Intermolecular double prins-type cyclization: A facile and efficient synthesis of 1,6-dioxecanes

Article abstract of DOI:10.1002/anie.200804576

(Chemical Equation Presented) Double or nothing: The title reaction converts a range of aromatic aldehydes and allenylmethyl/allyl silanes into 1,6-dioxecane derivatives in good to excellent yields (see scheme; Ar=aryl, Tf=triflate, THF=tetrahydrofuran, T

Full text of DOI:10.1002/anie.200804576

Communications
DOI: 10.1002/anie.200804576
Synthetic Methods
Intermolecular Double Prins-Type Cyclization: A Facile and Efficient
Synthesis of 1,6-Dioxecanes**
Punna Reddy Ullapu, Sun-Joon Min, Satish N. Chavre, Hyunah Choo, Jae Kyun Lee,
Ae Nim Pae, Youseung Kim, Moon Ho Chang, and Yong Seo Cho*
Medium-sized oxygen heterocyclic ring systems,
particularly those with ten members, are
a
common structural feature of numerous natural
products as well as functionalized organic mole-
cules.[1] Owing to unfavorable entropic and
enthalpic factors,[2] synthetic routes towards such
compounds have been difficult to study and as a
result, the development of a practical and conven-
ient process to create rings of this size still remains
a major synthetic challenge.
The Prins-type cyclization is among the most
important ring-forming reactions. It involves an
electrophilic addition of an unsaturated carbon–
carbon bond to an aldehyde and ketone.[3] When
the electrophile is an oxonium ion that is generated
in situ from the condensation of an allylic alcohol
Scheme 1. Concept for the intermolecular double Prins-type cyclization for the
synthesis of 1,6-dioxecane derivatives.
with an aldehyde or acetal, the cyclization proceeds to form
oxacyclic compounds such as tetrahydropyran or tetrahydro-
furan derivatives. Recently, we have shown that the use of
(allenylmethyl)silane in the Prins-type cyclization can facil-
itate the terminating step to afford 3,4-dimethylidene tetra-
hydropyran compounds.[4] On the basis of this study, we have
devised a new plan to synthesize medium-sized oxacycles
through a Prins-type cyclization. As shown in Scheme 1, the
intramolecular 5-endo-trig cyclization of the oxonium inter-
mediate 2I, which is derived from (allenylmethyl)silane 1 and
an aldehyde, would be kinetically disfavored according to
Baldwinꢀs rule.[5] Thereby, a second oxonium ion 2III would
be generated by either dimerization of 2I (path a) or
intermolecular addition of 1 to 2I followed by a second
condensation of 2II with an aldehyde (path b). At this point,
we envisage that subsequent ring closure of 2III would occur
to afford 1,6-dioxecane derivatives 3 if the rate of Prins
cyclization is faster than that of polymerization. To our
knowledge, formation of such a medium-size ring system by
using consecutive Prins reactions has never been reported.[6]
Herein, we present the stereoselective synthesis of 1,6-
dioxecanes[7] from hydroxy(allenylmethyl)silane/allylsilane
and electron-rich aromatic aldehydes through an intermolec-
ular double Prins-type cyclization.
To test our idea, we first screened various Lewis acids
including InCl3 and TiCl4, which are conventional Lewis acids
for Prins-type cyclizations[8] (see the Supporting Informa-
tion). Among them, we found that TMSOTf proved to be the
best Lewis acid for this type of cyclization (Table 1, entry 1).
Indeed, when we applied one equivalent of TMSOTf to the
mixture of 1[9] and benzaldehyde in THF at ꢀ788C, and then
Table 1: Scope of the intermolecular double Prins-type cyclization of 1
with various aldehydes.
Entry
R
t [h]
Product
Yield [%][a]
1
2
3
4
5
6
7
8
Ph
7
7
6
9
6
9
6
10
6
6
3a
3b
3c
3d
3e
3 f
3g
3h
3i
73
55
83
50
75
66
85
76
[*] P. R. Ullapu, Dr. S.-J. Min, S. N. Chavre, Dr. H. Choo, Dr. J. K. Lee,
Dr. A. N. Pae, Dr. Y. Kim, Dr. M. H. Chang, Dr. Y. S. Cho
Center for Chemoinformatics Research
4-MeOC6H4
3-MeOC6H4
2-MeOC6H4
4-MeC6H4
3-MeC6H4
4-FC6H4
4-ClC6H4
4-NO2C6H4
2-NO2C6H4
2-thienyl
Korea Institute of Science and Technology
P.O. Box 131, Cheongryang, Seoul 130-650 (South Korea)
Fax: (+82)2-958-5189
E-mail: ys4049@kist.re.kr
[**] Financial support from the Korea Institute of Science and
Technology (KIST) is gratefully acknowledged (2K01640, 2E20430).
We also thank Dr. YoungSoo Kim for his skilled technical assistance
in HPLC separation and Dr. Heechul Ahn for the NMR analysis.
9
10
11
n.r.[b]
n.r.[b]
50
3j
3k
10
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200804576.
[a] Yield of isolated product. [b] No reaction. Tf=trifluoromethanesul-
fonyl, THF=tetrahydrofuran, TMS=trimethylsilyl.
2196
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2009, 48, 2196 –2200

Angewandte
Chemie
Table 2: Scope of the intermolecular double Prins-type cyclization of 5
with various aldehydes.
allowed the reaction mixture to warm to room temperature
over 7 h, we obtained 3a exclusively in 73% yield.[10] The
structure of 3a was determined by single-crystal X-ray
diffraction analysis (Figure 1).[11] Therefore, we selected
these reaction conditions for our study.
Entry
R
t [h]
Product
Yield [%][a]
1
2
3
4
5
6
7
8
Ph
7
10
10
6
10
10
6
10
6
6
5a
5b
5c
5d
5e
5 f
5g
5h
5i
72
40
70
74
52
59
71
51
4-MeOC6H4
3-MeOC6H4
2-MeOC6H4
4-MeC6H4
3-MeC6H4
4-FC6H4
4-ClC6H4
4-NO2C6H4
2-NO2C6H4
2-thienyl
9
n.r.[b]
n.r.[b]
45
10
11
12
5j
5k
5l
9
9
3-furanyl
26
[a] Yield of isolated product. [b] No reaction.
Figure 1. ORTEP plot of 1,6-dioxecane 3a. The thermal ellipsoids are
drawn at the 50% probability level.
To explore the effect that the aldehyde substituent had
upon the intermolecular double Prins-type cyclization, we set
up cross-over experiments, that is, the reactions of 1 with two
different aldehydes as illustrated in Table 3. As anticipated,
we observed three different cyclized products, which were
separated by HPLC.[14] We found that the ratios of the
products varied greatly according to the combination of
mixed aldehydes.[15] In particular, the significant quantities of
6, resulting from two different aldehydes, were generated in
good yield. Interestingly, the compounds derived from
cyclization of 3-methoxybenzaldehyde (3c, 6ac, 6cg) were
produced predominantly. These results prompted us to carry
out NMR experiments to investigate how our cyclization
reaction proceeds. Thus, we performed the reaction of 1 with
benzaldehyde and 4-fluorobenzaldehyde, and recorded
Next, we examined the scope of the aldehyde component
as shown in Table 1. At first, we found that a wide range of
aldehydes were tolerated under the optimized reaction
conditions. In general, the intermolecular double Prins-type
cyclization reactions of 1 with electron-rich benzaldehydes,
such as methoxybenzaldehyde and methylbenzaldehyde,
regardless of the substituent position, provided the corre-
sponding 1,6-dioxecane derivatives in good to excellent yield
(Table 1, entries 2–6). However, variation in the electronic
character of the aldehyde had a large influence on this
reaction. Indeed, halobenzaldehydes were still good sub-
strates for this cyclization process (Table 1, entries 7 and 8),
but no desired products were isolated from electron-poor
substrates such as nitrobenzaldehydes (Table 1, entries 9 and
10). We believe that the electron-withdrawing nature of the
nitro group destabilizes the oxonium intermediate and as a
result further cyclization by allenylmethylsilane cannot take
place. The reaction has also been validated with a hetero-
aromatic aldehyde such as thiophene-2-carbaldehyde
(Table 1, entry 11).
Table 3: Intermolecular double Prins-type cyclization of mixed benzal-
dehydes.
Encouraged by these results, we extended our protocol to
synthesize dimethylene-1,6-dioxecanes 5 using hydroxy allyl-
silane 4[12] as a precursor (Table 2). Again, various aromatic
aldehydes were tolerated (Table 2, entries 1–8) except for
ones with electron-deficient substituents (Table 2, entries 9
and 10). In comparison with the results obtained for 1, the
reaction efficiency slightly decreased. Additionally, hetero-
aromatic aldehydes proved to be effective electrophiles;
however, we could obtain only 26% of the desired 1,6-
dioxecane derivative from furan-3-carbaldehyde (Table 2,
entries 11 and 12). Notably, only single isomers of products
5 were generated in all cases. Structural assignment of 5a was
established based on the single-crystal X-ray diffraction study
(see the Supporting Information).[13]
R1
R2
Yield [%]
Products (ratio)[a]
Ph
Ph
4-FC6H4
3-MeOC6H4
4-FC6H4
81
70
52
3a/6ag/3g (2.1:3.4:1.0)
3a/6ac/3c (1.0:3.5:5.0)
3c/6cg/3g (1.6:2.7:1.0)
4-MeOC6H4
1
[a] The product ratios were determined by H NMR analysis.
Angew. Chem. Int. Ed. 2009, 48, 2196 –2200
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
2197

Communications
1H NMR spectra at different temperatures ranging from
Table 4: Intermolecular double Prins-type cyclization of mixed silanes 1
and 4.
ꢀ788C to 208C (Figure 2). A few new signals (d = 7.1, 5.6, and
4.1 ppm) that appeared after the addition of TMSOTf
continued to exist until the temperature reached ꢀ308C. We
R
Yield [%]
Products (ratio)[a]
Ph
76
71
72
3a/7a/5a (1.1:1.0:2.6)
3c/7c/5c (1.4:1.0:3.5)
3g/7g/5g (1.5:1.0:1.6)
3-MeOC6H4
4-FC6H4
1
[a] The product ratios were determined by H NMR analysis.
with tetracyanoethylene 8. On the basis of the X-ray structure
of 3a (see Figure 1), we thought that this transformation
might be difficult because the geometry of the diene in 3 (with
a 608 dihedral angle) is not suitable for the transition state of a
DA reaction. As expected, the initial attempt to explore a
thermal DA reaction to generate the cycloadduct 9 failed.
However, the cycloaddition of 3 with 8 in the presence of
tin(IV) chloride led to the desired tricyclic compounds 9 in
60% yield, respectively (Scheme 2).[19] Thus, this reaction
could provide access to a number of synthetically useful
tricyclic compounds that contain the 1,6-dioxecane core
structure.
1
Figure 2. A series of H NMR spectra at different temperatures in the
reaction of 1 with benzaldehyde and 4-fluorobenzaldehyde. The NMR
spectrum at the bottom was measured at 238C before the injection of
TMSOTf. ( : 1, ꢀ: benzaldehyde, +: 4-fluorobenzaldehyde, : plausible
*
*
intermediate).
believe that these signals belong to the oxonium intermediate
which is in equilibrium with the mixed aldehydes. As these
signals disappeared with increasing temperature, we observed
other new signals corresponding to those of the cyclized
products. These findings implied that the carbon–carbon bond
formation rapidly proceeded independent of whether the
intermediate came from the benzaldehyde or the 4-fluoro-
benzaldehyde.[16] In addition, the higher consumption of
benzaldehyde compared to that of 4-fluorobenzaldehyde (as
indicated by the NMR experiment) indicates that the product
ratios outlined in Table 3 may reflect the electronic stabiliza-
tion effect of each substituent.[17]
Finally, we have designed another interesting cross-over
experiment to gain some insight into the effect of (allenylme-
thyl)silane and allylsilane on our cyclization process
(Table 4). The reaction of a mixture of 1 (0.5 equiv) and 4
(0.5 equiv) with substituted benzaldehydes (1.0 equiv) in the
presence of TMSOTf afforded three desired cyclized products
in reasonable yields. Gratifyingly, the trimethylene dioxe-
canes 7 were separated by HPLC[14] and their structures were
determined by NMR analysis. In all cases, we could obtain the
dimethylene dioxecanes 5 as major isomers, which is not in
agreement with our postulation from each independent
experiment (Tables 1 and 2), that is, the reaction of the
more reactive (allenylmethyl)silane would proceed faster to
favor 3 or 7.[18] Although we cannot clearly explain this
incongruity, it is probably due to the rapid formation of the
first oxonium intermediate (see 2I, Scheme 1) regardless of
using an (allenylmethyl)silane or allylsilane substrate.
Scheme 2. Diels–Alder reactions of 3 and tetracyanoethylene 8.
In conclusion, we here described the synthesis of 1,6-
dioxecanes by an intermolecular double Prins-type cycliza-
tion of (allenylmethyl)silane or allylsilane with aromatic
aldehydes. This is the first method to show that inter- and
intramolecular Prins reactions in a single process can be
employed to construct entropically unfavorable medium-
sized oxacycles. In addition, we have shown that the Diels–
Alder cycloaddition of 3 with 8 can provide a tricyclic ring
system such as 9. We are continuing to probe the scope of our
protocol to synthesize ring systems of other sizes. The results
of these studies will be reported in due course.
To find a use for the cyclized product 3, our final efforts
focused on the Diels–Alder (DA) reaction of the bisdiene of 3
2198
www.angewandte.org
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2009, 48, 2196 –2200

Angewandte
Chemie
Ajamian, J. L. Gleason, Org. Lett. 2001, 3, 4161 – 4164; i) K. N.
Experimental Section
Cossey, R. L. Funk, J. Am. Chem. Soc. 2004, 126, 12216 – 12217;
j) J. E. Dalgard, S. D. Rychnovsky, Org. Lett. 2005, 7, 1589 –
1591; k) J. P. Vitale, S. A. Wolckenhauer, N. A. Do, S. D.
Rychnovsky, Org. Lett. 2005, 7, 3255 – 3258; l) L. S. Miranda,
B. A. Meireles, J. S. Costa, V. L. P. Pereira, Synlett 2005, 869 –
871; m) D. L. Aubele, S. Wan, P. E. Floreancig, Angew. Chem.
2005, 117, 3551 – 3554; Angew. Chem. Int. Ed. 2005, 44, 3485 –
3488; n) X. Tian, J. J. Jaber, S. D. Rychnovsky, J. Org. Chem.
2006, 71, 3176 – 3183; o) J. S. Yadav, N. N. Kumar, M. S. Reddy,
A. R. Prasad, Tetrahedron 2007, 63, 2689 – 2694; p) J. S. Yadav,
P. P. Rao, M. S. Reddy, N. V. Rao, A. R. Prasad, Tetrahedron
Lett. 2007, 48, 1469 – 1471.
Typical procedure for the preparation of 3,4,8,9-tetramethylene-2,7-
diphenyl-1,6-dioxecane (3a): TMSOTf (100 mg, 0.45 mmol) was
added dropwise to a stirred solution of the 1 (70 mg, 0.45 mmol)
and benzaldehyde (47.5 mg, 0.45) in dry THF (6.0 mL) at ꢀ788C
under nitrogen. The reaction mixture was slowly warmed to room
temperature over 4 hours and stirred at room temperature for a
further 3 hours. The resulting mixture was quenched with saturated
aqueous solution of NaHCO3 and diluted with CH2Cl2 (20 mL). The
organic layer was separated and dried over MgSO4, filtered, and
concentrated under reduced pressure. Purification of the residue by
column chromatography on silica gel (n-hexane/ethyl acetate 20:1!
1:1) afforded the 1,6-dioxecane 3a (56 mg, 73%) as a white solid.
M.p.: 170–1718C; 1H NMR (400 MHz, CDCl3): d = 7.40–7.29 (m,
10H), 5.38 (s, 2H), 5.28 (s, 2H), 5.13 (s, 2H), 4.91 (s, 2H), 4.71 (s, 2H),
4.35 (d, 2H, J = 11.2 Hz), 4.13 ppm (d, 2H, J = 10.8 Hz); 13C NMR
(100 MHz, CDCl3): d = 150.85, 146.02, 139.78, 128.18, 127.41, 127.30,
118.08, 117.80, 81.68, 71.84 ppm; IR (thin film): n˜ = 3058, 2928, 1629,
1209, 1110 cmꢀ1; HRMS (EI): m/z calcd for C24H24O2 [M+]: 344.1776;
found: 344.1777.
[4] Y. S. Cho, K. Karupaiyan, H. J. Kang, A. N. Pae, J. H. Cha, H. Y.
Koh, M. H. Chang, Chem. Commun. 2003, 2346 – 2347.
[5] a) J. E. Baldwin, J. Chem. Soc. Chem. Commun. 1976, 734 – 736;
b) J. E. Baldwin, R. C. Thomas, L. I. Kruse, L. Silberman, J. Org.
Chem. 1977, 42, 3846 – 3852.
[6] It has been reported that the intramolecular silyl-modified
Sakurai reaction of 10 and acetaldehyde in the presence of
BF3·OEt2 afforded trisubstituted tetrahydropyran 11 by an ene
reaction and subsequent Prins-type cyclization; a) I. E. Markꢃ,
D. J. Bayston, Tetrahedron Lett. 1993, 34, 6595 – 6598; b) I. E.
Markꢃ, J.-M. Plancher, Tetrahedron Lett. 1999, 40, 5259 – 5262;
c) I. E. Markꢃ, R. Dumeunier, C. Leclercq, B. Leroy, J.-M.
Plancher, A. Mekhalfia, D. J. Bayson, Synthesis 2002, 958 – 972.
Received: September 17, 2008
Revised: January 6, 2009
Published online: February 9, 2009
Keywords: cyclization · Diels–Alder reaction ·
.
Prins-type reaction · silanes · synthetic methods
[1] a) J. Breitenbach, J. Boosfeld, F. Vꢁgtle in Comprehensive
Supramolecular Chemistry, Vol. 2 (Ed.: J. M. Lehn), Pergamon,
New York, 1996, pp. 29 – 67; b) B. Dietrich, P. Viout, J. M. Lehn,
Macrocyclic Chemistry: Aspects of Organic and Inorganic
Supramolecular Chemistry, Wiley-VCH, Weinheim, 1993; for
selected references for representative compounds containing
medium-sized oxacycles and their syntheses, see: c) M. Nur-e-
Alam, M. Yousaf, S. Qureshi, I. Baig, S. Nasim, Atta-ur-
Rahman, M. I. Choudhary, Helv. Chim. Acta 2003, 86, 607 – 614;
d) T. Kamikawa, K. Inoue, T. Kubota, M. C. Woods, Tetrahedron
1970, 26, 4561 – 4587; e) N. Kise, A. Fujimoto, N. Moriyama, N.
Ueda, Tetrahedron: Asymmetry 2003, 14, 2495 – 2497; f) H. M. C.
Ferraz, F. I. Bombonato, M. K. Sano, L. S. Longo, Jr., Quim.
Nova 2008, 31, 885 – 900; g) I. Shiina, Chem. Rev. 2007, 107, 239 –
273; h) K. C. Nicolaou, G. E. A. Carenzi, V. Jeso, Angew. Chem.
2005, 117, 3963 – 3967; Angew. Chem. Int. Ed. 2005, 44, 3895 –
3899; i) J. H. Rigby, K. R. Fales, Tetrahedron Lett. 1998, 39,
1525 – 1528; j) M. Cinquini, F. Cozzi, F. Sannicolꢂ, A. Sironi, J.
Am. Chem. Soc. 1988, 110, 4363 – 4364; k) P. Davoli, A.
Spaggiari, L. Castagnetti, F. Prati, Org. Biomol. Chem. 2004, 2,
38 – 47; l) D. R. Spring, S. Krishman, S. L. Schreiber, J. Am.
Chem. Soc. 2000, 122, 5656 – 5657.
[7] Selected syntheses of dioxecane derivatives; a) R. W. Alder,
A. J. Miller, D. I. Ruchbrook, J. Chem. Soc. Chem. Commun.
1989, 277 – 279; b) F. Sondheimer, Y. Gaoni, J. Bergman,
Tetrahedron Lett. 1960, 1, 25 – 29; c) H. A. J. Carless, J. Bean-
land, S. Mwesigye-Kibende, Tetrahedron Lett. 1987, 28, 5933 –
5936; d) K. Nagai, M. Kakayama, S. Hayashi, Chem. Lett. 1973,
665 – 666.
[8] For Prins cyclizations promoted by titanium or indium catalysts,
see: a) C.-M. Yu, S.-K. Yoon, Y.-T. Hong, J. Kim, Chem.
Commun. 2004, 1840 – 1841; b) W. H. Bunnelle, D. W. Seamon,
D. L. Mohler, T. F. Ball, D. W. Thompson, Tetrahedron Lett.
1984, 25, 2653 – 2654; c) M. L. Melany, G. A. Lock, D. W.
Thompson, J. Org. Chem. 1985, 50, 3925 – 3927; d) Y. S. Cho,
H. Y. Kim, J. H. Cha, A. N. Pae, H. Y. Koh, J. H. Choi, M. H.
Chang, Org. Lett. 2002, 4, 2025 – 2028; e) C. Shin, S. N. Chavre,
J. H. Cha, A. N. Pae, H. Y. Koh, J. H. Choi, M. H. Chang, Y. S.
Cho, Org. Lett. 2005, 7, 1589 – 1591; f) S. N. Chavre, H. Choo,
J. K. Lee, A. N. Pae, Y. Kim, Y. S. Cho, J. Org. Chem. 2008, 73,
7467 – 7471; g) X.-F. Yang, M. Wang, Y. Zhang, C.-J. Li, Synlett
2005, 1912 – 1916; h) K.-P. Chan, T.-P. Loh, Tetrahedron Lett.
2004, 45, 8387 – 8397; i) K.-P. Chan, T.-P. Loh, Org. Lett. 2005, 7,
4491 – 4494; j) L. E. Overman, A. Castaꢄeda, T. A. Blumenkopf,
J. Am. Chem. Soc. 1986, 108, 1303 – 1304; k) A. P. Dobbs, S.
Martinovic, Tetrahedron Lett. 2002, 43, 7055 – 7057; l) C. E.
Davis, R. M. Coates, Angew. Chem. 2002, 114, 509 – 511; Angew.
Chem. Int. Ed. 2002, 41, 491 – 493.
[2] a) G. Illuminati, L. Mandolini, Acc. Chem. Res. 1981, 14, 95 –
102; b) L. Mandolini, Adv. Phys. Org. Chem. 1986, 22, 1 – 111;
c) C. G. Kreiter, K. Lehr, M. Leyendecker, W. S. Sheldrik, R.
Exner, Chem. Ber. 1991, 124, 3 – 12.
[3] For reviews, see: a) T. L. B. Boivin, Tetrahedron 1987, 43, 3309 –
3362; b) I. M. Pastor, M. Yus, Curr. Org. Chem. 2007, 11, 925 –
957; for representative Prin cyclization reactions, see: c) T. A.
Blumenkopf, G. C. Look, L. E. Overman, J. Am. Chem. Soc.
1990, 112, 4399 – 4403; d) R. C. Winstead, T. H. Simpson, G. A.
Lock, M. D. Schiavelli, D. W. Thompson, J. Org. Chem. 1986, 51,
277 – 279; e) T. A. Blumenkopt, M. Bratz, A. Castaneda, G. C.
Look, L. E. Overman, D. Rodriguez, A. S. Thompson, J. Am.
Chem. Soc. 1990, 112, 4386 – 4399; f) P. C. Ting, P. A. Bartlett, J.
Am. Chem. Soc. 1984, 106, 2668 – 2671; g) M. Labelle, Y.
Guindon, J. Am. Chem. Soc. 1989, 111, 2204 – 2210; h) A.
[9] 2-[(Trimethylsilyl)methyl]buta-2,3-dien-1-ol (1) should be pre-
pared just prior to use because it easily decomposes, even when
stored at ꢀ208C. For the preparation of 1, see: a) B. M. Trost, H.
Urabe, J. Am. Chem. Soc. 1990, 112, 4983 – 4984; b) P. H. Lee, K.
Bang, H. Ahn, K. Lee, Bull. Korean Chem. Soc. 2001, 22, 1385 –
1389.
Angew. Chem. Int. Ed. 2009, 48, 2196 –2200
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
2199

Communications
[10] We have also tested a catalytic amount of TMSOTf (0.3 equiv)
detection at 254 nm during a isocratic mode of 65% B over
45 min. tR min = 35.8 (3a), 32.2 (7a), 22.8 (5a), 26.6 (3c), 24.3
(7c), 18.1 (5c).
for the reaction, but observed only a small quantity of product.
Instead, the use of a protic catalyst such as triflic acid (1.0 equiv)
gave the cyclized product in 70% yield. It seems that the proton
generated upon hydrolysis of TMSOTf during the reaction plays
a crucial role in this protocol.
[15] To avoid variation of the ratios owing to the incomplete reaction,
the reactions proceeded until all the aldehydes were consumed
(as evident by TLC).
[11] CCDC 699781 (3a) contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via www.
ccdc.cam.ac.uk/data_request/cif.
[12] 2-[(Trimethylsilyl)methyl]prop-2-en-1-ol (5) was prepared by
the deacetylation of commercially available 2-[(trimethylsilyl)-
methyl]allyl acetate. The spectroscopic data of 5 is identical to
that of the reported (T. V. Lee, R. J. Boucher, J. R. Porter, D. A.
Taylor, Tetrahedron 1988, 44, 4233 – 4242).
[13] CCDC 699782 (5a) contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via www.
ccdc.cam.ac.uk/data_request/cif..
[14] Two conditions were used for HPLC separation; a) for Table 3
and 4-FC6H4CHO in Table 4, reverse-phase HPLC was per-
formed by using binary gradients of solvents A and B, where A
was 0.1% TFA in water and B was 0.09% TFA in acetonitrile.
Analytical reverse-phase HPLC was performed by using a
YMC-Pack Pro C18 column at a flow rate of 1 mLminꢀ1, with
detection at 254 nm during a isocratic mode of 70% B over
45 min. tR min = 23.4 (3a), 25.1 (6ag), 25.6 (3g), 20.2 (6ac), 21.3
(6cg), 22.7 (7g), 17.0 (5g); b) for PhCHO and 3-MeOC6H4CHO
in Table 4, analytical RP-HPLC was performed by using a YMC-
Pack Pro C18 column at a flow rate of 1 mLminꢀ1, with
[16] We have tried to isolate a reaction intermediate by quenching
the reaction at low temperature or by using an acyl protected
form of hydroxy(allenylmethyl)silane as a competitive substrate.
However, we were not able to identify any intermediate in both
cases.
[17] It is possible to assume that the product ratios outlined in Table 3
may be affected by the relative stability of the final products if
ring opening is promoted by acid. However, the product stability
is unlikely to effect the ratios because treatment of 3a and 3c
with TMSOTf or triflic acid under the same reaction condition
led to none of the mixed product 6ag.
[18] The heat of hydrogenation for one carbon–carbon bond of an
allene (ꢀ41 kcalmolꢀ1) is lower than that of a simple alkene
(ꢀ29 kcalmolꢀ1). This extra energy makes the allene a more
reactive component compared to the alkene. In addition, it was
reported that the energy of the p1,2 molecular orbital of 1-
substitued allenes is increased by electron-donating groups such
as alkyl, OH, or F. For the reactivity of allenes, see: a) N. Krause,
A. S. K. Hashmi, Modern Allene Chemistry, Vol. 2, Wiley-VCH,
Weinheim, 2004; b) D. J. Pasto, J. Am. Chem. Soc. 1979, 101, 37 –
46; c) D. J. Pasto, Tetrahedron 1984, 40, 2805 – 2827.
[19] E. Wada, N. Nagasaki, S. Kanemasa, O. Tsuge, Chem. Lett. 1986,
1491 – 1494.
2200 www.angewandte.org
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2009, 48, 2196 –2200