Regioselective synthesis of heterospirocyclic isobenzofuranones and medium-sized lactones by multiple anion capture reactions of 1,3-dianions

Article abstract of DOI:10.1002/1099-0690(200104)2001:8<1511::AID-EJOC1511>3.0.CO;2-D

The multicomponent reaction of 1,3-dianions with ketones and oxalic acid dichloride or diethylmalonic dichloride afforded six- to eight-membered lactones. Treatment of the dianion of 3-acetylindole with benzophenone and diethylmalonic dichloride resulted in the formation of a cyclic 1,3,5-triketooctene. The reaction of 1,3-dianions with ketones and phthalic dichloride resulted in the formation of heterospirocyclic isobenzofuranones rather than of medium-sized rings.

Full text of DOI:10.1002/1099-0690(200104)2001:8<1511::AID-EJOC1511>3.0.CO;2-D

FULL PAPER
Regioselective Synthesis of Heterospirocyclic Isobenzofuranones and Medium-
Sized Lactones by Multiple Anion Capture Reactions of 1,3-Dianions
Peter Langer,*[a] Manfred Döring,[b] and Helmar Görls[b]
Keywords: Carbanions / Lactones / Medium-sized rings / Multi-component reactions / Spiro compounds
The multicomponent reaction of 1,3-dianions with ketones
and oxalic acid dichloride or diethylmalonic dichloride af-
forded six- to eight-membered lactones. Treatment of the di-
lonic dichloride resulted in the formation of a cyclic 1,3,5-
triketooctene. The reaction of 1,3-dianions with ketones and
phthalic dichloride resulted in the formation of heterospiro-
anion of 3-acetylindole with benzophenone and diethylma- cyclic isobenzofuranones rather than of medium-sized rings.
Domino and multi-component reactions have found ation of the negative charge through the phenyl rings), the
widespread applications in organic synthesis.[1] Multiple an- carbon attached to the phenyl groups is less nucleophilic
ion capture reactions involve attack of a carbanion on a than the terminal carbon of the dianion. Subsequent addi-
relais species to form an intermediate which is subsequently tion of Me3SiCl gave the open-chain silyl ethers 3a and 3b
reacted with an electrophile. Recent examples include the in high yields (Scheme 1). Reaction of intermediate A with
reaction of carbon nucleophiles with allenes and sub- dichloro-diphenylsilane afforded the 1,3,2-dioxasilinane 3c
sequent cyclization with acrylates,[2] and reactions involving in 76% yield.
isocyanates[3] or allenyl isothiocyanates as the relais spe-
cies.[4] Multiple anion capture reactions involving nitriles as
the relais species have been observed in the reaction of bisli-
thiated 2,3-methylbutadiene with benzonitrile,[5] and in the
1,4-addition of nitriles to (butadiene)zirconocene.[6] In the
course of our program[7] directed at the development of cyc-
lization reactions of dianions[8] and dianion equivalents
with dielectrophiles, we have recently studied nitriles as re-
lais species in reactions of 1,3-dianions[9aϪ9c] and dilithiated
allenes.[9d] We wish to report full details of our studies re-
lated to multiple anion capture reactions of 1,3-dianions
with ketones and carboxylic acid dichlorides.[10] These reac-
tions provide an efficient access to medium-sized lactones
and novel heterospirocyclic isobenzofuranones.[11Ϫ13]
Results and Discussion
Scheme 1. Reaction of the dianion of 1,1-diphenylacetone with
benzophenone and chlorosilanes
Synthesis of Lactones and Silyl Ethers
Chlorosilanes were used in our first experiments aimed
Three-component cyclizations of dianions with ketones
at demonstrating the concept of multiple anion capture re-
and dicarboxylic acid dichlorides were studied next. These
actions of dianions with ketone relais species. The dian-
reactions can, in principle, result in the formation of differ-
ion[14] of 1,1-diphenylacetone 1 was generated by treatment
ent regioisomeric cyclization products, as well as macro-
of 1 with potassium hydride and nBuLi. The dianion was
cyclic or polymeric products. In fact, we have found that
condensed in situ with one equivalent of benzophenone 2a
they provide an efficient access to medium-sized dilactones.
to give the dianionic intermediate A by regioselective attack
Reaction of the dianion of 1 with benzophenone, and sub-
of the terminal carbon atom of the dianion at the carbonyl
sequent cyclization with oxalyl chloride gave the 1,4-dioxe-
group. Owing to steric and electronic reasons (delocaliz-
pane-2,3-dione 4. Reaction of the dianion of 1,1-di-
phenylacetone (1) with benzophenone (2a) or bis(p-tolyl)
[a]
Institut für Organische Chemie der Georg-August-Universität
ketone (2b) and subsequent addition of diethylmalonic
dichloride afforded the eight-membered 1,5-dioxocane-2,4-
diones 5a and 5b, respectively, in good yields (Scheme 2).
Reaction of the dianion of 2-methylbenzimidazole (6),[15]
Göttingen,
Tammannstrasse 2, 37077 Göttingen, Germany
Institut für Anorganische und Analytische Chemie der
Universität Jena,
[b]
August-Bebel-Strasse 2, 07743 Jena, Germany
Eur. J. Org. Chem. 2001, 1511Ϫ1517
WILEY-VCH Verlag GmbH, 69451 Weinheim, 2001
1434Ϫ193X/01/0408Ϫ1511 $ 17.50ϩ.50/0
1511

P. Langer, M. Döring, H. Görls
FULL PAPER
(an aza analogue of 1) with benzophenone, and subsequent attack at C-4 of the indole system, as an attack at the nitro-
treatment with oxalyl chloride resulted in the release of gen atom would lead to a highly strained product. The ex-
CO,[16] and in the formation of the 3,4-dihydrobenzo[4,5]- ocyclic double bond CϭCPh2 is formed by elimination of
imidazo[1,2-c][1,3]oxazin-1-one (7) (Scheme 3). Oxazepins water during the aqueous workup.[18]
are known to undergo decarbonylation reactions at elevated
temperatures, and have been used for the synthesis of reser-
pine alkaloids.[17] Reaction of the dianion of 6 with benzo-
phenone and subsequent aqueous quench gave the alcohol
8 (85%) which was reacted with diethylmalonic dichloride
to give the eight-membered ring 9. A direct synthesis of
dilactone 9 from 6 was not possible.
Scheme 4. Reaction of the dianion of 3-acetylindole with benzo-
phenone and diethylmalonic dichloride
Synthesis of Heterospirocyclic Isobenzofuranones
Reaction of the dianion of 1,1-diphenylacetone with
benzophenone, and subsequent addition of phthalic
dichloride (13) afforded the novel spiro-annulated 1,3-diox-
ane-2,1Ј-isobenzofuran-3Ј-one 14 in 89% yield, rather than
the isomeric nine-membered ring 15 (Scheme 5). Similarly,
the multiple anion capture reaction of the dianion of 2-
Scheme 2. Synthesis of medium-sized dilactones derived from 1,1-
diphenylacetone
methylbenzimidazole with benzophenone and phthalic
dichloride afforded a 2:1 mixture (72%) of the spirocyclic
amino orthoester 16, which was isolated in a pure form in
32% yield, and of the nine-membered ring isomer 17. Un-
fortunately, complex mixtures were formed when the dian-
ions A and B were reacted with succinic dichloride. The
structures of the isobenzofuranones 14 and 16 were estab-
lished by means of spectroscopic analysis. For the eight-
membered dilactone 5a, a singlet was observed for the CH2
group (1H NMR). In contrast, an AB-system (J ϭ 16 Hz)
was observed for the orthoesters 14 and 16. In contrast to
dilactones 5, only one carbonyl signal was detected for 14
and 16 (13C NMR and IR spectroscopy).
The structure of isobenzofuranone 16 was independently
confirmed by crystal structure analysis (Figure 1). The geo-
metry in the spiro carbon atom C-4 is only slightly distorted
from that of an ideal tetrahedron (the bond angles vary
from 103.3° to 114.6°). The bond length C4ϪO1 is signific-
antly shorter than C3ϪO1, presumably due to the anomeric
effect within the spiro-orthoester function.[19] The C4ϪO2
bond is relatively long and the C29ϪO2 bond is short, ow-
ing to the electronic influence of the neighboring carbonyl
Scheme 3. Reaction of the dianion of 2-methylbenzimidazole with
benzophenone and dicarboxylic acid dichlorides
Reaction of the dianion 11 of 3-acetylindole (10) with group. Only minor difference in the bond length is observed
benzophenone and subsequent addition of Et2C(COCl)2 re- in the annulated benzene moieties. The N2ϪC1 bond,
sulted in the formation of a complex mixture, from which which is part of the amidine function, is slightly shorter
the 1,3,5-triketooctene 12 could be isolated (18%) than the N2ϪC10 bond. An AB-system (1H NMR) is de-
(Scheme 4). Interestingly, 12 contained an eight-membered tected for the diastereotopic CH2 hydrogen atoms. Interest-
ring annulated at the 3- and 4-positions of the indole moi- ingly, deshielding is drastically decreased for the resonance
ety. As an excess of LDA was used, regeneration of an enol- assigned to H9, which is located within the anisotropic cone
ate anion appears to be possible after condensation of 11 of the isobenzofuran-3Ј-one moiety and is shifted upfield
with benzophenone. The carbon center of the enolate reacts by 1.4 ppm relative to the respective signal of 2-methyl-
with the dielectrophile, and subsequent ring closure involves benzimidazole.
1512
Eur. J. Org. Chem. 2001, 1511Ϫ1517

Multiple Anion Capture Reactions of 1,3-Dianions
FULL PAPER
tion of the dianionic intermediates A and B with the un-
symmetric isophthalic dichloride 13Ј, which is formed in
situ from 13 by Lewis acid catalysis (LiCl) under the reac-
tion conditions.[21] Alternatively, initial formation of the
medium-sized ring isomers and subsequent base-mediated
rearrangement of the latter to form the heterospirocyclic
isobenzofuranones represents a possible mechanism.[22]
The dianions of salicylic and anthranilic acid,[23] which
represent analogues of dianions A and B, respectively, were
employed next as starting materials. To our satisfaction, re-
action of the lithium salt of salicylic acid with phthalic
dichloride afforded the known[23] oxaspirocyclic isobenzof-
uranone 18 (Scheme 6). The base-mediated reaction of
anthranilic acid with phthalic dichloride proceeded equally
successfully and gave the known[23] oxazaspirocyclic prod-
uct 19.
Scheme 6. Synthesis of heterospirocyclic isobenzofuranones 18
and 19
The reaction of the dianion of 1,3-diphenylacetone 20[24]
with benzophenone and trimethylchlorosilane afforded the
silyl enol ether PhCHϭC(OSiMe3)CH(Ph)ϪC(OSiMe3)Ph2
(21) in 83% yield. In contrast, complex mixtures were ob-
tained when diethylmalonic dichloride and phthalic dichlor-
ide were used. Reaction of the dianion of acetanilide (22)[25]
with benzophenone and subsequent reaction with phthalic
dichloride resulted in the formation of the oxazaspirocyclic
isobenzofuranone 23 in low yield (Scheme 7). The main
Scheme 5. Synthesis of heterospirocyclic isobenzofuranones derived
from 1,1-diphenylacetone and 2-methylbenzimidazole
Figure 1. ORTEP plot of 16. The thermal ellipsoids of 50% probab-
ility are shown for the non-hydrogen atoms. Selected bond lengths
˚
[A] and angles [°]: C(1)ϪC(4) 1.370(3), O(2)ϪC(29) 1.372(3),
O(3)ϪC(29) 1.200(3), N(1)ϪC(5) 1.392(3), N(2)ϪC(10) 1.396(3),
N(2)ϪC(1) 1.381(3), N(2)-(4) 1.442(3), C(2)ϪC(3) 1.530(3),
C(5)ϪC(6) 1.390(3), C(6)ϪC(7) 1.369(5), C(1)ϪC(2) 1.472(4),
C(5)ϪC(10) 1.399(4), C(7)ϪC(8) 1.393(5), C(8)ϪC(9) 1.381(4),
C(9)ϪC(10) 1.385(4), O(1)ϪC(3) 1.476(3), O(2)ϪC(4) 1.462(3),
N(1)ϪC(1) 1.299(3); C(4)ϪO(1)ϪC(3) 120.5(2), C(1)ϪN(1)ϪC(5)
105.2(2), C(1)ϪN(2)ϪC(4) 124.8(2), N(1)ϪC(1)ϪN(2) 112.9(2),
N(2)ϪC(1)ϪC(2)
N(1)ϪC(1)ϪC(2)
117.8(2),
129.3(3),
C(10)ϪN(2)ϪC(4)
C(1)ϪC(2)ϪC(3)
128.2(2),
108.6(2),
C(29)ϪO(2)ϪC(4) 110.6(2), C(1)ϪN(2)ϪC(10) 107.0(2).
The formation of the isobenzofuranone rather than of
the medium-sized ring isomers can be explained on thermo-
Scheme 7. Reaction of the dianion of acetanilide with benzo-
dynamic grounds,[20] and presumably proceeds by cycliza- phenone and phthalic dichloride
Eur. J. Org. Chem. 2001, 1511Ϫ1517
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P. Langer, M. Döring, H. Görls
FULL PAPER
δ ϭ 10.20, 16.23. Ϫ C34H40O2Si2: calcd. C 76.06, H 7.51; found C
75.96, H 7.51.
product (66%) was N-phenylphthalimide (24), which was
presumably formed by a transamination process via inter-
mediates C and D.
2,4-Bis(tert-butyldimethylsilyloxy)-1,1,4,4-tetraphenyl-1-butene
(3b): Starting with 1,1-diphenylacetone (2.62 g, 12.5 mmol) and
benzophenone (2.55 g, 14.0 mmol), 3b was isolated as a colorless
solid (6.51 g, 84%), m.p. 78 °C. Ϫ 1H NMR (200 MHz, CDCl3):
δ ϭ Ϫ0.43, Ϫ0.19 (2 ϫ s, 2 ϫ 6 H, SiMe2), 0.68, 0.81 [2 ϫ s, 2 ϫ
9 H, C(CH3)3], 3.43 (s, 2 H, CH2), 6.69 (m, 2 H, Ph), 6.94Ϫ7.65
(m, 16 H, Ph), 7.82 (m, 2 H, Ph). Ϫ 13C NMR (50 MHz, CDCl3):
δ ϭ Ϫ3.73, Ϫ3.06 (SiMe2), 18.16, 18.46 [C(CH3)3], 26.03, 26.10
[C(CH3)3], 46.34 (CH2), 83.14 (C, OCPh2), 126.54 (ϭCPh2), 126.95,
127.30, 127.95, 128.26, 128.59, 130.04, 130.87, 131.10, 132.38 (CH,
Ph), 141.69, 142.56, 146.58, 146.71 (C, Ph). Ϫ IR (KBr): ν˜ ϭ 3058
(w) cmϪ1, 3027 (w), 2956 (w), 2928 (m), 1661 (m), 1599 (m), 1494
(m), 1445 (m), 1278 (m), 1256 (m), 1220 (m), 1056 (m). Ϫ MS (CI,
H2O); m/z: 621 (Mϩ ϩ 1, 6), 297 (100).
In summary, we have reported multiple anion capture re-
actions of 1,3-dianions with ketones and dielectrophiles.
These reactions provide a convenient access to novel me-
dium-sized lactones and heterospirocyclic isobenzofur-
anones. Medium-sized lactones[11,12] and heterospiro-
cycles[13] are of pharmacological relevance. Heterospiro-
cyclic systems are also of interest as photochromic mat-
erials.[26] Our current work is directed towards further
exploring the preparative scope of the cyclization reactions
presented.
Experimental Section
6-(Diphenylmethylidene)-2,2,4,4-tetraphenyl-1,3-dioxa-2-silacyclo-
hexane (3c): Starting with 1,1-diphenylacetone (2.62 g, 12.5 mmol),
benzophenone (2.55 g, 14.0 mmol) and diphenyldichlorosilane
(3.16 g, 12.5 mmol), 3c was isolated as a colorless solid (5.40 g,
General: All solvents were dried by standard methods and all reac-
tions were carried out under an inert atmosphere. Petroleum ether
(PE, bp 40Ϫ70 °C), diethyl ether (E) and tert-butyl methyl ether
1
76%), m.p. 70 °C. Ϫ H NMR (200 MHz, CDCl3): δ ϭ 3.52 (s, 2
1
(MTBE) were distilled prior to use. Ϫ For H NMR, CDCl3 and
H, CH2), 7.00Ϫ7.80 (m, 30 H, Ph). Ϫ 13C NMR (50 MHz, CDCl3):
δ ϭ 43.48 (CH2), 82.06 (C, OϪCPh2), 121.83 (Ph2Cϭ), 125.79,
126.65, 127.42, 127.83, 128.23, 129.97, 130.03, 130.72, 130.89 (CH,
Ph), 126.08, 127.02, 127.91 (CH, SiPh2), 134.77 (C, SiPh2), 139.81,
140.78, 145.05 (C, Ph), 145.95 (ϭCOSi). Ϫ 29Si NMR (50 MHz,
CDCl3): δ ϭ Ϫ27.83. Ϫ C40H32O2Si: calcd. C 83.88, H 5.63; found
C 84.04, H 5.38.
CD2Cl2 were used as solvents, with TMS as internal standard, or
[D8]THF as solvent δ ϭ 1.73, 3.58; for 13C NMR, CDCl3 was used
as solvent, with TMS as internal standard, or [D8]THF as solvent,
δ ϭ 25.5, 67.7. The multiplicity of the C atoms was determined by
the DEPT 135 technique and quoted as: CH3, CH2, CH and C for
primary, secondary, tertiary and quaternary carbon atoms. Ϫ MS:
EI, 70 eV; CI, H2O: chemical ionization with water. Ϫ Preparative
scale chromatography: J. T. Baker silica gel (60Ϫ200 mesh). Ϫ
Melting points are uncorrected and were measured using a Büchi
apparatus. Ϫ Elemental analyses: Microanalytical laboratory of the
Universities of Hannover and Jena.
7-(Diphenylmethylidene)-5,5-diphenyl-1,4-dioxepan-2,3-dione
(4):
Starting with 1,1-diphenylacetone (2.62 g, 12.5 mmol), benzo-
phenone (2.55 g, 14.0 mmol) and oxalyl chloride (1.60 g), 4 was
isolated as a colorless solid (2.01 g, 36%), m.p. 162 °C (dec.). ؊ 1H
NMR (200 MHz, CDCl3): δ ϭ 3.61 (s, 2 H, CH2), 6.90Ϫ7.40 (m,
20 H, Ph). Ϫ MS (EI); m/z: 446 [Mϩ], 402 (Mϩ Ϫ CO2), 402 (Mϩ
Ϫ CO2, Ϫ CO). Ϫ C30H22O4: calcd. C 80.70, H 4.97; found C
81.08, H 4.66.
General Procedure for Multiple Anion Capture Reactions of the Di-
anion of 1,1-Diphenylacetone (1): To a THF suspension (50 mL) of
potassium hydride (0.5 g, 12.5 mmol) was added a THF solution
(10 mL) of 1,1-diphenylacetone (2.62 g, 12.5 mmol). Evolution of
hydrogen was observed. After stirring for 20 min at 20 °C, nBuLi
(17.5 mL, 28 mmol, 1.6  solution in hexane) was added by syringe
at 0 °C. After stirring for 8 min, a red suspension was formed. A
THF solution (30 mL) of benzophenone (2.28 g, 12.5 mmol) was
added over 10 min at 0 °C. The color of the solution became deep
blue. After stirring for 2 h at 20 °C, a THF solution (20 mL) of the
respective dielectrophile (12.5 mmol) was added at 0 °C using a
metal cannula. In the case of 14, the cyclization product precipit-
ated immediately, and was filtered off and washed with water and
diethyl ether. For 3aϪc, 4 and 5aϪb, the solution was stirred for
12 h at 20 °C, and the solvent was subsequently removed in vacuo.
The residue was extracted with toluene (3 ϫ 50 mL). The extracts
were filtered through Celite, the solution was concentrated in vacuo
to 50 mL, and the product was precipitated by the addition of hex-
ane (20 mL). The precipitate was filtered off and washed with di-
ethyl ether.
8-(Diphenylmethylidene)-3,3-diethyl-6,6-diphenyl-1,5-dioxocan-2,4-
dione (5a): Starting with 1,1-diphenylacetone (2.62 g, 12.5 mmol),
benzophenone (2.55 g, 14.0 mmol) and diethylmalonic dichloride
(2.46 g, 12.5 mmol), 5a was isolated as colorless crystals (4.02 g,
62%), m.p. 186 °C. Ϫ 1H NMR (200 MHz, CDCl3): δ ϭ 0.86 (t,
J ϭ 7 Hz, 6 H, CH3), 2.01 (q, J ϭ 7 Hz, 4 H, CH2CH3), 3.51 (s, 2
H, CH2), 6.17 (d, J ϭ 10.5 Hz, 2 H, Ar), 6.95 (t, J ϭ 10.5 Hz, 2
H, Ar), 7.00Ϫ7.40 (m, 16 H, Ph). Ϫ 13C NMR (50 MHz, CDCl3):
δ ϭ 8.64 (CH3), 22.48 (CH2CH3), 38.87 (CH2), 64.60 (C, CEt2),
87.02 (C, CPh2), 126.24, 126.87, 126.98, 127.45, 127.67, 128.21,
128.87, 129.36, 130.27 (CH, Ph), 136.68 (C, CϭCPh2), 138.67,
139.35, 142.83, 144.52 (C, CϭCϪO, Ph), 169.90, 170.34 (CO). Ϫ
IR (KBr): ν˜ ϭ 3058 (m) cmϪ1, 2972 (m), 2879 (s), 1763 (s, CO),
1600 (s), 1494 (m), 1447 (m), 1197 (m), 1116 (s), 1060 (m), 1010
(m). Ϫ MS (EI) m/z: 516 [Mϩ], 374, 194. Ϫ C35H32O4: calcd. C
81.37, H 6.24; found C 81.12, H 6.40.
1,1,4,4-Tetraphenyl-2,4-bis(trimethylsilyloxy)-1-butene (3a): Start-
8-(Diphenylmethylidene)-3,3-diethyl-6,6-di(p-tolyl)-1,5-dioxocan-
ing with 1,1-diphenylacetone (2.62 g, 12.5 mmol) and benzo- 2,4-dione (5b): Starting with 1,1-diphenylacetone (2.62 g,
phenone (2.55 g, 14.0 mmol), 3a was isolated as a colorless solid
12.5 mmol), bis(p-tolyl) ketone (2.94 g, 14.0 mmol) and diethylma-
lonic dichloride (2.46 g, 12.5 mmol), 5b was isolated as colorless
(5.80 g, 86%), m.p. 68 °C. Ϫ 1H NMR (200 MHz, CDCl3): δ ϭ
Ϫ0.05, Ϫ0.03 (s, 18 H, SiMe3), 3.56 (s, 2 H, CH2), 7.00Ϫ7.60 (m, crystals (3.87 g, 60%), m.p. 168 °C. Ϫ 1H NMR (200 MHz,
20 H, Ph). Ϫ 13C NMR (50 MHz, CDCl3): δ ϭ 0.27, 2.03 (SiMe3), CDCl3): δ ϭ 0.82 (t, J ϭ 7 Hz, 6 H, CH3), 2.05 (q, J ϭ 7 Hz, 4 H,
46.78 (CH2), 82.04 (C, OCPh2), 125.65 (ϭCPh2), 125.98, 126.66,
CH2CH3), 2.25 (s, 6 H, CH3), 3.50 (s, 2 H, CH2), 6.20 (d, J ϭ
127.19, 127.20, 127.28, 127.79, 128.32, 130.87 (CH, Ph), 142.02, 11 Hz, 2 H, Ar), 6.90 (t, J ϭ 11 Hz, 2 H, Ar), 7.00Ϫ7.40 (m, 14
142.38, 146.44 (C, Ph), 147.15 (ϭCOSi). Ϫ 29Si NMR (CDCl3): H, Ar). Ϫ IR (KBr): ν˜ ϭ 3060 (m) cmϪ1, 2972 (m), 2881 (s), 1764
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Eur. J. Org. Chem. 2001, 1511Ϫ1517

Multiple Anion Capture Reactions of 1,3-Dianions
FULL PAPER
(s, CO), 1604 (s), 1496 (m), 1446 (m), 1198 (m), 1112 (s), 1062 (m),
residue was purified by column chromatography (silica gel, ether/
1010 (m). Ϫ MS (EI) m/z: 544 [Mϩ], 374, 194. Ϫ C37H36O4: calcd. petroleum ether ϭ 1:1) to give 9 as a colorless oil (315 mg, 15%).
C 81.59, H 6.66; found C 81.30, H 6.50.
؊ 1H NMR (200 MHz, CDCl3): δ ϭ 0.85 (t, J ϭ 7 Hz, 6 H, CH3),
1.95 (q, J ϭ 7 Hz, 4 H, CH2CH3), 3.55 (s, 2 H, CH2), 7.00Ϫ7.80
(m, 14 H, Ar). Ϫ IR (Nujol): ν˜ ϭ 3060 (m) cmϪ1, 2974 (m), 2880
(s), 1770 (s, CO), 1763 (s, CO), 1604 (s), 1494 (m), 1570 (s). Ϫ MS
(CI, MeOH); m/z: 438 (22) [Mϩ].
6-Diphenylmethylidene-4,4-diphenylspiro[1,3-dioxan-2,1Ј(3ЈH)-iso-
benzofuran]-3Ј-one (14): Starting with 1,1-diphenylacetone (2.62 g,
12.5 mmol), benzophenone (2.55 g, 14.0 mmol) and phthalic
dichloride (2.54 g), 14 was isolated as colorless crystals (5.80 g,
1
89%), m.p. 190 °C. Ϫ H NMR (200 MHz, CDCl3): δ ϭ 3.45 (d, 3Ј,4Ј-Dihydro-3Ј,3Ј-diphenylspiro[isobenzofuran-1(3H),1Ј-[1H][1,3]-
J ϭ 16 Hz, 1 H, CH2), 3.91 (d, J ϭ 16 Hz, 1 H, CH2), 6.90Ϫ7.90
oxazino[3,4-a]benzimidazol-3-one (16): Starting with 2-methylbenz-
(m, 24 H, Ph). Ϫ 13C NMR (50 MHz, CDCl3): δ ϭ 36.95 (CH2), imidazole (1.58 g, 12.0 mmol), benzophenone (2.55 g, 14.0 mmol)
83.20 (C, OCPh2), 117.29 (spiro atom), 121.66 (Ph2Cϭ), 123.06, and phthalic dichloride (2.43 g, 12.0 mmol), 16 was isolated as co-
125.23, 126.30, 126.55, 127.22, 127.55, 127.78, 128.18, 128.44,
129.79, 130.52, 131.61, 134.87 (CH, Ph), 138.05, 139.50, 142.00, NMR (200 MHz, CDCl3): δ ϭ 3.95 (d, J ϭ 16 Hz, 1 H, CH2), 4.40
143.04, 144.21 (C, Ar, ϭCO), 166.21 (CO). Ϫ IR (KBr): ν˜ ϭ 3058 (d, J ϭ 16 Hz, 1 H, CH2), 6.10 (d, J ϭ 12 Hz, 1 H, Ar), 6.95 (t,
(w) cmϪ1, 3052 (w), 2926 (w), 1781 (s, CO), 1597 (w), 1494 (m), J ϭ 12 Hz, 1 H, Ar), 7.25 (t, J ϭ 12 Hz, 1 H, Ar), 7.30Ϫ8.20 (m,
lorless crystals (from MTBE, 1.71 g, 32%), m.p. 176 °C. ؊ 1H
1449 (m), 1355 (s), 1313 (s), 1281 (s), 1220 (m), 1130 (s), 1108 (s),
15 H, Ar). Ϫ 13C NMR (50 MHz, CDCl3): δ ϭ 36.55 (CH2), 83.83
(C, OCPh2), 108.20 (spiro atom), 110.59, 119.83, 123.34, 125.66,
125.75, 127.19 (CH, Ar), 127.94, 128.32, 128.51 (CH, Ph), 128.57
(C, ArϪC to CO), 131.06 (C, Ph), 132.32, 135.44 (CH, Ar), 143.06,
144.58, 144.69 (C, Ar), 148.46 (CN2), 165.51 (CO). Ϫ IR (Nujol):
ν˜ ϭ 1770 (s, CO) cmϪ1, 1465 (s), 1453 (s), 1355 (s), 1380 (s), 1269
1084 (m), 1065 (m). Ϫ MS (CI, MeOH); m/z: 523 [Mϩ ϩ 1], 375
(Mϩ Ϫ C8H4O3), 357 (Mϩ Ϫ C8H4O3, Ϫ H2O), 149 (C8H4O3
ϩ
Hϩ). Ϫ C36H26O4: calcd. C 82.74, H 5.01; found C 82.42, H 5.13.
General Procedure for the Preparation and Cyclization Reactions of
the Dianion of 2-Methylbenzimidazole (6): To a THF solution
(50 mL) of 2-methylbenzimidazole (1.58 g, 12.0 mmol) was added
nBuLi (16.5 mL, 2.2 equiv., 1.6  solution in hexane) at 0 °C. A
yellow suspension was formed. After stirring for 60 min at 0 °C, a
THF solution (30 mL) of benzophenone (2.30 g, 12.5 mmol) was
added at 0 °C. The color of the solution became deep blue. The
solution was stirred at 0 °C for 15 min, and at room temperature
for 2 h. Subsequently, a THF solution (30 mL) of the respective
dielectrophile (12.5 mmol) was added at 0 °C. The THF was re-
moved in vacuo. The residue was dried and extracted with toluene
(3 ϫ 50 mL). The extracts were filtered through Celite, the solution
was concentrated in vacuo to 30 mL, and the product was precipit-
(s), 1220 (m), 1103 (s). Ϫ MS (CI, MeOH); m/z: 473 [Mϩ
ϩ
MeOH], 445 [Mϩ ϩ 1], 297 [Mϩ Ϫ C8H4O3], 149 [C8H4O3 ϩ Hϩ].
Ϫ C29H20O3N2: calcd. C 78.37, H 4.54, N 6.30; found C 78.12, H
4.65, N 6.59.
X-ray Crystal Structure Analysis of (16): The structure determina-
tion was carried out on an EnrafϪNonius CAD4 diffractometer
using graphite-monochromated Mo-Kα radiation. The crystals were
mounted in a cold nitrogen stream at Ϫ90 °C. Data were corrected
for Lorentz and polarization effects, but not for absorption.[27] The
structures were solved by direct methods (SHELXS)[28] and refined
by full-matrix least-squares techniques against F2 (SHELXL-93).
ated by the addition of hexane (20 mL). The product was filtered The hydrogen atoms were included at calculated positions with
and washed with diethyl ether.
fixed thermal parameters; all non-hydrogen atoms were refined an-
isotropically. XP (SIEMENS Analytical X-ray Instruments, Inc.)
was used for structure representations. Crystal Data:[30]
C29H20N2O3, Mr ϭ 444.5 gmolϪ1, colorless, size 0.40 ϫ 0.3 ϫ 0.10
mm3, monoclinic, space group P21/c No. 14, a ϭ 17.888(4), b ϭ
3,4-Dihydro-4,4-diphenyl-1H-[1,3]oxazino[3,4-a]benzimidazol-1-one
(7): Starting with 2-methylbenzimidazole (1.58 g, 12.0 mmol),
benzophenone (2.54 g, 14.0 mmol) and oxalyl chloride (1.53 g), 7
1
was isolated as a colorless solid (1.88 g, 46%), m.p. 175 °C. Ϫ H
˚
9.951(2), c ϭ 13.623(3) A, α ϭ 90.0, β ϭ 111.29(3), χ ϭ 90.0 °,
NMR (200 MHz, CDCl3): δ ϭ 3.87 (s, 2 H, CH2), 7.00Ϫ7.90 (m,
14 H, Ar). Ϫ 13C NMR (50 MHz, CDCl3): δ ϭ 36.69 (CH2), 88.51
(C, OCPh2), 114.36, 119.81, 125.15, 128.71 (CH, Ar), 125.67,
128.91, 129.61 (CH, Ph), 131.23 (C, Ph), 140.80, 142.63 (C, Ar),
145.84 (CN2), 149.10 (C, CO). Ϫ IR (Nujol): ν˜ ϭ 1767 (s, CO)
cmϪ1, 1569 (s). Ϫ MS (CI, MeOH); m/z: 369 (Mϩ ϩ MeOH), 341
[Mϩ ϩ 1], 297 (Mϩ Ϫ CO2). Ϫ C22H16O2N2: calcd. C 77.63, H
4.74; N 8.23; found C 77.96, H 4.64, N 7.88.
3
V ϭ 2259.4(8) A , Z ϭ 4, ρcalcd. ϭ 1.31 gcmϪ3, µ (Mo-Kα) ϭ 0.85
˚
cmϪ1, F(000) ϭ 928, 8094 reflections in Ϯh, Ϯk, ϩl, measured in
the range 2.75° Յ Θ Յ 23.71°, 7804 independent reflections, Rint ϭ
0.028, 4566 reflections with Fo Ͼ 4σ(Fo), 387 parameters, R ϭ
0.063, wR2 ϭ 0.128, GOF ϭ 1.23, largest difference peak: 0.23
Ϫ3
˚
e·A
.
1,3,4,4-Tetraphenyl-2,4-bis(trimethylsilyloxy)-1-butene (21): The
preparation of 21 follows the procedure for the preparation of 3a.
Starting with 1,3-diphenylacetone (2.62 g, 12.5 mmol) and benzo-
phenone (2.55 g, 14.0 mmol), 21 was isolated as colorless crystals
(5.61 g, 83%) from hexane, m.p. 68 °C. ؊ 1H NMR (300 MHz,
CDCl3): δ ϭ Ϫ0.04, 0.20 (s, 18 H, SiMe3), 4.17 (s, 1 H, CH), 6.47
(s, 1 H, ϭCHPh), 7.00Ϫ7.80 (m, 20 H, Ph). Ϫ 13C NMR (75 MHz,
CDCl3): δ ϭ 0.67, 2.44 (SiMe3), 63.26 (CH), 85.67 (C, OCPh2),
112.18 (CH, ϭCHPh), 125.42, 126.32, 126.43, 126.80, 127.06,
127.31, 127.61, 127.87, 128.14, 128.61, 129.35, 131.68 (CH, Ph),
137.31, 138.61, 145.54, 146.76 (C, Ph), 152.12 (ϭCOSi). Ϫ IR (Nu-
jol): ν˜ ϭ 3061 (m) cmϪ1, 3024 (m), 1601 (m), 1455 (s), 1377 (s),
1251 (s), 1132 (s), 1072 (s), 1009 (s). Ϫ C34H40O2Si2: calcd. C 76.06,
H 7.51; found C 75.84, H 7.62.
Lactone 9: The dianion of 2-methylbenzimidazole (1.58 g,
12.0 mmol) was generated and treated with benzophenone (2.28 g,
12.5 mmol) as described in the general procedure. After stirring for
2 h at 20 °C, the solution was poured into an aqueous solution of
hydrochloric acid (1 , 200 mL). The solution was extracted with
diethyl ether (3 ϫ 100 mL), and the combined organic layers were
dried (MgSO4), filtered and the solvent of the filtrate was removed
in vacuo. The product was precipitated by the addition of hexane
to the residue to give 8 as a colorless solid (3.20 g, 85%). A THF
solution (200 mL) of 8 (1.50 g, 4.8 mmol), diethylmalonic dichlor-
ide (1 equiv.), and NEt3 (2 equiv.) was stirred at 0 °C for 2 h, at 20
°C for 20 h, and at 50 °C for 24 h. The reaction mixture was poured
into water and the aqueous layer was repeatedly extracted with
diethyl ether. The combined organic layers were dried (MgSO4), Synthesis of Heterospirocyclic Isobenzofuranones 18 and 19: To a
filtered and the solvent of the filtrate was removed in vacuo. The
THF solution (30 mL) of LDA (2.2 equiv.) was added a THF solu-
Eur. J. Org. Chem. 2001, 1511Ϫ1517
1515

P. Langer, M. Döring, H. Görls
FULL PAPER
tion (10 mL) of salicylic or anthranilic acid (2.0 mmol). The solu-
tion was stirred for 1 h at 0 °C, and subsequently phthalic dichlor-
ide (1.0 mmol) was added by syringe. After stirring for 12 h at 20
°C, the solution was concentrated to 10 mL and hexane (20 mL)
was added. The precipitated solid was filtered off and washed with
water and diethyl ether to give the products as colorless solids. The
synthesis of 18 and 19 has been previously reported in the literat-
ure.[23]
water (20 mL) and diethyl ether (80 mL) were added, and the solu-
tion was extracted with a saturated aqueous solution of NaHCO3.
The combined organic layers were dried (MgSO4), filtered and the
solvent of the filtrate was concentrated in vacuo to give a deep red
oil. Storage of a diethyl ether solution of the crude product at 0 °C
for 12 h resulted in the precipitation of 12 as a yellow solid (1.25 g,
1
18%). Ϫ H NMR (300 MHz, CDCl3): δ ϭ 0.83 (t, J ϭ 7 Hz, 6
H, CH3), 1.96 (q, J ϭ 7 Hz, 4 H, CH2CH3), 7.10Ϫ7.60 (m, 12 H,
Ph), 7.97 (s, 1 H, NH), 8.19, 8.44 (d, 2 H, J ϭ 12 Hz, Ar). Ϫ 13C
NMR (75 MHz, CDCl3): δ ϭ 9.23 (CH3), 28.45 (CH2CH3), 38.87
(CH2), 63.15 (C, CEt2), 77.20 (C, CϭCPh2), 114.17 (CH, Ar),
120.00 (C, Ar), 125.18, 125.76, 126.63, 127.94, 128.13, 128.45,
128.99, 129.38, 129.66 (CH, Ar), 131.73, 132.81, 134.78 (C, Ar),
139.46, 141.18 (C, ArϪC to N), 156.56 (C, CϭCPh2), 171.79,
186.22, 193.16 (CO). Ϫ IR (KBr): ν˜ ϭ 3420 (br) cmϪ1, 2978 (m),
1718 (s), 1720 (s), 1650 (m) 1582 (m), 1571 (m), 1531 (m), 1341
(m), 1318 (s), 1137 (s), 1086 (s). Ϫ MS (FAB); m/z: 448 (100) [Mϩ
ϩ 1].
Isobenzofuranone 18: Yield 82%, colorless crystals, m.p. 172 °C. ؊
1H NMR (200 MHz, CDCl3): δ ϭ 7.00Ϫ7.80 (m, 8 H, Ar). Ϫ IR
(KBr): ν˜ ϭ 3060 (w) cmϪ1, 3052 (w), 2925 (w), 1780 (s, CO), 1595
(w), 1492 (m), 1449 (m), 1354 (s), 1284 (s), 1220 (m), 1132 (s), 1108
(s), 1085 (m), 1063 (m). Ϫ MS (CI); m/z: 269 (100) [Mϩ ϩ 1]. Ϫ
C15H8O5: calcd. C 67.17, H 3.01; found C 67.32, H 3.22. Owing to
the low solubility of 18, no 13C NMR spectrum could be recorded.
Similar to the cases of 14 and 16, only one carbonyl absorption
was observed in the IR spectrum.
Isobenzofuranone 19: Yield 70%, colorless crystals, m.p. 160 °C. Ϫ
1H NMR (200 MHz, CDCl3): δ ϭ 7.00Ϫ7.80 (m, 8 H, Ar). Ϫ IR
(KBr): ν˜ ϭ 3062 (w) cmϪ1, 3048 (w), 2926 (w), 1778 (s, CO), 1596
(w), 1490 (m), 1450 (m), 1355 (s), 1285 (s), 1220 (m), 1130 (s), 1110
(s), 1085 (m), 1065 (m). Ϫ MS (CI); m/z: 268 (100) [Mϩ ϩ 1]. Ϫ
C15H9O4N: calcd. C 67.42, H 3.39; found C 67.30, H 3.52. Owing
to the low solubility of 19, no 13C NMR spectrum could be re-
corded. Similar to the case of 18, only one carbonyl absorption was
observed in the IR spectrum.
Acknowledgments
P. L. thanks Professor A. de Meijere for his support. Financial
support from the Fonds der Chemischen Industrie e. V. (Liebig-
scholarship and funds for P. L.) and the Deutsche Forschungsge-
meinschaft is gratefully acknowledged.
[1]
For a review of domino reactions, see: L. F. Tietze, U. Beifuss,
Angew. Chem. 1993, 105, 137; Angew. Chem. Int. Ed. 1993, 32,
Reaction of the Dianion of Acetanilide with Benzophenone and
Phthaloyl Dichloride: To a THF solution (30 mL) of acetanilide
(810 mg, 6.0 mmol) was added nBuLi (8.25 mL, 2.2 equiv., 1.6 
solution in hexane) at 0 °C. The color of the solution became yel-
low. After stirring for 45 min at 0 °C, a THF solution (10 mL) of
benzophenone (1.15 g, 6.3 mmol) was added at 0 °C. The color of
the solution changed to green. After stirring for 2 h at 20 °C, a
THF solution (30 mL) of phthalic dichloride (1.27 g, 6.3 mmol)
was added within 10 min at 0 °C. The solution was stirred at 0 °C
for 15 min, and at room temperature for 12 h. The solution was
then extracted with a saturated aqueous solution of NaHCO3. The
combined organic layers were dried (MgSO4), filtered and concen-
trated in vacuo. Addition of hexane to a diethyl ether solution of
the crude product resulted in the precipitation of N-phenylphthal-
imide (24) (722 mg, 54%) as a colorless solid. The product was
identified by 1H NMR spectroscopy and MS spectrometry, and
by its melting point (202Ϫ204 °C).[31] The filtrate was purified by
chromatography (silica gel, ether, petroleum ether) to give 23
(160 mg, 6%) and an additional amount of 24 (161 mg, 12%). Ϫ
23: 1H NMR (200 MHz, CDCl3): δ ϭ 3.40 (d, J ϭ 15 Hz, 1 H,
CH2), 3.80 (d, J ϭ 15 Hz, 1 H, CH2), 6.80Ϫ7.85 (m, 19 H, Ar). Ϫ
IR (KBr): ν˜ ϭ 3062 (w) cmϪ1, 3050 (w), 2925 (w), 1780 (s, CO),
1690 (s, CO), 1595 (w), 1490 (m), 1449 (m), 1351 (s), 1312 (s), 1280
(s), 1221 (m), 1130 (s), 1106 (s), 1064 (m). Ϫ MS (CI, MeOH);
m/z: 448 [Mϩ ϩ 1], 149 [C8H4O3 ϩ Hϩ].
´
131. For multi-component reactions: H. Bienayme, C. Huhme,
G. Oddon, P. Schmitt, Chem. Eur. J. 2000, 6, 3321.
A. Padwa, P. E. Yeske, J. Am. Chem. Soc. 1988, 110, 1617.
I. Khattak, R. Ketcham, E. Schaumann, G. Adiwidjaja, J. Org.
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[2]
[3]
[4]
[5]
K. Banert, H. Hückstädt, K. Vrobel, Angew. Chem. 1992, 104,
72; Angew. Chem. Int. Ed. Engl. 1992, 31, 90.
R. B. Bates, B. Gordon III, P. C. Keller, J. V. Rund, J. Org.
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G. Erker, M. Berlekamp, L. Lopez, M. Grehl, B.
[6b]
Schönecker, R. Krieg, Synthesis 1994, 212. Ϫ
G. Erker, Synthesis 1994, 1039.
M. Riedel,
[7]
For recent cyclization reactions of dianion equivalents with 1,2-
dielectrophiles from our laboratory, see: [7a] P. Langer, M. Stoll,
Angew. Chem. 1999, 111, 1919; Angew. Chem. Int. Ed. 1999,
[7b]
38, 1803. Ϫ
P. Langer, T. Schneider, M. Stoll, Chem. Eur.
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112, 3208; Angew. Chem. Int. Ed. 2000, 39, 3086. Ϫ
P.
Langer, T. Eckardt, Angew. Chem. 2000, 112, 4563; Angew.
[7e]
Chem. Int. Ed. 2000, 39, 4343. Ϫ
P. Langer, T. Krummel,
Chem. Commun. 2000, 967. Ϫ [7f] P. Langer, T. Eckardt, Synlett
[7g]
2000, 844. Ϫ
P. Langer, T. Schneider, Synlett 2000, 497. Ϫ
[7h]
P. Langer, J. Wuckelt, M. Döring, J. Org. Chem. 2000, 65,
[7i]
729. Ϫ
P. Langer, J. Wuckelt, M. Döring, H. Görls, J. Org.
Chem. 2000, 65, 3603. Ϫ [7j] P. Langer, I. Karime, Synlett 2000,
´
[7k]
[7l]
743. Ϫ
P. Langer, V. Köhler, Org. Lett. 2000, 1597. Ϫ
P.
P.
P.
[7m]
[7n]
Langer, B. Kracke, Tetrahedron Lett. 2000, 4545. Ϫ
Langer, M. Döring, Chem. Commun. 1999, 2439. Ϫ
Langer, Chem. Commun. 1999, 1217. Ϫ [7o] P. Langer, J. Wuck-
elt, M. Döring, R. Beckert, Eur. J. Org. Chem. 1998, 1467. Ϫ
[7p]
P. Langer, M. Döring, D. Seyferth, Chem. Commun. 1998,
[7q]
1927. Ϫ
P. Langer, M. Döring, Synlett 1998, 396.
1,3,5-Tricarbonyloctene (12): To a THF solution (80 mL) of 3-
acetylindole (2.50 g, 15.5 mmol) was added a THF solution of
LDA, prepared by the addition of nBuLi (37.5 mL, 58.0 mmol,
[8]
[8a]
Reviews of dianions:
A. Maercker, Methoden Org. Chem.
[8b]
(Houben-Weyl) 4th ed., vol. E19d 1993, 448. Ϫ
C. M.
Thompson, D. Green, Tetrahedron 1991, 47, 4223. See also: Ϫ
1.6  solution in hexane) to
a
THF solution (30 mL) of
[8c]
D. Seebach, M. Pohmakotr, Tetrahedron 1981, 37, 4047. Ϫ
[8d]
diisopropylamine (7.65 mL, 58.0 mmol), at 0 °C. After stirring for
6 h at 20 °C, a THF solution (20 mL) of benzophenone (3.70 g,
20.15 mmol) was added at 0 °C. The solution was stirred at 0 °C
for 15 min, and at room temperature for 7 h, during which time
the color changed to deep green. Diethylmalonyl dichloride (3.4 g,
16.0 mmol) was subsequently added at 0 °C. After stirring for 12 h,
J. Vollhardt, H.-J. Gais, L. Lukas, Angew. Chem. 1985, 97,
[8e]
607; Angew. Chem. Int. Ed. Engl. 1985, 24, 608. Ϫ
A. Ma-
ercker, A. Groos, Angew. Chem. 1996, 108, 216; Angew. Chem.
[8f]
Int. Ed. Engl. 1996, 35, 210. Ϫ
A. R. Katritzky, C. N. Fali,
J. Li, J. Org. Chem. 1997, 62, 4148.
[9a] P. Langer, M. Döring, P. R. Schreiner, H. Görls, Chem. Eur.
[9]
[9b]
J. 2001, in print. Ϫ
P. Langer, M. Döring, Synlett 1998,
1516
Eur. J. Org. Chem. 2001, 1511Ϫ1517

Multiple Anion Capture Reactions of 1,3-Dianions
FULL PAPER
A. J. Kirby, The Anomeric Effect and Related Stereochemical
Effects at Oxygen, Springer: Berlin, 1983.
399. Ϫ [9c] P. Langer, M. Döring, H. Görls, R. Beckert, Liebigs
[19]
[20]
[9d]
Ann./Receuil 1997, 2553. Ϫ
P. Langer, M. Döring, D. Sey-
ferth, Chem. Commun. 1998, 1927.
The approximate energies of the isomers were estimated com-
putationally: The configurations of the isomers 14 and 15 were
generated, and the energies were subsequently minimized using
the MM2 force field which is implemented in release 3.0 of
HyperChem (N. L. Allinger, J. Am. Chem. Soc. 1977, 99,
8127). All input geometries were taken from the molecule ed-
[10]
[11]
For a preliminary communication, see: P. Langer, M. Döring,
D. Seyferth, Synlett 1999, 135.
Medium-sized rings: [11a] H.-J. Altenbach, in Organic Synthesis
Highlights (J. Mulzer, H.-J. Altenbach, M. Braun, K. Krohn,
[11b]
H.-U. Reissig, Eds.), VCH: Weinheim, 1991. Ϫ
K. C.
`
itor and optimized using the Polak-Ribiere algorithm. The
Nicolaou, C.-K. Hwang, B. E. Marron, S. A. DeFrees, E. A.
spiro isomer 14 is energetically favored by 20.33 kcalmolϪ1 rel-
ative to the nine-membered ring 15.
Couladouros, Y. Abe, P. J. Carroll, J. P. Snyder, J. Am. Chem.
Soc. 1990, 112, 3040 and cited literature. Ϫ [11c] L. E. Overman,
[11d]
[21]
[22]
Acc. Chem. Res. 1992, 25, 358. Ϫ
A. Brandes, H. M. R.
For the AlCl3-catalyzed transformation of 13 into 13Ј, see: S.
N. Naik, B. Pandey, N. R. Ayyanger, Synth. Commun. 1988,
18, 625.
Hoffmann, Tetrahedron 1995, 51, 145. Ϫ [11e] E. Alvarez, M. T.
Diaz, R. Perez, J. L. Ravelo, A. Regueiro, J. A. Vera, D. Zurita,
[11f]
J. D. Martin, J. Org. Chem. 1994, 59, 2848. Ϫ
R. A.
For the base-mediated transformation of a cyclic phthalate into
an orthoester, see: [22a] J. J. Zupancic, K. A. Horn, G. B. Schus-
Robinson, J. S. Clark, A. B. Holmes, J. Am. Chem. Soc. 1993,
[11g]
[22b]
115, 10400. Ϫ
1990, 46, 4487.
L. A. Paquette, T. J. Sweeney, Tetrahedron
ter, J. Am. Chem. Soc. 1980, 102, 5279. Ϫ
Am. Chem. Soc. 1956, 78, 2250.
F. D. Greene, J.
[12]
[13]
Macrolides: M. Bartra, F. Urpi, J. Vilarrasa, Methods Related
to the Synthesis of Macrolide Antibiotics; in Recent Progress in
the Chemical Synthesis of Antibiotics, (Eds.: G. Lukacs, M.
Ohno), Springer: Berlin, 1993.
[13a]
Spirocyclic acetals:
S. V. Ley, H. W. M. Priepke, Angew.
Chem. 1994, 33, 2292; S. V. Ley, H. W. M. Priepke, S. L. War-
[13b]
riner, Angew. Chem. Int. Ed. Engl. 1994, 33, 2290. Ϫ
S.
V. Ley, R. Downham, P. J. Edwards, J. E. Innes, M. Woods,
Contemporary Organic Synthesis 1995, 2, 365 and literature
[13c]
cited therein. Ϫ
A. Nadin, K. C. Nicolaou, Angew. Chem.
1996, 108, 1732; Angew. Chem. Int. Ed. Engl. 1996, 35, 1622.
Scheme 8
[13d]
Ϫ
G. R. Pettit, Z. A. Cichacz, F. Gao, C. L. Herald, R:
[13e]
M. Boyd, J. M. Schmidt, J. Org. Chem. 1993, 58, 1302. Ϫ
M. Kobayashi, S. Aoki, I. Kitagawa, Tetrahedron Lett. 1994,
[23]
[24]
H. P. Kaufmann, A. Seher, P. Hagedorn, Chem. Ber. 1954, 226.
D. Wilhelm, T. Clark, P. von R. Schleyer, J. Chem. Soc., Perkin
Trans 2 1984, 915.
[13f]
35, 1243. Ϫ
Y. Ichikawa, M. Isobe, D.-L. Bai, T. Goto,
[13g]
Tetrahedron 1987, 43, 4737, and following papers. Ϫ
S. V.
Ley, B. Lygo, F. Sternfeld, A. Wonnacott, Tetrahedron 1986,
42, 4333. Ϫ [13h] M. Drögenmüller, R. Jautelat, E. Winterfeldt,
Angew. Chem. 1996, 108, 1669; Angew. Chem. Int. Ed. Engl.
1996, 35, 1572.
G. B. Trimitsis, J. M. Hinkley, R. TenBrink, A. L. Faburada,
M. Anderson, M. Poli, B. Christian, G. Gustafson, J. Erdman,
D. Rop, J. Org. Chem. 1983, 48, 2957.
[25]
I. T. Barnish, C. R. Hauser, J. Org. Chem. 1968, 33, 2116.
[26] [26a]
V. Malatesta, R. Millini, L. Montanari, J. Am. Chem. Soc.
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1517