Carbonylation of cis-disubstituted epoxides to trans-β-lactones: Catalysts displaying steric and contrasteric regioselectivity

Article abstract of DOI:10.1021/jo501899e

trans-β-Lactones are a versatile and useful class of compounds, but reliable methods for their direct synthesis are still limited. Addressing this problem, we present herein two catalysts for the regioselective carbonylation of cis-disubstituted epoxides. The two catalysts show high activities and opposing regioselectivities so that either one of the two possible β-lactone regioisomers can be obtained selectively.

Full text of DOI:10.1021/jo501899e

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pubs.acs.org/joc
Carbonylation of cis-Disubstituted Epoxides to trans-β-Lactones:
Catalysts Displaying Steric and Contrasteric Regioselectivity
Michael Mulzer and Geoffrey W. Coates*
Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, New York 14853-1301, United States
S
* Supporting Information
ABSTRACT: trans-β-Lactones are a versatile and useful class of compounds, but reliable methods for their direct synthesis are
still limited. Addressing this problem, we present herein two catalysts for the regioselective carbonylation of cis-disubstituted
epoxides. The two catalysts show high activities and opposing regioselectivities so that either one of the two possible β-lactone
regioisomers can be obtained selectively.
approach is very direct, only a few selective catalytic systems
have been described for this transformation. Elegant con-
tributions to this field were recently made by Peters and co-
workers9a−c as well as Calter and co-workers.9d
INTRODUCTION
■
β-Lactones represent a valuable class of organic compounds
due to their occurrence in natural products,1 their ability to
serve as monomers in the synthesis of polyesters,2 and their
versatility as synthetic intermediates.3,4 The latter part is based
on the high inherent reactivity of β-lactones and often used in
the synthesis of aldol-type products.5 trans-β-Lactones in
racemic or enantioenriched form are particularly valuable for
this purpose because the resulting anti-aldol products are often
less readily available than their syn-counterparts when using
traditional aldol chemistry.6 Unfortunately, not many methods
are currently available to make trans-β-lactones stereoselectively
in a direct and economical fashion (Figure 1).3a,7,8 Typical
routes include the cyclization of aldol products or (formal) [2 +
2] cycloadditions of ketenes with aldehydes. Although the latter
Carbonylation of epoxides using catalysts of the form [Lewis
acid]+[Co(CO)4]− has recently emerged as a reliable direct
approach to β-lactones when using terminal or symmetrically
2,3-disubstituted epoxides as substrates.10,11 Unsymmetrically
cis- or trans-disubstituted epoxides, however, are prone to giving
mixtures of regioisomeric β-lactones.11 Presumably, an
indiscriminate SN2-ring opening reaction of the cobaltate
nucleophile in the case of electronically or sterically unbiased
substrates causes these mixtures (Scheme 1). This is a general
problem associated with this class of epoxides.12
Our group recently addressed part of this challenge by
introducing two new catalysts that could carbonylate racemic
and enantioenriched trans-disubstituted epoxides to the
corresponding cis-β-lactones with high and opposing regiose-
lectivities.13 This method would be of significant value if it
could be adapted to the regioselective production of trans-β-
lactones from the corresponding cis-epoxides because of the
anti-aldol-type products resulting from them. In addition,
almost all naturally occurring β-lactones display a trans-
configuration.14 Previously reported carbonylation catalysts
usually show unsatisfactory regioselectivities with cis-epoxides,15
Special Issue: Mechanisms in Metal-Based Organic Chemistry
Received: August 17, 2014
Figure 1. Common approaches to trans-β-lactones and regioselective
epoxide carbonylation as a versatile alternative.
© XXXX American Chemical Society
A
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more sterically hindered.16 In the case of racemic 2a, this meant
that the 3-butyl-4-methyl-substituted β-lactone 4a, and not the
4-butyl-3-methyl isomer 3a, was the predominant lactone
species at low levels of epoxide conversion. Indeed, when
reacting only the kinetically preferred enantiomer of cis-2,3-
heptene oxide (ent-2a) with (R)-1a, i.e., the matched case
between substrate and catalyst, a high contrasteric selectivity
(41:1) was observed.16 The mismatched case, i.e., 2a reacting
with (R)-1a, on the other hand, produced a reduced selectivity
(8:1) in favor of the steric product.
a
Scheme 1. Simplified Mechanism of Epoxide Carbonylation
Based on this information, we proposed that the use of rac-1a
instead of (R)-1a would induce formation of mainly one
regioisomer of the β-lactone, albeit in racemic form (Scheme 2,
bottom part). In order to be successful, each enantiomer of the
catalyst must react only with its matched enantiomer of the
epoxide; i.e., the catalyst must show an appreciable krel,17 and
the matched enantiomer of the epoxide must be carbonylated
with high regioselectivity. Only then would one expect
predominant formation of only one of the two regioisomers
of the β-lactone.18 Given the previous insight, these conditions
were seemingly met if catalyst rac-1a were used in the
carbonylation of racemic cis-2,3-heptene oxide (rac-2a).
A test reaction using rac-1a and rac-2a showed that the
contrasteric β-lactone product rac-4a was indeed formed
preferentially (Scheme 3). The observed selectivity of 4.0:1
a
For a more detailed discussion, see reference 10d.
which necessitated the design of new carbonylation catalysts.
Herein, we report how previously gained mechanistic insight
led to a catalyst that shows good activity and high contrasteric
regioselectivity in the carbonylation of cis-disubstituted
epoxides. A carbonylation catalyst selectively yielding the steric
carbonylation product is reported as well.
RESULTS AND DISCUSSION
■
The development of the contrasteric carbonylation catalyst was
based on insight gained during our investigation of the
regiodivergent carbonylation of cis-2,3-disubstituted epoxides.16
In this process, an enantiopure carbonylation catalyst such as
(R)-1a transforms a racemic cis-2,3-disubstituted epoxide rac-2
into a mixture of two regioisomeric β-lactones 3 and 4, both of
which are highly enantioenriched (Scheme 2, top part).
Scheme 3. Evaluation of Catalysts for the Carbonylation of
cis-Disubstituted Epoxide rac-2a with Contrasteric Selectivity
While following the regiodivergent carbonylation of racemic
cis-2,3-heptene oxide (rac-2a) in detail, we made the unusual
observation that incorporation of CO was kinetically more
facile at the methine carbon of the epoxide that was seemingly
Scheme 2. Observations Made during the Study of
Regiodivergent Carbonylation of cis-Epoxides and the
Implied Possibility of Regioselective Carbonylation
correlates very well with the very high contrasteric
regioselectivity and the krel of ca. 4 that were determined
previously for this reaction (vide supra). With the goal of
increasing the selectivity further, previously reported catalyst
rac-1b16 was also tested in the same reaction (Scheme 3).
Although this catalyst showed a slightly lower contrasteric
regioselectivity when reacting (R)-1b with enantiopure ent-2a
(24.6:1),19 we theorized that the increased steric bulk of the
Lewis acid part might significantly increase the krel value.
Unfortunately, the opposite case was true. The observed low
regioselectivity of 1.9:1 is most likely the result of the reduced
regioselectivity in the matched case in combination with a
lower krel value. Extensive experimentation eventually revealed
catalyst rac-1c to be the most suitable catalyst for the
carbonylation of cis-disubstituted epoxides with contrasteric
regioselectivity so far (Scheme 3). This catalyst most likely
retains the high regioselectivity observed with 1a and b in the
B
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matched case,20 so that the improved outcome of the reaction
can be attributed to a superior krel value.
those achieved with the less hindered epoxides rac-2a−e, and
even ratios as high as 32.3:1 and 24.0:1 (entries 9 and 11) were
obtained. The only limitation arose when steric bulk was
situated very close to the epoxide (entries 7 and 8).
Nevertheless, the observed ratios of 4.9:1 and 1.3:1 in favor
of lactones rac-4f and g, respectively, are still good given how
sterically shielded the corresponding methine carbons are from
nucleophilic attack. This fact is also reflected in the high
selectivity with which lactones rac-3f and g are formed when
using a carbonylation catalyst with steric selectivity (vide infra,
Table 4). Lastly, cis-epoxides with sterically very similar
substituents such as racemic cis-3,4-octene oxide were
carbonylated with low regioselectivity by rac-1c.22
The two resulting lactones rac-3 and 4 could generally not be
separated quantitatively from one another using flash column
chromatography. Therefore, the resulting trans-β-lactones were
isolated as mixtures in good yields, except for those derived
from the sterically encumbered epoxides rac-2f and g. However,
ring opening of lactones rac-3 and 4 to the corresponding aldol-
type methyl esters by quenching the reaction with MeOH/
NaOMe allowed for facile separation of the two regioisomers.
Equally good yields were obtained using this approach, which is
shown for a selected range of epoxides in Table 1 (entries 1 and
2 and 9−12).
Moreover, changing the solvent from THF to 1,4-dioxane
further improved the observed selectivity from 11.5:1 to 24.0:1.
Structurally related ethereal solvents such as tetrahydropyran
and diethyl ether also showed markedly different results in
terms of selectivity and activity.19 This observation underlines
the importance of the previously determined interaction
between solvent and carbonylation catalysts of the type
[Lewis acid]+[Co(CO)4]−.10d However, the specific effect of
solvent structure on regioselectivity is not understood at this
point.
With a competent contrasteric catalyst in hand, the scope of
this regioselective carbonylation reaction was investigated
(Table 1). Selective formation of lactones rac-4 using catalyst
Table 1. Regioselective Carbonylation of Racemic Cis-
Disubstituted Epoxides 2 Yielding β-Lactones rac-4 Using
a
Catalyst rac-1c
Catalyst rac-1c most likely operates under the mechanism
proposed in Scheme 1. However, this mechanism was
elucidated for carbonylation catalysts bearing salen ligands
coordinating in a trans- instead of cis-α-fashion and with
terminal instead of internal epoxides as substrates. These
changes may seem minor but could influence which step in the
catalytic cycle becomes rate-determining. In the case of
terminal epoxides, ring-closing to the lactone is thought to be
rate-determining (cf. Scheme 1) and all prior steps to be fully
reversible. It seems unlikely that this also holds for internal
epoxides because then the observed regioselectivity would be
the result of thermodynamic instead of kinetic control. Given
the conformational flexibility of a ring-opened epoxide, the
ligand would have a hard time discriminating between the two
regioisomeric species effectively. A more likely scenario is that
the nucleophilic attack of the cobaltate anion on the internal
epoxide, once it has coordinated to the Lewis acid, has become
the rate- and selectivity-determining step in this reaction.
Given the success of the Lewis acid moiety of catalyst 1c in
inducing contrasteric ring opening of cis-epoxides, the use of a
different nucleophile was explored. The use of chloride instead
of [Co(CO)4]− as the anion, and thus the synthesis of vicinally
disubstituted chlorohydrins, seemed particularly attractive
because they are important functional groups,23 yet methods
for their regioselective synthesis are scarce.24 Moreover,
compounds of the type [LnAl]-Cl, which are commonly used
as precursors in the synthesis of carbonylation catalysts, seemed
ideal catalysts for the regioselective formation of chlorohydrins.
Indeed, complex rac-5c, the precursor to rac-1c (Scheme 3),
turned out to be a selective and active catalytic system.
Addition of 2,4,6-trimethylpyridine hydrochloride as a mild
surrogate for hydrochloric acid led to complete conversion of
assorted cis-epoxides in the presence of rac-5c (Table 2). In the
absence of rac-5c, only negligible amounts of conversion were
detected.19
b
entry
R (epoxide)
ratio 3:4
product
rac-6b
yield (%)
1
2
3
4
5
Et (rac-2b)
nPr (rac-2c)
nBu (rac-2a)
nPent (rac-2d)
nHex (rac-2e)
nBu (2a)
1:10.1
1:15.7
1:24.0
1:24.0
1:19.0
1:24.0
1:4.9
70
77
69
74
72
rac-6c
rac-(3a + 4a)
rac-(3d + 4d)
rac-(3e + 4e)
3a + 4a
c
d
6
>95
d
7
CH2Cy (rac-2f)
CH2Ph (rac-2g)
(CH2)2Ph (rac-2h)
rac-(3f + 4f)
rac-(3g + 4g)
rac-6h
83
d
8
1:1.3
18
9
1:32.3
1:19.0
1:24.0
1:13.3
1:10.1
83
78
81
80
82
i
10
11
12
13
(CH2)2 Pr (rac-2i)
rac-6i
(CH2)2OTBS (rac-2j)
(CH2)3OTBS (rac-2k)
(CH2)3OAc (rac-2l)
rac-6j
rac-6k
rac-(3l + 4l)
a
b
Reaction conditions: [rac-2] = 0.5 M, 22 °C, 20 h. Determined by
c
1H NMR analysis of crude reaction mixture. (2S,3R)-heptene oxide
d
(99% ee) was used. Percent conversion to β-lactone (1H NMR
analysis). All reactions gave full conversion (GC or 1H NMR analysis),
except for rac-2f,g. Catalyst rac-1c was prepared in situ (LnAlCl (rac-
5c) + NaCo(CO)4).
rac-1c proceeded extremely well, with ratios in favor of rac-4
exceeding 10.0:1 for nearly all cis-epoxides rac-2 tested. Even
rac-2b, an epoxide with sterically very similar substituents, gave
a very good selectivity of 10.1:1 (entry 1). Slightly better ratios
were achieved with epoxides bearing longer alkyl chains
(entries 2−5). It is worth noting that catalyst rac-1c did not
show much variance in selectivity as the length of the linear
alkyl chain in the substituent R was altered, the only exception
being rac-2b. Furthermore, rac-1c carbonylated enantioen-
riched epoxides such as 2a with equally high regioselectivity
(entry 6). Given the availability of enantioenriched epoxides,21
this makes for a convenient entry into enantioenriched β-
lactones and aldol-type products. Epoxides with additional
steric hindrance in R also underwent regioselective carbon-
ylation reactions with rac-1c and still yielded the contrasteric
lactone rac-4 preferentially (entries 7−13). Interestingly, the
selectivities observed with these epoxides were comparable to
The observed contrasteric selectivity with preferential
formation of chlorohydrins rac-8 is consistent with the results
obtained with rac-1c in Table 1. Interestingly, contrasteric
selectivity is also observed in the absence of rac-5c or when
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or branched alkyl chains as substituent R when using rac-5c
(entries 1, 2, and 5). However, regioselectivity dropped in cases
where the steric bulk was located too close to the epoxy group
(entry 3) or became too large (entry 4). Nonetheless, all
chlorohydrins were readily isolated in good yields.
Table 2. Regioselective Formation of Chlorohydrins rac-8
from Racemic Cis-Disubstituted Epoxides 2 Using Catalyst
rac-5c
a
Having established a good methodology to access the
contrasteric β-lactone product rac-4, it now seemed sensible
to find a catalyst that would selectively produce the steric
regioisomer. The resulting β-lactones rac-3 would give rise to
potentially useful propionate aldol-type motifs commonly
found in natural products synthesis.25 Because of the recent
success of salen-based complexes with trans-geometry in the
regioselective carbonylation of trans-epoxides,13 we hoped that
the salen framework could be modified to yield a catalyst with
steric selectivity for cis-epoxides. To this end, a variety of salen-
based carbonylation catalysts were synthesized and screened for
the selective synthesis of rac-3a starting from epoxide rac-2a
(Table 3).
Test reactions using literature-known catalysts 9a−c already
yielded good conversions and selectivities for lactone rac-3a
(entries 1−3). Interestingly, the use of chromium as Lewis
acidic metal ion produced a more active yet less selective
catalyst in comparison to the aluminum-based system (entries 1
and 2) and, thus, was not pursued further. Introduction of
bulky aryl substituents in position ortho to the phenol moiety
(substituent R2) showed no benefit in terms of selectivity
entry
R (epoxide)
nBu (rac-2a)
nHex (rac-2e)
ratio 7:8
product
yield (%)
b
1
2
1:6.7
rac-8a
rac-8e
rac-8g
rac-8h
68
77
55
75
68
c
1:6.1
d
c
3
CH2Ph (rac-2g)
(CH2)2Ph (rac-2h)
1:2.8
c
4
5
1:4.9
b
i
(CH2)2 Pr (rac-2i)
1:6.7
rac-8i
a
b
Reaction conditions: [rac-2] = 0.5 M, 22 °C, 48 h. Determined by
c
GC analysis of crude reaction mixture. Determined by 1H NMR
d
analysis of crude reaction mixture. 7.5 mol % rac-5c used. All
reactions gave full conversion (GC or H NMR analysis). See the
Supporting Information for additional tables concerning control
experiments and solvent optimization.
1
opening the epoxide directly using hydrochloric acid in diethyl
ether.19 However, the selectivities obtained in those cases are
significantly less when compared to the results with rac-5c.
Ratios in favor of rac-8 exceeded 6.0:1 for epoxides with linear
a
Table 3. Evaluation of Catalysts for the Carbonylation of Cis-Disubstituted Epoxide rac-2a with Steric Selectivity
b
b
entry
1
linker
R1
R2
catalyst
ratio 3a:4a
conv (%)
L1
L1
L2
L2
L2
L3
L3
L3
L3
L3
tBu
tBu
tBu
Me
Me
tBu
tBu
Me
Me
Ar3
tBu
tBu
tBu
Ar1
Ar2
tBu
Me
Me
H
9a
3.0:1
2.1:1
2.7:1
1.6:1
3.0:1
3.3:1
2.0:1
2.1:1
2.1:1
2.1:1
2.9:1
74
95
72
74
c
2
9b
3
rac-9c
rac-9d
rac-9e
9f
4
d
5
72
6
>95
>95
>95
>95
>95
>95
7
9g
8
9h
9
9i
10
tBu
9j
e
11
10
a
b
1
Reaction conditions: [rac-2a] = 0.5 M, 22 °C, 20 h. Conversion to lactone and ratio of regioisomers determined by GC or H NMR analysis of
c
d
e
crude reaction mixture. Cr3+ used as the Lewis acidic metal ion. The remainder was 3-heptanone. 2 mol % of 10 was used. All catalysts except 9a−
c and 10 were prepared in situ (LnAlCl + NaCo(CO)4).
D
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(entries 4 and 5). Changing the diamine linker to 2,3-
dimethylbutane-2,3-diamine (L3) preserved the good steric
regioselectivity observed with linkers L1 and L2 and further
increased the activity of the catalytic system (catalyst 9f, entry
6). Keeping linker L3 but reducing the steric size of substituents
R1 and R2 had no beneficial effect in terms of selectivity (entries
7−9). Installation of a very bulky substituent in position R1 also
brought no further advantage (entry 10). Consequently, 9f was
the catalyst of choice for selective production of lactone rac-3a
from rac-2a. Lastly, it should be noted that porphyrin catalyst
10 also displayed good activity and steric selectivity (entry 11).
However, modifications of this framework were not pursued
further.
more probable that ring opening of the epoxide is the rate-
limiting step with these substrates.
CONCLUSION
■
Two new catalysts, rac-1c and 9f, were introduced for the
regioselective carbonylation of racemic and enantioenriched cis-
2,3-disubstituted epoxides 2. The development of rac-1c, which
shows contrasteric selectivity, was based on insight gained
previously from our study of the regiodivergent carbonylation
of cis-disubstituted epoxides.16 On the other hand, catalyst 9f
displayed steric regioselectivity, and its development was based
on our previous work on the regioselective carbonylation of
trans-disubstituted epoxides.13 Because of the opposing
regiopreference of rac-1c and 9f, either one of the two
regioisomeric trans-β-lactones rac-3 and rac-4 could be accessed
in high yield and selectivity. Furthermore, ring opening of rac-3
and 4 using a one-pot procedure gave rise to anti-aldol-type
compounds that were readily separable by column chromatog-
raphy. Lastly, a structurally related catalyst rac-5c was applied to
the regioselective synthesis of vicinally disubstituted chlorohy-
drins rac-8 from cis-epoxides rac-2. This transformation also
proceeded with synthetically useful yields and contrasteric
selectivity. It was surmised that the regioselective carbonylation
of cis-disubstituted epoxides follows the previously determined
mechanism. However, the occurrence of regioselectivity was
rationalized better by assuming that ring opening of the epoxide
is the rate-determining step with these substrates.
When using catalyst 9f in the carbonylation of a variety of
racemic cis-epoxides, selectivities of >3.0:1 in favor of lactone
rac-3 were usually observed (Table 4). As with catalyst rac-1c,
Table 4. Regioselective Carbonylation of Cis-Disubstituted
Epoxides rac-2 Yielding β-Lactones rac-3 Using Catalyst 9f
a
b
entry
1
R (epoxide)
ratio 3:4
product
yield (%)
Et (rac-2b)
nPr (rac-2c)
nBu (rac-2a)
3.2:1
2.9:1
3.3:1
3.8:1
3.5:1
5.7:1
19.0:1
3.5:1
3.3:1
4.0:1
2.7:1
rac-(3b + 4b)
rac-(3c + 4c)
rac-(3a + 4a)
rac-(3d + 4d)
rac-(3e + 4e)
rac-(3f + 4f)
rac-(3g + 4g)
rac-(3h + 4h)
rac-(3i + 4i)
rac-(3j + 4j)
66
62
80
74
91
88
90
86
90
87
92
c
2
EXPERIMENTAL SECTION
See the Supporting Information for general considerations, methods,
and materials used.
3
4
5
6
■
nPent (rac-2d)
nHex (rac-2e)
CH2Cy (rac-2f)
CH2Ph (rac-2g)
(CH2)2Ph (rac-2h)
The following compounds were prepared according to literature
procedures: rac-(2R,3S)-2-ethyl-3-methyloxirane (rac-2b),16 rac-
(2R,3S)-2-methyl-3-propyloxirane (rac-2c),16 rac-(2R,3S)-2-butyl-3-
methyloxirane (rac-2a),26 (2R,3S)-2-butyl-3-methyloxirane (2a),16
rac-(2R,3S)-2-butyl-3-ethyloxirane,27 rac-(2R,3S)-2-methyl-3-pentylox-
irane (rac-2d),16 rac-(2R,3S)-2-hexyl-3-methyloxirane (rac-2e),16 rac-
(2R,3S)-2-isopentyl-3-methyloxirane (rac-2i),16 rac-tert-butyldimethyl-
(3-((2R,3S)-3-methyloxiran-2-yl)propoxy)silane (rac-2k),16 rac-3-
((2R,3S)-3-methyloxiran-2-yl)propyl acetate (rac-2l),28 rac-MesBina-
mAlCl (rac-5a, precursor to rac-1a, rac-MesBinam = rac-3,3″-(([1,1′-
binaphthalene]-2,2′-diylbis(azanylylidene))bis(methanylylidene))bis-
(2′,4′,5,6′-tetramethyl-[1,1′-biphenyl]-2-olate)),16 rac-Xyl2BinamAlCl
(rac-5b, precursor to rac-1b, rac-Xyl2Binam = rac-5′,5″-((1E,1′E)-
([1,1′-binaphthalene]-2,2′-diylbis(azanylylidene))bis(methanylyl-
idene))bis(2,2″,6,6″-tetramethyl[1,1′:3′,1″-terphenyl]-4′-olate),16
[salphAl(THF)2]+[Co(CO)4]− (9a, salph =6,6′-((1E,1′E)-(1,2-
phenylenebis(azanylylidene))bis(methanylylidene))bis(2,4-di-tert-bu-
tylphenolate)),10a [salphCr(THF)2]+[Co(CO)4]− (9b),10c rac-
[salcyAl(THF)2]+[Co(CO)4]− (rac-9c, salcy = N,N′-bis(3,5-di-tert-
butylsalicylidene)-1,2-cyclohexanediamine),29 rac-3,3″-((1E,1′E)-
((1S,2S)-cyclohexane-1,2-diylbis(azanylylidene))bis(methanylyl-
idene))bis(2′,5,6′-trimethyl-[1,1′-biphenyl]-2-olate)aluminum chlor-
ide (precursor to rac-9d),13 rac-3,3″-((1E,1′E)-((1S,2S)-cyclohexane-
1,2-diylbis(azanylylidene))bis(methanylylidene))bis(4′-tert-butyl-
2′,5,6′-trimethyl-[1,1′-biphenyl]-2-olate)aluminum chloride (precursor
to rac-9e),13 6,6′-((1E,1′E)-((2,3-dimethylbutane-2,3-diyl)bis-
(azanylylidene))bis(methanylylidene))bis(2,4-di-tert-butylphenolate)
aluminum chloride (precursor to 9f),13 [ClTPPAl(THF)2]+[Co-
(CO)4]− (10, ClTPP = meso-tetra(4-chlorophenyl)porphyrinato),30
3′,5′-di-tert-butyl-2-hydroxy-5-methyl-[1,1′-biphenyl]-3-carbalde-
hyde,31 5-tert-butyl-2-hydroxy-3-methylbenzaldehyde,32 4-bromo-2-
(tert-butyl)phenol,33 2,3-dimethylbutane-2,3-diamine,34 NaCo-
(CO)4,35 (Z)-tert-butyldimethyl(pent-3-en-1-yloxy)silane,36 (Z)-but-
2-en-1-ylbenzene,37 (Z)-1-phenyl-3-pentene,38 and 2,4,6-trimethylpyr-
idine hydrochloride.39
c
7
c
8
i
9
(CH2)2 Pr (rac-2i)
c
10
(CH2)2OTBS (rac-2j)
(CH2)3OTBS (rac-2k)
11
rac-(3k + 4k)
a
b
Reaction conditions: [rac-2] = 0.5 M, 22 °C, 20 h. Determined by
c
1H NMR analysis of crude reaction mixture. 7.5 mol % of 9f used. All
reactions gave full conversion (GC or H NMR analysis).
1
epoxides with linear alkyl chains as substituent R showed good
selectivities in the range of 2.9 to 3.8:1 irrespective of the length
of the alkyl chain (entries 1−5). In the case of epoxides with
sterically more demanding substituents R, one would predict an
increase in selectivity due to a stronger inherent steric bias.
Indeed, such additional bias benefited selectivity as long as it
was situated close to the epoxide (entries 6 and 7). Distancing
it further away, however, lessened the influence quickly (entries
8−11), and the obtained selectivities resembled those achieved
with epoxides rac-2a−e. Interestingly, epoxides rac-2f and g
gave very different ratios of rac-3 and 4 despite their structural
similarity. As before, the resulting trans-β-lactones were isolated
as mixtures in good yields due to the inseparability of the
regioisomeric products.
From a mechanistic viewpoint, the arguments made during
the discussion of catalyst rac-1c should also apply to 9f.
Although catalyst 9f most likely displays trans-coordination of
the salen ligand, it seems unlikely that good regioselectivities
could be obtained if the ring-closing step were still the rate-
determining step with internal epoxides. As before, it seems
E
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General Procedure A: Epoxidation of Alkenes to Epoxides
Using m-CPBA. m-Chloroperoxybenzoic acid (m-CPBA, ≤77%) was
added in portions at 0 °C to a solution of the corresponding alkene in
DCM, and the resulting mixture was stirred at the same temperature
until TLC analysis indicated complete consumption of the alkene.
After excess m-CPBA was destroyed by addition of aqueous NaHSO3
at 0 °C, the reaction mixture was filtered and the organic phase washed
with NaHCO3 (satd, aq, 3×), dried with sodium sulfate, filtered, and
concentrated under reduced pressure. The residue was purified via
either distillation or flash column chromatography.
General Procedure B: Assembly of Salen Compounds via
Imine Condensation. The appropriate salicylaldehyde derivative was
mixed under air with either methanol or ethanol at the indicated
temperature. The appropriate diamine was added and the reaction
mixture stirred at the same temperature for the time indicated. The
reaction mixture was allowed to reach 22 °C, and the resulting
precipitate was isolated by filtration, followed by washings with small
amounts of cold methanol or ethanol to give the corresponding salen-
compound after drying in vacuo at 80 °C.
mixture was concentrated under reduced pressure and the product
isolated as indicated.
rac-(2R,3S)-2-(Cyclohexylmethyl)-3-methyloxirane (rac-2f). Meth-
yllithium (1.6 M, Et2O, 21.5 mL, 34.4 mmol) was added dropwise at
−78 °C to a solution of prop-2-yn-1-ylcyclohexane (3.81 g, 31.2
mmol) in THF (55 mL), and the resulting solution was stirred at −78
°C for 0.5 h. Methyl iodide (10.5 g, 74.0 mmol) was added dropwise at
−78 °C, the reaction mixture was slowly warmed to 22 °C and stirred
for 12 h. NaHCO3 (satd, aq) was added and the aqueous phase
extracted with pentane. The combined organic layers were dried with
sodium sulfate, filtered, and concentrated under reduced pressure.
THF (14 mL) was added to the residue and the resulting solution
degassed by two freeze−pump−thaw cycles. The solution was then
added to a solution of 9-BBN (0.5 M, THF, 72 mL, 36 mmol) at 0 °C,
and the resulting reaction mixture was stirred at 22 °C until TLC
analysis indicated complete disappearance of the alkyne. Methanol
(1.0 mL) was added followed by glacial acetic acid (20.0 mg) as a
solution in methanol (2.6 mL) and the resulting mixture stirred for 2 h
at 22 °C. Pentane was added, followed by controlled addition of
NaOH (1 M, aq, 40 mL) and H2O2 (30%, aq, 20 mL) under ice
cooling. The aqueous layer was extracted with pentane, and the
combined organic layers were washed with NaHCO3 (aq, satd), dried
with sodium sulfate, filtered, and concentrated under reduced pressure.
The crude product was filtered through a plug of silica gel using
pentane, and the filtrates were concentrated under reduced pressure.
Following general procedure A, the residue was reacted with m-
CPBA (9.00 g) in DCM (40 mL) to give rac-2f (1.12 g, 23%) as a
colorless liquid. 1H NMR (400 MHz, CDCl3): δ 3.02 (dtd, J = 5.3, 4.3
Hz, 1H), 2.94 (td, J = 6.0, 4.2 Hz, 1H), 1.79−1.62 (m, 5H), 1.51−1.33
(m, 3H), 1.30−1.08 (m, 3H), 1.25 (d, J = 5.5 Hz, 3H), 1.04−0.89 (m,
2H). 13C{1H} NMR (75 MHz, CDCl3): δ 56.0, 52.7, 36.2, 35.0, 33.8,
33.3, 26.6, 26.41, 26.38, 13.5. HRMS (ESI-TOF) m/z: [M + H]+ calcd
for C10H19O 155.1430, found 155.1443.
rac-(2R,3S)-2-Benzyl-3-methyloxirane (rac-2g). Following general
procedure A, (Z)-but-2-en-1-ylbenzene37 (0.446 g, 3.37 mmol) was
reacted with m-CPBA (0.960 g) in DCM (17 mL) to give rac-2g
(0.390 g, 78%) as a colorless liquid. The analytical data were in
accordance with that reported in the literature.41 1H NMR (400 MHz,
CDCl3): δ 7.35−7.31 (m, 2H), 7.27−7.23 (m, 3H), 3.18−3.11 (m,
2H), 2.94 (dd, J = 14.7, 5.8 Hz, 1H), 2.79 (dd, J = 14.7, 6.3 Hz, 1H),
1.41 (d, J = 5.4 Hz, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 137.9,
128.9, 128.7, 126.6, 57.4, 53.0, 34.2, 13.6.
rac-(2R,3S)-2-Methyl-3-phenethyloxirane (rac-2h). Following gen-
eral procedure A, (Z)-1-phenyl-3-pentene38 (2.71 g, 18.5 mmol) was
reacted with m-CPBA (5.50 g) in DCM (45 mL) to give rac-2h (2.19
g, 73%) as a colorless liquid. The analytical data were in accordance
with that reported in the literature.38 1H NMR (400 MHz, CDCl3): δ
7.31−7.28 (m, 2H), 7.22−7.18 (m, 3H), 3.04 (qd, J = 5.5, 4.2 Hz,
1H), 2.95 (td, J = 6.3, 4.3 Hz, 1H), 2.85 (ddd, J = 14.6, 9.2, 5.8 Hz,
1H), 2.74 (ddd, J = 13.9, 8.9, 7.4 Hz, 1H), 1.93−1.69 (m, 2H), 1.19
(d, J = 5.5 Hz, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 141.5,
128.55, 128.55, 126.2, 56.6, 53.0, 32.8, 29.6, 13.3.
General Procedure C: Metalation of Salen Compounds
Using Et2AlCl. The appropriate salen compound was dissolved in the
indicated amount of DCM and cooled to 0 °C. Et2AlCl (1.0 M,
hexanes, pyrophoric) was added in one portion under vigorous stirring
at 0 °C, and the resulting solution was stirred at 22 °C for 12 h. The
resulting metal complex was then isolated as indicated.
General Procedure D: Regioselective Carbonylation of cis-
Epoxides Using Catalyst 9f. In a glovebox, a 2 fluid dram glass vial
equipped with a Teflon-coated magnetic stir bar was charged with
catalyst 9f and THF. The vial was then placed in a custom-made six-
well high-pressure reactor40 which itself was placed in a glovebox
freezer at −34 °C for 30 min. The appropriate epoxide (also cooled to
−34 °C) was then added to the vial and the reactor removed from the
freezer, subsequently sealed, taken out of the glovebox, placed in a
well-ventilated hood, and pressurized with carbon monoxide (900 psi).
It is important to keep the temperature of the reactor below 0 °C once
it is removed from the freezer to minimize isomerization of the
epoxide to ketone products. The reactor was then sealed again, placed
in a 22 °C water bath, and stirred for the time indicated. The reactor
was carefully vented in a well-ventilated hood, the crude reaction
mixture concentrated under reduced pressure, and the product isolated
as indicated.
General Procedure E: Regioselective Carbonylation of
Epoxides with in Situ Formation of Catalyst rac-1c. In a
glovebox, a 2 fluid dram glass vial equipped with a Teflon-coated
magnetic stir bar was charged with NaCo(CO)4, 1,4-dioxane, and the
precursor to rac-1c, compound rac-5c. The vial was then placed in a
custom-made 6-well high-pressure reactor,40 which itself was placed in
a glovebox freezer at −34 °C for 30 min. The appropriate epoxide
(also cooled to −34 °C) was added to the vial and the reactor
removed from the freezer, subsequently sealed, taken out of the
glovebox, placed in a well-ventilated hood and pressurized with carbon
monoxide (900 psi). It is important to keep the temperature of the
reactor below 0 °C once it is removed from the freezer to minimize
isomerization of the epoxide to ketone products. The reactor was then
sealed again, placed in a 22 °C water bath, and stirred for the time
indicated. The reactor was carefully vented in a well-ventilated hood,
the crude reaction mixture concentrated under reduced pressure, and
the product isolated as indicated.
rac-tert-Butyldimethyl(2-((2R,3S)-3-methyloxiran-2-yl)ethoxy)-
silane (rac-2j). Following general procedure A, (Z)-tert-butyldimethyl-
(pent-3-en-1-yloxy)silane36 (2.74 g, 13.7 mmol) was reacted with m-
CPBA (4.10 g) in DCM (35 mL) to give rac-2j (2.34 g, 79%) as a
1
colorless liquid. H NMR (300 MHz, CDCl3): δ 3.80−3.75 (m, 2H),
3.09−3.03 (m, 2H), 1.82−1.63 (m, 2H), 1.26 (d, J = 5.4 Hz, 3H), 0.89
(s, 9H), 0.05 (s, 6H). 13C{1H} NMR (75 MHz, CDCl3): δ 60.6, 54.8,
52.7, 31.2, 26.1, 18.5, 13.6, −5.2. HRMS (ESI-TOF) m/z: [M + Na]+
calcd for C11H24NaO2Si 239.1438, found 239.1445.
Please note: In the case of substrates rac-2b, rac-2c, rac-2h, rac-2i,
rac-2j, and rac-2k, the general procedure was slightly altered: The
reactor was carefully vented in a well-ventilated hood, and the crude
reaction mixture was treated with methanol and sodium methoxide,
stirred for 5 min at 22 °C, and then concentrated under reduced
pressure. The product was then isolated as indicated.
General Procedure F: Regioselective Chlorohydrin Forma-
tion Using Catalyst rac-5c. In a glovebox, a 2 fluid dram glass vial
equipped with a Teflon-coated magnetic stir bar was charged with
catalyst rac-5c, 2,4,6-trimethylpyridine hydrochloride, THF, and the
appropriate epoxide. The vial was sealed with a Teflon-coated cap, and
the reaction mixture stirred at 22 °C for 48 h. The crude reaction
5-tert-Butyl-4-hydroxy-2′,4′,6′-triisopropyl[1,1′-biphenyl]-3-car-
baldehyde (11). 4-Bromo-2-tert-butylphenol33 (1.6 g, 7.0 mmol) was
added in small portions to a mixture of sodium hydride (95%, dry, 0.23
g, 9.6 mmol) and THF (7 mL) at 0 °C, followed by stirring at 22 °C
for 10 min. Pd(OAc)2 (Strem, 0.107 g, 0.351 mmol) was added,
followed by 2,4,6-triisopropylphenylmagnesium bromide (0.5 M,
THF, 30 mL, 15 mmol), and the resulting mixture was refluxed for
12 h. Upon cooling to 0 °C, H2O was carefully added to destroy
residual Grignard reagent and sodium hydride. HCl (2 M, aq) was
F
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added followed by Celite, and the resulting mixture was filtered
through a pad of Celite. The resulting phases were separated, and the
aqueous phase was extracted with Et2O (3×). The combined organic
layers were washed with brine, dried with sodium sulfate, filtered, and
concentrated under reduced pressure. The resulting residue was
subjected to flash column chromatography. The isolated product (1.88
g) was contaminated with approximately 5% of 2-tert-butylphenol and
34.0, 31.6, 23.3, 15.9. HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C30H45N2O2 465.3476, found 465.3471.
5,5″-((1E,1′E)-((2,3-Dimethylbutane-2,3-diyl)bis(azanylylidene))-
bis(methanylylidene))bis(3-tert-butyl-2′,4′,6′-triisopropyl[1,1′-bi-
phenyl]-4-ol) (15). Following general procedure B, 11 (381 mg, 1.00
mmol), 2,3-dimethylbutane-2,3-diamine34 (58 mg, 0.50 mmol), and
methanol (15 mL) were mixed and then stirred at 70 °C for 12 h.
Following filtration and drying in vacuo, 15 (319 mg, 76%) was
1
was used without further purification in the next step. H NMR data
1
obtained as a yellow powder. Mp: >200 °C. H NMR (500 MHz,
for the main component, 3-tert-butyl-2′,4′,6′-triisopropyl[1,1′-biphen-
1
CDCl3): δ 14.51 (s, 2H), 8.45 (s, 2H), 7.14 (d, J = 2.1 Hz, 2H), 7.08
(s, 4H), 6.97 (d, J = 2.1 Hz, 2H), 2.97 (hept, J = 6.9 Hz, 2H), 2.70
(hept, J = 6.8 Hz, 4H), 1.47 (s, 12H), 1.45 (s, 18H), 1.33 (d, J = 6.9
Hz, 12H), 1.13 (d, J = 6.9 Hz, 12H), 1.09 (d, J = 6.8 Hz, 12H).
13C{1H} NMR (126 MHz, CDCl3): δ 162.5, 159.4, 147.8, 147.2,
137.1, 136.9, 131.5, 130.6, 129.9, 120.7, 118.5, 65.4, 35.1, 34.4, 30.4,
29.7, 24.7, 24.3, 23.5. HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C58H85N2O2 841.6606, found 841.6605.
yl]-4-ol, are provided. H NMR (400 MHz, CDCl3): δ 7.06 (s, 1H),
7.05 (s, 2H), 6.88−6.85 (m, 1H), 6.68 (d, J = 7.9 Hz, 1H), 4.72 (s,
1H), 2.94 (p, J = 6.9 Hz, 1H), 2.70−2.50 (m, 2H), 1.41 (d, J = 1.3 Hz,
9H), 1.31 (d, J = 6.9 Hz, 6H), 1.09 (d, J = 6.7 Hz, 6H), 1.07 (d, J = 6.8
Hz, 6H).
Methylmagnesium bromide (3 M, Et2O, 2.2 mL, 6.6 mmol) was
added slowly to 3-tert-butyl-2′,4′,6′-triisopropyl[1,1′-biphenyl]-4-ol
(1.88 g, ca. 5 mmol) in THF (13 mL) at 0 °C. After the mixture
was warmed to 22 °C, toluene (26 mL), triethylamine (1.3 mL, 9.3
mmol), and paraformaldehyde (0.42 g, 14 mmol) were added, and the
resulting reaction mixture was stirred at 80 °C for 12 h. After the
mixture was cooled to 0 °C, H2O and then HCl (2 M, aq) were added,
and the resulting phases were separated. The aqueous phase was
extracted with Et2O (3×). The combined organic layers were washed
with brine, dried with sodium sulfate, filtered, and concentrated under
reduced pressure. The residue was subjected to flash column
chromatography followed by recrystallization from methanol to give
11 (1.32 g, 50% over two steps) as an off-color solid. Mp: 144−143 °C
3,3″-((1E,1′E)-([1,1′-Binaphthalene]-2,2′-diylbis(azanylylidene))-
bis(methanylylidene))bis(3′,5′-di-tert-butyl-5-methyl[1,1′-biphenyl]-
2-ol) (16). 3′,5′-Di-tert-butyl-2-hydroxy-5-methyl[1,1′-biphenyl]-3-car-
baldehyde31 (324 mg, 0.999 mmol), racemic [1,1′-binaphthalene]-
2,2′-diamine (142 mg, 0.499 mmol), and ethanol (8 mL) were mixed
and then refluxed for 12 h. After the reaction mixture was allowed to
reach 22 °C, the resulting precipitate was isolated by filtration and
washed with a small amount of ethanol and finally pentane to give 16
1
(372 mg, 83%) as a powder of orange color. Mp: 196−198 °C. H
NMR (400 MHz, CDCl3): δ 12.36 (s, 2H), 8.62 (s, 2H), 8.01 (d, J =
8.8 Hz, 2H), 7.89 (d, J = 8.2 Hz, 2H), 7.56 (d, J = 8.8 Hz, 2H), 7.38
(dt, J = 8.1, 4.0 Hz, 2H), 7.33 (t, J = 1.8 Hz, 2H), 7.26 (d, J = 1.8 Hz,
2H), 7.22 (d, J = 3.2 Hz, 2H), 7.14 (d, J = 2.1 Hz, 2H), 6.92 (d, J = 2.2
Hz, 2H), 2.24 (s, 6H), 1.35 (s, 36H). 13C{1H} NMR (101 MHz,
CDCl3): δ 162.6, 156.2, 150.0, 144.4, 136.6, 135.0, 133.4, 132.5, 131.6,
130.09, 130.05, 129.3, 128.3, 127.6, 127.0, 126.6, 125.8, 123.8, 121.0,
119.4, 117.3, 35.0, 31.8, 20.5. HRMS (ESI-TOF) m/z: [M + H]+ calcd
for C64H69N2O2 897.5354, Found 897.5382.
1
(methanol). H NMR (500 MHz, CDCl3): δ 11.80 (s, 1H), 9.87 (s,
1H), 7.36 (d, J = 2.2 Hz, 1H), 7.22 (d, J = 2.1 Hz, 1H), 7.08 (s, 2H),
2.96 (hept, J = 6.9 Hz, 1H), 2.61 (hept, J = 6.9 Hz, 2H), 1.43 (s, 9H),
1.32 (d, J = 6.9 Hz, 6H), 1.12 (d, J = 6.9 Hz, 6H), 1.09 (d, J = 6.9 Hz,
6H). 13C{1H} NMR (126 MHz, CDCl3): δ 197.4, 160.0, 148.4, 147.1,
137.9, 136.3, 135.9, 132.4, 131.6, 120.9, 120.4, 35.1, 34.5, 30.5, 29.55,
29.55, 24.5, 24.23, 24.20. HRMS (EI-quadrupole) m/z: [M]+ calcd for
C26H36O2 380.2715, found 380.2709.
6,6′-((1E,1′E)-((2,3-Dimethylbutane-2,3-diyl)bis(azanylylidene))-
bis(methanylylidene))bis(4-tert-butyl-2-methylphenolate)alumi-
num Chloride (17, Precursor to 9g). Following general procedure C,
Et2AlCl (1.0 M, hexanes, 950 μL, 0.950 mmol) was added to 14 (360
mg, 0.775 mmol) in DCM (5.0 mL). After the solution was stirred at
22 °C, the volatiles were removed in vacuo. The residue was broken
up and dried in vacuo at 80 °C for 1 h to give 17 (276 mg, 68%) as a
yellow powder. Mp: >200 °C. 1H NMR (500 MHz, CDCl3): δ 8.45 (s,
2H), 7.42 (d, J = 1.5 Hz, 2H), 7.10 (d, J = 2.6 Hz, 2H), 2.39 (s, 6H),
1.55 (s, 6H), 1.34 (s, 6H), 1.31 (s, 18H). 13C{1H} NMR (126 MHz,
CDCl3): δ 167.1, 162.3, 139.3, 135.0, 130.4, 126.7, 117.5, 66.3, 34.0,
31.5, 25.8, 24.4, 16.4. HRMS (ESI-TOF) m/z: [M − Cl]+ Calcd for
C30H42AlN2O2 489.3056, found 489.3065.
6,6′-((1E,1′E)-((2,3-Dimethylbutane-2,3-diyl)bis(azanylylidene))-
bis(methanylylidene))bis(2,4-dimethylphenolate)aluminum Chlor-
ide (18, Precursor to 9h). Following general procedure C, Et2AlCl
(1.0 M, hexanes, 750 μL, 0.750 mmol) was added to 13 (228 mg,
0.599 mmol) in DCM (4.0 mL). After the solution was stirred at 22
°C, the volatiles were removed in vacuo. The residue was broken up
and dried in vacuo at 80 °C for 1 h to give 18 (193 mg, 73%) as a
yellow powder. Mp: >200 °C. 1H NMR (500 MHz, CDCl3): δ 8.40 (s,
2H), 7.20 (s, 2H), 6.95 (s, 2H), 2.36 (s, 6H), 2.26 (s, 6H), 1.54 (s,
6H), 1.33 (s, 6H). 13C{1H} NMR (126 MHz, CDCl3): δ 166.8, 162.2,
138.3, 130.7, 130.4, 125.8, 118.1, 66.3, 25.7, 24.3, 20.4, 16.0. HRMS
(ESI-TOF) m/z: [M − Cl]+ calcd for C24H30AlN2O2 405.2117, found
405.2122.
2,2′-((1E,1′E)-((2,3-Dimethylbutane-2,3-diyl)bis(azanylylidene))-
bis(methanylylidene))bis(4-methylphenol) (12). Following general
procedure B, 2-hydroxy-5-methylbenzaldehyde (204 mg, 1.50 mmol),
2,3-dimethylbutane-2,3-diamine34 (87.0 mg, 0.749 mmol), and
methanol (4.5 mL) were mixed, and then the mixture was stirred at
70 °C for 11 h. Following filtration and drying in vacuo, 12 (189 mg,
1
72%) was obtained as a yellow powder. Mp: 198−199 °C. H NMR
(500 MHz, CDCl3): δ 13.81 (s, 2H), 8.32 (s, 2H), 7.11 (dd, J = 8.3,
2.2 Hz, 2H), 7.06 (d, J = 2.3 Hz, 2H), 6.85 (d, J = 8.3 Hz, 2H), 2.28 (s,
6H), 1.37 (s, 12H). 13C{1H} NMR (126 MHz, CDCl3): δ 161.7,
159.3, 133.1, 131.9, 127.6, 118.7, 116.9, 65.3, 23.2, 20.5. HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C22H29N2O2 353.2224, found
353.2225.
6,6′-((1E,1′E)-((2,3-Dimethylbutane-2,3-diyl)bis(azanylylidene))-
bis(methanylylidene))bis(2,4-dimethylphenol) (13). Following gen-
eral procedure B, 2-hydroxy-3,5-dimethylbenzaldehyde (225 mg, 1.50
mmol), 2,3-dimethylbutane-2,3-diamine34 (87.0 mg, 0.749 mmol), and
methanol (4.5 mL) were mixed and then stirred at 70 °C for 12 h.
Following filtration and drying in vacuo, 13 (228 mg, 80%) was
obtained as a yellow powder. Mp: 178−179 °C. 1H NMR (500 MHz,
CDCl3): δ 14.07 (s, 2H), 8.33 (s, 2H), 7.01 (s, 2H), 6.92 (s, 2H), 2.26
(s, 12H), 1.39 (s, 12H). 13C{1H} NMR (126 MHz, CDCl3): δ 161.9,
157.7, 134.4, 129.5, 127.0, 125.8, 117.9, 65.2, 23.3, 20.5, 15.6. HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C24H33N2O2 381.2537, found
381.2538.
6,6′-((1E,1′E)-((2,3-Dimethylbutane-2,3-diyl)bis(azanylylidene))-
bis(methanylylidene))bis(4-tert-butyl-2-methylphenol) (14). Follow-
ing general procedure B, 5-tert-butyl-2-hydroxy-3-methylbenzalde-
hyde32 (384 mg, 2.00 mmol), 2,3-dimethylbutane-2,3-diamine34 (116
mg, 0.998 mmol), and methanol (6.0 mL) were mixed and then stirred
at 70 °C for 8 h. Following filtration and drying in vacuo, 14 (362 mg,
2,2′-((1E,1′E)-((2,3-Dimethylbutane-2,3-diyl)bis(azanylylidene))-
bis(methanylylidene))bis(4-methylphenolate)aluminum Chloride
(19, Precursor to 9i). Following general procedure C, Et2AlCl (1.0
M, hexanes, 650 μL, 0.650 mmol) was added to 12 (188 mg, 0.533
mmol) in DCM (4.0 mL). After the solution was stirred at 22 °C, the
volatiles were removed in vacuo. The residue was broken up and dried
in vacuo at 80 °C for 1 h to give 19 (170 mg, 78%) as a yellow
1
78%) was obtained as a yellow powder. Mp: 171−173 °C. H NMR
1
(500 MHz, CDCl3): δ 14.1 (s, 2H), 8.40 (s, 2H), 7.23 (s, 2H), 7.12 (s,
2H), 2.30 (s, 6H), 1.40 (s, 12H), 1.31 (s, 18H). 13C{1H} NMR (126
MHz, CDCl3): δ 162.2, 157.7, 140.7, 130.9, 125.8, 125.4, 117.5, 65.2,
powder. Mp: >200 °C. H NMR (500 MHz, CDCl3): δ 8.43 (s, 2H),
7.28 (dd, J = 8.7, 2.4 Hz, 2H), 7.15−7.11 (m, 2H), 7.10 (s, 1H), 7.08
(s, 1H), 2.28 (s, 6H), 1.55 (s, 6H), 1.32 (s, 6H). 13C{1H} NMR (126
G
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MHz, CDCl3): δ 166.9, 163.4, 137.9, 133.1, 126.6, 122.6, 118.8, 66.5,
25.6, 24.4, 20.3. HRMS (ESI-TOF) m/z: [M − Cl]+ calcd for
C22H26AlN2O2 377.1804, found 377.1813.
previously been reported. 1H NMR (400 MHz, CDCl3): δ 4.38 (qd, J
= 6.1, 4.0 Hz, 1H, 4a), 4.15 (ddd, J = 7.2, 6.3, 4.0 Hz, 1H, 3a), 3.20
(qd, J = 7.5, 4.0 Hz, 1H, 3a), 3.17−3.12 (m, 1H, 4a), 1.90−1.68 (m,
2H + 2H, 3a + 4a), 1.53 (d, J = 6.1 Hz, 3H, 4a), 1.37 (d, J = 7.5 Hz,
3H, 3a), 1.48−1.26 (m, 4H + 4H, 3a + 4a), 0.93−0.88 (m, 3H + 3H,
3a + 4a). 13C{1H} NMR (126 MHz, CDCl3): δ 172.2 (3a), 171.5
(4a), 79.7 (3a), 74.7 (4a), 57.7 (4a), 50.8 (3a), 33.9 (3a), 29.1 (4a),
27.5 (4a), 27.2 (3a), 22.5 (4a), 22.4 (3a), 20.4 (4a), 14.0 (3a), 13.9
(4a), 12.6 (3a).
5,5″-((1E,1′E)-((2,3-Dimethylbutane-2,3-diyl)bis(azanylylidene))-
bis(methanylylidene))bis(3-tert-butyl-2′,4′,6′-triisopropyl[1,1′-bi-
phenyl]-4-olate)aluminum Chloride (20, Precursor to 9j). Following
general procedure C, Et2AlCl (1.0 M, hexanes, 650 μL, 0.650 mmol)
was added to a suspension of 15 (281 mg, 0.334 mmol) in DCM (7.0
mL). After the solution was stirred at 22 °C, the volatiles were
removed in vacuo. The residue was broken up and dried in vacuo at 80
°C for 1 h to give 20 (254 mg, 84%) as a yellow powder. Mp: >200
°C. 1H NMR (500 MHz, CDCl3): δ 8.44 (s, 2H), 7.33 (d, J = 2.3 Hz,
2H), 7.09 (d, J = 4.8 Hz, 4H), 6.99 (d, J = 2.2 Hz, 2H), 2.97 (hept, J =
6.9 Hz, 2H), 2.79 (p, J = 6.9 Hz, 2H), 2.78 (p, J = 6.9 Hz, 2H), 1.61 (s,
6H), 1.58 (s, 18H), 1.41 (s, 6H), 1.34 (d, J = 6.9 Hz, 12H), 1.17 (d, J
= 6.9 Hz, 6H), 1.16 (d, J = 6.9 Hz, 6H), 1.12 (d, J = 6.8 Hz, 6H), 1.10
(d, J = 6.8 Hz, 6H). 13C{1H} NMR (126 MHz, CDCl3): δ 167.6,
163.6, 147.9, 147.6, 147.2, 141.4, 136.8, 135.7, 132.3, 129.0, 120.8,
120.6, 119.3, 66.4, 35.7, 34.4, 30.5, 30.4, 30.0, 25.8, 24.79, 24.77, 24.6,
24.33, 24.32, 24.27, 24.25. HRMS (ESI-TOF) m/z: [M − Cl]+ calcd
for C58H82AlN2O2 865.6186, found 865.6186.
3,3″-((1E,1′E)-([1,1′-Binaphthalene]-2,2′-diylbis(azanylylidene))-
bis(methanylylidene))bis(3′,5′-di-tert-butyl-5-methyl[1,1′-biphenyl]-
2-olate)aluminum Chloride (rac-5c, Precursor to rac-1c). Following
general procedure C, Et2AlCl (1.0 M, hexanes, 950 μL, 0.950 mmol)
was added to a solution of 16 (774 mg, 0.863 mmol) in DCM (8.0
mL) at 0 °C. After being stirred at 22 °C for 12 h, approximately half
of the solvent was removed in vacuo. The remainder was cooled to 0
°C, and the precipitate isolated by filtration. The solid, still kept at 0
°C, was washed with cold DCM, then cold pentane, and subsequently
dried in vacuo at 80 °C for 1 h to give rac-5c (549 mg, 66%) as a
yellow powder. Mp: >200 °C. 1H NMR (500 MHz, CDCl3, −55 °C):
δ 8.20 (s, 1H), 7.96 (s, 1H), 7.82 (d, J = 8.7 Hz, 1H), 7.76 (d, J = 8.3
Hz, 1H), 7.69−7.67 (m, 2H), 7.62 (s, 2H), 7.57 (d, J = 8.6 Hz, 1H),
7.30 (t, J = 7.7 Hz, 1H), 7.27−7.24 (m, 2H), 7.21 (s, 1H), 7.13 (s,
1H), 7.11−7.03 (m, 4H), 6.98−6.95 (m, 3H), 6.86 (d, J = 8.7 Hz,
1H), 6.67 (s, 2H), 1.99 (s, 3H), 1.97 (s, 3H), 1.01 (s, 18H), 0.83 (s,
18H). 13C{1H} NMR (126 MHz, CDCl3, −55 °C): δ 174.1, 168.9,
162.8, 159.3, 149.5, 149.4, 144.2, 143.9, 140.8, 138.9, 136.6, 136.5,
134.0, 133.2, 133.0, 132.45, 132.40, 132.3, 131.8, 131.7, 130.5, 129.4,
128.6, 128.4, 127.2, 127.0, 126.9, 126.8, 126.5, 126.28, 126.25, 126.23,
126.0, 125.9, 125.8, 125.24, 125.22, 124.9, 124.48, 124.45, 124.12,
124.05, 120.6, 120.2, 119.3, 118.7, 34.9, 34.6, 31.5, 31.2, 20.5, 20.4.
HRMS (ESI-TOF) m/z: [M − Cl]+ calcd for C64H66AlN2O2
921.4934, found 921.4906.
rac-(3R,4R)-4-Ethyl-3-methyloxetan-2-one (rac-3b) and rac-
(3R,4R)-4-Methyl-3-propyloxetan-2-one (rac-4b). General procedure
D was followed using 9f (18.6 mg, 0.0209 mmol, 7.21 mol %), THF
(0.6 mL), and rac-2b (25.0 mg, 0.290 mmol). After being stirred at 22
°C for 20 h, the crude reaction mixture was subjected to bulb-to-bulb
distillation to give a mixture of rac-3b and rac-4b (22.0 mg, 66%) as a
yellow oil. Analytical data for rac-3b9a and rac-4b42 have previously
1
been reported. H NMR (400 MHz, CDCl3): δ 4.41 (qd, J = 6.1, 4.0
Hz, 1H, 4b), 4.13 (td, J = 6.6, 4.0 Hz, 1H, 3b), 3.22 (qd, J = 7.5, 4.0
Hz, 1H, 3b), 3.13 (ddd, J = 8.4, 6.7, 4.0 Hz, 1H, 4b), 1.94−1.73 (m,
4H), 1.55 (d, J = 6.1 Hz, 3H, 4b), 1.39 (d, J = 7.5 Hz, 3H, 3b), 1.03 (t,
J = 7.5 Hz, 3H, 3b), 1.00 (t, J = 7.6 Hz, 3H, 4b). 13C{1H} NMR (126
MHz, CDCl3): δ 172.1 (3b), 171.2 (4b), 80.6 (3b), 74.2 (4b), 59.0
(4b), 50.4 (3b), 27.3 (3b), 21.0 (4b), 20.4 (4b), 12.7 (3b), 11.2 (4b),
9.1 (3b).
rac-(3R,4R)-3-Methyl-4-propyloxetan-2-one (rac-3c) and rac-
(3R,4R)-3-Ethyl-4-methyloxetan-2-one (rac-4c). General procedure
D was followed using 9f (18.6 mg, 0.0209 mmol, 6.74 mol %), THF
(0.6 mL), and rac-3c (31.0 mg, 0.310 mmol). After being stirred at 22
°C for 20 h, the crude reaction mixture was subjected to flash column
chromatography to give a mixture of rac-3c and rac-4c (22.0 mg, 66%)
as a yellow oil. Analytical data for rac-3c9a and rac-4c43 have previously
1
been reported. H NMR (300 MHz, CDCl3): δ 4.40 (qd, J = 6.1, 3.9
Hz, 1H, 4c), 4.18 (ddd, J = 7.3, 6.2, 4.0 Hz, 1H, 3c), 3.24−3.14 (m,
2H), 1.89−1.78 (m, 2H), 1.76−1.65 (m, 2H), 1.55 (d, J = 6.1 Hz, 3H,
4c), 1.50−1.34 (m, 4H), 1.38 (d, J = 7.5 Hz, 3H, 3c), 0.98 (t, J = 7.5
Hz, 3H, 3c), 0.95 (t, J = 7.3 Hz, 3H, 4c). 13C{1H} NMR (126 MHz,
CDCl3): δ 172.2 (3c), 171.4 (4c), 79.5 (3c), 74.7 (4c), 57.5 (4c), 50.8
(3c), 36.2 (3c), 29.8 (4c), 20.4 (4c), 20.3 (4c), 18.5 (3c), 13.80 (3c),
13.79 (4c), 12.6 (3c).
rac-(3R,4R)-3-Methyl-4-pentyloxetan-2-one (rac-3d) and rac-
(3R,4R)-4-Methyl-3-pentyloxetan-2-one (rac-4d). General procedure
D was followed using 9f (17.8 mg, 0.0200 mmol, 6.58 mol %), THF
(0.6 mL), and rac-2d (39.0 mg, 0.304 mmol). After being stirred at 22
°C for 20 h, the crude reaction mixture was subjected to flash column
chromatography to give a mixture of rac-3d and rac-4d (35.2 mg, 74%)
as a colorless oil. Analytical data for rac-3d44 and rac-4d16 have
previously been reported. 1H NMR (400 MHz, CDCl3): δ 4.38 (qd, J
= 6.1, 3.9 Hz, 1H, 4d), 4.16 (td, J = 6.7, 4.0 Hz, 1H, 3d), 3.20 (qd, J =
7.6, 4.0 Hz, 1H, 3d), 3.16 (ddd, J = 8.9, 6.5, 3.9 Hz, 1H, 4d), 1.89−
1.79 (m, 2H), 1.78−1.6 (m, 2H), 1.54 (d, J = 6.0 Hz, 3H, 4d), 1.48−
1.24 (m, 12H), 1.38 (d, J = 7.5 Hz, 3H, 3d), 0.90−0.86 (m, 6H).
13C{1H} NMR (75 MHz, CDCl3): δ 172.2 (3d), 171.5 (4d), 79.7
6,6′-((1E,1′E)-((2,3-Dimethylbutane-2,3-diyl)bis(azanylylidene))-
35
bis(methanylylidene))bis(2,4-di-tert-butylphenolate)aluminum Co-
baltate (9f). NaCo(CO)4 (33.4 mg, 0.172 mmol), 6,6′-((1E,1′E)-
((2,3-dimethylbutane-2,3-diyl)bis(azanylylidene))bis(methanylyl-
idene))bis(2,4-di-tert-butylphenolate)aluminum chloride13 (100 mg,
0.164 mmol), and THF (2.5 mL) were mixed and stirred for 12 h at 22
°C. The reaction mixture was filtered through a 0.45 μm Teflon
syringe filter and the filtrate carefully layered with hexane and then
placed in a freezer at −34 °C for a day. The resulting crystals were
isolated by filtration, washed with hexanes, and then dried in vacuo to
give 9f (118 mg, 81%) as yellow crystals. 1H NMR (400 MHz, C6D6):
δ 8.75 (s, 2H), 7.87 (d, J = 2.6 Hz, 2H), 7.78 (d, J = 2.5 Hz, 2H),
3.47−3.23 (m, 8H, THF), 1.65 (s, 18H), 1.43 (s, 18H), 1.18 (s, 12H),
1.20−1.15 (m, 8H, THF). 13C{1H} NMR (126 MHz, C6D6 + THF-d8,
(1:1, v/v)): δ 171.0, 162.4, 139.4, 132.2, 130.5, 128.2, 119.9, 67.9
(THF), 67.6, 35.8, 34.5, 31.5, 29.8, 26.3, 25.9 (THF). IR (neat, cm−1):
1862.1 ν(CO). Anal. Calcd for C48H70AlCoN2O8: C, 64.85; H, 7.94;
N, 3.15. Found: C, 65.00; H, 8.18; N, 3.02.
(3d), 74.8 (4d), 57.7 (4d), 50.8 (3d), 34.2 (3d), 31.50 (4d), 31.46
(3d), 27.7 (4d), 26.6 (4d), 24.7 (3d), 22.54 (3d), 22.46 (4d), 20.4
(4d), 14.04 (4d), 14.02 (3d), 12.6 (3d).
rac-(3R,4R)-4-Hexyl-3-methyloxetan-2-one (rac-3e) and rac-
(3R,4R)-3-Hexyl-4-methyloxetan-2-one (rac-4e). General procedure
D was followed using 9f (13.3 mg, 0.0150 mmol, 5.02 mol %), THF
(0.6 mL), and rac-2e (42.5 mg, 0.299 mmol). After being stirred at 22
°C for 20 h, the crude reaction mixture was subjected to flash column
chromatography to give a mixture of rac-3e and rac-4e (48.3 mg, 95%)
as a colorless oil. Analytical data for rac-3e45 and rac-4e16 have
previously been reported. 1H NMR (300 MHz, CDCl3): δ 4.38 (qd, J
= 6.1, 4.0 Hz, 1H, 4e), 4.15 (td, J = 6.6, 3.9 Hz, 1H, 3e), 3.20 (qd, J =
7.5, 4.0 Hz, 1H, 3e), 3.14 (ddd, J = 8.9, 6.5, 3.9 Hz, 1H, 4e), 1.88−1.78
(m. 2H), 1.78−1.65 (m. 2H), 1.54 (d, J = 6.1 Hz, 3H), 1.47−1.21 (m,
16H), 1.37 (d, J = 7.6 Hz, 3H), 0.89−0.85 (m, 6H). 13C{1H} NMR
(75 MHz, CDCl3): δ 172.2 (3e), 171.5 (4e), 79.7 (3e), 74.7 (4e), 57.7
(4e), 50.8 (3e), 34.2 (3e), 31.7 (3e), 31.6 (4e), 29.00 (4e), 28.96
rac-(3R,4R)-4-Butyl-3-methyloxetan-2-one (rac-3a) and rac-
(3R,4R)-3-Butyl-4-methyloxetan-2-one (rac-4a). General procedure
D was followed using 9f (13.3 mg, 0.0150 mmol, 4.93 mol %), THF
(0.6 mL), and rac-2a (34.7 mg, 0.304 mmol). After being stirred at 22
°C for 20 h, the crude reaction mixture was subjected to flash column
chromatography to give a mixture of rac-3a and rac-4a (34.7 mg, 80%)
as a colorless oil. Analytical data for rac-3a9a and rac-4a16 have
H
dx.doi.org/10.1021/jo501899e | J. Org. Chem. XXXX, XXX, XXX−XXX

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(3e), 27.8 (4e), 26.9 (4e), 25.0 (3e), 22.60 (4e), 22.57 (3e), 20.4
(4e), 14.11 (4e), 14.11 (3e), 12.6 (3e).
followed using 9f (13.2 mg, 0.0149 mmol, 7.49 mol %), THF (0.4
mL), and rac-2j (43.0 mg, 0.199 mmol). After being stirred at 22 °C
for 21 h, the crude reaction mixture was subjected to flash column
chromatography to give a mixture of rac-3j and rac-4j (44.6 mg, 92%)
as a colorless oil. Analytical data for rac-3j have previously been
reported in the literature.46 1H NMR (500 MHz, CDCl3): δ 4.52 (qd,
J = 6.1, 4.0 Hz, 1H, 4j), 4.32 (td, J = 6.6, 4.0 Hz, 1H, 3j), 3.79−3.70
(m, 2H, 3j), 3.71−3.65 (m, 2H, 4j), 3.35 (qd, J = 7.6, 4.0 Hz, 1H, 3j),
3.28 (ddd, J = 9.5, 5.4, 4.0 Hz, 1H, 4j), 2.07−1.91 (m, 2H + 2H, 3j +
4j), 1.55 (d, J = 6.1 Hz, 3H, 4j), 1.39 (d, J = 7.6 Hz, 3H, 3j), 0.88 (s,
9H + 9H, 3j + 4j), 0.05 (s, 6H + 6H, 3j + 4j). 13C{1H} NMR (126
MHz, CDCl3): δ 172.3 (3j), 171.5 (4j), 77.6 (3j), 75.5 (4j), 61.0 (4j),
59.1 (3j), 55.6 (4j), 51.1 (3j), 37.0 (3j), 30.9 (4j), 25.98 (4j), 25.97
(3j), 25.97 (4j), 20.3 (4j), 18.4 (3j), 12.5 (3j), −5.37 (4j), −5.38 (3j).
IR (neat, cm−1): 1823.2 ν(CO). HRMS (ESI-TOF) m/z: [M + H]+
calcd for C12H25O3Si 245.1567, found 245.1564.
rac-(3R,4R)-4-(Cyclohexylmethyl)-3-methyloxetan-2-one (rac-3f)
and rac-(3R,4R)-3-(Cyclohexylmethyl)-4-methyloxetan-2-one (rac-
4f). General procedure D was followed using 9f (8.9 mg, 0.010 mmol,
5.0 mol %), THF (0.4 mL), and rac-2f (31.0 mg, 0.201 mmol). After
being stirred at 22 °C for 20 h, the crude reaction mixture was
subjected to flash column chromatography to give a mixture of rac-3f
and rac-4f (32.3 mg, 88%) as a colorless oil. Only analytical data for
1
rac-3f are provided: H NMR (300 MHz, CDCl3): δ 4.28−4.23 (m,
1H), 3.23−3.14 (m, 1H), 1.83−1.53 (m, 7H), 1.39 (d, J = 7.6 Hz,
3H), 1.50−1.34 (m, 1H), 1.32−1.12 (m, 3H), 1.08−0.89 (m, 2H).
13C{1H} NMR (126 MHz, CDCl3): δ 172.3, 78.4, 51.3, 42.0, 34.9,
33.5, 33.1, 26.4, 26.2, 26.1, 12.6. IR (neat, cm−1): 1817.8 ν(CO)
.
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C11H19O2 183.1380,
found 183.1390.
rac-(3R,4R)-4-Benzyl-3-methyloxetan-2-one (rac-3g) and rac-
(3R,4R)-3-Benzyl-4-methyloxetan-2-one (rac-4g). General procedure
D was followed using 9f (13.2 mg, 0.0148 mmol, 7.33 mol %), THF
(0.4 mL), and rac-2g (30.0 mg, 0.202 mmol). After being stirred at 22
°C for 21 h, the crude reaction mixture was subjected to flash column
chromatography to give a mixture of rac-3g and rac-4g (31.8 mg, 90%)
as a colorless oil. Only analytical data for rac-3g are provided. 1H NMR
(400 MHz, CDCl3): δ 7.36−7.27 (m, 3H), 7.23−7.20 (m, 2H), 4.40
(td, J = 6.5, 4.0 Hz, 1H), 3.33 (qd, J = 7.5, 4.0 Hz, 1H), 3.20 (dd, J =
14.2, 6.4 Hz, 1H), 3.04 (dd, J = 14.3, 6.5 Hz, 1H), 1.30 (d, J = 7.6 Hz,
3H). 13C{1H} NMR (126 MHz, CDCl3): δ 171.6, 135.3, 129.2, 128.9,
127.3, 79.0, 50.5, 40.1, 12.5. IR (neat, cm−1): 1816.1 ν(CO). HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C11H13O2 177.0910, found
177.0919.
rac-(3R,4R)-4-(3-((tert-Butyldimethylsilyl)oxy)propyl)-3-methylox-
etan-2-one (rac-3k) and rac-(3R,4R)-3-(3-((tert-Butyldimethylsilyl)-
oxy)propyl)-4-methyloxetan-2-one (rac-4k). General procedure D
was followed using 9f (8.9 mg, 0.010 mmol, 5.0 mol %), THF (0.4
mL), and rac-2k (46.0 mg, 0.200 mmol). After being stirred at 22 °C
for 21 h, the crude reaction mixture was subjected to flash column
chromatography to give a mixture of rac-3k and rac-4k (44.9 mg, 87%)
as a colorless oil. Analytical data for rac-3k have previously been
reported in the literature.47 1H NMR (500 MHz, CDCl3): δ 4.40 (qd,
J = 6.1, 3.9 Hz, 1H, 4k), 4.22 (td, J = 6.8, 4.0 Hz 1H, 3k), 3.68−3.61
(m, 2H + 2H, 3k + 4k), 3.25−3.18 (m, 1H + 1H, 3k + 4k), 1.93−1.78
(m, 2H + 2H, 3k + 4k), 1.70−1.53 (m, 2H + 2H, 3k + 4k), 1.54 (d, J
= 6.1 Hz, 3H, 4k), 1.38 (d, J = 7.6 Hz, 3H, 3k), 0.88 (s, 9H + 9H, 3k +
4k), 0.04 (s, 6H + 6H, 3k + 4k). 13C{1H} NMR (126 MHz, CDCl3):
δ 172.1 (3k), 171.3 (4k), 79.6 (3k), 74.8 (4k), 62.35 (3k), 62.34 (4k),
57.4 (4k), 50.9 (3k), 31.0 (3k), 29.9 (4k), 28.2 (3k), 26.03 (4k),
26.03 (3k), 24.5 (4k), 20.4 (4k), 18.42 (3k), 18.42 (4k), 12.7 (3k),
−5.23 (3k), −5.23 (4k). IR (neat, cm−1): 1822.7 ν(CO). HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C13H27O3Si 259.1724, found
259.1724.
rac-3-((2R,3R)-2-Methyl-4-oxooxetan-3-yl)propyl Acetate (rac-3l)
and rac-3-((2R,3R)-3-Methyl-4-oxooxetan-2-yl)propyl Acetate (rac-
4l). General procedure E was followed using rac-5c (14.4 mg, 0.0150
mmol, 5.00 mol %), 1,4-dioxane (0.3 mL), NaCo(CO)4 (3.0 mg, 0.015
mmol, 5.0 mol %), and rac-3l (1.00 M, 1,4-dioxane, 300 μL, 0.300
mmol). After the solution was stirred at 22 °C for 20 h, the reactor was
carefully vented in a well-ventilated hood. The crude reaction mixture
was concentrated under reduced pressure and then subjected to flash
column chromatography to give a mixture of rac-3l and rac-4l (46.0
mg, 82%) as a colorless oil. Only analytical data for rac-4l are provided.
1H NMR (400 MHz, CDCl3): δ 4.38 (qd, J = 6.1, 4.0 Hz, 1H), 4.05 (t,
rac-(3R,4R)-3-Methyl-4-phenethyloxetan-2-one (rac-3h) and rac-
(3R,4R)-4-Methyl-3-phenethyloxetan-2-one (rac-4h). General proce-
dure D was followed using 9f (13.2 mg, 0.0149 mmol, 7.30 mol %),
THF (0.4 mL), and rac-2h (33.1 mg, 0.204 mmol). After being stirred
at 22 °C for 20 h, the crude reaction mixture was subjected to flash
column chromatography to give a mixture of rac-3h and rac-4h (33.5
mg, 86%) as a colorless oil. Analytical data for rac-3h have previously
been reported in the literature.46 1H NMR (500 MHz, CDCl3): δ
7.33−7.30 (m, 2H + 2H, 3h + 4h), 7.25−7.19 (m, 3H + 3H, 3h + 4h),
4.32 (qd, J = 6.1, 3.9 Hz, 1H, 4h), 4.17 (ddd, J = 7.7, 5.8, 3.9 Hz, 1H,
3h), 3.20 (qd, J = 7.5, 4.0 Hz, 1H, 3h), 3.15 (ddd, J = 9.1, 6.5, 4.0 Hz,
1H, 4h), 2.83 (ddd, J = 14.2, 8.8, 5.5 Hz, 1H + 1H, 3h + 4h), 2.71 (dt,
J = 13.9, 8.0 Hz, 1H + 1H, 3h + 4h), 2.23−2.16 (m, 1H + 1H, 3h +
4h), 2.12−2.05 (m, 1H + 1H, 3h + 4h), 1.43 (d, J = 6.1 Hz, 3H, 4h),
1.33 (d, J = 7.6 Hz, 3H, 3h). 13C{1H} NMR (126 MHz, CDCl3): δ
171.9 (3h), 171.2 (4h), 140.2 (4h), 140.1 (3h), 128.67 (3h), 128.66
(4h), 128.5 (4h), 128.4 (3h), 126.5 (4h), 126.4 (3h), 78.7 (3h), 75.0
(4h), 56.8 (4h), 50.9 (3h), 35.8 (3h), 33.1 (4h), 31.3 (3h), 29.5 (4h),
20.1 (4h), 12.5 (3h). IR (neat, cm−1): 1815.5 ν(CO). HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C12H15O2 191.1067, found 191.1080.
rac-(3R,4R)-4-Isopentyl-3-methyloxetan-2-one (rac-3i) and rac-
(3R,4R)-3-Isopentyl-4-methyloxetan-2-one (rac-4i). General proce-
dure D was followed using 9f (13.2 mg, 0.0149 mmol, 5.16 mol %),
THF (0.6 mL), and rac-2i (37.0 mg, 0.289 mmol). After being stirred
at 22 °C for 20 h, the crude reaction mixture was subjected to flash
column chromatography to give a mixture of rac-3i and rac-4i (40.9
mg, 91%) as a colorless oil. Analytical data for rac-3i and rac-4i have
previously been reported in the literature.16 1H NMR (400 MHz,
CDCl3): δ 4.39 (qd, J = 6.1, 3.9 Hz, 1H, 4i), 4.13 (td, J = 6.7, 4.0 Hz,
1H, 3i), 3.21 (qd, J = 7.5, 4.0 Hz, 1H, 3i), 3.12 (ddd, J = 8.9, 6.5, 3.9
Hz, 1H, 4i), 1.88−1.80 (m, 2H), 1.78−1.69 (m, 2H), 1.62−1.51 (m,
2H), 1.55 (d, J = 6.2 Hz, 3H, 4i), 1.38 (d, J = 7.5 Hz, 3H, 3i), 1.35−
1.28 (m, 2H), 1.25−1.16 (m, 2H), 0.90 (d, J = 6.6 Hz, 6H, 4i), 0.89
(d, J = 6.6 Hz, 6H, 3i). 13C{1H} NMR (75 MHz, CDCl3): δ 172.2
(3i), 171.5 (4i), 79.9 (3i), 74.7 (4i), 57.8 (4i), 50.8 (3i), 35.9 (4i),
33.9 (3i), 32.2 (3i), 27.92 (4i), 27.86 (3i), 25.7 (4i), 22.51 (3i), 22.48
(3i), 22.45 (4i), 22.45 (4i), 20.47 (4i), 12.7 (3i).
J = 6.1 Hz, 2H), 3.18 (td, J = 7.5, 4.0 Hz, 1H), 2.01 (s, 3H), 1.90−1.64
(m, 4H), 1.53 (d, J = 6.1 Hz, 3H). 13C{1H} NMR (75 MHz, CDCl3):
δ 171.0, 170.8, 74.5, 63.5, 57.0, 26.0, 24.4, 21.0, 20.3. IR (neat, cm−1):
1810.0 ν(CO, lactone), 1732.7 ν(CO, ester). HRMS (ESI-TOF) m/z: [M
+ Na]+ calcd for C9H14NaO4 209.0784, found 209.0795.
rac-(2R,3R)-Methyl 2-ethyl-3-hydroxybutanoate (rac-6b). General
procedure E was followed using rac-5c (14.3 mg, 0.0149 mmol, 5.02
mol %), NaCo(CO)4 (3.3 mg, 0.017 mmol, 5.7 mol %), 1,4-dioxane
(0.3 mL), and rac-2b (0.990 M, 1,4-dioxane, 300 μL, 0.297 mmol).
After the solution was stirred at 22 °C for 21 h, the reactor was
carefully vented in a well-ventilated hood. The crude reaction mixture
was treated with methanol (0.4 mL) and sodium methoxide (ca. 20.0
mg, ca. 0.370 mmol), stirred for 5 min at 22 °C, and then concentrated
under reduced pressure. The residue was subjected to flash column
chromatography to give rac-6b (30.3 mg, 70%) as a colorless oil. The
analytical data were in accordance with those reported in the
literature.48 1H NMR (400 MHz, CDCl3): δ 3.91 (q, J = 5.5 Hz,
1H), 3.70 (d, J = 0.6 Hz, 3H), 2.55 (d, J = 5.5 Hz, 1H), 2.31 (dt, J =
8.7, 6.1 Hz, 1H), 1.73−1.59 (m, 2H), 1.21 (d, J = 6.3 Hz, 3H), 0.90 (t,
J = 7.5 Hz, 3H). 13C{1H} NMR (75 MHz, CDCl3): δ 176.0, 68.2, 54.4,
51.7, 22.7, 21.6, 11.8.
rac-(3R,4R)-4-(2-((tert-Butyldimethylsilyl)oxy)ethyl)-3-methyloxe-
tan-2-one (rac-3j) and rac-(3R,4R)-3-(2-((tert-Butyldimethylsilyl)-
oxy)ethyl)-4-methyloxetan-2-one (rac-4j). General procedure D was
rac-(R)-Methyl 2-((R)-1-Hydroxyethyl)pentanoate (rac-6c). Gen-
eral procedure E was followed using rac-5c (14.4 mg, 0.0150 mmol,
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5.07 mol %), 1,4-dioxane (0.3 mL), NaCo(CO)4 (3.0 mg, 0.015 mmol,
5.1 mol %), and rac-2c (0.988 M, 1,4-dioxane, 300 μL, 0.296 mmol).
After the solution was stirred at 22 °C for 20 h, the reactor was
carefully vented in a well-ventilated hood. The crude reaction mixture
was treated with methanol (0.4 mL) and sodium methoxide (ca. 20.0
mg, ca. 0.370 mmol), stirred for 5 min at 22 °C, and then concentrated
under reduced pressure. The residue was subjected to flash column
NaCo(CO)4 (3.0 mg, 0.015 mmol, 5.1 mol %), and rac-2k (0.991 M,
1,4-dioxane, 300 μL, 0.297 mmol). After the solution was stirred at 22
°C for 21 h, the reactor was carefully vented in a well-ventilated hood.
The crude reaction mixture was treated with methanol (0.4 mL) and
sodium methoxide (ca. 20.0 mg, ca. 0.370 mmol), stirred for 5 min at
22 °C, and then concentrated under reduced pressure. The residue
was subjected to flash column chromatography to give rac-6k (69.7
mg, 80%) as a colorless oil. 1H NMR (500 MHz, CDCl3): δ 3.92 (h, J
= 6.4 Hz, 1H), 3.70 (s, 3H), 3.59 (t, J = 6.2 Hz, 2H), 2.49 (d, J = 6.9
Hz, 1H), 2.40 (dt, J = 8.0, 6.4 Hz, 1H), 1.71−1.64 (m, 2H), 1.52−1.46
(m, 2H), 1.22 (d, J = 6.4 Hz, 3H), 0.87 (s, 9H), 0.03 (s, 6H). 13C{1H}
NMR (126 MHz, CDCl3): δ 176.1, 68.6, 62.7, 52.6, 51.7, 30.5, 26.1,
25.9, 21.7, 18.4, −5.2. IR (neat, cm−1): 1737.0 ν(CO). HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C14H31O4Si 291.1986, found
291.2000.
1
chromatography to give rac-6c (36.4 mg, 77%) as a colorless oil. H
NMR (300 MHz, CDCl3): δ 3.88 (h, J = 6.8 Hz, 1H), 3.69 (s, 3H),
2.57 (d, J = 7.1 Hz, 1H), 2.38 (dt, J = 9.3, 5.7 Hz, 1H), 1.70−1.45 (m,
2H), 1.29 (h, J = 7.3 Hz, 2H), 1.21 (d, J = 6.3 Hz, 3H), 0.89 (t, J = 7.3
Hz, 3H). 13C{1H} NMR (75 MHz, CDCl3): δ 176.1, 68.5, 52.7, 51.7,
31.7, 21.7, 20.7, 14.1. IR (neat, cm−1): 1735.3 ν(CO). HRMS (ESI-
TOF) m/z: [M + Na]+ calcd for C8H16NaO3 183.0992, found
183.0998.
rac-(2R,3R)-3-Chloroheptan-2-ol (rac-8a). General procedure F
was followed using rac-5c (14.8 mg, 0.0155 mmol, 5.20 mol %), THF
(0.6 mL), 2,4,6-trimethylpyridine hydrochloride (52.3 mg, 0.332
mmol), and rac-2a (34.0 mg, 0.298 mmol). The crude reaction
mixture was subjected to bulb-to-bulb distillation to give rac-8a (30.5
mg, 68%) as a colorless oil. 1H NMR (500 MHz, CDCl3): δ 3.86−3.80
(m, 2H), 2.06 (d, J = 5.9 Hz, 1H), 1.84−1.71 (m, 2H), 1.58−1.49 (m,
1H), 1.45−1.25 (m, 3H), 1.28 (d, J = 6.0 Hz, 3H), 0.92 (t, J = 7.2 Hz,
3H). 13C{1H} NMR (126 MHz, CDCl3): δ 70.7, 70.5, 34.5, 28.8, 22.4,
20.5, 14.1. Anal. Calcd for C7H15ClO: C, 55.81; H, 10.04; Cl, 23.53.
Found: C, 55.61; H, 9.98; Cl, 23.48. No molecular ion peak was
observed when performing EI-MS or ESI-MS analysis; consequently,
no HRMS data were acquired.
rac-(2R,3R)-Methyl 3-Hydroxy-2-phenethylbutanoate (rac-6h).
General procedure E was followed using rac-5c (14.4 mg, 0.0150
mmol, 5.26 mol %), 1,4-dioxane (0.3 mL), NaCo(CO)4 (3.0 mg, 0.015
mmol, 5.3 mol %), and rac-2h (0.950 M, 1,4-dioxane, 300 μL, 0.285
mmol). After the solution was stirred at 22 °C for 22 h, the reactor was
carefully vented in a well-ventilated hood. The crude reaction mixture
was treated with methanol (0.4 mL) and sodium methoxide (ca. 20.0
mg, ca. 0.370 mmol), stirred for 5 min at 22 °C, and then concentrated
under reduced pressure. The residue was subjected to flash column
1
chromatography to give rac-6h (52.6 mg, 83%) as a colorless oil. H
NMR (400 MHz, CDCl3): δ 7.31−7.26 (m, 2H), 7.21−7.17 (m, 3H),
3.94 (p, J = 6.4 Hz, 1H), 3.73 (s, 3H), 2.70−2.55 (m, 3H), 2.45 (dddd,
J = 9.4, 5.7, 4.8, 0.8 Hz, 1H), 2.09−1.99 (m, 1H), 1.90 (dddd, J = 14.0,
9.7, 6.9, 4.9 Hz, 1H), 1.22 (d, J = 7.2 Hz, 3H). 13C{1H} NMR (75
MHz, CDCl3): δ 175.7, 141.3, 128.50, 128.48, 126.1, 68.5, 52.3, 51.7,
33.6, 31.1, 21.6. IR (neat, cm−1): 1736.8 ν(CO). HRMS (ESI-TOF)
m/z: [M + Na]+ calcd for C13H18NaO3 245.1148, found 245.1155.
rac-(R)-Methyl 2-((R)-1-Hydroxyethyl)-5-methylhexanoate (rac-
6i). General procedure E was followed using rac-5c (14.4 mg, 0.0150
mmol, 5.00 mol %), 1,4-dioxane (0.3 mL), NaCo(CO)4 (3.0 mg, 0.015
mmol, 5.0 mol %), and rac-2i (1.00 M, 1,4-dioxane, 300 μL, 0.300
mmol). After the solution was stirred at 22 °C for 20 h, the reactor was
carefully vented in a well-ventilated hood. The crude reaction mixture
was treated with methanol (0.4 mL) and sodium methoxide (ca. 20.0
mg, ca. 0.370 mmol), stirred for 5 min at 22 °C, and then concentrated
under reduced pressure. The residue was subjected to flash column
rac-(2R,3R)-3-Chlorononan-2-ol (rac-8e). General procedure F
was followed using rac-5c (14.3 mg, 0.0149 mmol, 5.03 mol %), THF
(0.6 mL), 2,4,6-trimethylpyridine hydrochloride (52.0 mg, 0.330
mmol), and rac-2e (42.3 mg, 0.297 mmol). The crude reaction
mixture was subjected to flash column chromatography to give rac-8e
1
(40.8 mg, 77%) as a colorless oil. H NMR (500 MHz, CDCl3): δ
3.85−3.79 (m, 2H), 2.09 (d, J = 5.7 Hz, 1H), 1.83−1.70 (m, 2H),
1.59−1.51 (m, 1H), 1.46−1.23 (m, 7H), 1.27 (d, J = 5.8 Hz, 3H),
0.90−0.87 (m, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 70.7, 70.5,
34.7, 31.8, 28.9, 26.7, 22.7, 20.5, 14.2. Anal. Calcd for C9H19ClO: C,
60.49; H, 10.72; Cl, 19.84. Found: C, 60.32; H, 10.66; Cl, 19.74. No
molecular ion peak was observed when performing EI-MS or ESI-MS
analysis; consequently, no HRMS data were acquired.
rac-(2R,3R)-3-Chloro-4-phenylbutan-2-ol (rac-8g). General pro-
cedure F was followed using rac-5c (21.5 mg, 0.0225 mmol, 7.50 mol
%), THF (0.6 mL), 2,4,6-trimethylpyridine hydrochloride (52.0 mg,
0.330 mmol), and rac-2g (44.5 mg, 0.300 mmol). The crude reaction
mixture was subjected to flash column chromatography to give rac-8g
(30.7 mg, 55%) as a colorless oil. The analytical data were in
accordance with that reported in the literature.49 1H NMR (400 MHz,
CDCl3): δ 7.35−7.31 (m, 2H), 7.28−7.25 (m, 3H), 4.05 (ddd, J = 8.2,
6.5, 3.2 Hz, 1H), 3.91−3.84 (m, 1H), 3.23 (dd, J = 14.0, 6.5 Hz, 1H),
3.07 (dd, J = 14.0, 8.1 Hz, 1H), 1.97 (d, J = 8.1 Hz, 1H), 1.32 (d, J =
6.3 Hz, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 137.8, 129.5,
128.7, 127.0, 70.1, 68.6, 41.3, 21.1.
1
chromatography to give rac-6i (44.1 mg, 78%) as a colorless oil. H
NMR (400 MHz, CDCl3): δ 3.89 (p, J = 6.3 Hz, 1H), 3.69 (s, 3H),
2.54 (s, 1H), 2.33 (ddd, J = 9.3, 6.2, 5.2 Hz, 1H), 1.69−1.45 (m, 3H),
1.20 (d, J = 6.3 Hz, 3H), 1.22−1.04 (m, 2H), 0.86 (d, J = 3.1 Hz, 3H),
0.84 (d, J = 3.1 Hz, 3H). 13C{1H} NMR (75 MHz, CDCl3): δ 176.2,
68.5, 53.1, 51.7, 36.5, 28.2, 27.4, 22.7, 22.4, 21.7. IR (neat, cm−1):
1736.2 ν(CO). HRMS (ESI-TOF) m/z: [M + Na]+ calcd for
C10H20NaO3 211.1305, found 211.1317.
rac-(R)-Methyl 4-((tert-Butyldimethylsilyl)oxy)-2-((R)-1-hydroxy-
ethyl)butanoate (rac-6j). General procedure E was followed using
rac-5c (14.4 mg, 0.0150 mmol, 5.02 mol %), 1,4-dioxane (0.3 mL),
NaCo(CO)4 (3.0 mg, 0.015 mmol, 5.0 mol %), and rac-2j (0.998 M,
1,4-dioxane, 300 μL, 0.299 mmol). After the solution was stirred at 22
°C for 20 h, the reactor was carefully vented in a well-ventilated hood.
The crude reaction mixture was treated with methanol (0.4 mL) and
sodium methoxide (ca. 20.0 mg, ca. 0.370 mmol), stirred for 5 min at
22 °C, and then concentrated under reduced pressure. The residue
was subjected to flash column chromatography to give rac-6j (66.7 mg,
81%) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ 3.97−3.89 (m,
1H), 3.69 (s, 3H), 3.67 (dt, J = 11.6, 5.7 Hz, 1H), 3.58 (ddd, J = 10.4,
7.5, 5.2 Hz, 1H), 2.79 (d, J = 7.5 Hz, 1H), 2.60 (dt, J = 8.4, 5.4 Hz,
1H), 1.95−1.78 (m, 2H), 1.22 (d, J = 6.4 Hz, 3H), 0.87 (s, 9H), 0.02
(s, 6H). 13C{1H} NMR (75 MHz, CDCl3): δ 175.7, 68.3, 61.2, 51.7,
rac-(2R,3R)-3-Chloro-5-phenylpentan-2-ol (rac-8h). General pro-
cedure F was followed using rac-5c (14.4 mg, 0.0150 mmol, 4.95 mol
%), THF (0.6 mL), 2,4,6-trimethylpyridine hydrochloride (52.0 mg,
0.330 mmol), and rac-2h (49.2 mg, 0.303 mmol). The crude reaction
mixture was subjected to flash column chromatography to give rac-8h
1
(45.1 mg, 75%) as a colorless oil. H NMR (500 MHz, CDCl3): δ
7.33−7.30 (m, 2H), 7.23−7.21 (m, 3H), 3.88−3.82 (m, 1H), 3.79
(ddd, J = 7.9, 6.1, 4.5 Hz, 1H), 2.94 (dt, J = 13.8, 6.9 Hz, 1H), 2.77 (dt,
J = 13.9, 8.2 Hz, 1H), 2.13−2.08 (m, 3H), 1.27 (d, J = 6.3 Hz, 3H).
13C{1H} NMR (126 MHz, CDCl3): δ 140.9, 128.64, 128.64, 126.3,
70.6, 69.3, 36.3, 32.8, 20.4. Anal. Calcd for C11H15ClO: C, 66.49; H,
7.61; Cl, 17.84. Found: C, 66.49; H, 7.67; Cl, 17.92. No molecular ion
peak was observed when performing EI-MS or ESI-MS analysis;
consequently, no HRMS data were acquired.
49.5, 32.1, 26.0, 21.5, 18.4, −5.4, −5.3. IR (neat, cm−1): 1735.0 ν(CO)
.
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C13H29O4Si 277.1830,
found 277.1837.
rac-(2R,3R)-3-Chloro-6-methylheptan-2-ol (rac-8i). General pro-
cedure F was followed using rac-5c (14.3 mg, 0.0149 mmol, 5.03 mol
%), THF (0.6 mL), 2,4,6-trimethylpyridine hydrochloride (52.0 mg,
rac-(R)-Methyl 5-((tert-Butyldimethylsilyl)oxy)-2-((R)-1-hydroxy-
ethyl)pentanoate (rac-6k). General procedure E was followed using
rac-5c (14.4 mg, 0.0150 mmol, 5.05 mol %), 1,4-dioxane (0.3 mL),
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0.330 mmol), and rac-2i (38.0 mg, 0.296 mmol). The crude reaction
mixture was subjected to flash column chromatography to give rac-8i
(33.1 mg, 68%) as a colorless oil. H NMR (500 MHz, CDCl3): δ
(e) Purohit, V. C.; Richardson, R. D.; Smith, J. W.; Romo, D. J. Org.
Chem. 2006, 71, 4549−4588.
(9) (a) Kull, T.; Peters, R. Angew. Chem., Int. Ed. 2008, 47, 5461−
5464. (b) Kull, T.; Cabrera, J.; Peters, R. Chem.Eur. J. 2010, 16,
9132−9139. (c) Meier, P.; Broghammer, F.; Latendorf, K.; Rauhut, G.;
Peters, R. Molecules 2012, 17, 7121−7150. (d) Calter, M. A.; Tretyak,
O. A.; Flaschenriem, C. Org. Lett. 2005, 7, 1809−1812.
(10) (a) Getzler, Y. D. Y. L.; Mahadevan, V.; Lobkovsky, E. B.;
Coates, G. W. J. Am. Chem. Soc. 2002, 124, 1174−1175. (b) Schmidt,
J. A. R.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2005, 127,
11426−11435. (c) Kramer, J. W.; Lobkovsky, E. B.; Coates, G. W. Org.
Lett. 2006, 8, 3709−3712. For a mechanistic study, see: (d) Church,
T. L.; Getzler, Y. D. Y. L.; Coates, G. W. J. Am. Chem. Soc. 2006, 128,
10125−10133. For a review, see: (e) Church, T. L.; Getzler, Y. D. Y.
L.; Byrne, C. M.; Coates, G. W. Chem. Commun. 2007, 657−674.
(11) Kramer, J. W.; Rowley, J. M.; Coates, G. W. Org. React. 2014, in
press.
1
3.87−3.79 (m, 2H), 2.05 (d, J = 6.2 Hz, 1H), 1.86−1.70 (m, 2H),
1.62−1.51 (m, 1H), 1.44 (dddd, J = 13.1, 10.7, 7.2, 4.7 Hz, 1H), 1.35−
1.25 (m, 1H), 1.28 (d, J = 6.1 Hz, 3H), 0.90 (t, J = 6.6 Hz, 6H).
13C{1H} NMR (126 MHz, CDCl3): δ 71.1, 70.5, 35.8, 32.7, 27.9, 22.9,
22.4, 20.5. Anal. Calcd for C8H17ClO: C, 58.35; H, 10.41; Cl, 21.53.
Found: C, 58.49; H, 10.50; Cl, 21.62. No molecular ion peak was
observed when performing EI-MS or ESI-MS analysis; consequently,
no HRMS data were acquired.
ASSOCIATED CONTENT
■
S
* Supporting Information
Additional tables concerning control reactions and catalyst
1
optimization; copies of H and 13C{1H} NMR spectra. This
material is available free of charge via the Internet at http://
pubs.acs.org.
(12) Gansauer, A.; Fan, C.-A.; Keller, F.; Karbaum, P. Chem.Eur. J.
̈
2007, 13, 8084−8090.
(13) Mulzer, M.; Whiting, B. T.; Coates, G. W. J. Am. Chem. Soc.
2013, 135, 10930−10933.
AUTHOR INFORMATION
Corresponding Author
*E-mail: coates@cornell.edu.
■
(14) Wu, Y.; Sun, Y.-P. J. Org. Chem. 2006, 71, 5748−5751.
(15) It should be noted that previously reported carbonylation
catalysts can carbonylate cis-2,3-disubstituted epoxides with high
regioselectivities if they are electronically or sterically biased. For a
further discussion, see: Mulzer, M.; Tiegs, B. J.; Wang, Y.; Coates, G.
W.; O’Doherty, G. A. J. Am. Chem. Soc. 2014, 136, 10814−10820.
(16) Mulzer, M.; Ellis, C. W.; Lobkovsky, E. B.; Coates, G. W. Chem.
Sci. 2014, 5, 1928−1933.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We thank the Department of Energy for financial support (DE-
FG02-05ER15687).
■
(17) A high krel value prevents the occurrence of the mismatched case
between catalyst and epoxide, which leads to preferred formation of
the steric regioisomer.
(18) One reviewer raised the question of what the word “appreciable”
with regard to krel means and whether a krel > 1 is actually necessary to
observe regioselectivity. A discussion of both these questions is
provided in the Supporting Information.
(19) See the Supporting Information for more details.
(20) The contrasteric regioselectivity of 1c in the matched case could
not be determined because we were unable to isolate (R)-1c in pure
form. Test reactions using impure (R)-1c, however, indicated that the
contrasteric regioselectivity in the matched case is comparable to that
observed with (R)-1a and b.
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■
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