Beneficial effect of internal hydrogen bonding interactions on the β-fragmentation of primary alkoxyl radicals. Two-step conversion of D-xylo- and D-ribofuranoses into L-threose and D-erythrose, respectively

Article abstract of DOI:10.1021/jo0709551

(Chemical Equation Presented) Primary alkoxyl free radicals were generated from their readily synthesized N-phthalimido derivatives under reductive conditions. Primary alkoxyl radicals derived from their corresponding xylo- and ribofuranose derivatives underwent, exclusively, an unusual β-fragmentation affording L-threose and D-erythrose derivatives, respectively. This occurs because the alkoxyl radical is capable of achieving an internal hydrogen-bonding interaction leading to a stable six-membered ring intramolecular hydrogen-bonded structure. When the hydroxyl group is protected, the β-fragmentation pathway is prevented and the hydrogen atom transfer (HAT) pathway occurs. Computational studies provided strong support for the experimental observations.

Full text of DOI:10.1021/jo0709551

Beneficial Effect of Internal Hydrogen Bonding Interactions on the
â-Fragmentation of Primary Alkoxyl Radicals. Two-Step Conversion
of D-Xylo- and D-Ribofuranoses into L-Threose and D-Erythrose,
Respectively
Lu´ıs Herna´ndez-Garc´ıa, Leticia Quintero, Mario Sa´nchez,* and Fernando Sartillo-Piscil*
Centro de InVestigacio´n de la Facultad de Ciencias Qu´ımicas, BUAP, 14 Sur Esq. San Claudio,
Col. San Manuel, 72570, Puebla, Me´xico
fsarpis@siu.buap.mx
ReceiVed May 10, 2007
Primary alkoxyl free radicals were generated from their readily synthesized N-phthalimido derivatives
under reductive conditions. Primary alkoxyl radicals derived from their corresponding xylo- and
ribofuranose derivatives underwent, exclusively, an unusual â-fragmentation affording L-threose and
D-erythrose derivatives, respectively. This occurs because the alkoxyl radical is capable of achieving an
internal hydrogen-bonding interaction leading to a stable six-membered ring intramolecular hydrogen-
bonded structure. When the hydroxyl group is protected, the â-fragmentation pathway is prevented and
the hydrogen atom transfer (HAT) pathway occurs. Computational studies provided strong support for
the experimental observations.
Introduction
mediated fragmentation of carbohydrates (eq 2),3h,4 internal (and
external) hydrogen atom transfer (eq 3),3a,b,h,i,l,m,5 and radical-
mediated ring closing reactions (eq 4).3j,l,66 Generally, the driving
force for these reactions resides in the formation of the more
Alkoxyl free radicals are very important and highly reactive
intermediates that are present in atmospheric,1 biological,2 and
synthetic processes.3 In synthetic chemistry, alkoxyl radicals
have been employed in many chemical transformations, includ-
ing radical-mediated ring expansion (eq 1),3f,g,i,k,n radical-
(3) (a) Barton, D. H. R.; Beaton, J. M. J. Am. Chem. Soc. 1960, 82,
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* To whom correspondence should be addressed. Tel: +52 2222 2955500
ext 7387. Fax: +52 2222 454293.
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10.1021/jo0709551 CCC: $37.00 © 2007 American Chemical Society
Published on Web 09/27/2007
8196
J. Org. Chem. 2007, 72, 8196-8201

â-Fragmentation of Primary Alkoxyl Radicals
SCHEME 1. Common Alkoxyl Radical Reactions
SCHEME 2. Proposed Reaction
stable alkyl radical.7 Therefore, these reactions are usually
controlled by thermodynamic stability of the formed products,
although solvent effects and intrinsic geometric properties are
also important factors (Scheme 1).8
For example, Houk found by computational methods that
â-fragmentations of some alkoxyl radicals do not always depend
on the stability of the formed alkyl radical and that particular
bond interactions can sometimes slow the rate of â-fragmenta-
tion.9
treated with allyltributyltin, it gave 1,2-O-isopropylidene-L-
threose 24g,11 as a single product in very good yield. Not even
traces of the hydrogen atom transfer (HAT) product 4 were
detected (Scheme 2).
This unexpected result aroused our attention, not only because
of the apparent synthetic importance of the chiral building
blocks, 1,2-O-isopropylidene-L-threose 2,11 but also because new
findings on the â-fragmentation of alkoxyl radicals might be
uncovered. In this regard, Sua´rez and Herna´ndez12 previously
reported â-fragmentation of primary alkoxyl radicals under
oxidative conditions (PhI or DIB in the presence of I2); however,
neither experimental nor theoretical efforts were carried out to
clarify their unusual results.13 Although the scope of this work
did not specifically address their results, we believe that our
results may offer interesting findings not previously considered
in alkoxyl radical chemistry.
First, we needed to know if the presence of the allyltributyltin
caused the unexpected â-fragmentation reaction. To address this
question, the reaction was conducted with only Bu3SnH and a
catalytic amount of AIBN in refluxing benzene, and the result
was identical. We considered that the presence of the internal
free hydroxyl group might be responsible for â-fragmenta-
tion. To probe this, other alkoxyl radical precursors (5,10 8,
and 10) were synthesized from their respective commercially
available carbohydrate precursors applying Kim’s methodology6b
and subsequently treated under different reaction conditions
(Table 1).
Results and Discussion
As part of an ongoing research project on the generation of
primary alkoxyl radicals, we were trying to generate the 1,2-
O-isopropylidenexylofuranose-1-yl radical A (Scheme 2) from
its corresponding radical B in order to test its reactivity with
allyltributyltin (1f3). However, we observed an unexpected
result. Under classical tin conditions (Bu3SnH/AIBN), when
5-N-phthalimido-1,2-O-isopropylidene-R-D-xylofuranose 110 was
(4) (a) Armas, P.; Francisco, C. G.; Suarez, E. Angew. Chem., Int. Ed.
Engl. 1992, 31, 772. (b) Armas, P.; Francisco, C. G.; Suarez, E. J. Am.
Chem. Soc. 1993, 115, 8865. (c) Hernandez, R.; Leon, E. I.; Moreno, P.;
Suarez, E. J. Org. Chem. 1997, 62, 8974. (d) Francisco, C. G.; Freire, R.;
Gonzalez, C. C.; Suarez, E. Tetrahedron: Asymmetry 1997, 8, 1971. (e)
Francisco, C. G.; Martın, C. G.; Suarez, E. J. Org. Chem. 1998, 63, 2099.
(f) Francisco, C. G.; Martın, C. G.; Suarez, E. J. Org. Chem. 1998, 63,
8092. (g) Francisco, C. G.; Leon, E. I.; Martin. P.; Moreno, P.; Rodriguez,
M. S.; Suarez, E. J. Org. Chem. 2001, 66, 6967. (h) Gonzalez, C. C.;
Kennedy, A. R.; Leon, E. I.; Riesco-Fagundo, C.; Suarez, E. Angew. Chem.,
Int. Ed. 2001, 40, 2326. (i) Francisco, C. G.; Gonzales, C. C.; Paz, N. R.;
Suarez, E. Org. Lett. 2003, 5, 4171.
(5) (a) Bruke, S. D.; Kort, M. E.; Strickland, S. M. S.; Organ, H. M.;
Silks, L. A. Tetrahedron Lett. 1994, 35, 1503. (b) Hatakeyama, S.;
Kawamura, M.; Takano, S. J. Am. Chem. Soc. 1994, 116, 4081. (c)
Francisco, C. G.; Freire, R.; Herrera, A. J.; Perez-Martin, I.; Suarez, E.
Org. Lett. 2002, 4, 1959. (d) Crich, D.; Huang, X.; Newcomb, D. Org.
Lett. 1999, 1, 225. (e) Sartillo-Piscil, F.; Vargas, M.; Anaya de Parrodi, C.;
Quintero, L. Tetrahedron Lett. 2003, 44, 3919.
(6) (a) Johns, A.; Murphy, J. A. Tetrahedron Lett. 1988, 29, 837. (b)
Kim, S.; Lee, T. A.; Song, Y. Synlett 1998, 471. (c) Hartung, J.; Hiller,
M.; Schmidt, P. Liebigs Ann. 1996, 1425. (d) Hartung, J.; Hiller, P.; Schmidt,
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Chem. 2000, 1677.
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K. In Free Radicals; Kochi, J. K., Ed.; Wiley-Interscience: New York,
1973; Vol. 2, p 665.
We reasoned that varying the polarity of the solvent (benzene,
THF, and CH3CN) and using a less efficient hydrogen atom
(10) Cruz-Gregorio, S.; Hernandez, L.; Vargas, M.; Quintero, L.; Sartillo-
Piscil, F. J. Mex. Chem. Soc. 2005, 49, 20.
(11) Smith, A. B.; Sulikowski, G. A.; Sulikowski, M. M.; Fujimoto, K.
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(12) (a) Boto, A.; Hernandez, D.; Hernandez, R.; Suarez, E. J. Org. Chem.
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Tetrahedron Lett. 2004, 45, 1559.
(13) They reasoned that â-fragmentation of primary alkoxyl radicals in
carbohydrate chains occurs because the resulting radical is stabilized by
the adjacent oxygen, which under oxidative conditions produces an
oxycarbenium ion.
(8) (a) Bacha, J. D.; Kochi, J. K. J. Org. Chem. 1965, 30, 3272. (b)
Walling, C.; Wagner, P. J. J. Am. Chem. Soc. 1963, 85, 2333. (c) Walling,
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(9) Wilsey, S.; Dowd, P.; Houk, K. N. J. Org. Chem. 1999, 64, 8801.
J. Org. Chem, Vol. 72, No. 22, 2007 8197

Herna´ndez-Garc´ıa et al.
TABLE 1. â-Fragmentation versus HATa
a The reactions were performed in dry and degassed solvent at reflux temperature with 3.0 × 10-3 M of Bu3SnH. Addition time 1h. b Yields determined
after column chromatography.
donor ([(Me3)3Si]3SiH) could provide evidence for the hypoth-
esis of hydroxyl group participation in the â-fragmentation
pathway. As anticipated, 5-N-phthalimido-1,2-O-isopropylidene-
D-ribofuranose 5 afforded 1,2-O-isopropylidene-D-erythrose 614
as a single product when either Bu3SnH or [(Me3)3Si]3SiH was
used (entries 5 and 6, Table 1), very similar as for 1 (entries 1
and 2, Table 1). A dramatic decrease in the yield of the
â-fragmentation products 2 and 6, and subsequent increase in
the yields of hydrogen atom transfer products 4 and 7 was
observed when good hydrogen bond accepting solvents such
as THF and CH3CN were used (entries 3, 4 and 7). Interestingly,
the 5-N-phthalimido-3-O-methyl-1,2-O-isopropylidene-D-xylo-
furanose 8, and the 6-N-phthalimido-1,2:3,4-di-O-isopropy-
lidene-D-galactopyranose 10 yielded only the hydrogen atom
transfer products 9 and 11, respectively, under different reaction
conditions (entries 8-12, Table 1).
In the case of 8, the exclusive formation of the hydrogen
atom transfer product 9 may be due to both (1) a 1,6-internal
hydrogen atom transfer (IHAT) from the methyl group to the
alkoxyl radical followed by hydrogen atom transfer from
Bu3SnH to the respective alkyl radical E and (2) a 1,5-IHAT
from the anomeric hydrogen atom to the alkoxyl radical
followed by HAT from Bu3SnH to the respective alkyl radical
F (Scheme 3).
To demonstrate that 1,5- and 1,6-HAT processes do not
accelerate the formation of the reduction product 9 and
(14) Dhavale, D. D.; Tagliavini, E.; Trombini, C.; Umani-Ronchi, A.
Tetrahedron Lett. 1988, 29, 6163.
8198 J. Org. Chem., Vol. 72, No. 22, 2007

â-Fragmentation of Primary Alkoxyl Radicals
SCHEME 3. Plausible 1,5- and 1,6-HAT Reactions of
Alkoxyl Radical D
SCHEME 5. Hydrogen-Bonding Interactions Favoring the
â-Fragmentation
SCHEME 4. Labeling Experiment
consequently the inhibition of the respective â-fragmentation
product (not shown), we conducted deuterium-labeling experi-
ments. Treatment of the N-phathalimido 8 with n-Bu3SnD under
the same condition reactions as used with n-Bu3SnH or [(Me3)3-
Si]3SiH, it provided reduction product 9, without deuterium
incorporation at methyl group or anomeric position (Scheme
4).15 This result is consistent with the suggestion that internal
hydrogen bonding favors the â-fragmentation of a primary
alkoxyl radical.
Therefore, in the light of above results, the hypothesis of
internal hydroxyl group participation in the â-fragmentation
process seems to be occurring. Accordingly, we propose that
the semi-filled p-orbital (SOMO) of the alkoxyl radicals B and
G (which are generated from N-phathalimide derivatives 1 and
5, respectively) is interacting with the hydrogen atom of the
hydroxyl group, forming, in the case of B, a six-membered boat
conformation, and in the case of G, a six-membered chair
conformation (Scheme 5). Thus, a parallel or pseudoparallel
orientation between the semifilled p-orbitals of B and G and
their respective C4-C5 bonding orbital is achieved, leading to
hyperconjugative stabilization (Scheme 5).
As is shown in Scheme 5, suitable conformations for 1,5-
HAT (B′ and G′) can be prevented by internal hydrogen bonding
interactions. The apparent conformational equilibria for B T
B′ and G T G′ is strongly directed toward B and G structures.
Accordingly, if the overall chair and boat geometries are
retained, these arrangements should lead, as postulated above,
to hyperconjugative stabilization, and consequently, â-fragmen-
tation. Besides considering the participation of hydrogen bond
donation to the alkoxyl radical center, the HAT from Bu3SnH
or [(Me3)3Si]3SiH can also be prevented (Scheme 5).
It is important to mention that in atmospheric studies the
participation of internal hydrogen bond donation to alkoxyl or
peroxyl radical centers as a common motif in â-hydroxyperoxyl
and â-hydroxyalkoxyl radicals have been postulated.16 Further-
more, to the best of our knowledge, there have been no reports
where internal hydrogen bonding interaction of an alkoxyl free
radical is invoked as the driving force for a â-fragmentation
process of an alkoxyl free radical. However, it has been reported
that a large acceleration of â-fragmentation of alkoxyl radicals
can be favored by intermolecular hydrogen bonding.17 Therefore,
we were obliged to use quantum chemical methods to provide
evidence in support of the hypothesis above.
Computational Methods
The geometry of each stationary point was fully optimized using
the Gaussian 03 software package18 with the UHF/B3LYP/6-31+G-
(d) method.19 All stationary points were characterized as minima
by calculating the harmonic vibrational frequencies using analytical
second derivatives. All of structures were visualized using the
Chemcraft 1.5 program. To save computational time, the two methyl
(16) (a) Dibble, T. S. J. Phys. Chem. A 2004, 108, 2199 and references
therein. (b) Dibble, T. S.; Pham, T. Phys. Chem. Chem. Phys. 2006, 8, 456
and references therein.
(17) (a) Mendenhall, G. D.; Stewart, L. C.; Scaiano, J. C. J. Am. Chem.
Soc. 1982, 104, 5109. (b) Avila, D. V.; Brown, C. E.; Ingold, K. U.; Lusztyk,
J. J. Am. Chem. Soc. 1993, 115, 466.
(18) Frisch, M. J. T. G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M.
A.; Cheeseman, J. R.; Montgomery Jr., J. A.; Vreven, T.; Kudin, K. N.;
Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.;
Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.;
Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.;
Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li,
X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.;
Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.;
Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.;
Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich,
S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A.
D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A.
G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.;
Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham,
M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.;
Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian,
Revision B.05 ed.; Gaussian, Inc.: Wallingford, CT, 2004.
(15) It is important to mention that 35% of deuterium incorporation at
anomeric position occurs when more diluted conditions (1.4 × 10-3 M)
are used and addition of Bu3SnD is very slow (3 h).
(19) (a) Krisnan, R.; Binkley, J. S.; Seeger, R.; Pople, J. A. J. Chem.
Phys. 1980, 72, 650. (b) Becke, A. D. J. Chem. Phys. 1993, 98, 5648. (c)
Lee, C.; Yang, W.; Parr, R. G. Phys. ReV. B 1988, 37, 785.
J. Org. Chem, Vol. 72, No. 22, 2007 8199

Herna´ndez-Garc´ıa et al.
FIGURE 1. Optimized structures for B, G, and J.
FIGURE 3. Electron-wave distribution SOMO for B, G, and J.
TABLE 2. NBO Analysis (Second-Order Perturbation Theory) of
Hyperconjugative Interactions, nπOfσ*C4-C5 and nπOfσ*H-O, in
Free Radical Structures B, G, and J
donor orbital acceptor orbital E(2) (kcal/mol) ꢀi - ꢀj (au) Fij (au)
structure B
nπO
nπO
nπO
σ*C4-C5
σ*C5-H
σ*H-O
5.10
4.93
1.49
0.68
0.72
0.77
0.074
0.076
0.043
structure G
nπO
nπO
σ*C4-C5
σ*C5-H
σ*H-O
4.73
4.67
0.62
0.69
0.71
0.82
0.072
0.073
0.029
nπO
structure J
nπO
nπO
σ*C5-H
σ*C4-C5
4.91
4.64
0.73
0.75
0.076
0.074
interaction leading now to a different conformation (chair). In
addition, it is important to notice that the C4-C5 bond length in
the structures that lack the H-bond have an average value of 1.527
Å, whereas where the structures with a H-bond is present, the C4-
C5 bond has an average value of 1.577 Å. This reveals that the
C4-C5 bond is debilitated by the hydrogen-bonding interactions.
The natural bond orbital (NBO) analysis20 clearly shows the
difference of the electronic distribution for the SÃΜÃ for radicals
B, G, and J. Note that radicals B and G have very similar electronic
distribution onto oxygen radical, thus permitting free movement
toward the C4-C5 antibonding orbital and thereby providing further
support of the hyperconjugative interactions that favor the â-frag-
mentation process (see Figure 3 and Table 2).
Essentially, Table 2 shows selected interactions between filled
(donor) Lewis-type NBOs and empty (acceptor) non-Lewis NBOs
and estimating their energetic importance by second-order perturba-
tion theory. In this case, Table 2 summarizes E(2) energies between
the oxygen lone pair nπO, from the alkoxyl radical with C4-C5,
C5-H, or H-O antibonds. It is noteworthy that higher values for
structures B and G, are for nπOfσ*C4-C5 interactions, while the
higher value of E(2), in structure J is for the nπOfσ*C5-H
interaction. This explains the elongation of C4-C5 bonds in
structures B and G discussed above.
FIGURE 2. Potential energy surface for radical B.
groups of the 1,2-O-isopropylidene moiety of radicals B, G, and J
were replaced by two hydrogen atoms. Free radical J which contains
the C-3 hydroxyl group protected represents a good model for
comparative investigation.
Thus, electronic structures B and G have shown the intramo-
lecular hydrogen bonding with a distance of 2.22 Å and 2.37 Å for
B and G, respectively (Figure 1). Additional important information
extracted from this theoretical calculation is the C4-C5 bond
distance for the radicals B, G, and J. As in case of B and G where
the internal hydrogen bonding is present, so does hyperconjugative
interactions, bond distances are considerably longer (1.585 Å for
B and 1.576 Å for G) than radical J (1.529 Å). This means that
C4-C5 bond distances for radical B and radical G are 0.056 Å
and 0.047 Å, respectively, longer than radical J; therefore, this
provides additional proof for the favorable â-fragmentations in B
and G.
Additionally, we computed structures and energies of other
conformers for radical B in order to demonstrate that the hydrogen-
bonded structure possesses a local minimum and thereby the driving
force for â-fragmentation. Therefore, by computing the potential
energy surface for radical B (at the same level of theory) along the
C4-C5 bond, we found two other minima (b and c, Figure 2).
Interestingly, rotamer b showed another internal hydrogen-bonding
(20) (a) Foster, P.; Weinhold, F. J. Am. Chem. Soc. 1980, 102, 7211.
(b) Reed, A. E.; Weinhold, F. J. Chem. Phys. 1983, 78, 4066. (c) Reed, A.
E.; Weihstock, R. B.; Weinhold, F. J. Chem. Phys. 1985, 83, 735. (d) Reed,
A. E.; Weinhold, F. J. Chem. Phys. 1985, 83, 1736. (e) Reed, A. E.; Currtis,
L. A.; Weinhold, F. Chem. ReV. 1988, 88, 899.
8200 J. Org. Chem., Vol. 72, No. 22, 2007

â-Fragmentation of Primary Alkoxyl Radicals
Although in this work it has been demonstrated that â-fragmen-
tation of a primary alkoxyl radical is favored by an internal
hydrogen-bonding interaction between the semifilled p-orbital
(rather than the lone pair of the alkoxyl radical) and a hydroxyl
group, the previous â-fragmentation of a primary alkoxyl radical
observed by Suarez and Herna´ndez cannot be explained on the basis
of the present study. Evidently, the driving force that governs the
â-fragmentation in our reductive conditions is completely different
to that of their oxidative conditions. However, from a mechanistic
point of view, this â-fragmentation of primary alkoxyl radicals under
reductive conditions contradicts the previous assumption which
postulated that the driving force for â-fragmentation of a primary
alkoxyl radical in carbohydrate chains resides in the formation of
a stable alkyl radical with an adjacent oxygen which eventually
form an oxycarbenium ion.12
furanose 1 (100 mg, 0.29 mmol) was dissolved in dry and degassed
benzene (50 mL), and the resulting solution was heated at 80 °C
before addition of a solution of Bu3SnH (112 mg, 0.39 mmol) and
AIBN (20 mg) in dry and degassed benzene (50 mL) dropwise
(1 h approximately). After the addition was complete, the reaction
mixture was stirred for 4 h and the solvent was removed under
reduced pressure. The residue was purified by column chromatog-
raphy on silica gel (230-400 mesh) with ether-EtOAc (v/v ) 3/1)
to afford 1,2-O-isopropylidene-D-threose 24g,11 in 89% yield as white
solid: mp ) 84-85 °C; [R]D ) +16.6 (c 1.0, CHCl3) [lit.4g [R]D
1
) +13.4 (c 0.8)]; H NMR (400 MHz, CDCl3) δ 1.34 (s, 3H),
1.47 (s, 3H), 3.87 (dd, 1H, J ) 9.6, 0.8 Hz), 4.08 (dd, 1H, J )
10.4, 3.2 Hz), 4.26 (d, 1H, J ) 2.8 Hz), 4.50 (d, 1H, J ) 3.6 Hz),
5.95 (d, 1H, J ) 3.6 Hz); 13C NMR (100 MHz, CDCl3) δ 26.1,
26.6, 72.8, 77.3, 84.9, 105.1, 111.9.
In summary, a novel and highly efficient two step conversion
of D-xylo and D-ribofuranose derivatives into L-threose and D-
erythreose derivatives, respectively, is reported. The key step for
these syntheses is a very unusual â-fragmentation of primary alkoxyl
radicals derived from their corresponding N-phthalimido derivatives.
Interestingly, internal hydrogen bonding has shown to be the driving
force for such reactions.
Acknowledgment. We thank Dr. Rodney A Fernandez of
the Indian Institute of Technology, Bombay, for helpful dis-
cussions. This work was supported by PROMEP-BUAP and
I.Q.-UNAM.
Supporting Information Available: Experimental procedures,
analytical data, copies of 1H NMR and 13NMR spectra for unknown
compounds, and Cartesian coordinates for B, G, and J. This material
is available free of charge via the Internet at http://pubs.acs.org.
Experimental Section
General Procedure for the Synthesis of L-Threose and
D-Erythrose Derivatives 2 and 6, Respectively. The â-Fragmen-
tation Protocol. 5-N-Phthalimido-1,2-O-isopropylidene-R-D-xylo-
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