Boron carboxylate catalysis of homoallylboration

Article abstract of DOI:10.1021/jo500599h

Boron tris(trifluoroacetate) is identified as the first effective catalyst for the homoallyl- and homocrotylboration of aldehydes by cyclopropylcarbinylboronates. NMR spectroscopic studies and theoretical calculations of key intermediates and transition states both suggest that a ligand-exchange mechanism, akin to our previously reported PhBCl ₂-promoted homoallylations, is operative. Our experimental and theoretical results also suggest that the catalytic activity of boron tris(trifluoroacetate) might originate from more facile catalytic turnover of the trifluoroacetate ligands (in agreement with DFT calculations) or from a lower propensity for formation of off-pathway reservoir intermediates (as observed by ¹H NMR). This work shows that carboxylates are viable catalytic ligands for homoallyl- and homocrotylations of carbonyl compounds and opens the door to the development of catalytic asymmetric versions of this transformation.

Full text of DOI:10.1021/jo500599h

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Boron Carboxylate Catalysis of Homoallylboration
Gabrielle J. Dugas,† Yu-hong Lam,‡ K. N. Houk,*,‡ and Isaac J. Krauss*,†
†Department of Chemistry, Brandeis University, Waltham, Massachusetts 02454-9110, United States
‡Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095-1569, United States
S
* Supporting Information
ABSTRACT: Boron tris(trifluoroacetate) is identified as the first effective
catalyst for the homoallyl- and homocrotylboration of aldehydes by
cyclopropylcarbinylboronates. NMR spectroscopic studies and theoretical
calculations of key intermediates and transition states both suggest that a
ligand-exchange mechanism, akin to our previously reported PhBCl2-
promoted homoallylations, is operative. Our experimental and theoretical
results also suggest that the catalytic activity of boron tris(trifluoroacetate)
might originate from more facile catalytic turnover of the trifluoroacetate
ligands (in agreement with DFT calculations) or from a lower propensity
1
for formation of off-pathway reservoir intermediates (as observed by H
NMR). This work shows that carboxylates are viable catalytic ligands for
homoallyl- and homocrotylations of carbonyl compounds and opens the door to the development of catalytic asymmetric
versions of this transformation.
Table 1. Selected Preliminary Experiments
INTRODUCTION
■
Allylboration of carbonyl compounds is an extensively studied
transformation whose regio- and stereochemical outcomes are
readily predicted from reagent structure via Zimmerman−
Traxler transition-state models.1 We have recently shown that
cyclopropanated allyl- and crotylboron reagents (1−3) are also
capable of reacting through Zimmerman−Traxler transition
states, affording homoallylation products (5−7) with complete
regio-, diastereo-, and enantioselectivity (Scheme 1).2
We previously established PhBCl2 as an effective promoter
for this reaction.2a Theoretical calculations and NMR studies
support the involvement of (cyclopropylcarbinyl)-
dichloroboranes (8) as the homoallylating species, generated
a
entry
catalyst
amount (mol %)
solvent
time (h) yield (%)
b
1
2
PhBCl2
15
5
DCM
3
2
0
0
b
b
b
b
c
Sc(OTf)3
Sc(OTf)3
AlCl3
CDCl3
CDCl3
CDCl3
CDCl3
DCM
3
10
10
10
15
15
15
15
20
24
168
0
4
0
5
Cu(OTf)2
B(OTFA)3
B(OTFA)3
B(OTFA)3
B(OTFA)3
B(OTFA)3
0
6
0.5
74
3
7
Et2O
18
18
4
Scheme 1. Homoallylation via the Allylation Paradigm
8
THF
1
9
pentane
toluene
1
10
15
1.5
26
a
b
NMR yield, except entry 6. Forcing the reaction with higher
temperatures resulted in self-aldol products from 4a and/or ring
c
opening of reagent 1. Isolated yield.
in situ by ligand exchange between 1−3 and PhBCl2. However,
the PhBCl2 promoter must be used in excess and is strongly
Lewis acidic. For greater substrate compatibility, it would be
desirable to develop milder promoters which could be used
catalytically. Moreover, in the case of achiral unsubstituted
cyclopropylcarbinyl reagent 1, asymmetric homoallylation
Received: March 13, 2014
Published: April 23, 2014
© 2014 American Chemical Society
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a
Table 2. Catalytic Homoallylation Scope
a
b
Reagents 2 and 3 were used in racemic form. All reactions were performed with 3.0 equiv f boronates 1−3, except where indicated. Entries 3−8
c
are reactions run at 45 °C, and all others were run at rt. Isolated yields for reactions on 0.1−0.3 mmol scale, except where indicated. For volatile
substrates, NMR yields are listed in parentheses. The diastereomeric ratios, as determined by 1H NMR integration, were >20:1 for 6a−k and >12:1
d
for 7a−k. Isolated yield for reaction run on 1 mmol scale and with 2.0 equiv of 1.
would only be possible with a chiral promoter, in which case it
would also be preferable to use catalytic amounts.
reaction times. On the other hand, we found that 15 mol % of
boron tris(trifluoroacetate) (B(OTFA)3)5 effectively promoted
the homoallylation in 74% yield. As we had previously seen
with the stoichiometric PhBCl2-promoted homoallylation,2a
coordinating solvents such as Et2O and THF hindered the
reaction, and another noncoordinating solvent, toluene,
effected a slower, lower yielding reaction.
We thus investigated the scope of the B(OTFA)3 catalyst
with a panel of aldehydes and cyclopropylcarbinylboronates 1−
3 (Table 2). In parallel with what we had observed for
stoichiometric PhBCl2-promoted reactions, under B(OTFA)3
RESULTS AND DISCUSSION
■
For these reasons, we tested several promoters under catalytic
conditions (Table 1). When a catalytic amount (15 mol %) of
PhBCl2 was used, no homoallylation product was observed at
all. Other Lewis acids previously reported to catalyze allylation,
such as Sc(OTf)3,3 AlCl3,4 and Cu(OTf)2,3b also failed to
produce any homoallylation product, although aldehyde self-
aldol products were observed in most cases after extended
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1
Figure 1. 400 MHz H NMR spectra of 1 in the presence of 0−300 mol % of B(OTFA)3.
catalysis, the cis (2) and trans boronates (3) reacted faster and
gave higher yields than the unsubstituted reagent 1.
Interestingly, 15 mol % of B(OTFA)3 also promoted a faster
reaction than did stoichiometric PhBCl2. As seen in entry 1, the
reaction of dihydrocinnamaldehyde (4a) was complete after 30
min at room temperature, as compared with 14 h with our
previous PhBCl2-promoted conditions.2a Similarly, pivaldehyde
(4f) reacted completely with 2 in about 60 min under
B(OTFA)3 catalysis (entry 14), as compared with 7 days under
PhBCl2 conditions.2b The ester (4g), the silyl ether (4h), and
the terminal alkyne (4i) were all well tolerated. The
compatibility of the B(OTFA)3 catalyst with the benzyl ether
(4j and 4k) is also noteworthy, as attempted PhBCl2-mediated
reactions with these substrates result in immediate debenzyla-
tion.6
In order to investigate the possible structure of the active
homoallylating species, we conducted 1H and 11B NMR
spectroscopic studies. To begin, B(OTFA)3 showed a 11B
NMR resonance at δ 3.4, consistent with tetracoordinate boron,
suggesting a bridged dimer structure, [B(OTFA)3]2 (although,
for simplicity, we will continue to refer to this compound as a
monomer).7 The dimeric nature of boron trifluoroacetates was
1
further evident from the H NMR spectrum (Figure 1) upon
mixing boronate 1 (spectrum a)2a with various amounts of
B(OTFA)3 (spectra b−g). As B(OTFA)3 was titrated in, an
intermediate set of cyclopropylcarbinyl resonances (11C−F),
and later a final set (12C−F), became visible, simultaneous with
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the conversion of propanediol derived peaks from 1A,B to just
one new set of peaks, 9A,B. Conversion of 1 entirely to 12 and 9
was complete only upon addition of two full equivalents of
B(OTFA)3 (spectrum f) and could be driven backward again by
adding more 1. Furthermore, no peak corresponding to
unreacted B(OTFA)3 could be seen in the 19F NMR spectra
when 1 was combined with 1−2 equiv of B(OTFA)3. Together,
these observations strongly support a picture in which
cyclopropylcarbinylB(OTFA)2 (11) initially generated from 1
+ B(OTFA)3 is ultimately captured as a heterodimeric complex
RB(OTFA)2·B(OTFA)3 (12). Because only two sets of
propanediol CH2−O peaks were ever observed at around δ 4,
we rule out the possibility that the peaks 11C−F could
correspond to a partial ligand transfer product 10, and we
speculate that 11 is either the monomeric or dimeric
RB(OTFA)2 species. Consistent with this overall picture, the
mixture of 11/12 is converted to a single cyclopropylcarbinyl
species (13C−F, spectrum h) upon addition of THF, which we
have assigned as the THF complex 13.
which then slowly converts to product. After 1 was mixed with
15% B(OTFA)3, we added aldehyde 4f and observed only
product peaks and unconsumed aldehyde in the H NMR. No
peaks corresponding to putative OTFA adduct 15 were
observed in the ∼4.6−7 ppm δ region, suggesting that 15 is
most likely absent.
We performed density functional theory (DFT) calculations
to investigate the possible intermediates implicated in these
homoallylations. As shown in Scheme 3, the ligand-exchange
reaction between 1 and B(OTFA)3 to form 11 and 9 is
exergonic, with ΔGrxn = −7.7 kcal/mol (eq 1). The Lewis acid−
base reaction between 1 and B(OTFA)3 forming adduct 17 is
less exergonic and has a ΔGrxn value of only −6.2 kcal/mol (eq
2). The Zimmerman−Traxler transition structures for the
homoallylation of acetaldehyde involving 11 and 17 were also
computed (Figure 2). The free energy of activation (ΔG⧧) is
1
1
Scheme 2. −OTFA/RCHO Adducts Not Observed by H
NMR
Figure 2. Zimmerman−Traxler transition structures (B3LYP-D3/
TZVP, ΔG⧧ values in kcal/mol) for homoallylborations of
acetaldehyde by 11 (A) and 17 (B).
Upon addition of the aldehyde to 11/12, we also looked for
possible formation of OTFA adducts to the aldehyde carbon
(15), analogous to chloride adduct 16, which we had observed
as reservoir species when PhBCl2 was used as promotor
(Scheme 2).2b When aldehyde is added to the PhBCl2-
promoted reaction, it is immediately converted entirely to 16,
19.0 kcal/mol involving 11 (TS-11), but 24.5 kcal/mol starting
from 17 (TS-17). Thus, the DFT calculations suggest that the
homoallylating species is the spectroscopically observable
species 11 generated in situ from 1 and B(OTFA)3.
Scheme 3. Energetics of Formation of Intermediates 11 and 17 (B3LYP-D3/TZVP, in kcal/mol).
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The proposed mechanism of catalysis is depicted in Scheme
4. Exchange of diol and OTFA ligands between 1 and
the boron of 11. By contrast, prior to turnover, species 1 and 18
both contain mixtures of electron-donating and -withdrawing
ligands, intuitively a lower energy arrangement. By this
reasoning, the analogous turnover step ought to be even
more uphill in the case of the more electronegative X = Cl, and
this notion is consistent with the computational result. Apart
from the increased difficulty of the turnover step, an alternative
explanation for the difference in catalytic activity for X = Cl vs
OCOCF3 is the fact that the chlorides from PhBCl2 are largely
sequestered as aldehyde adduct 16 (Scheme 2), whereas the
less nucleophilic trifluoroacetates seem not to form analogous
adduct 15 and thus remain mobile between boron atoms.
Scheme 4. Proposed Catalytic Cycle
CONCLUSION
■
In conclusion, we have identified boron tris(trifluoroacetate) as
an effective catalyst for the homoallylation of aldehydes.
Spectroscopic studies and DFT calculations suggest that the
active homoallylating species is the ligand-exchange product 11
rather than the Lewis adduct 17. The problem of aldehyde
sequestration by nucleophilic addition of a ligand on the boron
Lewis acid, which was previously observed under PhBCl2-
promoted conditions,2b is circumvented as the trifluoroacetate
ligand in the active catalyst is less nucleophilic than chloride.
Studies with structurally related chiral boron catalysts are under
way and will be reported in due course.
EXPERIMENTAL SECTION
■
General Information and Methods. All solvents for routine
isolation of products and chromatography were reagent grade.
Aldehydes were purchased from commercial sources and freshly
distilled, except for aldehydes 4g,9 4h,10 4i,11 and 4k,12 which were
synthesized based on literature procedures. Flash chromatography was
performed using Silicycle R10030B F60 SiliaFlash silica gel (230−400
mesh) with the indicated solvents. All reactions were monitored by
thin-layer chromatography on 0.25 mm silica plates (F-254), except for
the reactions with isobutryaldehyde (4d) and pivaldehyde (4f), which
were monitored by GC/MS (see below). TLC plates were stained
with vanillin or KMnO4. Reactions with volatile products were
monitored by GC/MS with a triple-axis detector. NMR spectra were
recorded with 400 MHz spectrometers (proton frequency) for 1H, 11B,
B(OTFA)3 produces 11 (possibly dimeric), which reacts with
aldehyde to afford product 18.8 Trifluoroacetates then exchange
with the propanediol ligand on the next catalytic equivalent of 1
to regenerate 11. In the analogous PhBCl2-promoted reaction,
chlorides may fail to turn over for multiple reasons. We
computed the reaction energies for the ligand exchange step
involved in catalytic turnover, using a methyl group to
represent the alkyl chain in the homoallylated products 18−
20 (Scheme 5). With ΔG = 2.7 kcal/mol, the ligand exchange
1
13C, and 19F NMR. The H NMR data are reported as the chemical
shift in parts per million, multiplicity (s, singlet; d, doublet; dd, doublet
of doublets; t, triplet; q, quartet; m, multiplet), and number of protons.
11B spectra are reported as ppm relative to BF3·OEt2. 13C spectra are
referenced to the central peak of CDCl3 as 77.0 ppm. 19F spectra are
reported as ppm relative to CFCl3. HRMS was performed using
electrospray (ES) or electron-impact (EI) ionization, as needed.
Synthesis of Boronates. Starting boronates 1, 2, and 3 were
prepared according to our previous literature procedure, and
characterization data were reported previously, with the trans reagent
(2) containing ∼5% cis isomer by 1H NMR.2 The catalyst B(OTFA)3
was prepared according to a literature procedure.5 Thus, a solution of
trifluoroacetic acid in pentane (3.0 equiv, or 3.0 mL in 100 mL
pentane) was transferred by cannulation to a solution of BBr3 in
pentane (1.0 equiv, or 1.3 mL in 100 mL pentane), followed by 50 mL
of pentane rinse. After 1 h of stirring, the solvent was distilled off in
vacuo (using manifold vacuum, not a rotary evaporator), and the
resulting material was subjected to ∼1 mmHg vacuum overnight to
yield a white powder in 64% yield (3 g). NMR spectroscopic data for
this compound have not previously been reported: 13C NMR (100
Scheme 5. Energetics of Ligand Exchange Implicated in
Catalytic Turnover (B3LYP-D3/TZVP, in kcal/mol)
in the chloride system (X = Cl) is calculated to be
thermodynamically less favorable than the system employing
the trifluoroacetate ligand (X = OCOCF3), for which we
calculated a ΔG value of 1.3 kcal/mol. The uphill nature of this
turnover step is intuitive because of the electronic properties of
the ligands. In the formation of 11 and 19 from 1 and 18, all
resonance electron-donating ligands (3 alkoxides) must be
collected together on the boron atom of 19, and all electron-
withdrawing ligands (OCOCF3 and alkyl) must be collected on
MHz, CDCl3) δ 163.2 (q, JCF = 46 Hz), 113.7 (q, JCF = 284 Hz); 11
B
NMR (128 MHz, CDCl3) δ 3.4. 19F NMR (376 MHz, CDCl3) δ 75.7.
General Experimental Procedure for the Synthesis of
Bishomoallyl alcohols. To a solution of B(OTFA)3 (7.5 mol %)
in anhydrous DCM (enough to produce a 0.2 M solution of aldehyde)
in an oven-dried Schlenk tube was added boronate (3.0 equiv). The
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solution was stirred under nitrogen for 1 min. Aldehyde (1.0 equiv)
was added, and the reaction mixture was stirred at 45 °C (for products
5c−h) or room temperature (all other products). After TLC analysis
showed consumption of aldehyde, the reaction was quenched with 3
M sodium hydroxide, and the mixture was extracted with EtOAc three
times. The organic layers were then dried over MgSO4, combined, and
concentrated on a rotary evaporator, and the crude reaction mixture
was purified by flash chromatography (EtOAc/hexane) to yield the
desired product. For reactions with benzyl-protected products
(employing 4j and 4k), flash chromatography was performed with
5% EtOAc/toluene. For volatile substrates (4d,f), reactions were
monitored by GC/MS, extraction was done with DCM, and solvent
was removed with no lower than 200 Torr vacuum, until a small
amount of solvent remained, at which point the remaining solvent was
blown off under a gentle stream of nitrogen. For these substrates,
chromatography was performed with Et2O/pentane solvent mixtures.
Characterization Data of New Compounds.
60.8, 44.5, 38.9, 35.7, 31.9, 20.4, 14.3; IR (neat) 3402 (br), 3071, 2970,
2929, 2869, 1712, 1610, 1452, 1274, 1176, 1104, 1021, 912, 856, 763;
HRMS (ES-TOF) calcd for C17H25O3 (M + H)+ 277.1804, found
277.1802.
6h: colorless oil (0.202 mmol scale, 67.1 mg, 81%); 1H NMR (400
MHz, CDCl3) δ 7.70−7.62 (m, 4H), 7.44−7.32 (m, 6H), 5.77 (ddd, J
= 17.4, 10.2, 7.8 Hz, 1H), 5.01 (app d, J = 17.4 Hz, 1H), 4.93 (app d, J
= 10.2 Hz, 1H), 3.67 (t, 6.4 Hz, 2H), 3.69−3.60 (m, 1H), 2.32 (app
sept, J = 7 Hz, 1H), 1.69−1.30 (m, 9 H + H2O), 1.05 (s, 9H), 1.01 (d,
6.7 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 145.2, 135.6, 134.1,
129.5, 127.6, 112.7, 70.3, 63.8, 44.4, 37.4, 35.4, 32.5, 26.9, 21.7, 20.2,
19.2; IR (neat) 3374 (br), 3071, 2930, 2858, 1960, 1890, 1822, 1725,
1460, 1427, 1108, 701; HRMS (ES-TOF) (m/z) calcd for
C26H38O2NaSi (M + Na)+ 433.2539, found 433.2537.
1
6i: colorless oil (0.191 mmol scale, 24.1 mg, 76%); H NMR (400
1
5h: colorless oil (0.130 mmol scale, 21.2 mg, 41%); H NMR
MHz, CDCl3) δ 5.78 (ddd, 1H, J = 17.2, 10.3, 8.0), 5.04 (ddd, 1H, J =
17.2, 1.6, 1.0), 4.95 (ddd, 1H, J = 10.2, 1.6, 0.6), 3.76−3.66 (m, 1H),
2.33 (app sept, 1H, J = 7.1), 2.23 (td, 2H, J = 6.6, 2.7), 1.95 (t, 1H, J =
2.7), 1.76−1.36 (m, 7H + water), 1.02 (d, 3H, J = 6.6); 13C NMR
(100 MHz, CDCl3) δ 145.0, 113.0, 84.4, 70.0, 68.4, 44.5, 36.5, 35.6,
24.5, 20.3, 18.4; IR (neat) 3388 (br), 3299, 3075, 2924, 2118 (weak),
1839, 1818, 1638, 1454, 1092, 994, 912; HRMS (EI-TOF) calcd for
C11H18O (M+) 166.1358, found 166.1358.
(400 MHz, CDCl3) δ 7.71−7.61 (m, 4H), 7.45−7.32 (m, 6H),
5.90−5.77 (m, 1H), 5.04 (app d, J = 17.3 Hz, 1H), 4.97 (app d,
J = 10.2 Hz, 1H), 3.67 (t, J = 6.3 Hz, 2H), 3.64−3.53 (m, 1H),
2.26−2.05 (m, 2H), 1.70−1.30 (m, 9H + H2O), 1.05 (s, 9H);
13C NMR (100 MHz, CDCl3) δ 138.6, 135.6, 134.1, 129.5,
127.6, 114.7, 71.4, 63.8, 37.1, 36.4, 32.5, 30.0, 26.9, 21.9, 19.2;
IR (neat) 3356 (br), 3070, 2931, 2858, 1724, 1466, 1427, 1109,
702; HRMS (ES-TOF) (m/z) calcd for C25H37O2Si (M + H)+
397.2568, found 397.2563.
1
6j: colorless oil (0.151 mmol scale, 23.2 mg, 69%); H NMR (400
MHz, CDCl3) δ 7.29−7.39 (m, 5H), 5.73−5.81 (m, 1H), 4.99 (d, J =
17 Hz, 1H), 4.93 (d, J = 10 Hz, 1H), 4.57 (s, 2H), 3.86−3.94 (m, 1H),
3.52 (dd, J = 3, 9 Hz, 1H), 3.34 (dd, J = 8, 10 Hz, 1H), 2.31−2.36 (m,
2H), 1.56−1.60 (m, 1H + H2O), 1.31−1.38 (m, 1H) 1.03 (d, J = 7 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 144.6, 138.0, 128.4, 127.8,
127.7, 112.7, 74.5, 73.3, 68.6, 39.7, 34.3, 19.8; IR (neat) 3468, 3064,
3028, 2963, 2924, 2866, 1638, 1453, 1099, 912, 749 cm−1; HRMS (ES-
TOF) (m/z) [M + Na]+ calcd for C14H20O2Na 243.1361, found
243.1362.
6b: colorless oil (0.324 mmol scale, 55.5 mg, 86%); 1H NMR (400
MHz, CDCl3) δ 5.78 (ddd, 1H, J = 17.3, 10.2, 7.8), 5.03 (br d, 1H, J =
17.2), 4.93 (br d, 1H, J = 10.2), 3.72−3.63 (m, 1H), 2.33 (app sept,
1H, J = 7.1), 1.53−1.19 (m, 15H), 1.02 (d, 3H, J = 6.7), 0.88 (t, 3H, J
= 6.8); 13C NMR (100 MHz, CDCl3) δ 145.2, 112.7, 70.4, 44.4, 37.7,
35.5, 31.8, 29.6, 29.3, 25.5, 22.6, 20.2, 14.1; IR (neat) 3341 (br), 3070,
2958, 2923, 2856, 1641, 1557, 1459, 994, 909, 725; HRMS (EI-TOF)
calcd for C13H26O (M+) 198.1984, found 198.1982.
1
6k: colorless oil (0.173 mmol scale, 24.3 mg, 60%); H NMR (400
6d: colorless oil (0.250 mmol scale, 16.8 mg, 47%); 1H NMR (400
MHz, CDCl3) δ 5.81 (ddd, 1H, J = 17.2, 10.2, 7.7), 5.04 (ddd, 1H, J =
17.2, 1.4, 1.4), 4.94 (br d, 1H, J = 10.3), 3.52−3.44 (m, 1H), 2.34 (app
sept, 1H, J = 7.0), 1.71−1.58 (m, 1H), 1.50 (br d, 1H, J = 4.4), 1.48−
1.33 (m, 2H), 1.02 (d, 3H, J = 6.6), 0.92 (d, 3H, J = 6.8), 0.90 (d, 3H,
J = 6.8); 13C NMR (100 MHz, CDCl3) δ 145.4, 112.6, 75.0, 41.1, 35.5,
33.7, 19.9, 18.7, 16.9; IR (neat) 3359 (br), 3072, 2961, 2883, 1638,
1461, 1374, 988, 910; HRMS (EI-TOF) calcd for C6H11O (M −
iPr−)+ 99.0810, found 99.0812, calcd for C4H9O (M − homocrotyl−)
73.0753, found 73.0654.
MHz, CDCl3) δ 7.27−7.38 (m, 5H), 5.72−5.81 (m, 1H), 5.00 (d, J =
17 Hz, 1H), 4.93 (d, J = 10 Hz, 1H), 4.53 (s, 2H), 3.85−3.93 (m, 1H),
3.70−3.75 (m, 1H), 3.63−3.68 (m, 1H), 2.85 (s, 1H), 2.29−2.39 (m,
1H), 1.72−1.79 (m, 2H), 1.55−1.62 (m, 2H), 1.31−1.38 (m, 1H),
1.03 (d, J = 7 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 145.0, 137.9,
128.4, 127.7, 127.6, 112.5, 73.3, 69.4, 69.1, 44.2, 36.6, 34.7, 19.9; IR
(neat) 3425, 3065, 3031, 2960, 2930, 2866, 1638, 1458, 1098, 911, 748
cm−1; HRMS (ES-TOF) (m/z) [M + Na]+ calcd for C15H22O2Na
257.1517, found 257.1519.
7h: colorless oil (0.173 mmol scale, 59.8 mg, 84%); 1H NMR (400
MHz, CDCl3) δ 7.70−7.63 (m, 4H), 7.44−7.32 (m, 6H), 5.67 (ddd, J
= 17.3, 10.2, 8.3 Hz, 1H), 5.02 (app d, 17.3 Hz, 1H), 4.95 (app d, 10.2
Hz, 1H), 3.67 (t, J = 6.3 Hz, 2H), 3.63−3.55 (m, 1H), 2.46−2.35 (m,
1H), 1.65−1.30 (m, 9H + H2O); 1.05 (s, 9H), 1.01 (d, 6.7 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ 144.2, 135.5, 134.1, 129.5, 127.6,
113.4, 69.6, 63.8, 44.2, 37.6, 34.7, 32.5, 26.9, 21.8, 21.2, 19.2; IR (neat)
3356 (br), 3070, 2930, 2858, 1960, 1890, 1820, 1724, 1460, 1427,
1108, 700; HRMS (ES-TOF) (m/z) calcd for C26H38O2NaSi (M +
Na)+ 433.2539, found 433.2538.
1
6g: colorless oil (0.124 mmol scale, 38.6 mg, 77%); H NMR (400
MHz, CDCl3) δ 7.96 (app d, 2H, J = 8.2), 7.26 (app d, 2H, J = 8.1),
5.76 (ddd, 1H, J = 17.2, 10.2, 8.0), 5.01 (br d, 1H, J = 17.2), 4.93 (br
dd, 1H, J = 10.3, 1.3), 4.36 (q, 2H, J = 7.1), 3.77−3.62 (m, 1H), 2.93−
2.79 (m, 1H), 2.79−2.64 (m, 1H), 2.32 (app sept, 1H, J = 7.1), 1.96−
1.65 (m, 3H), 1.54 (app dt, 1H, J = 13.9, 8.1), 1.44 (app td, 1H, J =
6.8, 4.2), 1.38 (t, 3H, J = 7.1), 1.00 (d, 3H, J = 6.8); 13C NMR (100
MHz, CDCl3) δ 166.6, 147.7, 144.9, 129.6, 128.4, 128.1, 113.0, 69.8,
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Featured Article
ASSOCIATED CONTENT
■
S
* Supporting Information
1
7i: colorless oil (0.242 mmol scale, 37.5 mg, 93%); H NMR (400
MHz, CDCl3) δ 5.57 (ddd, J = 8.2, 10.3, 17.7 Hz, 1H) 5.03 (d, 17.7
Hz, 1H), 4.97 (d, 10.3 Hz, 1H), 3.71−3.61 (m, 1H), 2.46−2.34 (m,
1H), 2.26−2.17 (m, 2H) 1.95 (t, 2.6 Hz, 1H), 1.78−1.63 (m, 1H),
1.63−1.33 (m, 6H + H2O), 1.02 (d, J = 6.8 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 144.0, 113.5, 83.3, 69.2, 68.4, 44.3, 36.8, 34.7, 24.6,
21.1, 18.4 IR (neat) 3400 (br), 3301, 3078, 2950, 2115 (weak), 1639,
1454, 995, 912; HRMS (EI-TOF) calcd for C11H18O (M+) 166.1358,
found 166.1359.
1H NMR and 13C NMR spectra. Full citation of ref 33.
Computational details and energies and Cartesian coordinates
of all computed structures. This material is available free of
charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Authors
*E-mail: houk@chem.ucla.edu.
*E-mail: kraussi@brandeis.edu.
■
Notes
7j: colorless oil (0.191 mmol, 23.6 mg, 56%); 1H NMR (400 MHz,
CDCl3) δ 7.28−7.38 (m, 5H), 5.60−5.69 (m, 1H), 5.03 (d, J = 17 Hz,
1H), 4.96 (d, J = 10 Hz, 1H), 4.55 (s, 2H), 3.84−3.90 (m, 1H), 3.48
(dd, J = 3, 9 Hz, 1H), 3.32 (dd, J = 8, 10 Hz, 1H), 2.37−2.49 (m, 1H),
2.25−2.33 (m, 1H), 1.44−1.52 (m, 1H), 1.26−1.33 (m, 1H), 1.03 (d, J
= 7 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 143.7, 138.0, 128.4,
127.7, 127.6, 113.6, 74.9, 73.3, 68.4, 39.9, 34.4, 21.2; IR (neat) 3463,
3065, 2961, 2928, 2865,1640, 1495, 1275, 1260, 1104, 913, 750 cm−1;
HRMS (ES-TOF) (m/z) [M + Na]+ calcd for C14H20O2Na 243.1361,
found 243.1359.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
I.J.K. gratefully acknowledges the generous support of Brandeis
University, the Donors of the American Chemical Society
Petroleum Research Fund (51975-DNI), and the National
Science Foundation CAREER program (CHE-1253363). We
are grateful to Prof. Casey Wade insightful discussions. K.N.H.
acknowledges financial support by the National Institute of
General Medical Sciences, National Institutes of Health
(GM36700). The computational resources from UCLA
Institute for Digital Research and Education and the National
Science Foundation through XSEDE resources provided by the
XSEDE Science Gateways program are also acknowledged.
7k: colorless oil (0.101 mmol, 12.5 mg, 52%); 1H NMR (400 MHz,
CDCl3) δ 7.27−7.37 (m, 5H), 5.64−5.73 (m, 1H), 5.04 (d, J = 17 Hz,
1H), 4.97 (d, J = 10 Hz, 1H), 4.52 (s, 2H), 3.82−3.90 (m, 1H), 3.62−
3.74 (m, 2H), 2.76 (s, 1H), 2.38−2.47 (m, 1H), 1.72−1.78 (m, 2H),
1.48−1.55 (m, 2H), 1.31−1.37 (m, 1H), 1.02 (d, J = 7 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ 144.1, 138.0, 128.4, 127.7, 127.6, 113.3,
73.3, 69.1, 69.0, 44.4, 37.0, 34.5, 21.1; IR (neat) 3411, 3065, 3031,
2959, 2923, 2865, 1639, 1453, 1275, 1097, 913, 749 cm−1; HRMS (ES-
TOF) (m/z) [M + Na]+ calcd for C15H22O2Na 257.1517, found
257.1513.
Scale, weights, yields, and references listing spectral data
for reactions producing known compounds: 5a13 (1.00 mmol
scale, 158 mg, 83%); 5b14 (0.215 mmol scale, 28 mg, 70%); 5c15
(0.200 mmol scale, 13 mg, 38%); 5d16 (0.120 mmol scale, 3.8 mg, 25%
(56% NMR)); 5e17 (0.139 mmol scale, 12 mg, 49%); 5f18 (0.116
mmol scale, 8.3 mg, 50% (64% NMR)); 5g2a (0.156 mmol scale, 30
mg, 74%); 6a19 (0.255 mmol scale, 41 mg, 78%); 6c20 (0.192 mmol
scale, 23 mg, 62%); 6e21 (0.238 mmol scale, 27 mg, 62%); 6f21 (0.217
mmol scale, 20 mg, 58% (78% NMR)); 7a19 (0.246 mmol scale, 44
mg, 87%); 7b2b (0.179 mmol scale, 25 mg, 69%); 7c2b (0.122 mmol
scale, 13 mg, 54%); 7d2b (0.135 mmol scale, 7.5 mg, 39% (67%
NMR)); 7e2b (0.168 mmol scale, 23 mg, 75%); 7f2b (0.141 mmol
scale, 12 mg, 53% (70% NMR)); 7g2b (0.204 mmol scale, 46 mg,
81%).
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