Rh-catalyzed formation of dioxolanes from α-alkyl diazoesters: Diastereoselective cycloadditions of carbonyl ylides with selectivity over β-hydride elimination

Article abstract of DOI:10.1021/jo702308f

(Chemical Equation Presented) Described here is a diastereoselective Rh-catalyzed method for the preparation of dioxolanes from α-alkyl- α-diazoesters. This represents the first general method for generating carbonyl ylides from α-diazoesters that possess β-hydrogens, as such diazo compounds typically give rise to alkenes via β-hydride elimination. Subsequent cycloaddition with aromatic aldehydes gives tetrasubstituted dioxolanes with unusually high diastereoselectivity. A model is set forth to explain the diastereoselectivity of the cycloaddition.

Full text of DOI:10.1021/jo702308f

Rh-Catalyzed Formation of Dioxolanes from r-Alkyl Diazoesters:
Diastereoselective Cycloadditions of Carbonyl Ylides with Selectivity
over â-Hydride Elimination
Andrew DeAngelis, Patricia Panne, Glenn P. A. Yap, and Joseph M. Fox*
Brown Laboratories, Department of Chemistry and Biochemistry, UniVersity of Delaware,
Newark, Delaware 19716
jmfox@udel.edu
ReceiVed October 24, 2007
Described here is a diastereoselective Rh-catalyzed method for the preparation of dioxolanes from R-alkyl-
R-diazoesters. This represents the first general method for generating carbonyl ylides from R-diazoesters
that possess â-hydrogens, as such diazo compounds typically give rise to alkenes via â-hydride elimination.
Subsequent cycloaddition with aromatic aldehydes gives tetrasubstituted dioxolanes with unusually high
diastereoselectivity. A model is set forth to explain the diastereoselectivity of the cycloaddition.
SCHEME 1. Issues of Chemo- and Diastereoselectivity for
Rh-Catalyzed Generation and Reactions of Carbonyl Ylides
Introduction
The transition metal-catalyzed reaction of R-diazoesters with
aldehydes is a well-established route to substituted 1,3-diox-
olanes.1,2 This 3-component transformation proceeds through a
putative3 carbonyl ylide intermediate, and is an attractive method
for the rapid assembly of molecular complexity. However,
realizing chemo- and diastereoselectivity is a challenge for
intermolecular reactions of carbonyl ylides, as is illustrated for
rhodium carbene 1 and carbonyl ylide 2 in Scheme 1. Thus,
ylide 2 can cyclize to epoxides 34 (two possible diastereomers)
(1) Reviews on carbonyl ylide cycloadditions: (a) Padwa, A.; Horn-
buckle, S. F. Chem. ReV. 1991, 91, 263. (b) Doyle, M. P.; McKervey, M.
A.; Ye, T. Modern Catalytic Methods for Organic Synthesis with Diazo
Compounds; John Wiley: New York, 1998. (c) Adams, J.; Spero, D. M.
Tetrahedron 1991, 47, 1765.
(2) (a) de March, P.; Huisgen, R. J. Am. Chem. Soc. 1982, 104, 4953.
(b) Doyle, M. P.; Forbes, D. C.; Protopopova, M. N.; Stanley, S. A.;
Vasbinder, M. M.; Xavier, K. R. J. Org. Chem. 1997, 62, 7210. (c) Russell,
A. E.; Brekan, J.; Gronenberg, L.; Doyle, M. P. J. Org. Chem. 2004, 69,
5269. (d) Jiang, B.; Zhang, X.; Luo, Z. Org. Lett. 2002, 4, 2453. (e) Nair,
V.; Mathai, S.; Mathew, S. C.; Rath, N. P. Tetrahedron 2005, 61, 2849. (f)
Lu, C.-D.; Chen, Z.-Y.; Liu, H.; Hu, W.-H.; Mi, A.-Q. Org. Lett. 2004, 6,
3071. (g) Alt, M.; Mass, G. Tetrahedron 1994, 50, 7435. (h) Wenkert, E.;
Khatuya, H. Tetrahedron Lett. 1999, 40, 5439. For an elegant approach to
controlling diastereoselective reactions of carbonyl ylides with a pendant
Co-cluster, see: (i) Skaggs, A. J.; Lin, E. Y.; Jamison, T. F. Org. Lett.
2002, 4, 2277.
or undergo [3+2]-cycloaddition with a second aldehyde equiva-
lent to yield dioxolanes 42 (four possible diastereomers). For
R-alkyl diazoesters, the scenerio is further challenged by
intramolecular â-hydride elimination to give alkenes (5)sa side
reaction that often precludes intermolecular chemistry of
rhodium carbenoids.5 Navigating these divergent reaction
pathways to selectively produce a single product has proven
challenging.
Examples of highly diastereoselective transformations that
produce 1,3-dioxolanes from aldehydes and diazoesters are
unusual. Jiang and co-workers have observed that the Rh2-
(OAc)4-catalyzed reactions of aldehydes with methyl R-diaz-
(3) There is evidence that some carbonyl ylides may be associated to
Rh-carbenes.2b,12
(5) For the Rh-catalyzed preparation of (Z)-alkenes via â-hydride
elimination, see: Taber, D. F.; Herr, R. J.; Pack, S. K.; Geremia, J. M. J.
Org. Chem. 1996, 61, 2908 and references cited therein.
(4) (a) Doyle, M. P.; Hu, W.; Timmons, D. J. Org. Lett. 2001, 3, 933.
(b) Davies, H. M. L.; DeMesse, J. Tetrahedron Lett. 2001, 42, 6803.
10.1021/jo702308f CCC: $40.75 © 2008 American Chemical Society
Published on Web 01/12/2008
J. Org. Chem. 2008, 73, 1435-1439
1435

DeAngelis et al.
TABLE 1. Optimization of Conditionsd
otrifluoromethylacetate leads to only one diastereomer in a
majority of the cases studied.2d Diastereoselectivity is much
lower with other diazoesters, and in some cases all four of the
possible dioxolane diastereomers are produced.2 Even with
diazomalonate, where only two diastereomers are possible, both
diastereomers are usually6 formed.
Padwa has elegantly demonstrated that intramolecular reac-
tions between carbonyls and putative Rh-carbenes can produce
carbonyl ylides with selectivity over â-hydride elimination.7
However, no examples of intermolecular Rh-catalyzed reactions
to form carbonyl ylides with selectivity over â-hydride elimina-
tion were known to us. Our group recently described conditions
for two intermolecular Rh-catalyzed transformations of R-alkyl
diazoesters that tolerate â-hydrogens: alkyne cyclopropenation
and a tandem alkyne insertion/Bu¨chner cascade to give dihy-
droazulenes.8 Low reaction temperatures (-78 °C)9 and the use
of sterically demanding carboxylate ligands10 [dirhodium tet-
rapivaloate (Rh2Piv4) or dirhodium tetra(triphenylacetate) (Rh2-
TPA4)] were key to the success of these reactions. In contrast,
dirhodium tetraoctanoate (Rh2Oct4) led primarily to alkenes via
â-hydride elimination.
Described herein is a Rh-catalyzed method for generating
putative carbonyl ylides from R-alkyl diazoesters with selectivity
over â-hydride elimination. The putative carbonyl ylides are
unusually reactive, and they combine with aromatic aldehydes
at -78 °C to produce dioxolane products. Subsequent cycload-
dition reactions with aromatic aldehydes proceed with excellent
diastereoselectivity to give predominantly one dioxolane prod-
uct.
a Regardless of the catalyst that was employed, the same level of
diastereoselectivity ((3%) was measured for all of the reactions studied at
-78 °C. b Racemic 4a was obtained from the reaction with Rh2(S-DOSP)4.
c Determination of the dr by 1H NMR analysis was prevented by an impurity
with 1H NMR resonances that overlapped with those of the minor
diastereomer. d Ethyl R-diazobutanoate was added by syringe pump over a
3 h period. Yields and diastereomer ratios were determined by 1H NMR
analysis.
Results and Discussion
effective catalyst in terms of yield and selectivity (56% yield,
11:1 dioxolane/â-hydride elimination; Table 1, entry 4). While
other carboxylate ligands were less effective than pivalate, the
steric effect of the ligand was not as dramatic as was observed
for cyclopropenation.8 Thus, 4a was still produced in 42% yield
with Rh2Oct4sa catalyst that was completely ineffective for
cyclopropenation. Temperature was a critical variable for
achieving selective dioxolane formation. At -78 °C, the
reactions are efficient. However, compound 4a was formed only
in low yield (11%) when the Rh2Piv4-catalyzed reaction of ethyl
R-diazobutanoate with benzaldehyde was carried out at rt (Table
1, entry 5).
The selectivity of reactions of that involve carbonyl ylides
can sometimes be altered by the nature of the Rh-catalyst, and
in those cases it has been proposed that the cycloadditions
involve metal-complexed dipoles.2b,12 For the results presented
in Table 1, it is proposed that the Rh-catalyst does not influence
the final cycloaddition to form 4a. Within the error of measure-
ment by 1H NMR integration ((3%), the same level of
diastereoselectivity (90:10 dr) was observed for all of the
reactions studied at -78 °C irrespective of the catalyst that was
used. Davies’ Rh2(S-DOSP)4 gave racemic 4a in 23% yield and
in 90:10 dr. The lack of catalyst influence on diastereoselectivity
and the lack of asymmetric induction by the chiral catalyst
support the hypothesis that the reaction to form 4a involves
the cycloaddition of a “free” ylide.
A variety of rhodium(II) complexes were screened in the
reaction of ethyl R-diazobutanoate with benzaldehyde (3 equiv)
at -78 °C to form dioxolane 4a. Competing reactions included
â-hydrogen elimination to give cis-ethylcrotonate 5a and the
formation of azine 611 as a single isomer (Table 1). Epoxides
were not observed as side products. Rh2Piv4 was the most
(6) The Rh2OAc4-catalyzed reaction of diazomalonate, phenanthrene-
quinone and aldehydes gives single diasteromers.2e
(7) (a) Padwa, A.; Zhang, Z. J.; Zhi, L. J. Org. Chem. 2000, 65, 5223.
(b) Padwa, A.; Kulkarni, Y. S.; Zhang, Z. J. Org. Chem. 1990, 55, 4144.
(c) Padwa, A.; Herzog, D. L.; Chinn, R. L. Tetrahedron Lett. 1989, 30,
4077. (d) Padwa, A.; Deen, D. C.; Hertzog, D. L.; Nadler, W. R.; Zhi, L.
Tetrahedron 1992, 48, 7565.
(8) (a) Panne, P.; Fox, J. M. J. Am. Chem. Soc. 2007, 129, 22. For other
examples of Rh-catalyzed transformations that tolerate â-hydrogens, see
refs 9 and 10.
(9) Hashimoto and co-workers had noted in enantioselective, intramo-
lecular C-H insertions that higher selectivities over â-hydride elimination
were obtained at -78 °C: Minami, K.; Saito, H.; Tsutsui, H.; Nambu, H.;
Anada, M.; Hashimoto, S. AdV. Synth. Catal. 2005, 347, 1483.
(10) For O-H insertion or intramolecular C-H insertions, modest
improvements in selectivity over â-hydride elimination had been observed
with Rh2(Piv)4 or Rh2(9-adamantoate)4: (a) Cox, G. G.; Haigh, D.; Hindley,
R. M.; Miller, D. J.; Moody, C. J. Tetrahedron Lett. 1994, 35, 3139. (b)
Taber, D. F.; Joshi, P. V. J. Org. Chem. 2004, 69, 4276. (c) Taber, D. F.;
Hennessy, M. J.; Louey, J. P. J. Org. Chem. 1992, 57, 436.
(11) The stereochemistry of 6 was not assigned. For precedent for the
formation of azines in Rh-catalyzed reactions of diazocompounds, see ref
10c and: (a) Petrukhina, M. A.; Andreini, K. W.; Walji, A. M.; Davies, H.
M. L. J. Chem. Soc., Dalton Trans. 2003, 4221. (b) Ohno, M.; Itoh, M.;
Umeda, M.; Furuta, R.; Kondo, K.; Eguchi, S. J. Am. Chem. Soc. 1996,
118, 7075. (c) Ace, K. W.; Husain, N.; Lathbury, D. C.; Morgan, D.
Tetrahedron Lett. 1995, 36, 8141. (d) Pomerantz, M.; Levanon, M.
Tetrahedron Lett. 1990, 31, 4265. (e) Doyle, M. P.; Bagheri, V.; Wandless,
T. J.; Harn, N. K.; Brinker, D. A.; Eagle, C. T.; Loh, K.-L. J. Am. Chem.
Soc. 1990, 112, 1906.
(12) (a) Padwa, A. J. Organomet. Chem. 2005, 690, 5533. (b) Hodgson,
D. M.; Stupple, P. A.; Pierard, F. Y. T. M.; Labande, A. H.; Johnstone, C.
Chem. Eur. J. 2001, 7, 4465. (c) Hodgson, D. M.; Pierard, F. Y. T. M.;
Stupple, P. A. Chem. Soc. ReV. 2001, 30, 50. (d) Doyle, M. P.; Forbes, D.
C. Chem. ReV. 1998, 98, 911. (e) Kitigaki, S.; Anada, M.; Kataoka, O.;
Matsuno, K.; Umeda, C.; Watanabe, N.; Hashimoto, S.-i. J. Am. Chem.
Soc. 1999, 121, 1417.
1436 J. Org. Chem., Vol. 73, No. 4, 2008

Formation of Dioxolanes from R-Alkyl Diazoesters
TABLE 2. Chemoselective, Diastereoselective Dioxolane Synthesisd
SCHEME 2. Acetal Hydrolysis Provides Vicinal Diols
improved significantly upon increasing to 5 equiv of aldehyde.
Dioxolane formation is successful with R-diazopropionate,
R-diazobutanoate, and R-diazohydrocinnamate. The success of
R-diazohydrocinnimate is notable given the susceptiblility of
benzylic hydrogens to undergo â-hydride elimination.
Dioxolane products were obtained in 53-78% yield. The
method is broadly applicable to aromatic aldehydes. Functional
groups that are tolerated on the benzaldehyde component include
alkyl, alkoxy, halogen, nitro, and ethynyl groups. Ortho-
substituted benzaldehydes, â-naphthaldehyde, and 2-thiophen-
ecarboxaldehyde are also viable reaction partners. We also know
of several limitations to the method described in Table 2: ethyl
R-diazoisovalerate led only to ethyl 3-methylcrotonatesthe
product of â-hydride elimination. Complex mixtures were
obtained in the reactions of ethyl R-diazopropionate with
cinnamaldehyde, octanal, or acetaldehyde. The reaction of ethyl
R-diazopropionate with N-lauroylindole-3-carboxaldehyde was
also unsuccessful and led to a complex mixture.
For each reaction described in Table 2, the major product
was assigned as the diastereomer with the aryl groups and the
ester situated on the same face of the dioxolane ring; the minor
diasteromer was assigned to have the opposite stereochemistry
at C-4. For the syntheses of 4p-t, the diastereomer ratios were
less than 90:10 with ethyl R-diazohydrocinnamate. Previously,
Doyle and co-workers demonstrated that sterically demanding
esters gave improved diastereoselectivity in dioxolane formation
from carbonyl ylides.2b Accordingly, we investigated the
reactivity of tert-butyl R-diazohydrocinnamate. With this modi-
fication, it was possible to attain >90% diastereoselectivity for
all but one of the entries (4t) in Table 2, and in the preparations
of several derivatives [4b, 4e, 4i, 4p(tBu), and 4s(tBu)] only
the major diastereomer could be detected by 1H NMR. Because
2-aryl-1,3-dioxolanes can be hydrolyzed, the described method
constitutes a stereoselective synthesis of Vicinal diols. Thus,
dioxolane 4b was converted to diol 7 in 86% yield under acidic
conditions as shown in Scheme 2.
1
Stereochemical assignments were made on the basis of H
NMR analysis and X-ray crystal structures for the major
diastereomers of 4b, 4k, 4j, 4o, 4r (R′ ) Et), and 4s (R′ ) Et),
and for the minor diastereomers of 4r (R′ ) Et) and 4s (R′ )
Et). A model that is consistent with the observed diastereose-
lectivity is proposed in Figure 1. The major product is proposed
to arise from endo approach of the aldehyde to ylide conformer
A, and the minor diastereomer from endo approach to conformer
B.
The cycloadditions of carbonyl ylides to form dioxolanes are
facile at -78 °C. To prove that the cycloaddition reactions were
completed at -78 °C, and not while the reactions were being
warmed to rt, the following experiment was conducted: 5 min
after the addition of ethyl R-diazohydrocinnamate to the solution
of Rh2Piv4/4-chlorobenzaldehyde (4 equiv) was completed, a
cold (-78 °C) solution of 4-fluorobenzaldehyde (4 equiv) in
CH2Cl2 was added. The mixture was then allowed to warm to
a The detection threshold for NMR analysis was considered to be 5%.
b The isolated yield of 4a was slightly lower than the yield measured by
1H NMR shown in Table 1. The dr (95:5) measured for 4a when 4 equiv
of benzaldehyde was used (this table) was slightly higher than that measured
when 3 equiv of benzaldehyde was used (Table 1). c Isolated as a mixture
of two diastereomers. d Yields represent isolated yields (average of 2 runs)
of the major diastereomer, unless noted otherwise. Diastereomer ratios were
1
1
determined by H NMR analysis.
rt. Analysis of the crude H NMR indicated that 4m was the
only dioxolane product; 4l was not detected, nor were “crossed”
dioxolane products (Scheme 3). The experiment implies that
the ylide had completely reacted prior to addition of 4-fluo-
robenzaldehyde.
Optimized conditions for dioxolane formation were applied
to a variety of aldehydes, as shown in Table 2. Highest yields
were obtained with 4 equiv of aldehyde; the yield was not
J. Org. Chem, Vol. 73, No. 4, 2008 1437

DeAngelis et al.
diastereoselectivity. Rh2Piv4 is the optimal catalyst for the
transformations, and it is essential to carry out the reactions at
low temperature (-78 °C) in order to achieve high yield and
diastereoselectivity. A model is set forth to explain the diaste-
reoselectivity of the cycloaddition based on an endo transition
state.
FIGURE 1. Proposed model to explain diastereoselectivity.
Experimental Section
SCHEME 3. “Crossover” Experiment Demonstrates That
the 1,3-Dipolar Cycloaddition Had Taken Place at -78 °C,
and Not While the Reaction Warmed to Room Temperature
Representative Procedures for Dioxolane Formation: 2â,5â-
Di(4-fluorophenyl)-4â-ethoxycarbonyl-4R-ethyl-1,3-dioxolane (4g).
A dry round-bottomed flask was charged with Rh2(piv)4 (2 mg,
0.004 mmol) and the flask was evacuated and filled with nitrogen.
Anhydrous CH2Cl2 (5 mL) and 4-fluorobenzaldehyde (332 mg, 2.68
mmol) were added, and the flask was cooled by a bath of dry ice/
acetone. Ethyl 2-diazobutanoate (95 mg, 0.67 mmol) was dissolved
in 3 mL of anhydrous CH2Cl2 and added to the reaction mixture
via syringe pump at a rate of 1 mL/h. Following addition, the
reaction mixture was allowed to warm to room temperature and
mesitylene (80 mg, 0.67 mmol) was added. 1H NMR analysis was
then performed and the diastereomer ratio was determined to be
>95:5. The solvent was then removed and the residue was
chromatographed on silica gel with 1-5% ethyl acetate/hexanes
as the eluent to give 168 mg (70%) of the title compound as a
clear oil. A similar experiment gave the title compound in 61%
yield. 1H NMR (CDCl3, 400 MHz) δ 7.85 (m, 2H), 7.35 (m, 2H),
7.14 (m, 2H), 7.03 (m, 2H), 6.13 (s, 1H), 4.99 (s, 1H), 3.77-3.88
(m, 1H), 3.52-3.62 (m, 1H), 2.20-2.31 (m, 1H), 1.88-2.01 (m,
1H), 1.06 (t, J ) 7.2 Hz, 3H), 0.94 (t, J ) 7.3 Hz, 3H); 13C NMR
1
(CDCl3, 100 MHz) δ 170.5 (u), 163.9 (u) (d, J(CF) ) 246 Hz),
163.0 (u) (1J(CF) ) 246 Hz), 132.4 (u) (d, 4J(CF) ) 3 Hz), 131.2
(u) (d, 4J(CF) ) 3 Hz), 129.9 (dn) (d, 3J(CF) ) 8 Hz), 128.2 (dn)
(d, 3J(CF) ) 8 Hz), 115.5 (dn) (d, 2J(CF) ) 21 Hz), 115.2 (dn) (d,
2J(CF) ) 22 Hz), 103.5 (dn), 89.0 (u), 87.1 (dn), 61.1 (u), 29.0
(u), 13.7 (dn), 8.8 (dn); IR (neat, cm-1) 2967, 1736, 1607, 1511,
1346, 1225, 1054, 1012, 832; HRMS-ESI m/z [M + Na] calcd for
C20H20O4F2Na 385.1227, found 385.1241.
Carbonyl ylides derived from R-alkyl-R-diazoesters are
unusual because they form and react productively at -78 °C.
Under similar conditions (-78 °C) to those reported in Table
2, ethyl diazoacetate and benzaldehyde give only diethyl maleate
and diethyl fumerate. The sense of diastereoselectivity is also
unusual. Endo transition states via conformer B (Figure 1) have
been proposed for the reactions of carbonyl ylides derived from
methyl R-trimethylsilyl-R-diazoacetate,2g methyl R-trifluorom-
ethyl-R-diazoacetate,2d and methyl R-phenyl-R-diazoacetate.2f
The reason that the reactions of carbonyl ylides derived from
R-alkyl-R-diazoesters apparently arise from conformer A may
be related to steric considerations. An empirical observation
from Table 2 is that the diastereoselectivity is highest when
the alkyl substitutent is small and the ester substitutent is large.
For example, the ethyl ester 4c (R ) Me) is produced with
94:6 dr, whereas the ethyl esters 4f (R ) Et) and 4r(Et) (R )
Bn) are produced in 90:10 and 86:14 dr, respectively. Thus,
the increase in the size of the R-alkyl substitutent (Bn > Et >
Me) is accompanied by a decrease in diastereoselectivity (Me
> Et > Bn). This trend can be countered by increasing the size
of the ester substitutent. Thus, t-Bu ester 4r(t-Bu) (R ) Bn) is
formed with 94:6 dr. Therefore, these observations are consistent
with prior observations in the literature that carbonyl ylides with
relatively large R-alkyl substitutents (Ph,2f TMS,2g CF32d) are
controlled by endo approach via conformer B.
2â,5â-Di(4-nitrophenyl)-4â-ethoxycarbonyl-4R-benzyl-1,3-di-
oxolane (4r). A dry round-bottomed flask was charged with Rh2-
(piv)4 (1 mg, 0.003 mmol) and the flask was evacuated and filled
with nitrogen. Anhydrous CH2Cl2 (5 mL) and 4-nitrobenzaldehyde
(302 mg, 2.00 mmol) were added, and the flask was cooled by a
bath of dry ice/acetone. Ethyl 2-diazohydrocinnamate (102 mg, 0.50
mmol) was dissolved in 3 mL of anhydrous CH2Cl2 and added to
the reaction mixture via syringe pump at a rate of 1 mL/h. Following
addition, the reaction mixture was allowed to warm to room
1
temperature and mesitylene (60 mg, 0.50 mmol) was added. H
NMR analysis was then performed and the diastereomer ratio was
determined to be 84:16. The solvent was then removed and the
residue was chromatographed on silica gel with 5-8% ethyl acetate/
hexanes as the eluent to give 139 mg (59%) of the title compound
as a white solid, mp 55-59 °C. Also isolated was 26 mg (11%) of
4r (minor diastereomer) as a white solid. A similar experiment gave
4r in 54% yield.
Spectoscopic data for 4r: 1H NMR (CDCl3, 400 MHz, δ): 8.37
(d, J ) 9.0 Hz, 2H), 8.28 (d, J ) 9.0 Hz, 2H), 7.97 (d, J ) 9.0 Hz,
2H), 7.62 (d, J ) 8.9 Hz, 2H), 7.32-7.46 (m, 5H), 5.98 (s, 1H),
5.27 (s, 1H), 3.65 (m, 1H), 3.47 (m, 1H), 3.45 (d, J ) 14.7 Hz,
1H), 3.30 (d, J ) 14.7 Hz, 1H), 0.87 (t, J ) 7.3 Hz, 3H); 13C
NMR (CDCl3, 100 MHz) δ 169.5 (u), 148.9 (u), 148.2 (u), 142.6
(u), 141.9 (u), 134.5 (u), 130.9 (dn), 130.8 (dn), 128.6 (dn), 127.5
(dn), 127.4 (dn), 123.7 (dn), 123.6 (dn), 103.2 (dn), 88.2 (u), 84.8
(dn), 61.5 (u), 40.2 (u), 13.7 (dn); IR (neat, cm-1) 2364, 2343,
1736, 1520, 1497, 1439, 1345, 1291, 1200, 1085, 1013, 851, 746,
697. Anal. Calcd for C25H22N2O8: C 62.76, H 4.63, N 5.86, O
26.75. Found: C 62.77, H 4.71, N 5.74, O 26.49.
In summary, general conditions are described for the Rh-
catalyzed generation of carbonyl ylides from R-diazoesters that
possess â-hydrogens. Subsequent cycloaddition with aromatic
aldehydes gives tetrasubstituted dioxolanes with unusually high
1438 J. Org. Chem., Vol. 73, No. 4, 2008

Formation of Dioxolanes from R-Alkyl Diazoesters
Spectroscopic data for 4r (minor diastereomer): 1H NMR
(CDCl3, 400 MHz) δ 8.39 (d, J ) 8.5 Hz, 2H), 8.37 (d, J ) 8.5
Hz, 2H), 7.88 (d, J ) 8.5 Hz, 2H), 7.71 (d, J ) 8.5 Hz, 2H), 7.22
(m, 3H), 7.09 (m, 2H), 6.18 (s, 1H), 5.54 (s, 1H), 4.26 (m, 2H),
2.60 (d, J ) 13.7 Hz, 1H), 2.45 (d, J ) 13.7 Hz, 1H), 1.24 (t, J )
7.3 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ 171.9 (u), 148.9 (u),
148.2 (u), 142.8 (u), 142.2 (u), 134.4 (u), 129.8 (dn), 128.6 (dn),
128.3 (dn), 128.0 (dn), 127.3 (dn), 123.9 (dn), 123.8 (dn), 102.6
(dn), 87.3 (u), 83.8 (dn), 62.2 (u), 41.7 (u), 14.2 (dn).
2H), 8.09 (d, J ) 7.7 Hz, 2H), 7.99 (m, 2H), 7.91 (m, 3H), 7.70
(d, J ) 8.8 Hz, 1H), 7.51-7.61 (m, 6H), 7.40 (app t, J ) 7.7 Hz,
2H), 7.37 (m, 1H), 6.12 (s, 1H), 5.41 (s, 1H), 3.54-3.64 (m, 2H),
0.86 (s, 9H); 13C NMR (CDCl3, 100 MHz) δ 168.8 (u), 136.0 (u),
134.4 (u), 133.9 (u), 133.4 (u), 133.1 (u), 132.9 (u, 2 carbons),
130.9 (dn), 128.6 (dn), 128.4 (dn, 2 carbons), 128.3 (dn, 2 carbons),
128.1 (dn), 127.9 (dn, 2 carbons), 127.7 (dn, 2 carbons), 126.9 (dn),
126.6 (dn), 126.3 (dn), 125.9 (dn), 125.0 (dn), 124.7 (dn), 104.3
(dn), 87.7 (u), 86.3 (dn), 81.7 (u), 41.6 (u), 27.2 (dn); IR (neat,
cm-1) 1737, 1602, 1451, 1342, 1220, 1161, 1125, 1086, 953, 904,
823, 731, 698; HRMS-ESI m/z [M+] calcd for C35H32O4Na
539.2198, found 539.2191.
2â,5â-Di(2-naphthyl)-4â-tert-butoxycarbonyl-4R-benzyl-1,3-
dioxolane (4s(tBu)). A dry round-bottomed flask was charged with
Rh2(piv)4 (1 mg, 0.003 mmol) and the flask was evacuated and
filled with nitrogen. Anhydrous CH2Cl2 (5 mL) and 2-naphthalde-
hyde (283 mg, 1.81 mmol) were added, and the flask was cooled
by a bath of dry ice/acetone. tert-Butyl 2-diazohydrocinnamate (105
mg, 0.45 mmol) was dissolved in 3 mL of anhydrous CH2Cl2 and
was added to the reaction mixture via syringe pump at a rate of 1
mL/h. Following addition, the reaction mixture was allowed to
warm to room temperature and mesitylene (54 mg, 0.45 mmol)
Acknowledgment. This work was supported by NIH grant
GM068640-01.
Supporting Information Available: Full experimental and
characterization details for all compounds. copies of 1H NMR
and13C NMR spectra for new compounds, and CIF files for
compounds 4b, 4k, 4j, 4r, 4r (minor), 4o, 4s and 4s (minor), as
well as a detailed explanation for stereochemical assignments. This
material is available free of charge via the Internet at http://pubs.
acs.org.
1
was added. No diastereomers of 4s(tBu) were detected upon H
NMR analysis. The solvent was then removed and the residue was
chromatographed on silica gel with 0.5-2.0% ethyl acetate/hexanes
as the eluent to give 194 mg (83%) of the title compound as a
white solid, mp 151-153 °C. A similar experiment gave the title
1
compound in 73% yield. H NMR (CDCl3, 400 MHz) δ 8.27 (m,
JO702308F
J. Org. Chem, Vol. 73, No. 4, 2008 1439