Facile preparation and functionalization of chiral stabilized ylides from common chiral auxiliaries using triphenyl-phosphoranylideneketene (the Bestmann ylide) and their use in Wittig reactions

Article abstract of DOI:10.1021/jo061732y

Camphor-derived lactams and other related chiral controllers have been found to react with the Bestmann ylide (triphenyl-phosphoranylideneketene) upon heating in toluene. The resulting parent ylides provide convenient access to a structurally diverse set

Full text of DOI:10.1021/jo061732y

CHART 1
CHART 2
Facile Preparation and Functionalization of
Chiral Stabilized Ylides from Common Chiral
Auxiliaries Using Triphenyl-
phosphoranylideneketene (the Bestmann Ylide)
and Their Use in Wittig Reactions
Robert K. Boeckman, Jr.,* Xinyi Song, and Joseph E. Pero
Department of Chemistry, UniVersity of Rochester, Rochester,
New York 14627-0216
rkb@rkbmac.chem.rochester.edu
ReceiVed August 21, 2006
access to their more functionalized counterparts via well-
established alkylation and acylation chemistry.7
We identified triphenylphosporanylideneketene (5), the Best-
mann ylide, as a likely starting point as it is readily available
in multigram quantities in one step from commercial starting
materials (Chart 2).8,9 Our first attempts involving conversion
of camphor lactam 6 to the Li or K salts with nBuLi or KH
followed by addition of 5 were not promising. Complex mixtures
containing high molecular weight materials were observed. This
seemed surprising because 5 was well known to react with a
variety of electrophiles and nucleophiles, including amines, alco-
hols, and thiols, and chiral alcohols that afford chiral ester sta-
bilized ylides.10,11 Consideration of the electronic structure of
5 suggested that the use of the amide anion was counterproduc-
Camphor-derived lactams and other related chiral controllers
have been found to react with the Bestmann ylide (triphenyl-
phosphoranylideneketene) upon heating in toluene. The result-
ing parent ylides provide convenient access to a structurally
diverse set of chiral stabilized ylides via functionalization.
The utility of these chiral ylides for Wittig reactions has been
briefly investigated and the effects of R-substitution noted.
tive. In actuality, ylide
5 reacts smoothly with rela-
tively acidic neutral nucleophiles because proton transfer and not
nucleophilic addition is likely the rate-determining step. Although
R amino esters,12 acidic NH heterocycles,10a,13 vinylogous amides
and thioamides,13 and sulfonamides10a have been observed to
react, generally nucleophiles with a pKa > ∼18 (apparent upper
limit of the basicity of 5) such as NH-carboxamides and lactams
have not been employed previously in reactions with 5.
We were gratified that simply heating a mixture of 5 and lac-
tam 6 in toluene at reflux smoothly afforded the desired stabil-
ized imide ylide 7 in 90% yield (Table 1). The estimated pKa
of lactam 6 is 20-25. Thus, the apparent upper limit of the basi-
city of 5 can now be regarded as in that range. We found that
the reaction was general for other camphor-derived lactams such
as 8 and 9, as well as other prototypical chiral auxiliaries such
as Evan’s oxizolidinones 1014 and the Oppolzer sultam 11,15
Phosphorus ylides stabilized by a variety electron-withdrawing
groups (EWG) have found wide use in the Wittig reaction.1,2
Isolated examples of the preparation of such ylides bearing a
removable oxazolidinone or camphor sultam auxiliaries have
appeared.3,4 Their utility for complex molecule synthesis is
increasingly well established as additional examples of their use
and the use of the related chiral Horner-Wadsworth-Emmons
(HWE) phosphonates are reported.5,6 We required a convenient
route to sizable quantities of chiral stabilized ylides such as 1-4
(Chart 1). Convenient access to the parent ylides should afford
(6) Leading references: (a) Wipf, P.; Hopkins, T. D. Chem. Commun.
2005, 3421-3423. (b) Nicolaou, K. C.; Piscopio, A. D.; Bertinato, P.;
Chakraborty, T. K.; Minowa, N.; Koide, K. Chem.-Eur. J. 1995, 1, 318-
333. (c) Broka, C. A.; Ehrler, J. Tetrahedron Lett. 1991, 32, 5907-
5910.
(1) Cadogan, J. I. G., Ed.; Organophosphorus Reagents in Organic
Synthesis; 1979.
(2) (a) Abell, A. D.; Edmonds, M. K. Organophosphorus Reagents 2004,
99-127. (b) Edmonds, M.; Abell, A. Mod. Carbonyl Olefination 2004, 1-17.
(c) Nicolaou, K. C.; Harter, M. W.; Gunzner, J. L.; Nadin, A. Liebigs Ann./
Recueil 1997, 1283-1301. (d) Maercker, A. Org. React. 1965, 14, 270-490.
(3) (a) Williams, D. R.; Nold, A. L.; Mullins, R. J. J. Org. Chem. 2004,
69, 5374-5382. (b) Mamaghani, M.; Tabatabaeian, K.; Badrian, A.
Phosphorus, Sulfur Silicon Relat. Elem. 2004, 179, 1347-1353. (c) Noguchi,
H.; Aoyama, T.; Shioiri, T. Heterocycles 2002, 58, 471-504. (d) Suzuki,
M.; Yamazaki, T.; Ohta, H.; Shima, K.; Ohi, K.; Nishiyama, S.; Sugai, T.
Synlett 2000, 189-192. (e) Badone, D.; Bernassau, J.-M.; Cardamone, R.;
Guzzi, U. Angew. Chem., Int. Ed. Engl. 1996, 35, 535-538. (f) Evans, D.
A.; Black, W. C. J. Am. Chem. Soc. 1993, 115, 4497-4513.
(4) Cheng, P. T. W.; Chen, S.; Devasthale, P.; Ding, C. Z.; Herpin, T.
F.; Wu, S.; Zhang, H.; Wang, W.; Ye, X.-Y. Bristol-Myers Squibb Co.,
USA, Patent No. 2004004665, 2004; 543 pp.
(5) Selected recent examples: (a) Kouko, T.; Matsumura, K.; Kawasaki,
T. Tetrahedron 2005, 61, 2309-2318. (b) Ni, Y.; Amarasinghe, K. K. D.;
Ksebati, B.; Montgomery, J. Org. Lett. 2003, 5, 3771-3773. (c) Lee, K.;
Cha, J. K. J. Am. Chem. Soc. 2001, 123, 5590-5591.
(7) Bestmann, H. J.; Zimmerman, R. Carbon-Carbon Bond Form. 1979,
1, 353-426.
(8) (a) Schobert, R. Org. Synth. 2005, 82, 140-145. (b) Bestmann, H.
J.; Sandmeier, D. Chem. Ber. 1980, 113, 274-277.
(9) Schobert, R.; Loffler, J.; Siegfried, S. Targets Heterocycl. Syst. 1999,
3, 245-264.
(10) (a) Bestmann, H. J.; Schmid, G.; Sandmeier, D. Chem. Ber. 1980,
113, 912-918. (b) Bestmann, H. J.; Schobert, R. Angew. Chem. 1985, 97,
783-784. (c) Schobert, R.; Siegfried, S.; Gordon, G. J. J. Chem. Soc., Perkin
Trans. 1 2001, 2393-2397.
(11) Bestmann, H. J.; Kellermann, W. Synthesis 1994, 1257-1261.
(12) Schobert, R.; Jagusch, C. Tetrahedron 2005, 61, 2301-2307.
(13) (a) Bestmann, H. J.; Schmid, G.; Sandmeier, D. Angew. Chem. 1976,
88, 92-93. (b) Nickisch, K.; Klose, W.; Nordhoff, E.; Bohlmann, F. Chem.
Ber. 1980, 113, 3086-3088. (c) Boulos, L. S.; Hafez, T. S.; Fahmy, A. A.;
Abdel-Hamid, M. M. Egypt. J. Pharm. Sci. 1988, 29, 515-520.
(14) Gage, J. R.; Evans, D. A. Org. Synth. 1990, 68, 77-82.
10.1021/jo061732y CCC: $33.50 © 2006 American Chemical Society
Published on Web 10/13/2006
J. Org. Chem. 2006, 71, 8969-8972
8969

TABLE 1. Preparation of Parent Stabilized Ylides
SCHEME 1. Wittig Reactions of Ylides 7 and 12
SCHEME 2. Attempted Wittig Reaction: Reduction of
Ylide 7
TABLE 2. Alkylation and Acylation of Ylides 7 and 12
The parent ylides 7 and 12 react smoothly with simple alde-
hydes, affording the expected (E)-R,â-unsaturated imides.
Exposure of either ylide 7 or 12 to isobutyraldehyde in hot
dichloromethane or dichloroethane afforded exclusively the
expected (E)-R,â-unsaturated imides 18 and 19 in excellent
yields (both 98%) as for the parent ylides 14 and 15 (Scheme
1).3,4
Somewhat surprisingly, more functionalized analogues of 7
and 12-15 have not been previously reported, and nothing was
known of their behavior (e.g., 16 and 17) upon exposure to
aldehydes. Ylides 16 and 17 should behave analogously to the
parent ylides 7 and 12. Surprisingly, the reactivity of these
materials differs markedly from the parent ylides.
Thus, upon exposure of 16a to isobutyraldehyde in refluxing
dichloroethane, none of the expected (E)-trisubstituted R,â-
unsaturated imide 20 was observed. Instead, a complex mixture
was obtained containing unreacted aldehyde, aldol condensation
products of isobutyaldehyde, and the propionimide 21,18 result-
ing from effective reduction of the ylide.
The precise origin of imide 21 is still uncertain. A plausible
mechanism would involve enolization of the aldehyde by the
ylide 16a followed by collapse of the enolate-phosphonium salt
ion pair by attack at phosphorus affording the enolate, and, sub-
sequently upon protonation, the propionimide 21 (Scheme 2).
Similar results were obtained using the ylide 17a with isobu-
tyraldehyde. No olefination occurred, and the analogous pro-
pionimide 2218 was observed (Chart 3).
To examine the role of steric hindrance in the aldehyde, we
reacted 16a with the unbranched butyraldehyde in dichloroeth-
ane (80 °C, 18 h), resulting in slow conversion to the expected
trisubstituted R,â-unsaturated imide 23 in 31% yield (Chart 3).
Because competing formation of imide 21 was noted, the scope
affording the imide or sulfonyl amide stabilized ylides 12,13
and 14,3c154 in excellent yields (Table 1).
Further functionalization of these ylides occurred smoothly
as expected. Alkylation or acylation of the parent ylides 7 or
12 with a variety of alkyl and acyl halides followed by treatment
with NaOH afforded the expected substituted ylides 16a-e and
17a-e in excellent yields (Table 2).16,17
(16) Bestmann, H. J.; Schulz, H. Tetrahedron Lett. 1960, 5-6.
(17) Werkhoven, T. M.; Van Nispen, R.; Lugtenburg, J. Eur. J. Org.
Chem. 1999, 2909-2914.
(18) Boeckman, R. K., Jr.; Boehmler, D. J.; Musselman, R. A. Org. Lett.
2001, 3, 3777-3780.
(15) (a) Towson, J. C.; Weismiller, M. C.; Lal, G. S.; Sheppard, A. C.;
Davis, F. A. Org. Synth. 1990, 69, 158-168. (b) Weismiller, M. C.; Towson,
J. C.; Davis, F. A. Org. Synth. 1990, 69, 154-157. (c) Oppolzer, W.
Tetrahedron 1987, 43, 1969-2004.
8970 J. Org. Chem., Vol. 71, No. 23, 2006

CHART 3
SCHEME 3. Olefination of Ylide 17a
FIGURE 1. Model (HF 3-21G* Spartan 2004) of ylides 16a, 7, 17a,
and 12.
oselectivity of reactions of R-substituted enones bearing typical
chiral controller units were significantly diminished because of
unfavorable allylic strain derived from interactions between the
chiral controller moiety and the R substituent.20,21
CHART 4
We wished to probe the origin of the apparently higher
basicity and relatively low reactivity of the R-substituted ylides
16a and 17a, which could arise from steric inhibition of
delocalization of the negative charge of the ylide moiety by
the R substituent. Thus, resonance form 16-1 (Chart 4) is
rendered the major contributor due to twisting about the N-C1
and/or the C1-C2 side chain bonds, reducing the stabilization
and increasing the basicity of 16a and 17a.
Examination of a computational model (HF 3-21G* Spartan
2004) of ylide 16a (Figure 1) lends some support to this argu-
ment. A relatively small (absolute value of the OC1C2P dihedral
angle: 23°) twist occurs about the C1-C2 bond. The parent
ylide 7 is only slightly twisted (absolute value of the OC1C2P
dihedral angle: 2°), so substantial delocalization should be
possible for both. However, the ylide carbon in 16a is effectively
buried within the molecular framework, shielded on both faces
by a combination of the bridgehead methyl, endocyclic carbonyl,
and two P-phenyl groups. It is actually quite remarkable that
any reactivity is seen at all. Tortional strain about the C1-C2
bond is reduced in ylides 17a and 12 as is evident from the
observed OC1C2P dihedral angles 4° and 1° as shown in Figure
1. Thus, some combination of resonance stabilization and
reduction steric shielding appears to be responsible for the more
normal reactivity and basicity observed for ylide 17a. As can
be seen, the lower face of ylide 17a appears more accessible
(from the bottom as depicted in Figure 1), that is partially
shielded by two P-phenyl moieties.
of reactivity of ylide class 16 seems limited. Thus, we examined
reaction of the less congested ylide 17a with several reactive,
unbranched and R-heteroatom branched aldehydes. Reactions
with 17a proceed smoothly in excellent yield (conditions unop-
timized) to afford exclusively the expected (E)-R,â-unsatur-
ated imides 24-26. However, the reactivity of ylide 17a is also
much lower than the parent ylide 12 (Scheme 3). Use of lower
temperatures and longer reaction times was necessary to achieve
complete conversion of 17a and avoid formation of the byprod-
uct imide 22. The chiral lactaldehyde affords imide 26 as a single
diastereomer with no observable epimerization of the chiral center.
At first, the low reactivity and apparently higher basicity of
these chiral ylides seemed anomalous. However, it can be seen
that these properties have their origin in the structure and
conformational requirements of the substituted ylides 16 and
17. Strain imparted by delocalization of the nitrogen lone pair
onto the endocyclic carbonyl group of imides derived from
bicyclic lactams such as 6-8 raises the energy of this resonance
contributor as shown by the participation of the exocyclic
carbonyl group in anchimeric assistance.19
Facile introduction of a chiral controller unit by olefination
enables diastereoselective conjugate addition,22 reduction,23 and
alkylation,24 making these attractive reagents for stereoselective
The major contributors to that stabilization are those depicted
for 7 (Chart 4). Strong dipole forces orient the carbonyl groups
anti in the absence of a chelating metal ion. That places the
hydrogen or alkyl substituent in 7 and the related ylides in a
very congested environment because the delocalization requires
coplanarity of the N-acyl substituent and the endocyclic carbonyl
group. It has previously been seen that reactivity and enanti-
(20) Evans, D. A.; Chapman, K. T.; Bisaha, J. J. Am. Chem. Soc. 1988,
110, 1238-1256.
(21) Boeckman, R. K., Jr.; Liu, Y. J. Org. Chem. 1996, 61, 7984-7985.
(22) (a) Williams, D. R.; Nold, A. L.; Mullins, R. J. J. Org. Chem. 2004,
69, 5374-5382. (b) Oppolzer, W.; Kingma, A. J. HelV. Chim. Acta 1989,
72, 1337-1345.
(23) Prashad, M.; Liu, Y.; Kim, H.-Y.; Repic, O.; Blacklock, T. J.
Tetrahedron: Asymmetry 1999, 10, 3479-3482.
(24) (a) Oppolzer, W.; Moretti, R.; Thomi, S. Tetrahedron Lett. 1989,
30, 5603-5606. (b) Evans, D. A.; Mathre, D. J.; Scott, W. L. J. Org. Chem.
1985, 50, 1830-1835.
(19) Boeckman, R. K., Jr.; Wrobleski, S. T. J. Org. Chem. 1996, 61,
7238-7239.
J. Org. Chem, Vol. 71, No. 23, 2006 8971

in vacuo to give a solid residue. This solid residue was purified by
chromatography on SiO2 with elution with 50-100% ethyl acetate
in hexane to provide the alkylated ylides 16a-d, 17a-e mainly as
white solids in 85-98% yield.
General Procedure for Condensation of Ylides 7, 12, 16a,
and 17a with Aldehydes. A solution of the ylide 7, 12, 16a, or
17a (1.5 equiv) and the aldehyde (1.0 equiv) in anhydrous CH2-
Cl2, (CH2Cl)2, or toluene was heated at 40-100 °C in a sealed
tube until no aldehyde could be detected by TLC analysis (4-74
h). The reaction mixture was cooled to room temperature and
concentrated in vacuo to provide crude oily products. The oily
residue was purified by chromatography on SiO2 with elution by
5% ethyl acetate in hexane to provide the unsaturated carbonyl
compounds as a colorless oil in 31-99% yields.
(1R,4S)-1,7,7-Trimethyl-2-[(2E)-4-methyl-pent-2-enoyl)]-2-
aza-bicyclo[2.2.1]heptan-3-one (18). A solution of 91.1 mg (0.2
mmol, 1.5 equiv) of ylide 7 and isobutyraldehyde (12.2 µL, 9.62
mg, 0.13 mmol) in anhydrous ClCH2CH2Cl was heated at ∼83 °C
in a sealed tube until no aldehyde could be detected by TLC analysis
(19 h). The reaction mixture was cooled to room temperature and
concentrated in vacuo to provide crude oily products. The oily
residue was purified by chromatography on SiO2 with elution by
5% ethyl acetate in hexane to provide 44.5 mg (89%) of unsaturated
imide 18 as a colorless oil having the spectral characteristics: 1H
NMR (400 MHz, CDCl3) 6.94 (dd, J1 ) 15 Hz, J2 ) 6 Hz, 1H),
6.86 (d, J ) 16 Hz, 1H), 2.50-2.49 (m, 1H), 2.34 (d, J ) 4 Hz,
1H), 2.04-2.00 (m, 2H), 1.84-1.81 (m, 1H), 1.61-1.60 (m, 1H),
1.48 (s, 3H), 1.07 (d, J ) 7 Hz, 6H), 1.03 (s, 3H), 0.91 (s, 3H);
13C NMR (125 MHz, CDCl3) 178.5, 167.3, 154.8, 121.9, 72.9, 55.4,
47.5, 32.1, 23.7, 21.4, 21.3, 18.6, 17.5, 13.3; IR (film) 2965, 1746,
1679, 1634, 1456 cm-1. HRMS (EI). Calcd for C15H24NO2 (M +
H)+: 250.1807. Found: 250.1804.
functionalization of acyclic systems. An application of such chi-
ral ylides to complex molecule synthesis has been recently
reported.25
Experimental Section26
General Procedure for the Preparation of Chiral Ylides 7,
12-15. A mixture of triphenylphosphoranylideneketene (the Best-
mann ylide) 58 (1.0-1.5 equiv) and 1.0 equiv of the chiral auxiliary
(6, 8-11) in toluene (1-2 M) was heated to reflux (6-26 h) until
1
no starting material was detected (monitored by H NMR). The
reaction mixture was concentrated in vacuo, and the residue was
isolated and purified by chromatography on SiO2 and/or recrystal-
lization to provide the stabilized ylides as a solid (7, 12-15).
(1R,4S)-1,7,7-Trimethyl-2-[2-(triphenylphosphanylidene)-
acetyl]-2-aza-bicyclo[2.2.1] heptan-3-one (7). According to the
general procedure above, ketene 58 (18.8 g, 0.062 mol, 1.5 equiv)
and lactam 6 (6.3 g, 0.041 mol) were dissolved in 21 mL of toluene,
and the resulting mixture was heated until no more 6 could be
detected by 1H NMR (∼24 h). The solvent was removed in vacuo,
and the residue was recrystallized from ethyl acetate at -20 °C,
affording 17.0 g (90%) of ylide 7 as a tan solid having mp 182-
20
184 °C, [R]D -55.9° (c 3.1, CH2Cl2), and spectral characteris-
tics: 1H NMR (400 MHz, CDCl3) 7.71-7.66 (m, 6H), 7.56-7.53
(m, 3H), 7.47-7.44 (m, 6H), 4.22 (d, J ) 25 Hz, 1H), 2.31 (d, J
) 4 Hz, 1H), 2.17-2.13 (m, 1H), 2.00-1.94 (m, 1H), 1.80-1.77
(m, 1H), 1.69-1.66 (m, 1H), 1.46 (s, 3H), 1.06 (s, 3H), 0.86 (s,
3H); 13C NMR (125 MHz, CDCl3) 177.8, 167.4, 133.2, 131.9,
128.8, 127.5 (d, JC-P ) 91 Hz), 71.9, 56.1, 48.2, 43.6 (d, JC-P
)
116 Hz), 33.0, 23.8, 18.7, 17.8, 13.4; 31P NMR (160 MHz, CDCl3)
14.5; IR (film) 2966, 1708, 1567, 1431 cm-1. HRMS (EI). Calcd
for C29H31NO2P (M + H)+: 456.2092. Found: 456.2091.
(1S,4R)-4,7,7-Trimethyl-2-[2-(triphenylphosphanylidene)-
acetyl]-2-aza-bicyclo[2.2.1]heptan-3-one (12). According to the
general procedure above, ketene 5 (9.07 g, 0.03 mol, 1.5 equiv)
and lactam 8 (3.07 g, 0.041 mol) were disolved in 10 mL of
anhydrous toluene, and the resulting mixture was heated until no
(1S,4R)-4,7,7-Trimethyl-2-[(2E,4S)-2-methyl-4-tert-butyldi-
methylsilyloxy-pent-2-enoyl]-2-aza-bicyclo[2.2.1]heptan-3-one (26).
A solution of 704.4 mg (1.5 mmol, 1.5 equiv) of ylide 17a and
188.3 mg of TBS protected (S)-lactaldehyde (1.0 mmol) in
anhydrous ClCH2CH2Cl was heated at ∼83 °C in a sealed tube
until no aldehyde could be detected by TLC analysis (74 h). The
reaction mixture was cooled to room temperature and concentrated
in vacuo to provide crude oily products. The oily residue was
purified by chromatography on SiO2 with elution by 5% ethyl
acetate in hexane to provide 0.353 g (86%) of unsaturated imide
26 as a colorless oil having the spectral characteristics: 1H NMR
(400 MHz, CDCl3) 5.81 (d, J ) 8 Hz, 1H), 4.62-4.55 (m, 1H),
4.11 (d, J ) 2 Hz, 1H), 2.01-1.93 (m, 1H), 1.82 (d, J ) 1 Hz,
3H), 1.81-1.67 (m, 2H), 1.57-1.50 (m, 1H), 1.25 (d, J ) 6 Hz,
3H), 1.03 (s, 3H), 0.97 (s, 3H), 0.92 (s, 3H), 0.85 (s, 9H), 0.05 (s,
3H), 0.01 (s, 3H); 13C NMR (125 MHz, CDCl3) 177.2, 171.0, 141.5,
129.3, 65.8, 64.8, 56.3, 47.2, 30.8, 26.6, 25.8, 23.2, 18.7, 18.1, 17.7,
13.5, 9.6, -4.6, -4.9; IR (film) 2959, 2939, 2857, 2360, 1752,
1672, 1473 cm-1. HRMS (EI). Calcd for C21H37NNaO3Si (M +
Na)+: 402.2440. Found: 402.2463
1
more 8 could be detected by H NMR (26 h). The solvent was
removed in vacuo, and the residue was purified by chromatography
on SiO2 with elution by 20-50% ethyl acetate in hexane, followed
by recrystallization from ethyl acetate at -20 °C, affording 7.98 g
of ylide 12 (88%) as a pale yellow solid having mp 222-224 °C,
20
[R]D +45.5° (c 2.67, CH2Cl2), and spectral characteristics: 1H
NMR (400 MHz, CDCl3) 7.77-7.65 (m, 6H), 7.55-7.52 (m, 3H),
7.47-7.42 (m, 6H), 4.84 (d, J ) 25 Hz, 1H), 4.36 (s, 1H), 1.94-
1.90 (m, 1H), 1.76-1.1.56 (m, 3H), 1.06 (s, 3H), 0.97 (s, 3H),
0.88 (s, 3H); 13C NMR (125 MHz, CDCl3) 178.7, 165.7, 133.3,
131.9, 129.1, 127.5 (d, JC-P ) 91 Hz), 63.1, 56.5, 47.9, 39.8 (d,
JC-P ) 119 Hz), 30.3, 27.3, 18.6, 18.0, 9.77; 31P NMR (160 MHz,
CDCl3) 14.4; IR (film) 2955, 1708, 1561, 1478, 1431 cm-1. HRMS
(EI). Calcd for C29H31NO2P (M + H)+: 456.2092. Found:
456.2097.
General Procedure: Alkylation of Ylides 7 and 12. A mixture
of ylide 7 (1.0 equiv) and alkyl bromide or iodide, or acyl chloride
(2.0 equiv), in anhydrous acetonitrile (0.5 M) was heated to reflux.
The resulting homogeneous mixture was kept at reflux for the time
period as specified (0.5-24 h). The reaction mixture was concen-
trated in vacuo, and the residue was redissolved in dichloromethane
(0.25 M). A 1 M solution of aqueous NaOH (2.0 equiv) was added,
and the mixture was stirred vigorously at room temperature for 2
h. The phases were separated, the aqueous phase was extracted
with twice the volume of dichloromethane, and the combined
organic phases were dried over magnesium sulfate and concentrated
Acknowledgment. We thank the National Science Founda-
tion (CHE-0305790) for support of these studies.
Supporting Information Available: A description of general
experimental methods, additional detailed experimental procedures,
1
analytical data, and the H NMR and selected 13C, 31P, and IR
spectra for 7, 12-15, 16a-e, 17a-e, 18, 19, and 24-26. This
material is available free of charge via the Internet at http://
pubs.acs.org.
(25) Boeckman, R. K., Jr.; Pero, J. E.; Boehmler, D. J. J. Am. Chem.
Soc. 2006, 128, 11032-11033.
(26) General experimental methods section and additional experimental
procedures and characterization data may be found in the Supporting
Information.
JO061732Y
8972 J. Org. Chem., Vol. 71, No. 23, 2006