Chiral N-acetyl selone-promoted aldol reactions

Article abstract of DOI:10.1080/00397910802419706

The chiral oxazolidineselone functionality was found to be an excellent partner in the stereospecific acetate aldol reaction with aldehydes via the titanium enolates. Good stereocontrol was obtained as determined by NMR spectroscopy. The oxazolidineselone

Full text of DOI:10.1080/00397910802419706

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Chiral N-Acetyl Selone-
Promoted Aldol Reactions
Louis A. Silks III a , David B. Kimball b , Duane Hatch
a , Morgane Ollivault-Shiflett a , Ryszard Michalczyk a
& Eddie Moody c
a National Stable Isotope Resource, Bioenergy and
Environmental Sciences Group (B8), Los Alamos
National Laboratory , Los Alamos, New Mexico, USA
b Advanced Measurement Science Group (B9),
Bioscience Division, Los Alamos National
Laboratory , Los Alamos, New Mexico, USA
c NMT Division, Los Alamos National Laboratory,
Bioscience Division , Los Alamos, New Mexico, USA
Published online: 28 Jan 2009.
To cite this article: Louis A. Silks III , David B. Kimball , Duane Hatch , Morgane
Ollivault-Shiflett , Ryszard Michalczyk & Eddie Moody (2009) Chiral N-Acetyl Selone-
Promoted Aldol Reactions, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 39:4, 641-653, DOI:
10.1080/00397910802419706
To link to this article: http://dx.doi.org/10.1080/00397910802419706
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Synthetic Communications1, 39: 641–653, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802419706
Chiral N-Acetyl Selone-Promoted Aldol
Reactions
Louis A. Silks III,1 David B. Kimball,2 Duane Hatch,1
Morgane Ollivault-Shiflett,1 Ryszard Michalczyk,1
and Eddie Moody3
1National Stable Isotope Resource, Bioenergy and Environmental
Sciences Group (B8), Los Alamos National Laboratory,
Los Alamos, New Mexico, USA
2Advanced Measurement Science Group (B9), Bioscience Division, Los
Alamos National Laboratory, Los Alamos, New Mexico, USA
3NMT Division, Los Alamos National Laboratory, Bioscience Division,
Los Alamos, New Mexico, USA
Abstract: The chiral oxazolidineselone functionality was found to be an excellent
partner in the stereospecific acetate aldol reaction with aldehydes via the titanium
enolates. Good stereocontrol was obtained as determined by NMR spectroscopy.
The oxazolidineselone also provided a straightforward way to establish the
stereopurity of the coupling reaction through 77Se NMR spectroscopy.
Keywords: Acetate aldol, enolate structure, selenocarbonyl, 77Se NMR spectro-
scopy
INTRODUCTION
The aldol reaction was reported by Wurtz in 1872[1] and involves a
carbon–carbon bond-forming process between an enolate and a b-carbo-
nyl to give rise to a b-hydroxy carbonyl functionality. This reaction has
Received June 19, 2008.
Address correspondence to L. A. ‘‘Pete’’ Silks, Ph.D., Los Alamos National
Laboratory, Bioscience Division, National Stable Isotope Resource, Group B8;
Bioenergy and Environmental Science, Bioscience Division, MS; E529, Los
Alamos, NM 87544, USA. E-mail: pete-silks@lanl.gov
641

642
L. A. Silks et al.
proven to be one of the most useful methods of stererospecifically creat-
ing two contiguous chiral carbon centers. The development of methods
for improved chiral auxilaries,[2] organo-catalytic processes,[3] novel
coreactants (e.g., Lewis acids=bases),[4] and recently reported ‘‘green’’ aqu-
eous aldol reactions[5] continues to be of interest in the research community.
Chiral auxiliaries were developed in the early 1980s to provide for a
predictable stereochemical result in the aldol bond-forming process. The
chiral oxazolinedinone amide boron bases enolate process developed by
Evans[6] has been pivotal for gaining easy access to syn-propionates
(Evans aldol). By simply using titanium(IV)-based enolates it was discov-
ered that the opposite syn-propionate could be selected (non-Evans aldol).
The use of thiazolidinethione-based systems by Crimmins[7] demonstrated
that both syn products could be obtained by using 1 or 2 equiv of the eno-
lizing base. Access to the anti-aldol manifold has proven to be more diffi-
cult, although some successful methods have been reported.[8]
We have been interested in developing new techniques for carbon–
carbon bond-formation using the chiral selone auxilary. The selone-
promoted Ti aldol reaction was found to give high stereroselectivety in
good to excellent yields. In addition, under certain conditions this chiral
auxiliary promoted a rare anti-aldol process. The selone functionality has
also served as an exquistely sensitive NMR reporter[9] for the determina-
tion of chirality at remotely disposed chiral centers and has been pivotal
in efforts to help define the solution state of the key Ti enolate in the
aldol process.[10] It has provided a straightforward general synthetic route
for the construction of the (2H and 13C) isotopomers of ribose and deox-
yribose used in the synthesis of labeled nucleic acids.[11]
Compared to other functional groups on the aldol donor, the use of
the acetate moiety is rare,[12] mostly because of varying stereoselectivity in
the resulting product. To attack this problem, designer molecular scaf-
folds have been created to increase the compactness and rigidity of the
transition state, thereby increasing the effects of strategically placed
groups on the energetically prefered conformation. Notable advances
have been reported by the Osorio-Lozada[13] and Ghosh[14] groups. The
Osorio-Lozada group recently reported that the incorporation of a thio-
carbonyl group into an oxazolidinone framework gives rise to very good
stereoselectivities in the selected aldol examples.
The success of some chiral auxiliaries with acetate side groups in
effecting stereoselective products prompted us to investigate the use of
the oxazolidineselone. In addition, the stereoselectivity of the reaction
could be interogated immediately upon reaction completion using 77Se
NMR spectroscopy.[15] The selenium nucleus is exquistly sensitive to its
1
electronic enviroment. It has a spin I ¼ 1=2, just as H, has a chemical
shift range of more than 3500 ppm, has a relative receptivity of 2.98

Chiral N-Acetyl Selone-Promoted Aldol Reactions
643
compared to 13C, and has a natural abundance of 7.5%. In these systems,
the observing selenium nucleus has been shown to detect chiral centers
removed by as many as eight bonds.
RESULTS AND DISCUSSION
Synthesis (Scheme 1) of N-acetyl valine derived selone was accomplished
through reaction of 1[16] with acetyl chloride and Hunig’s base in CH2Cl2.
Reaction of 2 with TiCl4 and Hunig’s base at 0 ꢀC gave the enolate, which
was treated with a variety of aldehydes at ꢁ78 ꢀC to give aldol products
3a–3i, Scheme 1. After workup, the crude products were examined by
77Se NMR spectroscopy to determine diastereomeric ratios (dr).
The absolute stereochemistry of the product for 3i was determined
through concurrent cleavage of the auxiliary and formation of the methyl
ester, followed by reaction with Mosher’s acid chloride.[17] NMR values
for both diastereomers were compared to literature values, and the major
isomer is shown in Scheme 1.
We found that 2 reacted somewhat sluggishly when only 1.1–1.2
equiv of TiCl4 were used. If, however, 1.7 equiv of TiCl4 were employed,
then only a trace amount of starting material was observed in the crude
NMR spectra. Yields and stereoselectivities were independent of the
amount of aldehyde added.
In general, crude yields and stereoselectivities were quite good for
aldehydes that had R groups capable of complexing Ti (entries a–e,
Table 1). For those aldehydes with saturated alkyl groups, reduced
stereoselectivity was alleviated by easy separation using column chroma-
tography, and good combined yields were obtained. The selone auxiliary
compares well with other known auxiliaries in both isolated yield and
stereoselectivity, although the oxazolidinethione developed by Guz and
Phillips[12a] is more consistently selective across different aldehyde types.
Scheme 1. Selone-promoted acetate aldol: (a) acetyl chloride, Hunig’s base; (b)
TiCl4, Hunig’s base followed by RCHO. R ¼ aryl alkyl, alkenyl, and benzyloxy.

644
L. A. Silks et al.
Table 1. Selone-promoted Ti aldol reactions of 2 with representative aldehydes
Entry
Aldehyde
dr
Yield
a
b
c
d
e
f
PhCHO
4-FPhCHO
CH3CH2CH ¼ CH(CH3)CHO
CH3CH ¼ CHCHO
BnOCH2CHO
96:4
96:4
93:7
88:12
91:9
77:23
77:23
74:26
65:35
95
93
90
85
90
83
93
88
86
2,4,6-(CH3)3PhCHO
CH3(CH2)2CHO
(CH3)2CHCHO
g
h
i
(C6H11)CHO
In Fig. 1, a representative example of the observation of the mixture of
aldol diastereomers through the observing selenium nucleus is shown. The
spectrum was taken on the crude material before silica-gel flash-
column chromatography. The spectrum also provides for an assessment
of the overall course of the chemical processing. A very minor peak was
observed, which was centered around 120 ppm. This peak corresponds to
the unacylated (acetate cleavage) selone. Moreover, the diasteromeric ratio
can be interrogated immediately upon quenching of the reaction. This mea-
surement at this time obviates the possible retroaldol or other reactions
occurring during purification, which could alter the amount of each diaster-
eomer present. Direct evaluation of the reaction solution can also be
Figure 1. 1D 77Se NMR spectrum of the crude mixture of 3.

Chiral N-Acetyl Selone-Promoted Aldol Reactions
645
assessed through the observing selenium nucleus by simply taking an
aliquot of the solution and immediately recording the NMR spectrum.
We have been particularily interested in gaining an understanding for
the basis of the stereochemical preference in our selone systems both com-
putationally and with 2D NMR. Solution structural information should
provide a logical basis for further auxiliary design improvements. In addi-
tion, to the best of our knowledge, there is a general lack of positional infor-
mation for the amine base partner in the enolate complex. Evans et al.[18]
speculated the complexes are aggregated with the amine and intimately
associated with the enolate, possibly through ion pairing. Recently
Nebot[19] and coworkers studied pentanone enolate systems in an effort
to elucidate if these systems exist as ‘‘real’’ enolates or ate-complexes and
also to determine the fate of the amine base and the disposition of the
ligands around the metal. In a more recent study, Moreira and cowor-
kers[20] have found, for the complexes studied, there is an apparent biradical
character to the titainium enolate (at varying temperatures up to 100 K).
Figure 2 shows the proton NMR spectrum of the enolate, which was
ꢀ
generated in CD2Cl2 using TiCl4 and Hunig’s base at 0 C. All proton reso-
nances were assigned, and the complex was found to be stable for at least
24h (deteremined by the general lack of observable additional peaks over
time). Remarkably, the excess Hunig’s base was observed as distinct
Figure 2. Proton NMR spectrum of the enolate complex.

646
L. A. Silks et al.
resonances from the complexed Hunig’s base, and the ammonium proton
resonance at 7.25ppm was observed as a broad singlet. Further refinement
of the NMR data with DFT calculations are under way.
In conclusion, we have extended the utility of the oxazolidineselone
auxiliary to aldol reactions, giving rise to good dr values.
EXPERIMENTAL
All one-dimensional product characterization NMR experiments were per-
formed in CDCl3, unless otherwise noted, on a DRX 300 MHz NMR spec-
trometer equipped with triple-axis gradient and a tunable broadband probe.
1H and 13C spectra were referenced to the TMS signal at 0.00 ppm through
the spectrometer’s lock frequency. 77Se spectra were referenced to diphenyl-
1
selenide at 465 ppm. H spectra were recorded at 300.1300056 MHz, 13C
spectra at 75.4677506 MHz, and 77Se spectra at 57.2397200 MHz. Mass
spectra were obtained on a Thermo Finnegan LCQ Deca XP Plus mass
spectrometer. Chemicals were obtained from commercial sources, were used
without purification, and were of reagent quality or better.
Typical Procedure, Oxazolidineselone-Based Acetate Aldol
To a flame-dried, round-bottom flask, 2 (100mg, 0.43 mmol) and dry
CH2Cl2 (10 mL) were added under Ar. The yellow solution was cooled to
0 ꢀC, and TiCl4 (0.75 mL, 1 M in CH2Cl2) was added dropwise. The orange
solution was stirred 5 min, and then i Pr2NEt (0.10 mL, 0.57mmol) was
added. The dark mixture was stirred 1 h, then chilled to ꢁ78ꢀC. The alde-
hyde (6.9 mmol) was added dropwise as a solution in CH2Cl2 (2 mL). The
mixture was stirred 1 hour, then allowed to warm to 0 ꢀC. After 30min at
0 ꢀC, saturated aq. NH4Cl was added until red precipitate was observed.
The mixture was diluted with 10% EtOAc in CH2Cl2 (ꢂ10mL), then
vacuum filtered through silica gel, eluting with 10% EtOAc in CH2Cl2. Sol-
vent was evaporated from the filtrate, and purification by column chroma-
tography (5% EtOAc in CH2Cl2) gave aldol products 3a–e, along with
minor amounts of starting 2 in some cases. NMR (1H, 13C, 77Se) and MS
analysis were consistent with the product structures.
Derivative Analysis: Mosher’s Acid Chloride Adduct of the Aldol Product
Compounds 3i (150 mg, 0.43 mmol) and 3i0 (100 mg, 0.29 mmol) were
separately treated under argon with 4-N,N-dimethylaminopyridine

Chiral N-Acetyl Selone-Promoted Aldol Reactions
647
Scheme 2. Mosher’s acid adduct of the aldol product.
(53 mg, 0.43 mmol, and 36 mg, 0.29 mmol, respectively) in 6 mL of 20%
methanol in CH2Cl2 (Scheme 2). The mixtures were stirred at room
temperature for 48 h. Each mixture was filtered through silica gel using
CH2Cl2 to elute. After evaporation of the solvent, purification by column
chromatography (10–20% EtOAc in hexanes) gave the esters 4 (50 mg,
60% yield) and 40 (30 mg, 54% yield) as slightly yellow oils. NMR analysis
was analogous to literature examples.[21]
The esters 4 and 40 were converted to the corresponding (S)-MTPA-
1
esters according to the literature, and the H NMR shifts for the MTPA
methoxy signals were compared. Resonances at d 3.70 for 5 and 3.60 for
50 confirmed the R configuration for the major isomer (3i, 4, and 5) and
the S configuration for the minor isomer (3i0, 40, and 50). Absolute con-
figurations for 3a–i were assigned by analogy and analysis of the 77Se
NMR shifts.
Data
Compound 3a (PhCHO)
1H NMR (CDCl3) d 7.48 (d, J ¼ 7.2 Hz, 2H), 7.42 (t, J ¼ 7.2 Hz, 2H), 7.34
(t, J ¼ 7.1 Hz, 1H), 5.35 (dt, J ¼ 9.0, 3.6 Hz, 1H), 4.78 (dt, J ¼ 8.4, 3.3 Hz,
1H), 4.47 (dd, J ¼ 9.5, 3.0 Hz, 1H), 4.39 (t, J ¼ 9.5 Hz, 1H), 4.06 (dd,
J ¼ 17.1, 3.3 Hz, 1H), 3.95 (dd, J ¼ 17.1, 8.4 Hz, 1H), 3.19 (d, J ¼ 4.2 Hz,
1H), 2.45–2.34 (m, 1H), 0.98 (d, J ¼ 6.9 Hz, 3H), 0.92 (d, J ¼ 6.9 Hz, 3H);
13C NMR (CDCl3) d 189.5, 172.9, 142.3, 128.6, 127.9, 125.9, 70.3, 69.6,
64.2, 46.7, 29.0, 18.2, 15.0; 77Se (CDCl3) d 461.3; MS (ESI) m=z 341.9
[M þ H]þ.
Compound 3b (4-F-PhCHO)
1H NMR (CDCl3) d 7.48–7.42 (quartet of triplets, J ¼ 8.4, 5.4, 2.1 Hz,
2H), 7.09 (triplet of triplets, J ¼ 8.4, 2.1 Hz, 2H), 5.32 (dt, 9.3, 3.6 Hz,
1H), 4.79 (dt, J ¼ 8.7, 3.3 Hz, 1H), 4.47 (dd, J ¼ 9.1, 3.0 Hz, 1H), 4.40
(t, J ¼ 9.1 Hz, 1H), 4.06 (dd, J ¼ 17.4, 3.3 Hz, 1H), 3.86 (dd, J ¼ 17.4,

648
L. A. Silks et al.
9.3 Hz, 1H), 3.27 (d, J ¼ 4.2 Hz, 1H), 2.43–2.33 (m, 1H), 0.98 (d,
J ¼ 7.2 Hz, 3H), 0.92 (d, J ¼ 7.0 Hz, 3H); 13C NMR (CDCl3) d 189.5,
172.7, 162.3 (d, J ¼ 244.4 Hz), 138.1 (d, J ¼ 3.2 Hz), 127.6 (d, J ¼ 8.1 Hz),
115.4 (d, J ¼ 21.3 Hz), 69.7, 69.6, 64.21, 46.8, 29.0, 18.1, 15.0;77Se
(CDCl3) d 461.4; MS (ESI) m=z 358.6 [M]þ.
Compound 3c (2-Methyl-2-pentenal)
1H NMR (CDCl3) d 5.54 (t, J ¼ 7.2 Hz, 1H), 4.78 (dt, J ¼ 8.4, 3.3 Hz, 1H),
4.62 (t, J ¼ 6.3 Hz, 1H), 4.47 (dd, J ¼ 12.6, 3.0 Hz, 1H), 4.43 (dd, J ¼ 12.6,
9.6 Hz, 1H), 3.74 (d, J ¼ 6.3 Hz, 2H), 2.73 (br s, 1H), 2.44–2.33 (m, 1H),
2.08 (quintet, J ¼ 7.2 Hz, 2H), 1.71 (s, 3H), 1.00 (t, 7.2 Hz, 3H), 0.97
(d, J ¼ 7.2 Hz, 3H), 0.92 (d, J ¼ 7.2 Hz, 3H); 13C NMR (CDCl3) d 189.5,
173.2, 134.5, 128.9, 73.1, 69.6, 64.2, 44.0, 29.0, 20.8, 18.2, 15.0, 13.9,
12.1;77Se (CDCl3) d 455.3; MS (ESI) m=z 332.3 [M]þ.
Compound 3d (Crotonaldehyde)
1H NMR (CDCl3) d 5.82 (dq, J ¼ 15.3, 6.3 Hz, 1H), 5.64 (ddd, J ¼ 15.3, 6.3,
1.5 Hz, 1H), 4.79 (dt, J ¼ 8.1, 3.3 Hz, 1H), 4.69 (br s, 1H), 4.48 (dd, J ¼ 9.4,
3.0 Hz, 1H), 4.41 (t, J ¼ 9.4 Hz, 1H), 3.86 (dd, J ¼ 17.4, 3.3 Hz, 1H), 3.62
(dd, J ¼ 17.4, 8.7 Hz, 1H), 2.82 (br s, 1H), 2.44–2.34 (m, 1H), 1.77 (d,
J ¼ 6.3 Hz, 3H), 0.98 (d, J ¼ 6.9 Hz, 3H), 0.93 (d, J ¼ 6.9 Hz, 3H); 13C
NMR (CDCl3) d 189.4, 172.9, 131.6, 127.7, 69.6, 68.8, 64.2, 45.3, 29.0,
18.2, 17.8, 15.0;77Se (CDCl3) d 459.0; MS (ESI) m=z 305.1 [M þ H]þ.
Compound 3e (BnOCH2CHO)
1H NMR (CDCl3) d 7.41–7.31 (m, 5H), 4.78 (dt, J ¼ 8.2, 3.1 Hz, 1H), 4.64
(s, 2H), 4.47 (dd, J ¼ 9.5, 3.1 Hz, 1H), 4.40 (dd, J ¼ 9.5, 9.3 Hz, 1H), 3.88
(dd, J ¼ 17.2, 9.3 Hz, 1H), 3.72 (dd, J ¼ 17.2, 3.8 Hz, 1H), 3.08
(d, J ¼ 5.0 Hz, 1H), 2.45–2.35 (m, 1H), 0.98 (d, J ¼ 7.0 Hz, 3H), 0.93
(d, J ¼ 6.9 Hz, 3H); 13C NMR (CDCl3) d 189.5, 172.9, 137.9, 128.4,
127.8, 127.7, 73.4, 73.0, 69.5, 67.6, 64.2, 42.2, 28.9, 18.1, 15.0;77Se
(CDCl3) d 455.5; MS (ESI) m=z 384.3 [M]þ, 366.1 [M – H2O]þ.
Compound 3f (Mesitylaldehyde, Major)
1H NMR (CDCl3) d 6.89 (s, 2H), 5.82 (d, J ¼ 10.2 Hz, 1H), 4.81 (dt,
J ¼ 8.1, 3.0 Hz, 1H), 4.51–4.39 (m, 3H), 3.62 (dd, J ¼ 18.3, 2.7 Hz, 1H),

Chiral N-Acetyl Selone-Promoted Aldol Reactions
649
2.73 (d, J ¼ 3.3 Hz, 1H), 2.5 (s, 6H), 2.46–2.41 (m, 1H), 2.31 (s, 3H), 1.00
(d, J ¼ 7.2 Hz, 3H), 0.94 (d, J ¼ 6.9 Hz, 3H); 13C NMR (CDCl3) d 189.4,
173.2, 137.1, 136.3, 134.6, 130.2, 69.6, 66.8, 64.4, 44.1, 29.1, 20.8, 18.2,
15.0;77Se (CDCl3) d 460.1; MS (ESI) m=z 382.3 [M]þ.
Compound 3f0 (Mesitylaldehyde, Minor)
1H NMR (CDCl3) d 6.89 (s, 2H), 5.76 (d, J ¼ 9.6 Hz, 1H), 4.82 (dt,
J ¼ 8.4, 3.3 Hz, 1H), 4.55–4.39 (m, 3H), 3.61 (dd, J ¼ 18.3, 2.7 Hz, 1H),
2.84 (d, 3.3 Hz, 1H), 2.51 (s, 6H), 2.50–2.44 (m, 1H), 2.31 (s, 3H), 1.02
(d, J ¼ 6.9 Hz, 3H), 0.98 (d, J ¼ 6.9 Hz, 3H); 13C NMR (CDCl3) d
189.3, 173.6, 137.2, 136.3, 134.5, 130.2, 69.6, 67.0, 64.3, 44.2, 29.0,
20.8, 18.2, 15.1;77Se (CDCl3) d 459.2; MS (ESI) m=z 382.2 [M]þ (MS
virtually identical to 3e).
Compound 3g (Butyraldehyde, Major)
1H NMR (CDCl3) d 4.78 (dt, J ¼ 6.8, 3.1 Hz, 1H), 4.47 (dd, J ¼ 9.5,
3.0 Hz, 1H), 4.40 (dd, J ¼ 9.5, 8.1 Hz, 1H), 4.25–4.17 (m, 1H), 3.85 (dd,
J ¼ 17.6, 2.6 Hz, 1H), 3.46 (dd, J ¼ 17.6, 9.3 Hz, 1H), 2.84 (d, J ¼ 3.8 Hz,
1H), 2.45–2.33 (m, 1H), 1.67–1.44 (m, 4H), 0.99 (t, J ¼ 6.8 Hz, 3H), 0.98
(d, J ¼ 6.9 Hz, 3H), 0.93 (d, J ¼ 6.9 Hz, 3H); 13C NMR (CDCl3) d 189.5,
173.6, 69.6, 67.8, 64.1, 45.3, 38.6, 29.0, 18.7, 18.1, 15.0, 14.0;77Se (CDCl3)
d 459.0; MS (ESI) m=z 306.3 [M]þ, 288.0 [M – H2O]þ.
Compound 3g0 (Butyraldehyde, Minor)
1H NMR (CDCl3) d 4.81 (dt, J ¼ 8.2, 3.4 Hz, 1H), 4.45 (dd, J ¼ 9.5,
3.0 Hz, 1H), 4.42 (t, J ¼ 8.9 Hz, 1H), 4.22–4.11 (m, 1H), 3.77 (dd,
J ¼ 17.2, 9.2 Hz, 1H), 3.61 (dd, J ¼ 17.1, 3.0 Hz, 1H), 3.01 (d, J ¼ 4.86,
1H), 2.45–2.35 (m, 1H), 1.72–1.43 (m, 4H), 1.03 (t, J ¼ 6.03 Hz, 3H),
0.99 (d, J ¼ 6.9 Hz, 3H), 0.95 (d, J ¼ 7.0 Hz, 3H); 13C NMR (CDCl3) d
189.6, 173.8, 69.6, 68.3, 64.1, 45.1, 38.8, 29.0, 18.7, 18.1, 15.0, 13.0;
77Se (CDCl3) d 450.6; MS (ESI) m=z 306.3 [M]þ, 288.0 [M – H2O]þ
(MS virtually identical to 3g).
Compound 3h (Isobutyraldehyde, Major)
1H NMR (CDCl3) d 4.77 (dt, J ¼ 8.1, 3.3 Hz, 1H), 4.46 (dd, J ¼ 9.3,
3.0 Hz, 1H), 4.40 (dd, J ¼ 9.3, 8.1 Hz), 3.96 (m, 1H), 3.77 (dd, J ¼ 17.4,

650
L. A. Silks et al.
2.4 Hz, 1H), 3.51 (dd, J ¼ 17.4, 9.9 Hz), 2.43–2.33 (m, 1H), 1.88–1.77
(m, 1H), 1.02 (d, J ¼ 3.9 Hz, 3H), 1.00 (d, J ¼ 3.9 Hz, 3H), 0.96 (d,
J ¼ 6.9 Hz, 3H), 0.91 (d, J ¼ 6.9 Hz, 3H); 13C NMR (CDCl3) d189.5,
174.0, 72.7, 69.6, 64.2, 42.8, 33.3, 29.0, 18.5, 18.2, 17.8, 15.0;77Se (CDCl3)
d 458.4; MS (ESI) m=z 308.0 [M þ H]þ.
Compound 3h0 (Isobutyraldehyde, Minor)
1H NMR (CDCl3) d 4.81 (ddd, J ¼ 8.2, 3.8, 3.0 Hz, 1H), 4.48 (dd,
J ¼ 9.5, 3.0 Hz, 1H), 4.41 (dd, J ¼ 9.5, 8.2 Hz, 1H), 3.93 (quartet of
doublets, J ¼ 10.2, 4.9, 2.1 Hz, 1H), 3.82 (dd, J ¼ 16.5, 10.0 Hz, 1H),
3.58 (dd, J ¼ 16.5, 2.1 Hz, 1H), 3.01 (d, J ¼ 5.0 Hz, 1H), 2.45–2.35 (m,
1H), 1.91–1.81 (m, 1H), 1.05 (d, J ¼ 5.0 Hz, 3H), 1.03 (d, J ¼ 5.0 Hz,
3H), 0.99 (d, J ¼ 7.0 Hz, 3H), 0.94 (d, J ¼ 6.9 Hz, 3H); 13C NMR
(CDCl3) d 189.7, 174.2, 73.4, 69.6, 64.1, 42.3, 33.6, 29.0, 18.5, 18.1,
17.8, 15.0;77Se (CDCl3) d 457.0; MS (ESI) m=z 308.0 [M þ H]þ (MS
virtually identical to 3h).
Compound 3i (Cyclohexane Carboxaldehyde, Major)
1H NMR (CDCl3) d 4.78 (dt, J ¼ 8.1, 3.6 Hz, 1H), 4.47 (dd, J ¼ 9.4,
3.0 Hz, 1H), 4.41 (t, J ¼ 9.4 Hz, 1H), 4.00–3.95 (m, 1H), 3.80 (dd,
J ¼ 17.5, 2.1 Hz, 1H), 3.54 (dd, J ¼ 17.5, 9.6 Hz, 1H), 2.76 (br s, 1H),
2.45–2.34 (m, 1H), 1.94 (d, J ¼ 12.6 Hz, 1H), 1.92–1.70 (m, 4H), 1.58–
1.45 (m, 1H), 1.34–1.05 (m, 5H), 0.98 (d, J ¼ 7.0 Hz, 3H), 0.95 (d,
J ¼ 6.9 Hz); 13C NMR (CDCl3) d 189.5, 174.1, 72.2, 69.6, 64.2, 43.2,
42.9, 29.0, 28.9, 28.4, 26.4, 26.2, 26.1, 18.2, 15.0;77Se (CDCl3) d 460.2;
MS (ESI) m=z 346.0 [M]þ.
Compound 3i0 (Cyclohexane Carboxaldehyde, Minor)
1H NMR (CDCl3) d 4.81 (dt, J ¼ 8.4, 3.3 Hz, 1H), 4.49 (dd, J ¼ 9.6,
3 Hz, 1H), 4.41 (t, J ¼ 8.4 Hz, 1H), 3.95–3.89 (m, 1H), 3.86 (dd,
J ¼ 16.2, 9.9 Hz, 1H), 3.55 (dd, J ¼ 16.2, 1.5 Hz, 1H), 3.01 (d,
J ¼ 4.8 Hz, 1H), 2.46–2.36 (m, 1H), 1.94 (d, J ¼ 12.6 Hz, 1H), 1.85–
1.67 (m, 4H), 1.58–1.46 (m, 1H), 1.34–1.07 (m, 5H), 0.98 (d, J ¼
7.2 Hz, 3H), 0.94 (d, J ¼ 6.9 Hz, 3H); 13C NMR (CDCl3) d 189.7, 174.3,
72.9, 69.6, 64.2, 43.4, 42.4, 29.0, 28.9, 28.4, 26.4, 26.2, 26.1, 18.1,
15.0;77Se (CDCl3) d 455.9; MS (ESI) m=z 346.1 [M]þ (MS virtually
identical to 3i).

Chiral N-Acetyl Selone-Promoted Aldol Reactions
ACKNOWLEDGMENTS
651
We thank the LANL LDRD program (X9DN) and the CDC for partial
support for this work.
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