3H, d,J6.4,
parameters were wR2¼0.033 and R1¼0.028 [I>3.0
s(I)].
Crystallographic data (excluding structure factors) has been
deposited with the Cambridge Crystallographic Data Centre as
supplementary publication number CCDC 776717. Copies of the
data can be obtained, free of charge, on application to CCDC, 12
Union Road, Cambridge CB2 1EZ, UK [fax: þ44(0) 1223 336033 or e-
mail: deposit@ccdc.cam.ac.uk].
C(
6.4, C(
7.30e7.44 (5H, m, Ph),10.22 (1H, s, C(10)H); dC (50 MHz, CDCl3) 24.5 (C
a)Me), 4.84 (1H, d, J 6.9, C(6)H), 4.91 (1H, t, J 6.4, C(4)H), 5.25 (1H, q, J
a)H), 5.65 (1H, dt, J 7.3,1.3, C(5)H), 6.22 (1H, dd, J 6.4,1.3, C(3)H),
(a)Me), 75.1 (C(6)), 78.7 (C(a)), 84.1 (C(4)), 92.6 (C(5)), 95.2 (C(3)),
125.2, 128.7, 129.6 (o,m,p-Ph), 141.2 (i-Ph), 144.6 (C(1)), 186.0 (C(10)),
231.7 (Cr(CO)3); m/z (CIþ) 363 ([MþH]þ, 18%), 278 ([MꢀC3O3]þ, 5%).
4.7.8. (1pR,10S, S)- and (1pR,10R, -Methylbenzyloxy)-2-(10-
a aS)-[1-(a
hydroxy-20, 20-dimethylpropyl)benzene]tricarbonylchromium(0) 13
and 18.
4.7.10. (1pR,
aS)-[1-(a-Methylbenzyloxy)-2-acetylbenzene]tricarbo-
nylchromium(0) 23.
Following general procedure 1, treatment of (S)-3 (500 mg,
1.50 mmol) with LDA (3.00 mL, 3.00 mmol) followed by acetalde-
hyde (330 mg, 7.50 mmol) gave a 70:30 mixture of 9 and 14, re-
spectively. Following general procedure 2, this mixture was treated
with Ac2O (15 mL, 0.16 mmol) and DMSO (22.5 mL) to give, after
purification by flash column chromatography (eluent 30e40 ꢁC
Following general procedure 1, treatment of (S)-3 (100 mg,
1.50 mmol) with LDA (0.6 mL, 0.60 mmol) followed by piv-
alaldehyde (129 mg, 1.50 mmol) gave a 75:25 mixture of 13 and 18,
respectively. Purification via flash column chromatography (eluent
30e40 ꢁC petroleum ether/Et2O, 5:1) gave 13 as a yellow oil (75 mg,
60%, >99:1 dr) and 18 as a yellow oil (19 mg, 15%, >99:1 dr).
Data for 13: C22H24CrO5 requires C, 62.9; H, 5.7%; found C, 63.0; H,
5.6%; mp 143e144 ꢁC (dec, pentane/Et2O); nmax (CHCl3) 3590, 2950,
petroleum ether/Et2O, 2:1), 23 as a red oil (355 mg, 63%, >99:1 dr);
25
C19H16CrO5 requires C, 60.6; H, 4.3%; found C, 60.6; H, 4.05%; [a]
D
þ237 (c 0.2 in CH2Cl2); nmax (CH2Cl2) 2960, 2940, 2870, 1975, 1900,

S.G. Davies et al. / Tetrahedron 66 (2010) 8076e8088
8083
1675, 1520, 1430, 1220, 1110, 1065, 1030, 1010, 1000, 930, 650, 630;
dH (200 MHz, CDCl3) 1.70 (3H, d, J 6.4, C(
)Me), 2.19 (3H, s, C(20)H3),
4.81e4.85 (2H, m, C(4)H, C(6)H), 5.29 (1H, q, J 6.3, C( )H), 5.60 (1H,
t, J 6.5, C(5)H), 6.24 (1H, d, J 6.9, C(3)H), 7.29e7.42 (5H, m, Ph); dC
(50 MHz, CDCl3) 24.4 (C( )), 78.6 (C(6)),
)Me), 31.3 (C(20)), 75.7 (C(
(1)), 142.6 (i-Ph), 204.2 (C(10)), 231.6 (Cr(CO)3); m/z (CIþ) 405
([MþH]þ, 7%), 301 ([MꢀC8H9]þ, 15%), 165 ([MꢀC11H9CrO3]þ, 53%).
a
a
4.7.13. (1pR,aS)-[1-(a-Methylbenzyloxy)-2-benzoylbenzene]tri-
carbonylchromium(0) 26.
a
a
84.3 (C(4)), 90.1 (C(2)), 95.9 (C(5)), 96.1 (C(3)), 125.1, 128.6, 129.4
(o,m,p-Ph), 141.1 (C(1)), 143.3 (i-Ph), 166.7 (C(10)), 195.7 (Cr(CO)3);
m/z (EIþ) 376 ([M]þ, 3%).
4.7.11. (1pR,aS)-[1-(a-Methylbenzyloxy)-2-propanoylbenzene]tri-
carbonylchromium(0) 24.
Following general procedure 1, treatment of (S)-3 (100 mg,
0.30 mmol) with LDA (0.6 mL, 0.60 mmol) followed by benzoyl
chloride (210 mg, 1.50 mmol) gave, after purification by flash col-
umn chromatography (eluent 30e40 ꢁC petroleum ether/Et2O, 2:1),
26 as a red oil (88 mg, 67%, >99:1 dr); C23H18CrO5 requires C, 65.75;
25
H, 4.1%; found C, 65.95; H, 4.0%; mp 110e111 ꢁC (pentane); [
a]
D
ꢀ200 (c 0.3 in CH2Cl2); nmax (CH2Cl2) 2950, 2940, 2930, 1980, 1900,
1670,1650,1600,1585,1520,1380,1095,1070,1030, 915, 635, 625; dH
Following general procedure 1, treatment of (S)-3 (500 mg,
1.50 mmol) with LDA (3.0 mL, 3.0 mmol) followed by propio-
naldehyde (436 mg, 7.50 mmol) gave a 65:35 mixture of 10 and 15,
respectively. Following general procedure 2, this mixture was
treated with Ac2O (15 mL, 0.16 mmol) and DMSO (22.5 mL) to give,
after purification by flash column chromatography (eluent
30e40 ꢁC petroleum ether/Et2O, 2:1), 24 as a red solid (450 mg,
(300 MHz, CDCl3) 1.24 (3H, d, J 6.4, C(
a)Me), 4.81e4.86 (2H, m, C(6)H,
C(4)H), 5.07 (1H, q, J 6.4, C( )H), 5.51 (1H, dt, J 6.6, 1.3, C(5)H), 5.95
a
(1H, dd, J 6.4,1.3, C(3)H), 7.11e7.14 (2H, m, Ph), 7.31e7.35 (3H, m, Ph),
7.50 (2H, t, J 7.7, Ph), 7.61 (1H, t, J 7.4, Ph), 7.91 (2H, dd, J 8.8,1.4, Ph); dC
(50 MHz, CDCl3) 24.0 (C(a)Me), 74.7 (C(6)), 78.4 (C(a)), 82.9 (C(4)),
95.0 (C(5)), 96.4 (C(2)), 97.2 (C(3)), 125.3, 125.8, 128.4, 129.2, 129.3,
133.0 (o,m,p-Ph), 138.6 (C(1)), 140.5, 141.7 (i-Ph), 192.9 (C(10)), 230.2
(Cr(CO)3); m/z (CIþ) 439 ([MþH]þ, 29%), 354 ([MꢀC3O3]þ, 68%).
77%, >99:1 dr); C20H18CrO5 requires C, 61.5; H, 4.6%; found C, 61.2;
25
H, 4.2%; mp 108e109 ꢁC (pentane/Et2O); [
a
]
þ203 (c 0.1 in
D
CH2Cl2); nmax (CH2Cl2) 2960, 2940, 2920, 2870, 1975, 1890, 1675,
1520, 1430, 1380, 1350, 1230, 1220, 1070, 925, 650, 645, 625; dH
4.7.14. (1pR,aS)-[1-(a
-Methylbenzyloxy)-2-(20,20-dimethylpropa-
noyl)benzene]tricarbonylchromium(0) 27.
(200 MHz, CDCl3) 1.26 (3H, t, J 7.1, C(30)H3),1.72 (3H, d, J 6.4, C(
a
)Me)
3.11 (2H, q, J 7.2, C(20)H2), 4.82e4.86 (2H, m, C(4)H, C(6)H), 5.28 (1H,
q, J 6.4, C( )H), 5.58 (1H, t, J 6.5, C(5)H), 6.24 (1H, dt, J 6.7, 1.4, C(3)H),
7.26e7.46 (5H, m, Ph); dC (50 MHz, CDCl3) 8.5 (C(30)), 24.5 (C(
)Me),
36.4 (C(20)), 75.8 (C(
)), 78.5 (C(6)), 84.3 (C(4)), 90.6 (C(2)), 96.0 (C
a
a
a
(5)), 96.1 (C(3)), 125.2, 128.6, 129.4 (o,m,p-Ph), 141.2 (C(þ1)), 142.9 (i-
Ph), 199.2 (C(10)), 232.1 (Cr(CO)3); m/z (EIþ) 390 ([M] , 75%), 306
([MꢀC3O3]þ, 18%), 201 ([MꢀC11H9O3]þ, 64%).
4.7.12. (1pR,aS)-[1-(a
-Methylbenzyloxy)-2-(20-methylpropanoyl)
benzene]tricarbonylchromium(0) 25.
Following general procedure 1, treatment of (S)-3 (100 mg,
0.30 mmol) with LDA (0.6 mL, 0.60 mmol) followed by pivaloyl
chloride (180 mg, 1.50 mmol) gave, after purification by flash col-
umn chromatography (eluent 30e40 ꢁC petroleum ether/Et2O, 2:1),
27 as a yellow solid (81 mg, 65%, >99:1 dr); C22H22CrO5 requires C,
25
63.15; H, 5.3%; found C, 63.4; H, 5.2%; mp 146e148 ꢁC (hexane); [
a]
D
ꢀ157 (c 0.1 in CH2Cl2); nmax (CH2Cl2) 2940, 2930, 2910, 2880, 1970,
1900, 1710, 1605, 1520, 1480, 1380, 1370, 1175, 1070, 1030, 925, 630;
dH (300 MHz, CDCl3) 1.33 (9H, s, CMe3), 1.59 (3H, d, J 6.5, C(
4.70e4.72 (2H, m, C(6)H, C(4)H), 5.12 (1H, q, J 6.4, C( )H), 5.33 (1H,
dt, J 6.7, 1.2, C(5)H), 5.49 (1H, dd J 6.2, 1.3, C(3)H), 7.31e7.44 (5H, m,
Ph); dC (50 MHz, CDCl3) 24.6 (C( )Me), 27.2 (CMe3), 45.1 (CMe3), 73.8
(C(6)), 79.4 (C(
a)Me),
a
Following general procedure 1, treatment of (S)-3 (500 mg,
1.50 mmol) with LDA (3.0 mL, 3.0 mmol) followed by iso-
butyraldehyde (541 mg, 7.50 mmol) gave a 65:35 mixture of 11 and
16, respectively. Following general procedure 2, this mixture was
treated with Ac2O (15 mL, 0.16 mmol) and DMSO (22.5 mL) to give,
after purification by flash column chromatography (eluent
30e40 ꢁC petroleum ether/Et2O, 2:1), 25 as a red solid (376 mg,
a
a
)), 81.7 (C(4)), 94.0 (C(5)), 94.3 (C(3)), 106.3 (C(2)),
125.2,128.5,129.4 (o,m,p-Ph),139.0 (C(1)),142.0 (i-Ph), 206.4 (C(10)),
232.7 (Cr(CO)3); m/z (CIþ) 419 ([MþH]þ, 3%), 334 ([MꢀC3O3]þ, 50%).
4.7.15. (1pR,10R, -Methylbenzyloxy)-2-(10-hydroxyethyl)
aS)-[1-(a
benzene]tricarbonylchromium(0) 14.
62%, >99:1 dr); C21H20CrO5 requires C, 62.4; H, 5.0%; found C, 62.5;
25
H, 5.1%; mp 137e138 ꢁC (pentane/Et2O); [
a
]
D
þ193 (c 0.2 in
CH2Cl2); nmax (CH2Cl2) 2950, 2940, 2930, 1975, 1900, 1675, 1520,
1220, 1215, 1065, 985, 925, 645, 625; dH (200 MHz, CDCl3) 0.88 (6H,
t, J 6.1, C(20)Me2), 1.70 (3H, d, J 6.4, C(
a
)Me), 3.65 (1H, sep, J 6.7, C(20)
)H), 5.59
H), 4.81e4.84 (2H, m, C(4)H, C(6)H), 5.29 (1H, q, J 6.4, C(
a
(1H, dt, J 6.2, 1.4, C(5)H), 6.10 (1H, dd, J 6.5, 1.4, C(3)H), 7.27e7.45
(5H, m, Ph); dC (50 MHz, CDCl3) 19.4 (C(20)MeA), 19.8 (C(20)MeB),
24.5 (C(
a
)Me), 39.3 (C(20)), 75.1 (C(
a
)), 78.5 (C(6)), 83.9 (C(4)), 91.2
Following general procedure 3, treatment of 23 (50 mg,
(C(2)), 95.6 (C(5)), 96.0 (C(3)), 124.9, 128.4, 129.2 (o,m,p-Ph), 141.0 (C
0.133 mmol) with LiBHEt3 (1.0 M in THF, 0.40 mL, 0.40 mmol) gave,

8084
S.G. Davies et al. / Tetrahedron 66 (2010) 8076e8088
after purification by flash column chromatography (eluent
30e40 ꢁC petroleum ether/Et2O, 5:1),14 as a yellow oil (49 mg, 97%,
>99:1 dr).
(20 mg, 40%, >99:1 dr) and 18 as a yellow oil (27 mg, 54%,
>99:1 dr).
4.7.20. (1pR,10S, -Methylbenzyloxy)-2-(10-hydroxyethyl)
aS)-[1-(a
benzene]tricarbonylchromium(0) 9.
4.7.16. (1pR,10R,
a
S)-[1-(
a
-Methylbenzyloxy)-2-(10-hydroxypropyl)
benzene]tricarbonylchromium(0) 15.
Et
OH
O
Ph
(CO)3Cr
Following general procedure 4, treatment of 22 (50 mg,
0.133 mmol) with MeMgBr (1.0 M in THF, 0.40 mL, 0.40 mmol) gave,
after purification byflash columnchromatography(eluent 30e40 ꢁC
petroleum ether/Et2O, 5:1), 9 as a yellow oil (46 mg, 88%, >99:1 dr).
Following general procedure 3, treatment of 24 (50 mg,
0.133 mmol) with LiBHEt3 (1.0 M in THF, 0.40 mL, 0.40 mmol) gave,
after purification by flash column chromatography (eluent
30e40 ꢁC petroleum ether/Et2O, 5:1),15 as a yellow oil (48 mg, 96%,
>99:1 dr).
4.7.21. (1pR,10S, -Methylbenzyloxy)-2-(10-hydroxypropyl)
aS)-[1-(a
benzene]tricarbonylchromium(0) 10.
4.7.17. (1pR,10R, -Methylbenzyloxy)-2-(10-hydroxy-20-meth-
aS)-[1-(a
ylpropyl)benzene]tricarbonylchromium(0) 16.
Following general procedure 4, treatment of 22 (50 mg,
0.133 mmol) with EtMgBr (1.0 M in THF, 0.40 mL, 0.40 mmol) gave,
after purification byflash columnchromatography(eluent 30e40 ꢁC
petroleum ether/Et2O, 5:1),10 as a yellow oil (41 mg, 76%, >99:1 dr)
Following general procedure 3, treatment of 25 (50 mg,
0.133 mmol) with LiBHEt3 (1.0 M in THF, 0.40 mL, 0.40 mmol) gave,
after purification by flash column chromatography (eluent
30e40 ꢁC petroleum ether/Et2O, 5:1),16 as a yellow oil (48 mg, 96%,
>99:1 dr).
and (1pR,
tricarbonylchromium(0) 28 as a yellow oil (12 mg, 24%, >99:1 dr).
Data for 28: dH (300 MHz, CDCl3) 1.66 (3H, d, J 6.4, C( )Me), 2.05
(1H, br s, OH), 4.52 (1H, br d, J 14.0, C(10)HA), 4.76 (1H, br d, J 14.0, C
(10)HB), 4.85 (2H, m, C(4)H, C(6)H), 5.13 (1H, q, J 6.4, C(
)H), 5.34
(1H, app t, J 6.5, C(3)H), 5.78 (1H, app d, J 6.0, C(5)H), 7.31e7.44 (5H,
m, Ph); dC (50 MHz, CDCl3) 24.7 (C( )),
)Me), 59.9 (C(10)), 76.8 (C(
aS)-[1-(a-methylbenzyloxy)-2-(hydroxymethyl)benzene]
a
a
4.7.18. (1pR,10R, -Methylbenzyloxy)-2-(10-hydroxy-10-phe-
aS)-[1-(a
nylmethyl)benzene]tricarbonylchromium(0) 17.
a
a
78.5 (C(6)), 85.0 (C(4)), 94.2 (C(5)), 95.3 (C(3)), 100.4 (C(2)), 125.1,
128.4, 129.4 (o,m,p-Ph), 140.7 (C(1)), 141.9 (i-Ph), 233.7 (Cr(CO)3); m/
z (CIþ) 382 ([MþNH4]þ, 5%), 364 ([M]þ, 25%), 334 ([MꢀOH]þ, 100%);
HRMS (CIþ) C18H16CrO5þ ([M]þ) requires 364.0397; found 364.0400.
4.7.22. (1pR,10S, -Methylbenzyloxy)-2-(10-hydroxy-20-meth-
aS)-[1-(a
ylpropyl)benzene]tricarbonylchromium(0) 11.
Following general procedure 3, treatment of 26 (50 mg,
0.133 mmol) with LiBHEt3 (1.0 M in THF, 0.40 mL, 0.40 mmol) gave,
after purification by flash column chromatography (eluent
30e40 ꢁC petroleum ether/Et2O, 5:1),17 as a yellow oil (46 mg, 92%,
>99:1 dr).
4.7.19. (1pR,10R, -Methylbenzyloxy)-2-(10-hydroxy-20,20-di-
aS)-[1-(a
methylpropyl)benzene]tricarbonylchromium(0) 18.
Following general procedure 4, treatment of 22 (50 mg,
0.133 mmol) with iPrMgCl (1.0 M in THF, 0.40 mL, 0.40 mmol) gave,
after purification by flash column chromatography (eluent
30e40 ꢁC petroleum ether/Et2O, 5:1),11 as a yellow oil (39 mg, 70%,
>99:1 dr) and 28 as a yellow oil (14 mg, 28%, >99:1 dr).
4.7.23. (1pR,10S,
aS)-[1-(a
-Methylbenzyloxy)-2-(10-hydroxy-10-phe-
nylmethyl)benzene]tricarbonylchromium(0) 12.
Following general procedure 3, treatment of 27 (50 mg,
0.133 mmol) with LiBHEt3 (1.0 M in THF, 0.40 mL, 0.40 mmol)
gave, after purification by flash column chromatography (elu-
ent 30e40 ꢁC petroleum ether/Et2O, 5:1), 13 as a yellow oil

S.G. Davies et al. / Tetrahedron 66 (2010) 8076e8088
8085
Following general procedure 4, treatment of 22 (50 mg, 0.133 mmol)
with PhMgCl (1.0 M in THF, 0.40 mL, 0.40 mmol) gave, after purifica-
tion by flash column chromatography (eluent 30e40 ꢁC petroleum
ether/Et2O, 5:1), 12 (56 mg, 92%, >99:1 dr).
127.6, 127.6, 128.7 (Ar, o,m,p-Ph), 132.8 (C(2)), 142.9 (i-Ph), 154.7 (C
(1)); m/z (CIþ) 256 ([M]þ, 21%), 239 ([MꢀOH]þ, 100%), 135
([MꢀC8H9O]þ, 45%), 105 ([MꢀC10H15O]þ, 25%).
4.7.27. (10R,
aS)-1-(a
-Methylbenzyloxy)-2-(10-hydroxy-20-methyl-
4.7.24. (1pR,10S, -Methylbenzyloxy)-2-(10-hydroxy-20,20-di-
aS)-[1-(a
propyl)benzene 31.
methylpropyl)benzene]tricarbonylchromium(0) 13.
Following general procedure 5, 16 (200 mg, 0.49 mmol) was
decomplexed to give, after purification by flash column chroma-
tography (eluent 30e40 ꢁC petroleum ether/Et2O, 5:1), 31 as a col-
Following general procedure 4, treatment of 22 (50 mg,
0.133 mmol) with tBuMgCl (1.0 M in THF, 0.40 mL, 0.40 mmol) gave,
after purification by flash column chromatography (eluent
30e40 ꢁC petroleum ether/Et2O, 5:1),13 as a yellow oil (48 mg, 83%,
>99:1 dr) and 28 as a yellow oil (5 mg, 10%, >99:1 dr).
ourless oil (95 mg, 71%, >99:1 dr); C18H22O2 requiresC, 80.0; H, 8.2%;
25
found C, 80.0; H, 8.0%; [
a]
þ84.3 (c 0.3 in CH2Cl2); nmax (CH2Cl2)
D
3610, 3560, 2960, 2940, 2930, 2880, 1600, 1590, 1490, 1230, 1070,
1020; dH (200 MHz, CDCl3) 0.91 (3H, d, J 6.8, C(20)Me), 1.13 (3H, d, J
6.6, C(20)Me),1.69 (3H, d, J 6.4, C( )Me), 2.22 (1H, sextet, J 6.8, C(20)H),
a
4.7.25. (10R, -Methylbenzyloxy)-2-(10-hydroxyethyl)benzene
aS)-1-(a
29.
2.63 (1H, br s, OH), 4.69 (1H, d, J 7.2, C(10)H), 5.38 (1H, q, J 6.4, C(
a)H),
6.73 (1H, d, J 8.0, Ar), 6.90 (1H, dt, J 7.4, 0.9, Ar), 7.09 (1H, dt, J 7.9, 1.8,
Ar), 7.28e7.40 (6H, m, Ar); dC (50 MHz, CDCl3) 18.5, 19.7 (C(20)Me2),
24.5 (C(a a)),113.0,120.4,125.4,
)Me), 34.4 (C(20)), 76.0 (C(10)), 76.8 (C(
127.6, 127.8, 128.2, 128.7 (Ar, o,m,p-Ph), 132.0 (C(2)), 142.9 (i-Ph),
154.8 (C(1)); m/z (CIþ) 270 ([M]þ, 7%), 253 ([MꢀOH]þ, 22%), 149
([MꢀC8H9O]þ, 18%), 105 ([MꢀC11H16O]þ, 100%).
4.7.28. (10R,
methyl)benzene 32.
aS)-1-(a
-Methylbenzyloxy)-2-(10-hydroxy-10-phenyl-
Following general procedure 5, 14 (200 mg, 0.53 mmol) was
decomplexed to give, after purification by flash column chroma-
tography (eluent 30e40 ꢁC petroleum ether/Et2O, 5:1), 29 as a col-
ourless oil (86 mg, 67%, >99:1 dr); C16H18O2 requires C, 79.3; H,
25
7.5%; found C, 79.4; H, 7.4%; [
a]
þ75.3 (c 0.3 in CH2Cl2), nmax
D
(CH2Cl2) 3600, 2960, 2930, 2870, 1600, 1590, 1490, 1225, 1080, 1010,
935; dH (200 MHz, CDCl3) 1.62 (3H, d, J 6.5, C(20)H3), 1.71 (3H, d, J
6.4, C(
q, J 6.4, C(
(1H, dt, J 7.8, 1.7, Ar), 7.25e7.78 (6H, m, Ar); dC (50 MHz, CDCl3) 23.1
(C(20)), 24.4 (C( )Me), 66.7 (C(10)), 76.1 (C(
)), 113.1, 120.8, 125.4,
a
)Me), 2.91 (1H, br s, OH), 5.26 (1H, q, J 6.5, C(10)H), 5.41 (1H,
a
)H), 6.76 (1H, d, J 8.1, Ar), 6.93 (1H, dt, J 7.0, 0.6, Ar), 7.11
Following general procedure 5, 17 (200 mg, 0.46 mmol) was
decomplexed to give, after purification by flash column chroma-
tography (eluent 30e40 ꢁC petroleum ether/Et2O, 5:1), 32 as a col-
a
a
126.2, 127.7, 128.0, 128.8 (Ar, o,m,p-Ph), 134.0 (C(2)), 142.8 (i-Ph),
154.7 (C(1)); m/z (CIþ) 242 ([M]þ, 27%), 225 ([MꢀOH]þ, 100%), 121
([MꢀC8H9O]þ, 45%).
ourless oil (126 mg, 91%, >99:1 dr); C21H20O2 requires C, 82.9; H,
25
6.6%; found C, 83.0; H, 6.6%; [
a
]
þ154 (c 0.1 in CH2Cl2); nmax
D
(CH2Cl2) 3600, 3560, 2940, 2930, 2920, 1600, 1590, 1490, 1400,
4.7.26. (10R, -Methylbenzyloxy)-2-(10-hydroxypropyl)ben-
aS)-1-(a
zene 30.
1220, 1180, 1110, 1070, 1020, 940; dH (300 MHz, CDCl3) 1.58 (3H, d, J
6.3, C(
br d, C(10)H), 6.71 (1H, d, J 8.2, Ar), 6.92 (1H, d, J 7.4, Ar), 7.08e7.12
(3H, m, Ar), 7.27e7.48 (9H, m, Ar); dC (50 MHz, CD2Cl2) 24.1 (C(
Me), 72.7 (C(
)), 75.8 (C(10)), 113.3, 120.7, 125.7, 126.1, 126.7, 127.1,
a)Me), 3.29 (1H, br d, OH), 5.34 (1H, q, J 6.4, C(a)H), 6.09 (1H,
a
)
a
127.5, 128.0, 128.5, 128.8 (Ar, o,m,p-Ph), 132.8 (C(2)), 142.9, 144.4 (i-
Ph), 154.9 (C(1)); m/z (CIþ) 287 ([MꢀOH]þ, 100%), 182
([MꢀC8H10O]þ, 41%).
4.7.29. (10R,
thylpropyl)benzene 33.
aS)-1-(a
-Methylbenzyloxy)-2-(10-hydroxy-20,20-dime-
Following general procedure 5, 15 (200 mg, 0.51 mmol) was
decomplexed to give, after purification by flash column chroma-
tography (eluent 30e40 ꢁC petroleum ether/Et2O, 5:1), 30 as a col-
ourless oil (90 mg, 69%, >99:1 dr); C17H20O2 requires C, 79.65; H,
25
7.9%; found C, 79.9; H, 7.9%; [
a
]
D
þ80.8 (c 0.3 in CH2Cl2); nmax
(CH2Cl2) 3600, 3560, 2960, 2940, 2930, 2880, 1600, 1590, 1490,
1225,1070,1010; dH (200 MHz, CDCl3) 1.03 (3H, t, J 7.5, C(30)H3),1.68
(3H, d, J 6.4, C(
OH), 4.95 (1H, br t, J 6.3, C(10)H), 5.38 (1H, q, J 6.4, C(
d, J 7.7, Ar), 6.90 (1H, dt, J 7.4, 1.0, Ar), 7.09 (1H, dt, J 7.7, 1.8, Ar),
7.26e7.41 (6H, m, Ar); dC (50 MHz, CDCl3) 10.5 (C(30)), 24.4 (C(
Me), 30.4 (C(20)), 65.8 (C(10)), 76.0 (C(
)), 113.0, 120.6, 125.4, 127.1,
a
)Me), 1.93 (2H, quin, J 7.0, C(20)H2), 2.79 (1H, br s,
a
)H), 6.73 (1H,
Following general procedure 5, 18 (200 mg, 0.48 mmol) was
decomplexed to give, after purification by flash column chroma-
tography (eluent 30e40 ꢁC petroleum ether/Et2O, 5:1), 33 as
a)
a

8086
S.G. Davies et al. / Tetrahedron 66 (2010) 8076e8088
a white solid (119 mg, 88%, >99:1 dr); C19H24O2 requires C, 80.2; H,
([MꢀOH]þ, 40%), 133 ([MꢀCH4O]þ, 51%), 123 ([MꢀC2H7O]þ, 100%),
105 ([MꢀC3H8O]þ, 25%).
8.5%; found C, 80.4; H, 8.55%; mp 73e74 ꢁC (pentane); [
a]
25 þ40.9
D
(c 0.1 in CH2Cl2); nmax (CH2Cl2) 3610, 3550, 2950, 2930, 2900, 2680,
1690, 1605, 1580, 1490, 1225, 1110, 1070, 1045, 1010, 935, 645, 610;
4.7.33. (R)-2-(10-Hydroxy-10-phenylmethyl)phenol 37.
dH (200 MHz, CD2Cl2) 1.10 (9H, s, CMe3), 1.71 (3H, d, J 6.5, C(
2.95 (1H, br s, OH), 4.97 (1H, br s, C(10)H), 5.37 (1H, q, J 6.4, C(
6.77 (1H, d, J 8.2, Ar), 6.96 (1H, t, J 7.4, Ar), 7.13 (1H, t, J 6.4, Ar),
7.33e7.47 (6H, m, Ar); dC (50 MHz, CD2Cl2) 24.5 (C( )Me), 26.1
(CMe3), 36.7 (CMe3), 76.9 (C(
)), 77.1 (C(10)), 113.2, 120.1, 125.6,
a
)Me),
a
)H),
a
a
127.7, 127.9, 128.9, 129.7 (Ar, o,m,p-Ph), 131.1 (C(2)), 143.7 (i-Ph),
155.7 (C(1)); m/z (CIþ) 266 ([MꢀOH]þ, 4%), 162 ([MꢀC8H10O]þ,
33%), 105 ([MꢀC12H19O]þ, 100%).
NH3 (2 mL) was condensed and added to a flask containing a so-
lution of (10R,
a
S)-32 (126 mg, 0.414 mmol) in THF (2 mL) at ꢀ78 ꢁC.
Sodium (24 mg, 1.03 mmol) was then added and stirring was con-
tinued at ꢀ78 ꢁC for 15 min. After this time MeOH (0.5 mL) was
added and the reaction mixture was allowed to warm to rt before
being concentrated in vacuo. Purification via flash column chro-
matography (eluent 30e40 ꢁC petroleum ether/Et2O, 5:1) gave (R)-
37 as a colourless oil (43 mg, 52%, >99:1 er); C13H12O2 requires C,
4.7.30. (R)-2-(10-Hydroxyethyl)phenol 34.
78.0; H, 6.0%; found C, 78.3; H, 6.1%; [
a
]
25 ꢀ35.1 (c 0.6 in CH2Cl2); dH
D
(200 MHz, CD2Cl2) 3.18 (1H, br s, OH), 6.01 (1H, s, C(10)H), 6.83e6.90
(3H, m, Ar), 7.19 (1H, t, J 6.6, Ar), 7.61e7.65 (5H, m, Ar), 7.90 (1H, br s,
OH); dC (50 MHz, CDCl3) 77.2 (C(10)), 117.5, 120.2, 127.0, 127.3, 128.5,
128.6, 129.0, 129.5 (Ar, o,m,p-Ph), 142.6 (i-Ph), 155.9 (C(1)); m/z (CIþ)
183 ([MꢀOH]þ, 100%), 105 ([MꢀC6H6O]þ, 4%).
Following general procedure 6, hydrogenolysis of (10R,
(86 mg, 0.36 mmol) gave (R)-34 as a yellow oil (46 mg, 94%, >99:1
aS)-29
20
er); C8H10O2 requires C, 69.55; H, 7.3%; found C, 69.5; H, 7.4%; [a]
D
þ20.5 (c 0.2 in CH2Cl2); nmax (CH2Cl2) 3590, 3380, 2940, 2910, 2880,
1620, 1590, 1490, 1225, 645; dH (200 MHz, CDCl3) 1.56 (3H, d, J 6.5, C
(20)H3), 5.02 (1H, q, J 6.5, C(10)H), 6.86e6.96 (2H, m, Ar), 6.98 (1H, d,
J 6.8, Ar), 7.17 (1H, t, J 7.7, Ar); dC (50 MHz, CDCl3) 23.3 (C(20)), 71.2 (C
(10)), 116.9, 120.0, 126.5, 128.6. 128.8 (Ar), 155.1 (C(1)); m/z (EIþ) 138
([M]þ, 23%), 120 ([MꢀOH]þ, 100%), 91 ([MꢀC2H6O]þ, 35%).
4.7.34. (R)-2-(10-Hydroxy-20,20-dimethylpropyl)phenol 38.
4.7.31. (R)-2-(10-Hydroxypropyl)phenol 35.
Following general procedure 6, hydrogenolysis of (10R,
aS)-33
(119 mg, 0.42 mmol) gave (R)-38 as a colourless oil (71 mg, 94%,
>99:1 er); C11H16O2 requires C, 73.3; H, 8.95%; found C, 73.6; H,
25
8.6%; mp 83e84 ꢁC (pentane); [
a
]
þ10.0 (c 0.1 in CH2Cl2); nmax
D
Following general procedure 6, hydrogenolysis of (10R,
aS)-30
(CH2Cl2) 3600, 3370, 2950, 2920, 2880,1620,1590,1490,1470,1400,
1370, 1220, 1160, 1100, 1030, 1000, 645; dH (200 MHz, CDCl3) 1.00
(9H, s, CMe3), 1.68 (1H, br s, OH), 4.55 (1H, s, C(10)H), 6.85e6.89 (3H,
m, Ar), 7.21e7.25 (1H, m, Ar); dC (50 MHz, CDCl3) 26.0 (CMe3), 37.3
(CMe3), 85.1 (C(10)), 117.3, 118.6, 123.6, 128.7, 129.7 (Ar), 156.2 (C(1));
m/z (CIþ) 180 ([M]þ, 9%), 163 ([MꢀOH]þ, 100%).
(94 mg, 0.38 mmol) gave (R)-35 as a colourless oil (55 mg, 95%,
>99:1 er); C9H12O2 requires C, 71.0; H, 7.9%; found C, 70.8, H, 7.9%;
[
a]
25 þ23.5 (c 0.7 in CH2Cl2); nmax (CH2Cl2) 3590, 3370, 2960, 2950,
D
2940, 2880, 1620, 1590, 1490, 1225, 1220, 650; dH (200 MHz, CDCl3)
0.94 (3H, t, J 7.4, C(30)H3), 1.86e1.90 (2H, m, C(20)H2), 4.68 (1H, t, J
6.8, C(10)H), 5.63 (1H, br s, OH), 6.85e6.91 (2H, m, Ar), 6.94 (1H, dd, J
8.1, 1.9, Ar), 7.15 (1H, dt, J 7.6, 1.8, Ar); dC (50 MHz, CDCl3) 10.1 (C(30)),
30.1 (C(20)), 76.9 (C(10)), 116.8, 119.7, 127.4, 128.4, 128.7 (Ar), 155.2 (C
(1)); m/z (EIþ) 152 ([M]þ, 15%), 134 ([MꢀOH]þ, 52%).
4.7.35. (S,S)-1-(a
-Methylbenzyloxy)-2-(10-hydroxyethyl)benzene
39.
4.7.32. (R)-2-(10-Hydroxy-20-methylpropyl)phenol 36.
Following general procedure 5, 9 (200 mg, 0.53 mmol) was
decomplexed to give, after purification by flash column chroma-
tography (eluent 30e40 ꢁC petroleum ether/Et2O, 5:1), 39 as
Following general procedure 6, hydrogenolysis of (10R,
aS)-31
(95 mg, 0.35 mmol) gave (R)-36 as a colourless oil (54 mg, 93%,
>99:1 er); C10H14O2 requires C, 72.3; H, 8.5%; found C, 72.2; H, 8.6%;
a colourless oil (92 mg, 72%, >99:1 dr); C16H18O2 requires C, 79.3;
24
H, 7.5%; found C, 79.0; H, 7.3%; [
a
]
þ40.8 (c 0.1 in CH2Cl2); nmax
D
[
a]
25 þ24.1 (c 0.2 in CH2Cl2); nmax (CH2Cl2) 3590, 3370, 2940, 2930,
(CH2Cl2) 3600, 2940, 2900, 2880, 1600, 1590, 1490, 1220, 1080,
D
2910, 2880, 1620, 1590, 1490, 1430, 1230, 1000, 650, 640; dH
(200 MHz, CDCl3) 0.85 (3H, d, J 6.8, C(20)MeA), 1.04 (3H, d, J 6.6, C(20)
MeB), 1.83 (1H, sextet, J 3.5, C(20)H), 4.47 (1H, d, J 7.1, C(10)H),
6.86e6.90 (3H, m, Ar), 7.15 (1H, dt, J 8.9, 1.9, Ar); dC (50 MHz, CDCl3)
18.1, 19.1 (C(20)Me2), 34.4 (C(20)), 81.5 (C(10)), 117.0, 119.6, 128.4,
128.5, 128.8 (Ar), 155.8 (C(1)); m/z (EIþ) 166 ([M]þ, 15%), 148
1010, 935, 610; dH (200 MHz, CDCl3) 1.62 (3H, d, J 6.4, C(20)H3), 1.71
(3H, d, J 6.4, C(
5.41 (1H, q, J 6.4, C(
1.0, Ar), 7.12 (1H, dt, J 7.5, 1.8, Ar), 7.28e7.40 (6H, m, Ar); dC
(50 MHz, CDCl3) 23.1 (C(20)), 24.5 (C( )Me), 66.6 (C(10)), 76.1 (C(
)),
113.0, 120.7, 125.3, 126.1, 127.6, 128.0, 128.8 (Ar, o,m,p-Ph), 133.9 (C
a
)Me), 2.96 (1H, br s, OH), 5.27 (1H, q, J 6.4, C(10)H),
a)H), 6.75 (1H, d, J 8.2, Ar), 6.94 (1H, dt, J 7.4,
a
a

S.G. Davies et al. / Tetrahedron 66 (2010) 8076e8088
8087
(2)), 142.8 (i-Ph), 154.7 (C(1)); m/z (CIþ) 225 ([MꢀOH]þ, 41%), 120
([MꢀC8H10O]þ, 100%).
(a
)), 76.0 (C(10)), 113.1, 120.7, 125.7, 127.3, 127.4, 127.6, 127.7, 128.1,
128.4, 128.8 (Ar, o,m,p-Ph), 133.0 (C(2)), 143.2, 144.3 (i-Ph), 154.8 (C
(1)); m/z (CIþ) 287 ([MꢀOH]þ, 100%), 182 ([MꢀC8H10O]þ, 47%).
4.7.36. (S,S)-1-(a
-Methylbenzyloxy)-2-(10-hydroxypropyl)benzene 40.
4.7.39. (S,S)-1-(
propyl)benzene 43.
a
-Methylbenzyloxy)-2-(10-hydroxy-20,20-dimethyl-
Following general procedure 5, 10 (200 mg, 0.51 mmol) was
decomplexed to give, after purification by flash column chromatog-
raphy (eluent 30e40 ꢁC petroleum ether/Et2O, 5:1), 40 as a colourless
oil (101 mg, 77%, >99:1 dr); C17H20O2 requires C, 79.65; H, 7.9%; found
Following general procedure 5, 13 (200 mg, 0.48 mmol) was
decomplexed to give, after purification by flash column chroma-
tography (eluent 30e40 ꢁC petroleum ether/Et2O, 5:1), 43 as a col-
C, 79.8; H, 8.1%; [
a
]
24 þ45.5 (c 0.1 in CH2Cl2); nmax (CH2Cl2) 3600, 3570,
D
2950, 2940, 2880, 2860, 1600, 1590, 1490, 1225, 1090, 1070, 1010, 940;
ourless oil (110 mg, 81%, >99:1 dr); C19H24O2 requires C, 80.2; H,
dH (200 MHz, CDCl3) 1.03 (3H, t, J 7.4, C(30)H3), 1.68 (3H, d, J 6.5, C(
Me), 1.92 (2H, app quin, J 7.2, C(20)H2), 2.80 (1H, br s, OH), 4.94 (1H, t, J
6.6, C(10)H), 5.37 (1H, q, J 6.5, C(
)H), 6.72 (1H, d, J 8.2, Ar), 6.92 (1H, t, J
7.4, Ar), 7.09 (1H, dt, J 7.7, 1.8, Ar), 7.27e7.39 (6H, m, Ar); dC (50 MHz,
CDCl3) 10.6 (C(30)), 24.5 (C( )Me), 30.3 (C(20)), 65.8 (C(10)), 76.2 (C(
)),
a)
25
8.5%; found C, 80.1; H, 8.7%; [
a
]
D
þ90.4 (c 0.1 in CH2Cl2); nmax
(CH2Cl2) 3610, 3540, 2950, 2940, 2930, 2880,1600,1580,1490,1395,
a
1225,1070,1045,1010,1005; dH (200 MHz, CDCl3) 1.01 (9H, s, CMe3),
1.66 (3H, d, J 6.4, C(
5.38 (1H, q, J 6.4, C(
7.08 (1H, dt, J 7.4, 1.8, Ar), 7.28e7.43 (6H, m, Ar); dC (50 MHz, CDCl3)
24.1 (C( )Me), 25.8 (CMe3), 36.5 (CMe3), 75.9 (C(
)), 76.0 (C(10)),
a
)Me), 2.44 (1H, br s, OH), 4.98 (1H, br s, C(10)H),
a
a
a)H), 6.74 (1H, d, J 8.2, Ar), 6.89 (1H, t, J 6.9, Ar),
113.1, 120.6, 125.3, 127.1, 127.6, 127.9, 128.7 (Ar, o,m,p-Ph), 132.7 (C(2)),
142.9 (i-Ph), 154.8 (C(1)); m/z (CIþ) 134 ([MꢀC8H10O]þ, 100%).
a
a
112.7,119.9,125.7,127.7,127.8,128.8,129.3 (Ar, o,m,p-Ph),131.2 (C(2)),
143.5 (i-Ph), 155.3 (C(1)); m/z (CIþ) 284 ([M]þ, 6%), 267 ([MꢀOH]þ,
15%), 163 ([MꢀC8H9O]þ, 24%), 105 ([MꢀC12H18O]þ, 100%).
4.7.37. (S,S)-1-(a
-Methylbenzyloxy)-2-(10-hydroxy-20-methylpropyl)
benzene 41.
4.7.40. (S)-2-(10-Hydroxyethyl)phenol 34.
Following general procedure 5, 11 (200 mg, 0.49 mmol) was
decomplexed to give, after purification by flash column chromatogra-
phy (eluent 30e40 ꢁC petroleum ether/Et2O, 5:1), 41 as a colourless oil
(98 mg, 74%, >99:1 dr); C18H22O2 requires C, 80.0; H, 8.2%; found C,
Following general procedure 6, hydrogenolysis of (S,S)-39
(92 mg, 0.38 mmol) gave (S)-34 as a colourless oil (48 mg, 92%,
>99:1 er); [
a]
25 ꢀ23.9 (c 0.3 in CH2Cl2).
D
79.8; H, 7.9%; [
a
]
25 þ51.0 (c 0.3 in CH2Cl2); nmax (CH2Cl2) 3610, 3560,
D
2960, 2940, 2880, 1600, 1590, 1490, 1225, 1070, 1010; dH (200 MHz,
CDCl3) 0.96 (3H, d, J 6.8, C(20)MeA),1.15 (3H, d, J 6.8, C(20)MeB),1.70 (3H,
4.7.41. (S)-2-(10-Hydroxypropyl)phenol 35.
d, J 6.4, C(
4.74 (1H, d, J 6.8, C(10)H), 5.37 (1H, q, J 6.4, C(
6.94 (1H, t, J 7.0, Ar), 7.11 (1H, dt, J 8.0, 1.6, Ar), 7.32e7.42 (6H, m, Ar); dC
(50 MHz, CDCl3) 18.4,19.8 (C(20)Me2), 24.6 (C( )Me), 34.4 (C(20)), 76.4 (C
a
)Me), 2.23 (1H, app sextet, J 6.8, C(20)H), 2.91 (1H, br s, OH),
a)H), 6.75 (1H, d, J 8.1, Ar),
a
(10)), 76.4 (C(
a)), 113.1, 120.5, 125.3, 127.6, 127.9, 128.2, 128.8 (Ar, o,m,p-
Following general procedure 6, hydrogenolysis of (S,S)-40
(101 mg, 4.0 mmol) gave (S)-35 as a colourless oil (56 mg, 94%,
Ph),132.2 (C(2)),143.0 (i-Ph),154.9 (C(1)); m/z (CIþ) 270 ([M]þ, 5%), 253
([MꢀOH]þ, 21%), 149 ([MꢀC8H9O]þ, 22%), 105 ([MꢀC11H16O]þ, 100%).
>99:1 er); [
a]
25 ꢀ24.0 (c 0.2 in CH2Cl2).
D
4.7.38. (S,S)-1-(a
-Methylbenzyloxy)-2-(10-hydroxy-10-phenylmethyl)
benzene 42.
4.7.42. (S)-2-(10-Hydroxy-20-methylpropyl)phenol 36.
Following general procedure 6, hydrogenolysis of (S,S)-41
(98 mg, 0.36 mmol) gave (S)-36 as a colourless oil (55 mg, 91%,
Following general procedure 5, 12 (200 mg, 0.46 mmol) was
decomplexed to give, after purification by flash column chroma-
tography (eluent 30e40 ꢁC petroleum ether/Et2O, 5:1), 42 as a col-
>99:1 er); [
a]
26 ꢀ27.4 (c 0.3 in CH2Cl2).
D
4.7.43. (S)-2-(10-Hydroxy-10-phenylmethyl)phenol 37.
ourless oil (105 mg, 76%, >99:1 dr); C21H20O2 requires C, 82.9; H,
25
6.6%; found C, 82.5; H, 6.7%; [
a
]
D
ꢀ226 (c 0.2 in CH2Cl2); nmax
(CH2Cl2) 3600, 2950, 2940, 2920,1600,1590,1490, 1400, 1225, 1165,
1160, 1070, 1015, 940, 610; dH (300 MHz, CDCl3) 1.53 (3H, d, J 6.4, C
(
a
)Me),3.05 (1H, br s, OH), 5.30 (1H, q, J 6.4, C(
H), 6.69 (1H, d, J 8.2, Ar), 6.93 (1H, J 7.4, Ar), 7.10e7.15 (2H, m, Ar),
7.25e7.46 (10H, m, Ar); dC (50 MHz, CD2Cl2) 24.2 (C( )Me), 72.1 (C
a
)H), 6.13 (1H, s, C(10)
a

8088
S.G. Davies et al. / Tetrahedron 66 (2010) 8076e8088
11. Kndig, E. P.; Quattropani, A. Tetrahedron Lett. 1994, 35, 3497.
NH3 (2 mL) was condensed and added to a flask containing a so-
12. Davies, S. G. Organotransition Metal Chemistry: Applications to Organic Synthesis;
Pergamon: Oxford, 1982; Blagg, J.; Davies, S. G.; Holman, N. J.; Laughton, C. A.;
Mobbs, B. E. J. Chem. Soc., Perkin Trans. 1 1986, 1581; Coote, S. J.; Davies, S. G.
Chem. Commun. 1988, 648; Coote, S. J.; Davies, S. G.; Middlemiss, D.; Naylor, A.
J. Chem. Soc., Perkin Trans. 1 1989, 2223; Davies, S. G.; Newton, R. F.; Williams, J.
M. J. Tetrahedron Lett. 1989, 30, 2867; Coote, S. J.; Davies, S. G.; Middlemiss, D.;
Naylor, A. Tetrahedron Lett. 1989, 30, 3581; Coote, S. J.; Davies, S. G.; Middlemiss,
D.; Naylor, A. Tetrahedron: Asymmetry 1990, 1, 33; Davies, S. G.; Donohoe, T. J.;
Lister, M. A. Tetrahedron: Asymmetry 1991, 2, 1085; Davies, S. G.; Donohoe, T. J.;
Lister, M. A. Tetrahedron: Asymmetry 1991, 2, 1089; Davies, S. G.; Donohoe, T. J.;
Williams, J. M. J. Pure Appl. Chem. 1992, 64, 379; Davies, S. G.; Donohoe, T. J. In
Selective Reactions of Metal-Activated Molecules; Werner, H., Griesbeck, A. G.,
Adam, W., Bringmann, G., Kiefer, W., Eds.; Vieweg: Braunschweig, 1992; p 9;
Coote, S. J.; Davies, S. G.; Fletcher, A. M.; Roberts, P. M.; Thomson, J. E. Chem.
Asian J. 2010, 5, 589.
lution of (S,S)-42 (105 mg, 0.35 mmol) in THF (2 mL) at ꢀ78 ꢁC. So-
dium (24 mg, 0.86 mmol) was then added and stirring was continued
at ꢀ78 ꢁC for 15 min. After this time MeOH (0.5 mL) was added and
the reaction mixture was allowed to warm to rt before being con-
centrated in vacuo. Purification via flash column chromatography
(eluent 30e40 ꢁC petroleum ether/Et2O, 5:1) gave (S)-37 as a colour-
less oil (39 mg, 56%, >99:1 er); [
a
]
26 þ36.1 (c 1.2 in CH2Cl2).
D
4.7.44. (S)-2-(10-Hydroxy-20,20-dimethylpropyl)phenol 38.
13. For reviews, see: Davies, S. G.; Donohoe, T. J. Synlett 1993, 323; Davies, S. G. J.
Organomet. Chem. 1990, 400, 223.
14. Davies, S. G.; Hume, W. E. J. Chem. Soc., Chem. Commun. 1995, 251.
15. Semmelhack, M. F.; Bisaha, J.; Czarny, M. J. Am. Chem. Soc. 1979, 101, 768.
16. We have previously employed mutual kinetic resolution protocols to assay the
level of enantiorecognition between two racemic species, see: Bailey, S.; Davies,
S. G.; Smith, A. D.; Withey, J. M. Chem. Commun. 2002, 2910; Davies, S. G.; Díez,
D.; El Hammouni, M. M.; Garner, A. C.; Garrido, N. M.; Long, M. J. C.; Morrison,
R. M.; Smith, A. D.; Sweet, M. J.; Withey, J. M. Chem. Commun. 2003, 2410;
Davies, S. G.; Bunnage, M. E.; Chippendale, A. M.; Parkin, R. M.; Smith, A. D.;
Withey, J. M. Org. Biomol. Chem. 2003, 1, 3698; Davies, S. G.; Bunnage, M. E.;
Parkin, R. M.; Roberts, P. M.; Smith, A. D.; Withey, J. M. Org. Biomol. Chem. 2004,
2, 3337; Davies, S. G.; Garner, A. C.; Long, M. J. C.; Smith, A. D.; Sweet, M. J.;
Withey, J. M. Org. Biomol. Chem. 2004, 2, 3355; Davies, S. G.; Garner, A. C.; Long,
M. J. C.; Morrison, R. M.; Roberts, P. M.; Smith, A. D.; Sweet, M. J.; Withey, J. M.
Org. Biomol. Chem. 2005, 3, 2762; Aye, Y.; Davies, S. G.; Garner, A. C.; Roberts, P.
M.; Smith, A. D.; Thomson, J. E. Org. Biomol. Chem. 2008, 6, 2195.
Following general procedure 6, hydrogenolysis of (S,S)-43
(110 mg, 0.387 mmol) gave (S)-38 as a colourless oil (64 mg, 92%,
25
>99:1 er); [
a]
ꢀ10.5 (c 0.1 in CH2Cl2).
D
Acknowledgements
The authors would like to thank the EPSRC for a studentship
(W.E.H.), and Dr. Alexander N. Chernega and the Oxford Chemical
Crystallography Service for X-ray crystal structure determination
and the use of their diffractometers.
17. We have also observed this colour change in related systems upon
deprotonation of Cr(CO)3 complexed arenes.
18. Davies, S. G.; Goodfellow, C. L. J. Chem. Soc., Perkin Trans. 1 1990, 393; Hayashi,
Y.; Isobe, K.; Kobyashi, T.; Minami, T.; Uemura, M. J. Org. Chem. 1986, 51, 2859.
19. The fact that 26 and 27 were produced as single diastereoisomers (>99:1 dr)
suggests that upon diastereoselective deprotonation and subsequent methyl-
ation of (S)-3 an epimerisation process is occurring to give 7 in 95:5 dr.
20. The higher carbonyl absorption frequency in the infrared spectrum of 27
(1700 cmꢀl) compared to that observed in the other acyl complexes 22ꢀ26
(w1670 cmꢀl) suggests that the carbonyl group of the tert-butyl ketone is not
able to adopt a geometry which is coplanar with the complexed aryl ring due to
unfavourable steric interactions.
References and notes
1. For a review, see: Rosillo, M.; Domínguez, G.; Pérez-Castells, J. Chem. Soc. Rev.
2007, 36, 1589.
2. Solladié-Cavallo, A.; Solladié, G.; Tsamo, E. J. Org. Chem. 1979, 44, 4189.
3. Bromley, L. A.; Davies, S. G.; Goodfellow, C. L. Tetrahedron: Asymmetry 1991, 2,139.
4. Top, S.; Jaouen, G.; Gillois, J.; Baldoli, C.; Maiorana, S. J. Chem. Soc., Chem.
Commun. 1988, 1284.
5. Alexakis, A.; Mandeney, P.; Marek, I.; Rose-Munch, F.; Rose, E.; Semra, A.;
Robert, F. J. Am. Chem. Soc. 1992, 114, 8288.
€
21. Tietze, C. F.; Dolle, A.; Schiemann, K. Angew. Chem., Int. Ed. Engl. 1992, 31, 1372.
6. Blagg, J.; Davies, S. G.; Goodfellow, C. L.; Sutton, K. H. J. Chem. Soc., Perkin Trans. 1
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CRYSTALS; Chemical Crystallography Laboratory: University of Oxford, UK,
2001; Issue 11.