Intramolecular nucleophilic acyl substitution reactions mediated by XTi(O-i-Pr)3 (X = Cl, O-i-Pr)/2i-PrMgBr reagent. Efficient synthesis of functionalized organotitanium compounds from unsaturated compounds

Article abstract of DOI:10.1021/ja953497z

Treatment of acetylenic or olefinic carbonates and esters with a low-valent titanium reagent diisopropoxy(η²-propene)titanium (1), readily generated by the reaction of Ti(O-i-Pr)₄ or ClTi(O-i-Pr)₃ with 2i-PtMgX, resulted in an intramolecular nucleophilic acyl substitution (INAS) reaction to afford organotitanium compounds having a carbonyl functional group, in good to excellent yields. Thus, the treatment of alkyl alkynyl carbonates 2 or alkyl alkenyl carbonates 4 with 1 gave organotitanium compounds having a lactone and/or ester group. Similarly, alkyl alkynoates 10 or alkynyl esters 14 of carboxylic acids reacted with 1 to give organotitanium compounds having a cyclic or acyclic ketone group, respectively. Thus, the reaction provides, after hydrolysis, five- or six-membered α-alkylidene lactones and/or α,β-unsaturated esters from 2, γ-butyrolactone derivatives from 4, five- or six-membered α-alkylidene cyclic ketones from 10, and acyclic α,β-unsaturated ketones 15 from 14. In all cases, the yields are excellent and the generation of the organotitanium compounds was confirmed by deuterolysis. The organotitaniums 6 and 11c reacted smoothly with iodine to afford 2-(iodomethyl)-4-butanolide (9) and α-[iodo(trimethylsilyl)methylidene]cyclopentanone, respectively. The organotitanium compounds obtained here also reacted with aldehydes to give the corresponding adducts, thus opening up a new access to substituted α,β-butenolides from 2, to γ-butyrolactones from 4, and to the corresponding tetrasubstituted furan from 10 and 14.

Full text of DOI:10.1021/ja953497z

2208
J. Am. Chem. Soc. 1996, 118, 2208-2216
Intramolecular Nucleophilic Acyl Substitution Reactions
Mediated by XTi(O-i-Pr)3 (X ) Cl, O-i-Pr)/2i-PrMgBr Reagent.
Efficient Synthesis of Functionalized Organotitanium
Compounds from Unsaturated Compounds
Sentaro Okamoto, Aleksandr Kasatkin,1 P. K. Zubaidha, and Fumie Sato*
Contribution from the Department of Biomolecular Engineering, Tokyo Institute of Technology,
4259 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226, Japan
ReceiVed October 18, 1995X
Abstract: Treatment of acetylenic or olefinic carbonates and esters with a low-valent titanium reagent diisopropoxy-
(η2-propene)titanium (1), readily generated by the reaction of Ti(O-i-Pr)4 or ClTi(O-i-Pr)3 with 2i-PrMgX, resulted
in an intramolecular nucleophilic acyl substitution (INAS) reaction to afford organotitanium compounds having a
carbonyl functional group, in good to excellent yields. Thus, the treatment of alkyl alkynyl carbonates 2 or alkyl
alkenyl carbonates 4 with 1 gave organotitanium compounds having a lactone and/or ester group. Similarly, alkyl
alkynoates 10 or alkynyl esters 14 of carboxylic acids reacted with 1 to give organotitanium compounds having a
cyclic or acyclic ketone group, respectively. Thus, the reaction provides, after hydrolysis, five- or six-membered
R-alkylidene lactones and/or R,â-unsaturated esters from 2, γ-butyrolactone derivatives from 4, five- or six-membered
R-alkylidene cyclic ketones from 10, and acyclic R,â-unsaturated ketones 15 from 14. In all cases, the yields are
excellent and the generation of the organotitanium compounds was confirmed by deuterolysis. The organotitaniums
6 and 11c reacted smoothly with iodine to afford 2-(iodomethyl)-4-butanolide (9) and R-[iodo(trimethylsilyl)-
methylidene]cyclopentanone, respectively. The organotitanium compounds obtained here also reacted with aldehydes
to give the corresponding adducts, thus opening up a new access to substituted R,â-butenolides from 2, to
γ-butyrolactones from 4, and to the corresponding tetrasubstituted furan from 10 and 14.
Intramolecular nucleophilic acyl substitution (INAS) reactions
can be classified into two types: one which enables the transfer
of carbon fragments from oxygen to carbon as represented in
eq 1 and the other which affords cyclic ketones from acyclic
esters and related compounds as shown in eq 2. In spite of
their high synthetic potential,2 however, INAS reactions are
rather rare because of the intrinsic difficulty entailed in carrying
them out. One of the difficulties associated with INAS reactions
is that a reactive nucleophilic species must be generated in the
presence of a carbonyl functional group, and at the same time
this nucleophile is expected to react only with the carbonyl group
in an intramolecular fashion, but not intermolecularly, with the
one present in the reaction product. Organometallics such as
zinc and boron compounds lack the nucleophilicity to undergo
INAS reactions, while organolithiums and -magnesiums are
generally too reactive.3 Thus, most of the published INAS
reactions involve the use of stabilized carbanions as exemplified
by base-promoted cyclization of diesters and keto esters as well
as rearrangement of o-(acyloxy)phenyl ketones.4
With respect to INAS reactions which do not involve
stabilized carbanions, samarium(II) iodide-mediated reaction of
(3) INAS reaction Via organolithium intermediates affording cyclic
ketones has been attained in some cases, see: Fadel, F.; Canet, J.-L.; Salaun,
J. Synlett 1990, 89. Souchet, M.; Clark, R. D. Synlett 1990, 151. Kitano,
Y.; Okamoto, S.; Sato, F. Chem. Lett. 1989, 2163. Van der Does, T.;
Klumpp, G. W.; Schakel, M. Tetrahedron Lett. 1986, 27, 519. Cooke, M.
P., Jr.; Houpis, I. N. Tetrahedron Lett. 1985, 26, 4987. Negishi, E.; Miller,
J. A. J. Am. Chem. Soc. 1983, 105, 6761.
(4) Hauser, C. R.; Swammer, F. W.; Adams, J. T. Org. React. 1954, 8,
59. Kraus, G. A.; Futton, B. S.; Woo, S. H. J. Org. Chem. 1984, 49, 3212.
Ohtsuka, Y; Oishi, T. Tetrahedron Lett. 1979, 20, 4487. Yates, P.; Anderson,
C. D. J. Am. Chem. Soc. 1963, 85, 2937. Wallace, P. Warren, S. Tetrahedron
Lett. 1985, 26, 5713. Wallace, P.; Warren, S. J. Chem. Soc., Perkin Trans.
1 1988, 2971. Schweitzer, E. E.; Creasy. W. S. J. Org. Chem. 1971, 36,
2379. Arey, P. M.; Warren, S. Tetrahedron Lett. 1989, 30, 4581. Jacobs,
H. K.; Gopalan, A. S. J. Org. Chem. 1994, 59, 2014. For the reaction using
Michael addition followed by Dieckmann condensation, see: Nugent, W.
A.; Hobbs, F. W., Jr. J. Org. Chem. 1983, 48, 5364. Honda, T.; Mori, M.
Chem. Lett. 1994, 1013. Crimmins, M. T.; Nantermet, P. G. J. Org. Chem.
1990, 55, 4235. Crimmins, M. T.; Nantermet, P. G.; Trotter, B. W.; Vallin,
I. M.; Watson, P. S.; McKerlie, L. A.; Reinhold, T. L.; W.-H. Cheung, A.;
Stetson, K. A.; Dedopoulou, D.; Gray, J. L. J. Org. Chem. 1993, 58, 1038.
Crimmins, M. T.; Watson, P. S. Tetrahedron Lett. 1993, 34, 199. Crimmins,
M. T.; Guise, L. E. Tetrahedron Lett. 1994, 35, 1657. Crimmins, M. T.
Huang, S.; Guise, L. E.; Borden Lacy, D. Tetrahedron Lett. 1995, 36, 7061.
X Abstract published in AdVance ACS Abstracts, February 15, 1996.
(1) On leave from Institute of Organic Chemistry, Ufa Research Center,
Russian Academy of Science.
(2) As represented by Claisen rearrangements (recent review: Hill, R.
K. In Asymmetric Synthesis; Morrison, J. D., Ed.; Academic Press: New
York, 1984; Vol. 3, p 305) and 2,3-sigmatropic Wittig rearrangements
(recent review: Nakai, T.; Mikami, K. Org. React. 1994, 46, 105), synthetic
sequences involving the transfer of carbon fragments from oxygen to carbon
play an important role in organic synthesis. Methodology for synthesis of
cyclic alkanones: Shaman, P. D., Jr.; Papa, A. J. Ketones. Kirk-Othmer
Encyclopedia of Chemical Technology, 3rd ed.; Grayson, M., Eckroth, D.,
Eds.; Wiley: New York, 1981; Vol. 13, p 894. Waring, A. J. In
ComprehensiVe Organic Chemistry; Barton, D., Ollis, D., Eds.; Pergamon:
Oxford, 1979; Vol. 1, p 1017. Jung, M. E. Tetrahedron 1976, 32, 3.
Thebtaranonth, C.; Thebtaranonth, Y. Tetrahedron, 1990, 46, 1385.
0002-7863/96/1518-2208$12.00/0 © 1996 American Chemical Society

Intramolecular Nucleophilic Acyl Substitution Reactions
J. Am. Chem. Soc., Vol. 118, No. 9, 1996 2209
Scheme 1
reaction afforded an INAS product, i.e., an alkenyltitanium
compound having a lactone moiety as shown in eq 3.9
Further studies on the scope of this unprecedented type of
titanium(II)-mediated INAS reaction have revealed that it affords
a general and practical method for synthesis of a variety of
organotitanium compounds having functional groups, thus
opening up a synthetically versatile new methodology.10,11
Results and Discussion
Ti(II)-Mediated INAS Reaction of Carbonates of Acety-
lenic Alcohols.9 The reaction of carbonates of a variety of
substituted acetylenic alcohols 2 with the Ti(O-i-Pr)4/2i-PrMgBr
reagent provided alkenyltitanium compounds having a lactone
and/or ester moiety in good to excellent yields, which was
confirmed by hydrolysis, deuterolysis, and the reaction with
aldehydes as summarized in Table 1.12 However, carbonates
having a terminal triple bond such as ethyl 3-butynyl carbonate
gave no INAS reaction product.
The reaction can be explained by the plausible reaction
mechanism shown in Scheme 2. Thus, the ligand exchange
reaction of the propene moiety in 1 with 2 affords titanacyclo-
propene intermediate 3 which undergoes INAS reaction Via path
a and/or path b. The fact that no product with an endocyclic
double bond was obtained by the attack of the other Ti-C bond
to the carbonate group in 3 presumably can be attributed to
conformational requirements. With acetylenic carbonates in
which the carbonate group and triple bond are separated by two
or three carbons, the acyl substitution proceeded mainly Via path
a to provide the corresponding alkenyltitanium compounds
having a five- or six-membered lactone moiety (entries 1-7 in
Table 1). In contrast, the reaction of the carbonate where both
the functional groups are separated by four carbons proceeded
Via path b providing the alkenyltitanium compound having an
ester group presumably due to lower stability of the seven-
membered lactone ring compared to five- or six-membered ones
(entry 8). The carbonates having an aromatic ring as a tether
between the triple bond and carbonate group react similarly,
thus providing an easy access to 3-isochromanone derivatives13
(entries 9 and 10).
alkyl iodides represents an exceptional, successful endeavor.
The reaction is applicable to both types of reaction and its scope
and limitations have been extensively investigated by Molander
and co-workers.5 The INAS reactions involving organochro-
mium, -copper (derived by transmetalation reaction from
organomercuric compounds), and -tin compounds have been
reported;6 however, the scope of these reactions has remained
unexplored. We report here a titanium-promoted INAS reaction
which is characterized by the fact that (i) the reaction provides
for the first time an organometallic compound as the product,
thus affording the opportunity for further functionalization
through manipulation of the resulting carbon-metal bond, and
(ii) the reaction is applicable to both types of reaction as shown
in eqs 1 and 2 and has a wide range of applicability.
Recently we have disclosed a highly efficient and practical
protocol for preparation of allenyltitanium compounds by the
reaction of propargyl alcohol derivatives including carbonates
with a Ti(O-i-Pr)4/2i-PrMgBr reagent.7 This formal oxidative
addition reaction can be explained by the plausible reaction
mechanism shown in Scheme 1 which involves generation of
diisopropoxy(η2-propene)titanium (1) from Ti(O-i-Pr)4 and 2
equiv of i-PrMgBr8 and subsequent replacement of the propene
coordinated in 1 by the acetylenic moiety of the substrate to
furnish a titanium-alkyne intermediate which then undergoes
â-elimination.
It should be noted that the vinyltitanium compounds derived
here are rather stable and versatile and afford addition products
with aldehydes.14 It is also noteworthy that the reaction products
With these results in hand, our attention turned to the reaction
of the Ti(O-i-Pr)4/2i-PrMgBr reagent with homopropargylic
carbonate 2a which has one additional carbon atom between
the carbonate group and triple bond, and we found that the
(9) For a preliminary account of this work, see: Kasatkin, A.; Okamoto,
S.; Sato, F. Tetrahedron Lett. 1995, 36, 6075.
(10) Other applications of the reagent 1 in organic synthesis: (a) Harada,
K.; Urabe, H.; Sato, F. Tetrahedron Lett. 1995, 36, 3203. (b) Urabe, H.;
Hata, T.; Sato, F. Tetrahedron Lett. 1995, 36, 4261. (c) Kasatkin, A.; Sato,
F. Tetrahedron Lett. 1995, 36, 6079. (d) Gao, Y.; Harada, K.; Sato, F.
Tetrahedron Lett. 1995, 36, 5913.
(11) Utility of functionalized organometallic reagents has been well
exemplified by zinc compounds, see: Knochel, P. Synlett, 1995, 393.
Knochel, P.; Singer, R. D. Chem. ReV. 1993, 93, 2117.
(12) For reviews on R-alkylidene- and R-arylidenebutyrolactones, see:
Lu, X.; Ma, S.; Ji, J.; Zhu, G.; Jiang, H. Pure Appl. Chem. 1994, 66, 1501.
Petragnani, N.; Ferraz, H. M. L.; Silva, G. V. Synthesis 1986, 157.
Hoffmann, H. M. R.; Rabe, J. Angew. Chem., Int. Ed. Engl. 1985, 24, 94
and see also reference 18.
(5) Molander, G. A.; Christina, R. H. J. Am. Chem. Soc. 1995, 117, 3705.
Molander G. A.; Shakya, S. R. J. Org. Chem. 1994, 59, 3445. Molander,
G. A.; McKie, J. A. J. Org. Chem. 1993, 58, 7216. Molander, G. A.; McKie,
J. A. J. Am. Chem. Soc. 1993, 115, 5821. Molander, G. A. Chem. ReV.
1992, 92, 29.
(6) Via organochromium compound: Ledoussal, B.; Gorgues, A.; Le Coq,
A. J. Chem. Soc., Chem. Commun. 1986, 171. Ledoussal, B.; Gorgues, A.;
Le Coq, A. Tetrahedron 1987, 43, 5841. Via organocopper compound:
Kocovsky, P.; Grech, J. M.; Mitchell, W. L. J. Org. Chem. 1995, 60, 1482.
Via organotin compound: Mori, M.; Kaneta, N.; Isono, N.; Shibasaki, M.
Tetrahedron Lett. 1991, 32, 6139. Mori, M.; Isono. N.; Kaneta. N.;
Shibasaki, M. J. Org. Chem. 1993, 58, 2972.
(7) Nakagawa, T.; Kasatkin, A.; Sato, F. Tetrahedron Lett. 1995, 36,
3207.
(8) (a) Kasatkin, A.; Nakagawa, T.; Okamoto, S.; Sato, F. J. Am. Chem.
Soc. 1995, 117, 3881. (b) Kulinkovich, O. G.; Sviridov, S. V.; Vasilevskii,
D. A.; Pritytskaya, T. S. Zh. Org. Khim. 1989, 25, 2244. (c) Kulinkovich,
O. G.; Sviridov, S. V.; Vasilevskii, D. A. Synthesis 1991, 234. (d) Corey,
E. J.; Rao, A.; Noe, M. C. J. Am. Chem. Soc. 1994, 116, 9345.
(13) Kobayashi, K.; Mannami, T.; Kawakita, M.; Tokimatsu, J.; Konishi,
H. Bull. Chem. Soc. Jpn. 1994, 67, 582 and references cited therein.
(14) Weidmann, B.; Maycock, C. D.; Seebach, D. HelV. Chim. Acta 1981,
64, 1552. Mead, K.; MacDonald, T. L. J. Org. Chem. 1985, 50, 423.
Boeckman, R. K.; O’Connor, K. J. Tetrahedron Lett. 1989, 30, 3271. Reetz,
M. T. Titanium in Organic Synthesis In Organometallics in Synthesis;
Schlosser, M., Ed.; Wiley: New York, 1994; p 195.

2210 J. Am. Chem. Soc., Vol. 118, No. 9, 1996
Okamato et al.
Table 1. Preparation of Alkenyltitanium Reagents Starting from 2
Scheme 2
and Their Reactions with Electrophilesa
Scheme 3
a All reactions were carried out using 1.0 equiv of an acetylenic
carbonate, 1.3 equiv of Ti(O-i-Pr)4, and 2.6 equiv of i-PrMgBr unless
stated otherwise. An alkenyltitanium compound was prepared in Et2O
at -45 ∼ -40 °C (1 h), and then an electrophile was added at -40
°C. b Only one stereoisomer was observed in all cases according to
1H- and 13C-NMR data. The assignment of the double-bond stereo-
chemistry is based on the chemical shift value of the vinyl proton (see
refs 27-29 and 40). c After addition of 2.0 equiv of PhCHO, the
reaction mixture was warmed up to 0 °C for 1 h. d Isolated yields based
on the acetylenic carbonates unless stated otherwise. e Deuterolysis of
the reaction mixture gave the product containing >98% D (1H-NMR
analysis). f 2.0 equiv of Ti(O-i-Pr)4 and 4.0 equiv of i-PrMgBr were
used. g Included 24% of (E)-3-(ethoxycarbonyl)-3-decen-1-ol. h EtCHO
instead of PhCHO was used, after addition of EtCHO, the reaction
mixture was stirred at 20 °C for 20 h. i 0.5 equiv of PhCHO was used,
isolated yield based on PhCHO. j An alkenyltitanium reagent was
prepared from 2.0 equiv of Ti(O-i-Pr)4 and 4.0 equiv of i-PrMgBr at
-45 ∼ -40 °C (2.5 h) followed by warming up to -15 °C for 1 h.
k The 74:26 mixture of two diastereoisomers (rotamers) according to
1H-NMR data. l H-NMR data. l The 43:37:20 mixture of three diaster-
titanium-alkene compounds (1 and that derived from the alkene
added) and their further coupling reactions with propene and/
or the alkene added.16 We, however, anticipated that the facile
INAS reaction of the intermediate 5 generated by the reaction
of 1 and 4 might act as a driving force for shifting the
equilibrium, thus impeding these side reactions, and afford the
acyl substitution product in a synthetically useful yield as shown
in Scheme 3.17
As expected, a variety of ethyl carbonates of homoallyl
alcohols provided the corresponding γ-butyrolactones in excel-
lent yields on reaction with 1 and subsequent hydrolysis. The
presence of alkyltitanium compound 6 was confirmed by
subjecting the reaction mixture to deuterolysis. The results are
summarized in Table 2.
1
eomers according to H-NMR data.
with aldehydes are recyclized substituted butenolides15 rather
than the initially formed R-alkylidene butanolides.
INAS Reaction with Olefinic Carbonates. Ti(II)-Mediated
INAS reaction of acetylenic carbonates reported above is
noteworthy for its efficient transfer of carbon fragments from
oxygen to carbon and for providing an easy access to function-
alized organotitanium compounds which are otherwise difficult
to get, thus providing a powerful synthetic methodology for
synthesis of a variety of butenolides. We next considered the
application of Ti(II)-promoted INAS reactions to olefinic
carbonates 4.
Although the reaction of 1 with alkynes provided titanium-
alkyne compounds quantitatively Via a ligand exchange reaction,10a
the reaction with alkene furnished a complex mixture of
titanacyclopentanes due to the equilibrium between the two
In contrast, the reaction of 1 with ethyl carbonate of 4-penten-
1-ol (the carbonate of bishomoallyl alcohol) did not afford the
(16) Harada, K.; Sato, F. Unpublished result. A similar result was reported
in the zirconium chemistry, see: Swanson, D. R.; Rousset, C. J.; Negishi,
E.; Takahashi, T.; Seki, T.; Saburi, M.; Uchida, Y. J. Org. Chem. 1989,
54, 3521.
(15) For reviews, see: Knight, D. W. Contemp. Org. Synth. 1994, 1,
287. Jacobi, P. A. AdV. Heterocycl. Nat. Prod. Synth. 1992, 2, 251.
(17) The reaction of 1 with allyl carbonate provides allyltitanium
compound; see reference 8a.

Intramolecular Nucleophilic Acyl Substitution Reactions
J. Am. Chem. Soc., Vol. 118, No. 9, 1996 2211
Table 2. Ti(II)-Mediated INAS Reaction of Olefinic Carbonates 4a
contrast with the alkenyltitanium compound obtained by the
INAS reactions of 2 (see entry 5 in Table 1). Treatment with
excess of iodine provided the iodo lactone 9 in 90% yield which,
upon treatment with Et3N, underwent elimination to furnish
R-methylene γ-butyrolactone in essentially quantitative yield.
Although many methods for synthesis of substituted γ-bu-
tyrolactones have been reported,18 the present method is unique
with respect to its reaction mode and starting materials and is
potentially useful as an attractive complementary methodology.
INAS Reaction of Esters of Acetylenic Acids. The INAS
reaction of carbonates of acetylenic alcohols mediated by 1
described above suggested that the analogous INAS reaction
of esters 10 of acetylenic acids should provide a convenient
method for synthesis of alkenyltitanium compounds containing
a cyclic ketone fragment (11) as shown in eq 4.
Realization of the INAS reaction of 10, however, was
expected to encounter problems associated with the enhanced
reactivity of the resulting ketone to nucleophiles. Thus, the
present goal of the methodology requires that the generated
titanium-alkyne intermediate reacts only with the ester group
of the substrates in an intramolecular fashion but not intermo-
lecularly, with the more reactive keto group of 11 formed;
moreover, 11 must be free of the self-condensation problem.
With the goal of developing the INAS reaction of 10 to 11,
the esters derived from 6-(trimethylsilyl)hex-5-ynoic acid were
chosen as substrates and subjected to the reaction with 1 under
various conditions. The yields of the expected R-alkylidene
cyclopentanone obtained by hydrolysis of the reaction mixture
are shown in entries 1-5 of Table 3. The results indicated that
the use of ClTi(O-i-Pr)3 instead of Ti(O-i-Pr)4 resulted in better
yield (entry 1 Vs 2).19 It can also be seen that the yield was
dependent on the nature of the ester group, and the isopropyl
ester 10c gave the highest and most synthetically useful yield
of 73%.
a All reactions were carried out using 1.0 equiv of an olefinic
carbonate (4), 1.3 equiv of Ti(O-i-Pr)4, and 2.6 equiv of i-PrMgCl.
The reaction mixture was stirred for 1 h at -45 ∼ -40 °C, and then
3 N HCl was added at -40 °C. b Treatment of the reaction mixture
with D2O instead of 3 N HCl gave the product containing >98% D
(1H-NMR analysis). c Isolated yield based on 4. d Obtained as a 1:1
mixture of diastereomers. e No INAS product was observed by 1H NMR
(see text).
Scheme 4
Although explanation of the effect of R2 in 10 on the yield
of the INAS reaction product must await further study, isopropyl
esters of a variety of acetylenic acids were subjected to the
reaction. As revealed by entries 6-8 in Table 3, the carbonate
10e which has one more carbon between the triple bond and
ester group compared to 10c, reacted similarly to afford the
corresponding R-alkylidene cyclohexanone in good yield, while
the substrates 10f and 10g which have two more or one less
carbon, respectively, did not provide the corresponding INAS
reaction products. These results might be caused by the fact
that the formation of transition states leading to four/seven-
membered cyclic ketones are disfavored by entropy as well as
enthalpy compared to those giving rise to five/six-membered
expected δ-lactone derivative, but gave a complex mixture of
products including the coupling product with propene (entry
8). This finding strongly indicates the importance of a facile
INAS path for the success of the reaction with olefinic
substrates. The sluggish reaction of ethyl carbonate derived
from (E)-3-hexen-1-ol which resulted in a lower yield compared
to the corresponding Z isomer (entry 5 Vs 6) may also be
attributed to the slower reaction rate of the INAS path because
of steric and/or conformational requirements.
The titanium compounds 6 can be intercepted with benzal-
dehyde or iodine as exemplified by the reactions shown in
Scheme 4. Thus, starting from 6, the addition product with
benzaldehyde was obtained as a mixture of lactones 7 and 8 in
61% total yield. It should be noted, however, that the reaction
with aliphatic aldehydes such as propanal did not proceed in
(18) For reviews, see: Kano, S.; Shibuya, S.; Ebata, T. Heterocycles
1980, 14, 661. Rao, Y. S. Chem. ReV. 1976, 76, 625. Grieco, P. A. Synthesis
1975, 67.
(19) The synthesis of 1 from ClTi(O-i-Pr)3 and i-PrMgX was reported
by Corey.8d One of the referees suggested (η2-propene)Ti(i-PrO)Cl as the
most likely species. However, this possibility seems to be slight because
use of Cl2Ti(O-i-Pr)2/2i-PrMgBr for the INAS reaction of 10c resulted in
low yield of INAS product (less than 10% yield) and recovery of 10c (∼70%
yield).

2212 J. Am. Chem. Soc., Vol. 118, No. 9, 1996
Okamato et al.
Table 3. Preparation of R-Alkylidenecycloalkanones by Reaction
of Esters 10 of Acetylenic Acids Using ClTi(O-i-Pr)3/2i-PrMgBra
Scheme 5
afforded the corresponding furan 12 or 13 in 44% or 69% yield,
respectively.22
INAS Reaction of Esters Derived from Acetylenic Alco-
hols. Since R,â-unsaturated ketones are valuable intermediates
in organic synthesis, development of an efficient methodology
for their preparation has attracted continued interest.20 The
results of Ti(II)-mediated INAS reactions of acetylenic carbon-
ates and esters of acetylenic acids led us to anticipate that
acetylenic esters of the type 14 might react in a similar fashion
and, thus, to afford a new general method for synthesis of R,â-
unsaturated ketones (eq 5).
Viability of the above concept was studied using 5-(trimeth-
ylsilyl)-4-pentynyl acetate (14a) as the substrate. To a solution
of 14a and Ti(O-i-Pr)4 (1.0 equiv) in ether was added i-PrMgBr
(2.0 equiv) at -78 °C, and the mixture was stirred at -50 ∼-40
°C for 1 h to furnish the expected R,â-unsaturated ketone 15a
in only 15% yield as the sole identified product even though
the starting 14a was consumed completely. Although the yield
is low, presumably due to further intermolecular carbonyl
addition reactions because of the enhanced reactivity of the
resulting ketone,10a,14 it was reproducible and was not reduced
even under prolonged reaction time. These findings suggested
to us that the reaction might involve at least two different
alkenyltitanium species, one of which must be free of the
problems arising from intermolecular condensation. With the
expectation of this possibility, we continued our efforts to find
the reaction conditions for the development of this approach to
a synthetically useful level, and we found that the use of 2 equiv
of ClTi(O-i-Pr)3/2i-PrMgBr reagent resulted in 68% yield of
15a.
Encouraged by this finding, we subjected a variety of esters
derived from acetylenic alcohols to the reaction with 2 equiv
of ClTi(O-i-Pr)3/2i-PrMgBr, and the results are summarized in
Table 4. It can be seen from the table that the esters 14 having
two, three, or even four carbons between the acetylene and ester
groups were good substrates, although in the last case (entry 2)
the yield is a little bit lower. It should be noted that in some
cases the reaction products were isolated as the corresponding
hemiacetals.
a Conditions: 1.0 equiv of 10, 1.5 equiv of ClTi(O-i-Pr)3, and 3.0
equiv of i-PrMgBr in Et2O at -50 ∼ -40 °C for 1 h. b Only one
stereoisomer was observed in all cases according to 1H- and 13C-NMR
data. The double-bond stereochemistry is (E)-configuration determined
by NOE-difference experiments. c The reaction was carried out using
Ti(O-i-Pr)4 instead of ClTi(O-i-Pr)3. d 1H-NMR yields using an internal
standard. e Deuterolysis of the reaction mixture gave the product
containing >98% D (1H-NMR analysis). f The same product was
obtained in 36% yield from methyl 6-(trimethylsilyl)hex-5-ynoate.
g 41% yield of isopropyl (Z)-8-(trimethylsilyl)oct-7-enoate was obtained.
h 35% yield of isopropyl (Z)-hept-4-enoate was obtained. i 45% of 10k
was recovered; the product and 10k were inseparable.
ketones. It can also be seen that the reaction of 10 which
contains a phenyl and/or ether group(s) as a part of the tether
between the triple bond and ester group proceeded smoothly to
afford the corresponding cyclic ketones in good to excellent
yields (entries 11 and 12). In any event, the present reaction
provides an efficient and general method for synthesis of
alkenyltitanium compounds having five- or six-membered cyclic
ketone fragment.20
The presence of the titanium intermediate 11 was confirmed
by deuterolysis (entries 4 and 6). The alkenyltitanium 11 can
also be intercepted with iodine or aldehydes as exemplified by
Scheme 5. In the case of the reaction with aldehydes, as
expected, the addition products were converted into the corre-
sponding furans during acidic workup.21 Thus, addition of
butanal or benzaldehyde to the reaction mixture of 10c and 1
Since a variety of 14 can be readily obtained by reactions of
acetylenic alcohols with carboxylic acids or their derivatives,
the present reaction which enables the transfer of the acyl group
(20) Patai, S.; Rappoport, Z., Eds. The Chemistry of Enones; Wiley:
Chichester, 1989; Vol 1. Ullenius, C.; Christenson, B. Pure Appl. Chem.
1988, 60, 57. For tri- and tetrasubstituted R,â-enones, see: Dieter, R. K.;
Silks, L. A., III. J. Org. Chem. 1986, 51, 4687 and references cited therein.
(21) Nishiyama, H.; Sasaki, M.; Itoh, K. Chem. Lett. 1981, 1363 and
references cited therein.
(22) For reviews on substituted furans and their utility, see: Compre-
hensiVe Heterocyclic Chemistry; Meth-Cohn, O., Ed.; Pergamon Press: New
York, 1984; Vol. 1. Meyers, A. I. Heterocycles in Organic Synthesis; Wiley
and Sons: New York, 1973. Lipshutz, B. H. Chem. ReV. 1986, 86, 795.
For recent synthetic methods, see: Katritzky, A. R.; Li, J.; Gordeer, M. F.
J. Org. Chem. 1993, 58, 3038 and references cited therein.

Intramolecular Nucleophilic Acyl Substitution Reactions
J. Am. Chem. Soc., Vol. 118, No. 9, 1996 2213
Experimental Section
Table 4. Preparation of R,â-Unsaturated Ketones by Reaction of
Esters 14 Derived from Acetylenic Alcohols Using ClTi(O-i-Pr)3/
2i-PrMgBra
General. Infrared spectra were recorded on a JASCO A-100 IR
spectrometer. 1H-NMR spectra were measured at 300 MHz on a Varian
Gemini-300 spectrometer with CDCl3 as a solvent at ambient temper-
ature, and the chemical shifts were described in parts per million
downfield from tetramethylsilane (δ ) 0 ppm) or based on residual
CHCl3 (δ ) 7.26 ppm) as an internal standard. 13C-NMR spectra were
recorded at 75 MHz on a Varian Gemini-300 spectrometer with CDCl3
as a solvent and referenced to the central line of the solvent (δ ) 77.0
ppm) The coupling constants (J) are reported in hertz. Mass spectra
(MS, EI, 70 eV) were measured on a Shimadzu QP-5000 GC mass
spectrometer. High resolution mass spectra (HRMS, EI, 70 eV) were
measured on a JEOL JMS-SX102 spectrometer. Analytical thin-layer
chromatography (TLC) was performed on aluminum sheets precoated
with silica gel (Merck, Kieselgel 60 F254). Visualization was ac-
complished by UV light (254 nm), KMnO4, phosphomolybdic acid,
iodine, and vanillin. All experiments were conducted under argon
atmosphere in oven-dried flasks. Tetrahydrofuran and diethyl ether
were distilled from sodium benzophenone ketyl immediately prior to
use.
Materials. Ti(O-i-Pr)4, benzaldehyde, propanal, and butanal were
distilled and stocked under argon. ClTi(O-i-Pr)3 was prepared from
Ti(O-i-Pr)4 and TiCl4 according to the procedure described in the
literature23 and stocked as a 2.0 M of ethereal solution under argon.
i-PrMgBr and i-PrMgCl were prepared from commercial magnesium
turnings and 2-bromo- or 2-chloropropane according to the conventional
procedure as a 1.1-1.8 M of ethereal solution, titrated, and stocked
under argon. The carbonates 2 and 4 were prepared from the
corresponding acetylenic or olefinic alcohols by treatment with ethyl
chloroformate and pyridine in ether.24 Compounds 10a-i were
prepared from the acetylenic acids, which were obtained by Jones
oxidation reaction of the corresponding alcohols, by treatment with
oxalic acid monochloride in benzene followed by addition of alcohol
(MeOH or EtOH) or a THF solution of lithium alcoholate (i-PrOLi or
t-BuOLi). Compound 10j was obtained from 2-[(trimethylsilyl)ethynyl]-
phenol25 by treatment with isopropyl iodoacetate and NaH in THF.
Compound 10k was synthesized from 2-[(trimethylsilyl)ethynyl]ben-
zaldehyde26 by Reformatsky reaction using isopropyl iodoacetate
followed by silylation. Compounds 14a-h were prepared from
acetylenic alcohols by treatment with the corresponding acid chloride
or anhydride in pyridine. Compounds 2, 4, 10, and 14 thus prepared
were purified by distillation and/or column chromatography prior to
use. Other reagents were purchased from commercial source and were
used without purification.
a Conditions: 1.0 equiv of 14, 2.3 equiv of ClTi(O-i-Pr)3, and 4.6
equiv of i-PrMgBr in E2O at -50 ∼ -40 °C for 1 h. b Only one
stereoisomer was observed in all cases according to 1H- and 13C-NMR
data. The double-bond stereochemistry is (E)-configuration determined
by NOE-difference experiments. c Treatment of the reaction mixture
with D2O afforded 15 contain >99% D (1H-NMR analysis) in all cases.
d 1H-NMR yield using an internal standard. e 9% of (Z)-6-(trimethyl-
silyl)hex-5-en-1-yl acetate was coproduced. f 19% of (Z)-6-(trimethyl-
silyl)hex-5-en-1-yl pivaloate was coproduced.
from oxygen to carbon provides a practical and general method
for preparation of a wide range of R,â-unsaturated ketones.
So far we have described the synthesis of R,â-unsaturated
ketones 15 by hydrolysis of the reaction product of 14 and 1.
Since the reaction affords the alkenyltitanium intermediate
shown in eq 5, which was confirmed by deuterolysis (see
footnote c in Table 4), it potentially expands the synthetic
application of this reaction. For example, condensation with
aldehydes can be used for synthesis of tetrasubstituted furan
derivatives22 as exemplified by eq 6.
Ti(II)-Mediated INAS Reaction of Carbonates 2 of Acetylenic
Alcohols. Preparation of Vinyl Titanium Reagents. To a solution
of Ti(O-i-Pr)4 (0.65 mmol) and an acetylenic carbonate (2) (0.50 mmol)
in ether (7.5 mL) was added dropwise i-PrMgBr (1.30 mmol, in ether)
at -50 °C. The resulting yellow solution was stirred for 1 h at -45
°C to -40 °C (the color of the mixture became red brown) to give a
solution of the alkenyltitanium reagent ready for the next reactions.
Hydrolysis. To a solution of the alkenyltitanium reagent prepared
above was added 1 N HCl (5 mL) at -40 °C. The mixture was warmed
up to room temperature and stirred for 30 min. The organic layer was
separated, and the aqueous layer was extracted with ether (10 mL).
The combined organic layers were washed with saturated aqueous
NaHCO3 (5 mL), dried over anhydrous MgSO4, and concentrated under
reduced pressure. The residue was purified by column chromatography
on silica gel to afford an R-alkylidene lactone and/or an R,â-unsaturated
ester. Deuterolysis. To a solution of the alkenyltitanium reagent was
added D2O (1.0 mL) at -40 °C. The mixture was warmed up to room
temperature and stirred for 15 min. To the resulting white suspension
was added 1 N HCl (5 mL), and the mixture was stirred for additional
30 min. Usual extractive workup with ether as described above and
concentration of the combined organic extracts furnished the crude
Conclusion
Ti(O-i-Pr)4/2i-PrMgBr and/or ClTi(O-i-Pr)3/2i-PrMgBr re-
agent mediates INAS reactions of unsaturated compounds to
afford organotitanium compounds containing functional groups.
Because of the versatility of organotitanium compounds, the
chemistry developed here provides an efficient, general method
for the synthesis of butenolides, butanolides, vinyl cyclic
ketones, R,â-unsaturated ketones, and furans. Moreover, the
reaction is practical since the reaction uses nontoxic, com-
mercially available inexpensive starting materials, and the
reaction procedure is operationally simple. Thus, the reaction
would be widely applicable in synthetic organic chemistry.
(23) Reetz, M. T.; Steinbach, R.; Kesseler, K. Angew. Chem., Int. Ed.
Engl. 1982, 21, 864. Angew. Chem. Suppl. 1982, 1899.
(24) Tsuji, J.; Sato, K.; Okumoto, H. J. Org. Chem. 1984, 49, 1341.
(25) Barton, T. J.; Groh, B. L. J. Org. Chem. 1985, 50, 158.
(26) Austin, W. B.; Bilow, N.; Kelleghn, W. J.; Lau, K. S. Y. J. Org.
Chem. 1981, 46, 2280.

2214 J. Am. Chem. Soc., Vol. 118, No. 9, 1996
Okamato et al.
1450, 1360, 1240, 1215, 1090, 1045, 1020, 850, 830, 755, 680 cm-1
Anal. Calcd for C12H24O3Si: C, 58.97; H, 9.90. Found: C, 59.56; H,
10.02.
Reaction with Benzaldehyde. To a solution of the alkenyltitanium
reagent prepared above from 1.3 mmol of Ti(O-i-Pr)4, 1.0 mmol of 2,
and 2.6 mmol of i-PrMgBr was added PhCHO (212 mg, 2 mmol or 53
mg, 0.5 mmol) at -40 °C. The mixture was slowly warmed to 0 °C
over 1 h and hydrolyzed by addition of 1 N HCl (5 mL). After stirring
at ambient temperature for 30 min and the following extractive workup
as described above, the crude product was purified by column
chromatography on silica gel.
monodeuterated product which was analyzed by 1H NMR. In all cases
only one stereoisomer was observed on 1H- and 13C-NMR analysis, and
the assignment of double bond stereochemistry is based on the chemical
shift value of the vinyl proton (for R-alkylidene lactones, see: references
27-29; for R,â-unsaturated esters, see: references 40).
(E)-2-[(Trimethylsilyl)methylene]-4-butanolide27 (entry 1 in Table
1): 1H-NMR and IR spectral data were in good agreement with those
described in the literature.
(E)-2-[(Trimethylsilyl)methylene]-4-ethyl-4-butanolide (entry 2
in Table 1): 1H NMR δ 0.17 (s, 9H), 0.98 (t, J 6.9, 3H), 1.67 (m,
2H), 2.50 (ddd, J 17.4, 6.0, 2.4, 1H), 3.01 (ddd, J 17.4, 6.6, 2.4, 1H),
4.43 (tt, J 6.3, 6.3, 1H), 6.88 (t, J 2.4, 1H); 13C NMR δ -1.5, 8.9,
29.2, 33.0, 78.2, 138.9, 140.2, 170.0; IR (neat) 2960, 1755, 1630, 1345,
1300, 1245, 1180, 1000, 960, 835, 750, 685 cm-1. Anal. Calcd for
C10H18O2Si: C, 60.56; H, 9.15. Found: C, 60.85; H, 9.62.
.
2-(2-Hydroxyethyl)-3-(trimethylsilyl)-4-phenyl-2-buten-4-olide (en-
try 1 in Table 1): 1H NMR δ 0.04 (s, 9H), 2.77 (t, J 5.8, 2H), 3.87
(t, J 5.8, 2H), 5.88 (s, 1H), 7.17 (m, 2H), 7.36 (m, 3H); 13C NMR δ
-1.1, 29.9, 61.1, 87.7, 128.0, 128.8, 129.5, 134.8, 138.4, 165.0, 175.1;
IR (Nujol) 3450, 1740, 1705, 1245, 1065, 1050, 1035, 975, 880, 840,
(E)-2-[(Trimethylsilyl)methylene]-4-phenyl-4-butanolide (entry 3
in Table 1): 1H NMR δ 0.20 (s, 9H), 2.86 (ddd, J 17.1, 6.6, 3.0, 1H),
3.40 (ddd, J 17.1, 8.1, 2.7, 1H), 5.51 (t, J 7.4, 1H), 7.02 (m, 1H), 7.37
(m, 5H); 13C NMR δ -1.4, 36.4, 77.7, 125.4, 128.5, 128.8, 139.5, 140.0,
170.0; IR (Nujol) 1730, 1640, 1300, 1280, 1170, 1005, 970, 855, 820,
760, 690 cm-1
. Anal. Calcd for C15H20O3Si: C, 65.18; H, 7.29.
Found: C, 65.22; 7.45.
2-(2-Hydroxybutyl)-3-(trimethylsilyl)-4-phenyl-2-buten-4-olide (en-
try 2 in Table 1): 1H NMR δ 0.02 (s, 9H), 1.01 (t, J 6.0, 3H), 1.58
(m, 2H), 2,56 (dd, J 11.7, 6.6, 1H), 2.70 (d, J 11.7, 1H), 2.75 (br s,
1H), 3.86 (m, 1H), 5.88 (s, 1H), 7.20 (m, 2H), 7.36 (m, 3H); 13C NMR
δ -1.1, 10.0, 30.9, 34.0, 71.8, 87.8, 128.0, 128.8, 129.5, 134.9, 138.7,
164.8, 175.3; IR (Nujol) 3450, 2950, 1720, 1240, 1115, 1075, 980,
835, 745, 685 cm-1. Anal. Calcd for C17H24O3Si: C, 67.06; H, 7.94.
Found: C, 66.64; H, 8.11.
740, 680 cm-1
. Anal. Calcd for C14H18O2Si: C, 68.25; H, 7.36.
Found: C, 68.46; H, 7.46.
(E)-2-Heptylidene-4-butanolide28 and (E)-3-(Ethoxycarbonyl)-3-
decen-1-ol (entry 4 in Table 1): 13C NMR δ 13.9, 22.4, 25.0, 28.0,
28.9, 30.2, 31.5, 65.3, 125.1, 140.9, 171.1 (1H NMR and IR spectral
data were in good agreement with those described in the literature)
2-(2-Hydroxyethyl)-3-phenyl-4-ethyl-2-buten-4-olide (entry 5 in
Table 1): 1H NMR δ 0.87 (t, J 7.2, 3H), 1.50 (m, 1H), 1.82 (br s,
1H), 1.91 (m, 1H), 2.73 (m, 2H), 3.90 (m, 2H), 5.38 (m, 1H), 7.39-
7.50 (m, 5H); 13C NMR δ 8.1, 25.5, 28.0, 60.8, 83.4, 125.8, 127.7,
129.1, 129.9, 131.2, 162.0, 175.0; IR (Nujol) 3375, 1720, 1630, 1320,
1
and H NMR δ 0.89 (t, J 6.9, 3H), 1.31 (m, 9H), 1.45 (m, 2H), 1.90
(br s, 1H), 2.22 (dt, J 7.5, 7.2, 2H), 2.60 (t, J 6.6, 2H), 3.69 (t, J 6.6,
2H), 4.20 (q, J 6.9, 2H), 6.98 (t, J 7.5, 1H); IR (neat) 3425, 2970,
2940, 2860, 1710, 1645, 1470, 1370, 1280, 1190, 1145, 1100, 1045,
860, 760 cm-1
. Anal. Calcd for C13H24O3: C, 68.38; H, 10.59.
1160, 1100, 1065, 1025, 960, 750, 680 cm-1
. Anal. Calcd for
Found: C, 68.08; H, 10.61, respectively.
C14H16O3: C, 72.39; H, 6.94. Found: C, 71.79; H, 6.99.
(E)-2-Benzylidene-4-butanolide29 (entry 5 in Table 1): mp 117
°C; 1H NMR δ 3.26 (dt, J 7.2, 2.7, 2H), 4.47 (t, J 7.2, 2H), 7.40-7.55
(m, 5H), 7.58 (t, J 2.7, 1H); 13C NMR δ 27.4, 65.4, 123.5, 128.9, 129.8,
129.9, 134.6, 136.6, 172.2.
2-(3-Hydroxypropyl)-3-(trimethylsilyl)-4-phenyl-2-buten-4-
olide (entry 6 in Table 1): 1H NMR δ 0.01 (s, 9H), 1.84 (tt, J 7.5,
6.0, 2H), 2.57 (t, J 7.5, 2H), 2.70 (br s, 1H), 3.69 (t, J 6.0, 2H), 5.81
(s, 1H), 7.14 (m, 2H) 7.33 (m, 3H); 13C NMR δ -1.2, 22.2, 32.2, 61.4,
87.2, 127.9, 128.7, 129.4, 135.0, 140.9, 163.2, 175.0; IR (neat) 3400,
2950, 1740, 1620, 1460, 1320, 1260, 1105, 1070, 1000, 845, 760, 705
cm-1. Anal. Calcd for C16H22O3Si: C, 66.17; H, 7.63. Found: C,
66.78; H, 7.76.
2-(3-Hydroxypropyl)-3-ethyl-4-phenyl-2-buten-4-olide (entry 7 in
Table 1): 1H NMR δ 0.98 (t, J 7.8, 3H), 1.81 (tt, J 7.5, 6.0, 2H), 2.02
(dq, J 15.6, 7.8, 1H), 2.45 (dq, J 15.6, 7.8, 1H), 2.47 (t, J 7.5, 2H),
2.78 (br s, 1H), 3.67 (t, J 6.0, 2H), 5.75 (s, 1H), 7.20 (m, 2H), 7.38
(m, 3H); 13C NMR δ 12.3, 19.4, 19.7, 31.1, 61.2, 83.9, 126.1, 126.8,
128.9, 129.2, 134.6, 165.4, 175.0; IR (neat) 3400, 2920, 1735, 1660,
1450, 1300, 1255, 1160, 1030, 1000, 840, 750, 695 cm-1. Anal. Calcd
for C15H18O3: C, 73.15; H, 7.37. Found: C, 72.66; H, 7.15.
2-[2-(Hydroxymethyl)phenyl]-3-(trimethylsilyl)-4-phenyl-2-buten-
4-olide (entry 9 in Table 1) (74:26 mixture of two diastereomers):
1H NMR δ -0.20 and -0.27 (s, 9H), 3.2 and 2.6 (br s, 1H), 4.48 and
4.55 (d, J 12.8, 1H), 4.60 and 4.71 (d, J 12.8, 1H), 6.08 and 6.04 (s,
1H), 7.15-7.60 (m, 9H); 13C NMR δ -0.94 and -0.71, 63.2 and 63.5,
87.7 and 88.0, 127.6, 127.9, 128.8, 129.0, 129.4, 129.6, 129.7, 129.9,
130.0, 130.5, 130.7, 134.5, 139.9, 141.0, 166.4, 168.0, 174.1; IR (Nujol)
3520, 1735, 1245, 1160, 1090, 1010, 995, 895, 845, 765, 750, 700
cm-1. Anal. Calcd for C20H22O3Si: C, 70.97; H, 6.55. Found: C,
70.69; H, 6.56.
2-[2-(1-Hydroxyethyl)phenyl]-3-(trimethylsilyl)-4-phenyl-2-buten-
4-olide (entry 10 in Table 1) (the mixture of three diastereomers): 1H
NMR δ -0.22 and -0.17 (s, 9H) 1.48 and 1.55 (d, J 7.5, 3H), 4.78,
4.83 and 4.96 (q, J 7.5, 1H), 6.04, 6.07 and 6.10 (s, 1H), 7.10-7.70
(m, 9H); 13C NMR (the two main diastereomers) δ -1.56 and -1.10,
225 and 24.8, 66.7 and 68.0, 87.2 and 88.1, 125.8, 126.1, 126.9, 127.2,
127.9, 128.0, 128.9, 129.6, 129.7, 130.0, 130.2, 130.3, 134.8, 135.0,
141.4, 144.3, 144.6, 166.6 and 167.0, 173.5 and 174.2; IR (Nujol) 3425,
1740, 1310, 1245, 1195, 1155, 1070, 995, 960, 895, 840, 750, 690
cm-1. Anal. Calcd for C21H24O3Si: C, 71.55; H, 6.86. Found: C,
71.34; H, 6.71.
(E)-2-[(Trimethylsilyl)methylene]-5-pentanolide (entry 6 in Table
1): 1H NMR δ 0.14 (s, 9H), 1.92 (tt, J 6.6, 5.4, 2H), 2.65 (t, J 6.6,
2H), 4.30 (dt, J 2.1, 5.4, 2H), 7.18 (t, J 2.1, 1H); 13C NMR δ -1.5,
23.2, 27.8, 69.0, 139.9, 145.6, 165.6; IR (neat) 2975, 1725, 1615, 1410,
1325, 1255, 1170, 1120, 1090, 980, 960, 850, 770, 700 cm-1. Anal.
Calcd for C9H16O2Si: C, 58.65; H, 8.75. Found: C, 58.28; H, 8.85.
(E)-2-Propylidene-5-pentanolide29a (entry 7 in Table 1): 13C NMR
δ 12.4, 21.4, 22.5, 23.3, 68.4, 124.8, 147.6, 166.5. 1H NMR and IR
spectral data were in good agreement with those described in the
literature.
(E)-4-[(Trimethylsilyl)methylene]-3-isochromanone (entry 9 in
1
Table 1): mp 68.5-69.0 °C; H NMR δ 0.20 (s, 9H), 5.23 (s, 2H),
7.16 (s, 1H), 7.20-7.50 (m, 4H); 13C NMR δ 0.26, 69.0, 124.5, 127.1,
128.0, 128.8, 132.0, 132.5, 139.7, 143.1, 168.3; IR (Nujol) 1750, 1730,
1250, 1225, 1180, 1170, 1035, 940, 905, 865, 840, 795, 760, 695 cm-1
.
Anal. Calcd for C13H16O2Si: C, 67.20; H, 6.94. Found: C, 66.94; H,
7.11.
(E)-1-Methyl-4-[(trimethylsilyl)methylene]-3-isochromanone (en-
try 10 in Table 1): 1H NMR δ 0.18 (s, 9H), 1.68 (d, J 6.6, 3H), 5.42
(q, J 6.6, 1H), 7.14 (s, 1H), 7.20-7.50 (m, 4H); 13C NMR δ 0.24,
20.8, 75.9, 123.6, 127.3, 127.9, 128.9, 132.0, 136.7, 140.2, 142.4, 168.3;
IR (neat) 1960, 1900, 1730, 1600, 1580, 1485, 1450, 1370, 1350, 1325,
1250, 1205, 1185, 1170, 1075, 1040, 1015, 915, 885, 860, 840, 790,
760, 690 cm-1
. Anal. Calcd for C14H18O2Si: C, 68.25; H, 7.36.
Found: C, 68.63; H, 7.80.
Ethyl (E)-2-(4-Hydroxybutyl)-3-(trimethylsilyl)propenoate (entry
8 in Table 1): 1H NMR δ 0.19 (s, 9H), 1.30 (t, J 6.9, 3H), 1.45-
1.70 (m, 4H), 2.09 (br s, 1H), 2.41 (m, 2H), 3.66 (t, J 6.0, 2H), 4.19
(q, J 6.9, 2H), 6.81 (s, 1H); IR (neat) 3375, 2940, 2850, 1705, 1595,
(27) Takeuchi, R.; Sugiura, M. J. Chem. Soc. Perkin Trans. 1 1993, 1031.
(28) Tanaka, K.; Tamura, N.; Kaji, A. Chem Lett. 1980, 595. Tanaka,
K.; Uneme, H.; Yamagisi, N.; Tanikaga, R.; Kaji, A. Bull. Chem. Soc. Jpn.
1980, 53, 2910.
2-(4-Hydroxybutyl)-3-(trimethylsilyl)-4-phenyl-2-buten-4-olide (en-
(29) (a) Murray, A. W.; Reid, R. G. Synthesis 1985, 35. (b) Bachi, M.
D.; Bosch, E. J. Org. Chem. 1992, 57, 4696.
try 8 in Table 1): 1H NMR δ 0.06 (s, 9H), 1.71 (m, 4H), 1.89 (br s,

Intramolecular Nucleophilic Acyl Substitution Reactions
J. Am. Chem. Soc., Vol. 118, No. 9, 1996 2215
1H) 2.52 (m, 2H), 3.76 (m, 2H), 5.82 (s, 1H), 7.17 (m, 2H) 7.38 (m,
3H); 13C NMR δ -1.1, 25.5, 25.9, 32.5, 62.3, 86.9, 127.9, 128.8, 129.4,
135.2, 141.4, 162.1, 174.5; IR (neat) 3440, 2960, 2875, 1745, 1620,
1500, 1460, 1415, 1320, 1255, 1110, 1075, 1035, 995, 880, 845, 770,
. Anal. Calcd for C17H24O3Si: C, 67.06; H, 7.94.
Found: C, 67.02; H, 7.94.
INAS Reaction of Esters 10 of Acetylenic Acids. Preparation
of Vinyltitanium Reagent 11. To a solution of ClTi(O-i-Pr)3 (0.75
mL, 2.0 M in ether, 1.5 mmol) and 10 (1.0 mmol) in ether (10 mL)
was added dropwise i-PrMgBr (3.0 mmol, in ether) at -78 °C. The
resulting mixture was warmed up to -50 °C over 0.5 h and stirred for
1-1.5 h at -50 °C to -45 °C to give the vinyltitanium reagent 11
ready for the next reactions.
Hydrolysis or Deuterolysis. To a solution of the vinyltitanium
reagent 11 prepared above was added H2O or D2O (0.5 mL) at -45
°C. The mixture was warmed up to room temperature over 0.5 h. After
addition of NaF (1.5 g) and Celite (1.5 g), the mixture was stirred for
1 h and then filtered through a pad of Celite. After concentration of
the filtrate in Vacuo, the residue was purified by column chromatography
on silica gel to afford the R-alkylidene cycloalkanone. Deuterolysis
gave the product contained >98% D on 1H NMR analysis (for entries
4 and 6 in Table 3). Only one stereoisomer was obtained in all cases
on 1H- and 13C-NMR analysis, and the double bond stereochemistry is
(E)-configuration determined by NOE-difference experiments.
Spectral data of (E)-2-[(trimethylsilyl)methylene]cyclohexanone37
(entry 6), (E)-2-(2,2-dimethylpropylidene)cyclohexanone38 (entry 9),
and (E)-2-benzylidenecyclohexanone39 (entry 10) obtained by the
reactions shown in Table 3 are in good agreement with those described
in the literature.
760, 700 cm-1
INAS Reaction with Olefinic Carbonates 4. Preparation of
Organotitanium Reagent 6. To a stirred solution of Ti(O-i-Pr)4 (1.3
mmol) and an olefinic carbonate (4) (1.0 mmol) in ether (7 mL) was
added dropwise i-PrMgCl (2.6 mmol, in ether) at -50 °C. The resulting
mixture was stirred for 1 h at -45 °C to -40 °C to give the titanium
reagent having lactone moiety (6) ready for the next reactions.
Hydrolysis. To a solution of the organotitanium reagent 6 prepared
above was added 3 N HCl (5 mL), and the reaction mixture was allowed
to stir for 30 min at room temperature. The organic layer was separated,
and the aqueous layer was extracted with ether (2 × 20 mL). The
combined organic layers were dried over Na2SO4, concentrated, and
chromatographed on silica gel to give the butenolide. Deuterolysis.
In a similar way quenching the organotitanium reagent 6 with D2O
followed by usual workup affords the monodeuterated product which
1
was analyzed by H NMR.
Spectral data of 2-methyl-4-butanolide30 (entry 1), 2,4-dimethyl-4-
pentanolide31 (entry 2), 2-methyl-4-phenyl-4-butanolide32 (entry 3), 2,3-
dimethyl-4-butanolide33 (entry 4), 2-propyl-4-butanolide34 (entry 5 and
6), and ethyl 2-(2-hydroxyphenyl)propionate35 (entry 7) obtained by
the reactions in Table 2 are in good agreement with those described in
the literature.
(E)-2-[(Trimethylsilyl)methylene]cyclopentanone (entries 1-5 in
Table 3): 1H NMR δ 0.15 (s, 9H), 1.86-2.00 (m, 2H), 2.31 (t, J 7.9,
2H), 2.68 (dt, J 2.6, 7.3, 2H), 6.65 (t, J 2.6, 1H); 13C NMR δ -1.2,
19.5, 29.5, 37.3, 133.4, 150.8, 205.8; IR (neat) 2960, 1720, 1620, 1410,
1250, 1160, 840, 760, 690 cm-1; MS (EI) m/z (relative intensity,
Reaction with Benzaldehyde. Benzaldehyde (2.0 mmol) was added
at -45 °C to the titanium reagent 6 prepared as above, and the reaction
mixture was allowed to warm to ambient temperature over 1 h. After
stirring for additional 6 h, usual acidic workup followed by chroma-
tography afforded the butanolide as a mixture of isomers 7 and 8.
proposed ion), 168 (3.3, M+), 153 (100, M+ - CH3), 140 (20.1, M+
CH2CH2); HRMS calcd for C9H16OSi 168.0970, found 168.0970.
-
(E)-4-[(Trimethylsilyl)methylene]chroman-3-one (entry 11 in
Table 3): 1H NMR δ 0.21 (s, 9H), 4.55 (s, 2H), 7.00 (s, 1H), 7.02-
7.12 (m, 2H), 7.31 (dt, J 1.6, 7.7, 1H), 7.42 (d, J 7.7, 1H); 13C NMR
δ -0.26, 72.3, 118.0, 122.4, 124.1, 128.6, 130.4, 139.0, 142.2, 155.1,
197.3; IR (neat) 29060, 2900, 1710, 1600, 1580, 1560, 1480, 1460,
1250, 1050, 855, 755 cm-1. Anal. Calcd for C13H16O2Si: C, 67.20;
H, 6.94. Found: C, 66.73; H, 6.96.
2-(2-Phenyl-2-hydroxyethyl)-4-butanolide (7) and 2-(2-Hydroxy-
ethyl)-4-phenyl-4-butanolide (8). 7 and 8 were inseparable from each
other by chromatography, and 1H-NMR analysis was performed using
the mixture. 1H NMR δ 2.05 (m, 2H), 2.20-2.31 (m, 2H), 4.12-4.35
1
(m, 2H), 5.02 (dd, J 7.8, 4.3, 1H), 7.35 (m, 5H) and H NMR δ 1.86
(E)-4-[(Trimethylsilyl)methylene]-1-[(tert-butyldimethylsilyl)oxy]-
1,2,3,4-tetrahydronaphthalen-3-one (entry 12 in Table 3): The
product and 10k were inseparable from each other by preparative HPLC
and distillation, and 1H-NMR spectra was measured using the mixture.
1H NMR δ -0.01 (s, 3H), 0.12 (s, 3H), 0.14 (s, 9H), 0.85 (s, 9H),
2.71 (dd, J 6.2, 16.4, 1H), 2.77 (dd, J 4.3, 16.4, 1H), 4.97 (dd, J 4.3,
6.2, 1H), 7.00 (s, 1H), 7.22-7.48 (m, 4H). [Compound 10k: 1H NMR
δ -0.17 and -0.06 (2s, each 3H), 0.28 (s, 9H), 0.85 (s, 9H), 1.24 (d,
J 8.1, 6H), 2.56 (dd, J 8.6, 14.7, 1H), 2.63 (dd, J 4.2, 14.7, 1H), 4.95-
5.08 (m, 1H), 5.67 (dd, J 4.2, 8.6, 1H), 7.18 (dt, J 1.5, 7.7, 1H), 7.32
(dt, J 1.6, 7.7, 1H), 7.39 (d, J 7.7, 1H), 7.53 (d, J 7.7, 1H); 13C NMR
δ -5.3, -4.8, 18.0, 21.9, 25.7, 45.0, 67.5, 69.6, 99.8, 102.3, 120.0,
126.0, 126.9, 128.7, 131.7, 146.5, 170.2; IR (neat) 2950, 2880, 2150,
1740, 1480, 1380, 1250, 1115, 1085, 960, 870, 840, 760 cm-1. Anal.
Calcd for C23H38O3Si2: C, 65.98; H, 9.15. Found: C, 66.07; H, 9.08.].
Iodolysis. To a solution of the vinyltitanium reagent was added a
solution of iodine (508 mg, 2.0 mmol) in ether (8 mL) at -45 °C. The
mixture was warmed up to 0 °C over 0.5 h and quenched by addition
of 1 N HCl (5 mL). The organic layer was separated, and the aqueous
layer was extracted with ether (10 mL). The combined organic layers
were washed with saturated aqueous Na2S2O3 (10 mL) and NaHCO3
(5 mL), dried over MgSO4, and concentrated in Vacuo. The residue
was purified by column chromatography on silica gel to give the alkenyl
iodide.
(m, 1H), 2.03 (m, 1H), 2.49 (dd, J 9.0, 6.0, 2H), 2.87 (m, 1H), 3.81
(m, 2H), 5.62 (t, J 6.9, 1H), 7.35 (m, 5H), respectively.
For confirmation of the structure, the mixture of 7 and 8 was treated
with LiAlH4 (2 equiv) in ether (2.5 h, refluxing) to afford a single
product, 5-phenyl-3-(hydroxymethyl)pentane-1,5-diol, in 86% yield: 1H
NMR δ 1.45-1.85 (m, 4H), 1.92 (m, 1H), 2.33 (br s, 1H), 3.50-3.73
(m, 4H), 4.17 (br s, 2H), 4.79 (m, 5H); 13C NMR δ 34.8, 34.9, 41.5,
60.2, 65.7, 71.7, 125.6, 127.3, 128.4, 145.0; IR (neat) 3330, 2950, 1610,
1505, 1465, 1340, 1210, 1120, 1050, 1015, 920, 760, 705 cm-1
.
Iodolysis. Addition of I2 (5.0 equiv) in THF to the organotitanium
reagent 6 at -40 °C followed by usual acidic workup afforded the
intermediate 2-(iodomethyl)-4-butanolide (9) which upon treatment with
triethylamine in CH2Cl2 underwent dehydroiodination to furnish
2-methylene-4-butanolide. Spectral data of the product thus obtained
are in good agreement with those described in the literature.36 A small
amount of unstable intermediate 9 was purified by passing through a
1
short silica gel column for H-NMR analysis.
2-(Iodomethyl)-4-butanolide (9): 1H NMR δ 2.19 (m, 1H), 2.53
(m, 1H), 2.91 (m, 1H), 3.33 (dd, J 10.3, 7.9, 1H), 3.51 (dd, J 10.3, 3.9,
1H), 4.25 (m, 1H), 4.41 (m, 1H); 13C NMR δ 3.4, 29.3, 41.4, 65.8,
175.8.
(30) Toder, B. H.; Branca, S. J.; Smith, A. B. J. Org. Chem. 1977, 42,
904. Falbe, J.; Huppes, N.; Korte, F. Chem. Ber. 1964, 97, 863. See also
reference 29b.
(31) Sucrow, W.; Slopianka, M.; Winkler, D. Chem. Ber. 1972, 105,
1621.
(32) Nakamura, E.; Oshino, H.; Kuwajima, I. J. Am. Chem. Soc. 1986,
108, 13.
(Z)-2-[Iodo(trimethylsilyl)methylene]cyclopentanone. This com-
pound is not stable to stock for a long time, and the following analyses
were performed immediately after rapid column chromatography. 1H
NMR δ 0.28 (s, 9H), 1.90-2.03 (m, 2H), 2.52 (t, J 8.0, 2H), 2.73 (t,
(33) Mohr, P.; Waespe Sarcevic, N.; Tamm, C. HelV. Chem. Acta 1983,
66, 2501.
(37) Fleming, I.; Perry, D. A. Tetrahedron 1981, 37, 4027.
(38) Paterson, I. Tetrahedron 1988, 44, 4207.
(34) Wiley, R. A.; Zenk, P. C. Synthesis 1984, 695.
(35) Stibor, I.; Srogl, J.; Janda, M.; Rozinek, R. Collect. Czech. Chem.
Commun. 1977, 42, 992.
(36) Ksander, G. M.; McMurry, J. E.; Johnson, M. J. Org. Chem. 1977,
42, 1180.
(39) Takaki, K.; Yasumura, M.; Negoro, K. J. Org. Chem. 1983, 48,
54.
(40) Ireland, R. E.; Norbeck, D. W. J. Org. Chem. 1985, 50, 2198.
Cunico, R. F.; Lee, H. M.; Herbach, J. J. Organometal. Chem. 1973, 52,
C7. Tanikaga, R.; Miyashita, K.; Ono, N.; Kaji, A. Synthesis 1982, 131.

2216 J. Am. Chem. Soc., Vol. 118, No. 9, 1996
Okamato et al.
J 7.4, 2H); IR (neat) 2960, 2900, 1720, 1560, 1410, 1240, 1180, 860,
(E)-5-(Trimethylsilyl)-4-(phenylcarbonyl)pent-4-en-1-ol (15d): 1H
NMR δ 0.19 (s, 9H), 1.65-1.75 (m, 2H), 2.65 (t, J 7.7, 2H), 3.62 (t,
J 6.3, 2H), 6.18 (s, 1H), 7.38-7.44 (m, 2H), 7.48-7.54 (m, 1H), 7.69-
7.72 (m, 2H); 13C NMR δ -0.3, 28.2, 32.4, 62.1, 128.1, 129.6, 132.1,
137.6, 142.2, 154.9, 199.3; IR (neat) 3380, 2920, 1650, 1600, 1450,
1240, 1060, 850 cm-1. Anal. Calcd for C15H22O2Si: C, 68.65; H,
8.45. Found: C, 68.14; H, 8.66.
840, 750 cm-1
.
Reaction with Aldehyde. To a solution of the vinyltitanium reagent
11 prepared from 1.0 mmol of 10 was added aldehyde (1.5 mmol) at
-45 °C. The mixture was warmed up to room temperature over 0.5
h. After addition of 1 N HCl (5 mL), the organic layer was separated
and the aqueous layer was extracted with ether (10 mL). The combined
organic layers were washed with brine (5 mL), dried over MgSO4, and
concentrated in Vacuo. The residue was purified by column chroma-
tography on silica gel to give the furan.
(E)-5-(Trimethylsilyl)-4-[[(E)-prop-1-enyl]carbonyl]pent-4-en-1-
ol (15e). The product (colorless oil) contained a small amount of
impurity even after column chromatography, and the yield was
calculated based on 1H-NMR analysis using an internal standard which
indicated 97% chemical purity on weight. 1H NMR δ 0.21 (s, 9H),
1.59-1.68 (m, 2H), 1.92 (dd, J 6.4, 1.5, 3H), 2.52 (t, J 7.4, 2H), 3.57
(t, J 6.2, 2H), 6.55 (s, 1H), 6.69 (dd, J 15.2, 1.5, 1H), 6.82-6.94 (m,
1H); 13C NMR δ -0.3, 18.4, 27.1, 32.9, 62.0, 127.3, 140.3, 143.8,
156.4, 193.4; IR (neat) 3400, 2950, 1720, 1660, 1615, 1440, 1245,
2-Propyl-3-(trimethylsilyl)-4,5-dihydrocyclopenta[b]furan (12):
1H NMR δ 0.20 (s, 9H), 0.95 (t, J 7,4, 3H), 1.56-1.71 (m, 2H), 2.35-
2.47 (m, 2H), 2.47-2.55 (m, 2H), 2.57 (t, J 7.5, 2H), 2.56-2.68 (m,
2H); 13C NMR δ 0.03, 13.9, 23.0, 24.2, 24.6, 27.8, 31.7, 110.8, 130.6,
157.0, 164.8; IR (neat) 2910, 1760, 1710, 1470, 1260, 840 cm-1; MS
(EI) m/z (relative intensity, proposed ion), 222 (46.4, M+), 207 (13.2,
M+ - CH3), 193 (100, M+ - C2H5), 179 (5.2, M+ - C3H7), 149 (2.7,
M+ - Si(CH3)3). Anal. Calcd for C16H22OSi: C, 70.21; H, 9.97.
Found: C, 69.64; H, 10.30.
1050, 850 cm-1
.
(E)-2-Hydroxy-2-tert-butyl-3-[(trimethylsilyl)methylene]tet-
rahydropyran (15f): 1H NMR δ 0.17 (s, 9H), 1.22 (s, 9H), 1.57-
1.63 (m, 2H), 2.42 (t, J 7.8, 2H), 3.61 (t, J 6.2, 2H), 5.76 (s, 1H); 13
C
2-Phenyl-3-(trimethylsilyl)-4,5-dihydrocyclopenta[b]furan (13):
1H NMR δ 0.21 (s, 9H), 2.41-2.53 (m, 2H), 2.62 (t, J 6.4, 2H), 2.74
(t, J 7.1, 2H), 7.25-7.62 (m, 5H); 13C NMR δ 0.25, 24.2, 25.1, 27.9,
103.6, 113.0, 123.1, 127.6, 128.0, 128.6, 132.7, 158.9; IR (neat) 2970,
2860, 1600, 1540, 1480, 1250, 840, 760 cm-1; MS (EI) m/z (relative
intensity, proposed ion), 256 (100, M+), 241 (34.9, M+ - CH3). Anal.
Calcd for C16H20OSi: C, 74.95; H, 7.86. Found: C, 74.88; H, 8.12.
NMR δ -0.02, 28.2, 30.3, 32.4, 43.6, 62.3, 131.2, 156.7, 213.8; IR
(neat) 3430, 2960, 1730, 1680, 1600, 1260, 1140, 860 cm-1. Anal.
Calcd for C13H26O2Si: C, 64.41; H, 10.81. Found: C, 64.25; H, 10.67.
(E)-2-Hydroxy-2-(trifluoromethyl)-3-[(trimethylsilyl)methylene]-
tetrahydropyran (15g): 1H NMR δ 0.16 (s, 9H), 1.65-1.78 (m, 1H),
1.94-2.08 (m, 1H), 2.55-2.63 (m, 1H), 2.94 (s, 1H), 6.05 (s, 1H);
13C NMR δ 0.3, 24.9, 26.4, 61.2, 120.7, 124.7, 131.3, 146.9; IR (neat)
3400, 2890, 1720, 1630, 1450, 1250, 1190, 1080, 960, 860, 840, 750
cm-1. Anal. Calcd for C10H17F3O2Si: C, 47.23; H, 6.74. Found: C,
47.00; H, 7.07.
(E)-5-Phenyl-4-(phenylcarbonyl)pent-4-en-1-ol (15h): 1H NMR
δ 1.78-1.90 (m, 2H), 2.87 (t, J 7.4, 2H), 3.66 (t, J 6.0, 2H), 7.17 (s,
1H), 7.28-7.62 (m, 8H), 7.77 (d, J 6.9, 2H); 13C NMR δ 23.6, 31.5,
61.8, 128.2, 128.6, 128.7, 129.2, 129.6, 131.9, 135.3, 138.4, 140.9,
142.6, 199.9; IR (neat) 3400, 2950, 2850, 1720, 1650, 1595, 1500,
1450, 1320, 1250, 1060, 960, 760, 720, 700 cm-1. Anal. Calcd for
C18H18O2: C, 81.17; H, 6.81. Found: C, 80.79; H, 6.99.
INAS Reaction of Esters Derived from Acetylenic Alcohols.
Preparation of a Vinyltitanium Reagent. To a solution of an ester
derived from acetylenic alcohol (14) (1.0 mmol) and ClTi(O-i-Pr)3 (2.3
mmol) in ether (10 mL) was added i-PrMgBr (4.6 mmol, in ether) at
-78 °C. The resulting mixture was warmed up to -50 °C over 0.5 h
and was stirred for 1 h at -50 to -40 °C to give the vinyltitanium
reagent ready for the next reactions.
Hydrolysis. To a solution of the vinyltitanium reagent prepared
above was added 3 N HCl (5 mL) at -40 °C. The mixture was warmed
up to room temperature over 0.5 h. The organic layer was separated,
and the aqueous layer was extracted with ether (10 mL). The combined
organic layers were washed with saturated aqueous NaHCO3 (10 mL)
and dried over MgSO4. After concentration in Vacuo, the residue was
purified by column chromatography on silica gel to afford 15.
Deuterolysis. To a solution of the vinyltitanium reagent was added
D2O (1.0 mL) at -40 °C. The mixture was warmed up to 0 °C over
1 h, and then 3 N HCl (5 mL) was added. After stirring for 10 min at
ambient temperature, the organic layer was separated and the aqueous
layer was extracted with ether (10 mL). The combined organic layers
were washed with saturated aqueous NaHCO3 (10 mL) and dried over
MgSO4. After concentration in Vacuo, the residue was purified by
column chromatography on silica gel to afford 15 containing >98% D
Reaction with Benzaldehyde. To a solution of the vinyltitanium
reagent prepared from 1.0 mmol of 4-(trimethylsilyl)-3-butynyl acetate
was added PhCHO (1.5 mmol) at -45 °C. The mixture was warmed
up to room temperature over 1 h, and then 1 N HCl (5 mL) was added.
After stirring for 0.5 h at ambient temperature, the organic layer was
separated and the aqueous layer was extracted with ether (10 mL). The
combined organic layers were washed with brine (5 mL), dried over
MgSO4, and concentrated in Vacuo. The residue was purified by
column chromatography on silica gel to give the furan.
2-Phenyl-3-(trimethylsilyl)-4-(2-hydroxyethyl)-5-methylfuran: 1H
NMR δ 0.16 (s, 9H), 2.31 (s, 3H), 2.74 (t, J 6.9, 2H), 3.76 (t, J 6.9,
2H), 7.34-7.41 (m, 3H), 7.44-7.47 (m, 2H); 13C NMR δ 1.1, 11.5,
29.0, 63.1, 114.9, 120.5, 127.8, 128.1, 129.1, 133.4, 148.9, 158.0; MS
(EI) m/z (relative intensity, proposed ion), 274 (75.7, M+), 259 (100,
M+ - CH3), 243 (57.4, M+ - CH2OH); HRMS calcd for C16H22O2Si
274.1389, found 274.1378.
1
which was determined by H-NMR analysis. Only one stereoisomer
was obtained in all cases on 1H and 13C NMR analysis and the double
bond stereochemistry is (E)-configuration determined by NOE-differ-
ence experiments.
(E)-5-(Trimethylsilyl)-4-acetylpent-4-en-1-ol (15a): 1H NMR δ
0.20 (s, 9H), 1.57-1.62 (m, 2H), 2.34 (s, 3H), 2.42 (t, J 7.6, 2H), 3.56
(t, J 6.2, 2H), 6.69 (s, 1H); 13C NMR δ -0.4, 25.7, 26.4, 33.2, 62.0,
142.7, 155.9, 201.0; IR (neat) 3400, 2930, 1660, 1580, 1360, 1240,
840 cm-1. Anal. Calcd for C10H20O2Si: C, 59.95; H, 10.06. Found:
C, 59.82; H, 9.95.
(E)-6-(Trimethylsilyl)-5-acetylhex-5-en-1-ol (15b): 1H NMR δ
0.16 (s, 9H), 1.30-1.41 (m, 2H), 1.54 (tt, J 6.9, 6.9, 2H), 2.29 (s, 3H),
2.31 (t, J 7.6, 2H), 3.6 (t, J 6.5, 2H), 6.59 (s, 1H); 13C NMR δ -0.4,
25.8, 26.1, 30.3, 32.6, 62.2, 141.4, 156.4, 200.6; IR (neat) 3400, 3050,
1770, 1700, 1518, 1410, 1360, 1217, 1005 cm-1. Anal. Calcd for
C11H22O2Si: C, 61.63; H, 10.34. Found: C, 61.45; H, 10.45.
Acknowledgment. We thank Mrs. K. Saijo (Taisho Phar-
maceutical Co., Ltd.) for help with HRMS. The award of a
postdoctoral fellowship (P.K.Z.) at Tokyo Institute of Technol-
ogy (1994-1995) from UNESCO is gratefully acknowledged.
This work was partially supported by Grants-in-Aid from the
Ministry of Education, Science and Culture, Japan (No.
07455359 and 07216223).
1
Supporting Information Available: Copies of H NMR
(E)-4-(Trimethylsilyl)-3-(phenylcarbonyl)but-3-en-1-ol (15c): 1H
NMR δ 0.21 (s, 9H), 2.80 (t, J 6.1, 2H), 3.77 (t, J 6.1, 2H), 6.3 (s,
1H), 7.40-7.59 (m, 3H), 7.74 (d, J 7.7, 2H); 13C NMR δ -0.2, 35.6,
62.7, 128.2, 129.9, 132.4, 137.3, 144.3, 152.5, 200.0; IR (neat) 3450,
2960, 2900, 1750, 1660, 1595, 1450, 1250, 1140, 1060, 1030, 870,
spectra (47 pages). This material is contained in many libraries
on microfiche, immediately follows this article in the microfilm
version of the journal, can be ordered from ACS, and can be
downloaded from the Internet; see any current masthead page
for ordering information and Internet access instructions.
840, 700 cm-1
Found: C, 67.89; H, 8.37.
. Anal. Calcd for C14H20O2Si: C, 67.70; H, 8.12.
JA953497Z