Highly efficient synthesis of functionalized tertiary alcohols catalyzed by potassium alkoxide-crown ether complexes

Article abstract of DOI:10.1016/j.tetlet.2009.01.028

A highly efficient Mukaiyama aldol reaction between ketones and trimethylsilyl enolates in the presence of potassium alkoxide-crown ether complexes as Lewis base catalysts (0.3-5 mol %), which minimized the competing retro-aldol reaction, was developed. T

Full text of DOI:10.1016/j.tetlet.2009.01.028

Tetrahedron Letters 50 (2009) 3171–3174
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Tetrahedron Letters
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Highly efficient synthesis of functionalized tertiary alcohols catalyzed
by potassium alkoxide–crown ether complexes
*
Manabu Hatano, Shinji Suzuki, Eri Takagi, Kazuaki Ishihara
Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa, Nagoya 464-6603, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A highly efficient Mukaiyama aldol reaction between ketones and trimethylsilyl enolates in the presence
of potassium alkoxide–crown ether complexes as Lewis base catalysts (0.3–5 mol %), which minimized
the competing retro-aldol reaction, was developed. These catalysts promoted other addition reactions
of trimethylsilyl reagents to ketones and aldimines, such as silyltrifluoromethylation, silylcyanation,
and silylphosphonylation. A direct hydrophosphonylation of ketones also proceeded when the catalysts
were used as a Brønsted base under mild reaction conditions.
Received 1 December 2008
Revised 6 January 2009
Accepted 9 January 2009
Available online 14 January 2009
Ó 2009 Elsevier Ltd. All rights reserved.
The efficient synthesis of tertiary alcohols using catalytic meth-
odologies is currently one of the most rapidly advancing fields in
organic chemistry. In particular, a carbon–carbon bond-forming
reaction between ketones and organometallic reagents is an
important strategy for synthesizing functionalized tertiary alco-
hols, which are versatile building blocks for the synthesis of natu-
ral products and pharmaceuticals.1,2 Organosilicon compounds are
quite useful reagents for synthesizing functionalized tertiary alco-
hols, particularly in the Mukaiyama aldol reaction, since Lewis acid
and/or Lewis base can promote reactions with carbonyl com-
pounds under mild reaction conditions.3 However, due to the ret-
ro-aldol reaction, the synthesis of tertiary aldols from ketones
and enolates has been limited,4 which is in sharp contrast to the
synthesis of secondary aldols from aldehydes and enolates.5
Recently, we reported an efficient Mukaiyama aldol reaction with
ketones using sodium phenoxide–phosphine oxides (1) as a Lewis
base catalyst (Scheme 1).6 The desired tertiary aldols, particularly
First, we examined the Mukaiyama aldol reaction between ben-
zophenone (3a) and TMS enolate (4a) in the presence of alkaline
metal alkoxide–crown ether complex as a Lewis base catalyst
(Table 1). As expected, the reactivity was in the order KOPh–18-
crown-6 (2a) > NaOPh–15-crown-5 ꢁ LiOPh–12-crown-4 (entries
1–3). The reaction proceeded with 0.3 mol % of catalyst 2a, and
the tertiary aldol (5a) was obtained quantitatively within 1 h
(entry 4). Low reactivity was observed without 18-crown-6 (entry
5). Interestingly, however, KOt-Bu–18-crown-6 (2b) showed much
less reactivity than 2a (entry 6).10 As a comparison, 1 mol % of 1
was necessary to give 5a in 97% yield in 1 h (entry 7).
Under the optimized reaction conditions, we next examined the
tertiary aldol synthesis of other TMS enolates with ketones in the
presence of 2a (0.3–5 mol %) in THF at ꢀ78 °C for 2 h, in which ter-
tiary aldols with an
a-quaternary or a-tertiary carbon center
would be formed (Table 2). The catalytic activity of 2a was much
higher than that of 1, and the desired tertiary alcohols were
obtained in 90ꢂ>99% yields with less catalyst for 2a than for 1.
with an
a-quaternary or a-tertiary carbon, were obtained in high
yields from a variety of ketones in the presence of 0.5–10 mol %
of 1 in THF at ꢀ78 °C. In this reaction, the naked PhOꢀ should act
as an active Lewis base species to activate a trimethylsilyl (TMS)
moiety to form the hypervalent silicate.7,8 With this catalytic
methodology, the activity should depend on the strength of the
basicity. In this Letter, we describe a potassium alkoxide–crown
ether complex (2) as an extremely active Lewis base catalyst9 for
the highly efficient Mukaiyama aldol reaction with ketones
(Scheme 1). Other reactions such as silyltrifluoromethylation, sily-
lcyanation, and silylphosphonylation with the corresponding TMS
reagents and ketones were also examined to afford a variety of
functionalized tertiary alcohols under mild reaction conditions.
OSiMe3
Me3SiO
O
O
1 (0.5—10 mol%)
R3
R1
R2
R5
+
R5
R1
R2
THF, —78 °C
R4
R3 R4
4
5
3
O
K
Ph
Ph
P
Ph
Ph
P
P
O
O
O
O
O
Na
P
O
Ph
Ph
Ph
O
O
Ph
O
OPh
OR
1
2
* Corresponding author. Tel.: +81 52 789 3331; fax: +81 52 789 3222.
E-mail address: ishihara@cc.nagoya-u.ac.jp (K. Ishihara).
Scheme 1. Highly efficient Mukaiyama aldol reaction with ketones using Lewis
base catalysts.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.01.028

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M. Hatano et al. / Tetrahedron Letters 50 (2009) 3171–3174
Table 1
Table 2
Mukaiyama aldol reaction of TMS enolate (4a) with benzophenone (3a) catalyzed by
2a-catalyzed Mukaiyama aldol reaction
alkaline metal alkoxide–crown ether complexes
OSiMe3
Me3SiO
O
O
2a (0.3—5 mol%)
R3
R1
R2
OSiMe3
R5
+
Me3SiO
Ph
Ph
O
R5
O
catalyst
R1
R2
THF, —78 °C, 2 h
R4
+
R3 R4
OMe
OMe
Ph
Ph
THF, —78 °C
3
4 (1.2 equiv)
5
4a (1.2 equiv)
3a
5a
Entry
Product (5)
Xa (mol %)
Yielda (%)
>99 (97)
Entry
Catalyst (mol %)
Reaction time
Yield (%)
Me3SiO
Ph
Ph
O
O
O
1
2
3
4
5
6
7
LiOPh–12-crown-4 [10]
30 min
30 min
15 min
1 h
2 h
15 min
1 h
0
1b
0.3 (1)
0.5 (1)
0.5 (1)
1 (5)
NaOPh–15-crown-5 [10]
KOPh–18-crown-6 (2a) [1]
2a [0.3]
82
>99
>99
6
11
97
OMe
(5a)
Me3SiO
Ph
Ph
KOPh
2
98 (87)
>99 (75)
90 (86)
>99 (71)
93 (83)
KOt-Bu–18-crown-6 (2b) [1]
1 [1]
Oi-Pr
(5b)
Me3SiO
Ph
Ph
3
OMe
O-TMS N,O-ketene acetal also reacted with 3a in 90% yield when
1 mol % of 2a was used (entry 4). Diphenylpropynone (entry 5)
and
(5c)
Me3SiO
Ph
Ph
O
a-diketone (entry 6) also reacted with TMS enolate, and the
4
functionalized tertiary aldols were obtained in high yield.
NMe2
(5d)
As expected, a tandem lactonization proceeded between 3a and
the phenylester-derived TMS enolate 4b, and 7 was obtained quan-
titatively (Eq. 1). Catalyst 2a was also highly effective in the Man-
nich-type reaction between N-Boc aldimine 8 and 4b, and the
adduct (9) was obtained quantitatively within 2 h at ꢀ78 °C (Eq. 2):
Me3SiO
O
Ph
5
5 (5)
OMe
Ph
(5e)
O
Me3SiO Ph
Ph
6
5 (5)
O
OSiMe3
OMe
O
O
2a (0.5 mol%)
O
(5f)
+
OPh
Ph
Ph
a
Ph
Ph
THF, —78 °C, 1 h
ð1Þ
ð2Þ
The results of catalyst 1 in place of 2a are shown in parentheses.
Reaction time was 1 h.
b
3a
4b (1.2 equiv)
7
>99%
(cf. 1 mol% of 1, —78 °C, 2 h: >99%)
to excellent yields (56ꢂ>99%). Furthermore, silylphosphonylation
of aldimine 8 also provided the corresponding adduct 18 in 83%
yield (Eq. 5):
Boc
Boc
NH
O
N
2a (3 mol%)
4b
(1.2 equiv)
+
Ph
OPh
>99%
THF, —78 °C, 2 h
Ph
H
Boc
Boc
NH
8
9
OSiMe3
N
2b (5 mol%)
+
OMe
OMe
(cf. 10 mol% of 1, —40 °C, 18 h: 95%)
P
P
ð5Þ:
Ph
THF, —40 °C, 3 h
MeO
OMe
Ph
H
O
Other TMS reagents were also examined. With 5 mol % of 2a,
silyltrifluoromethylation with TMSCF3 (10) (Eq. 3)11 and silylcya-
nation with TMSCN (12) (Eq. 4)12 proceeded with respective yields
of >99% and 87%:
8
16 (1.3 equiv)
18 83%
Interestingly, 2b was as an effective Brønsted base catalyst for
the direct hydrophosphonylation of ketones. Direct hydrophospho-
nylation of 3b with dimethyl phosphite (19) was examined in the
presence of 5 mol % of 2b in THF at 0 °C for 15 min, and the corre-
sponding tertiary alcohol (20a) was obtained in 89% yield (Eq. 6).
While this type of reaction usually proceeds slowly under basic
conditions with a stoichiometric or excess amount of alkaline metal
salts (Eq. 6, parentheses),16 we found that catalyst 2b efficiently
promoted the reaction. Remarkably, the reaction of 2-adamanta-
none (3c) with 19 proceeded smoothly, and the corresponding
adduct (20b) was obtained in 94% yield Eq. 7, although silylphos-
phonylation for the synthesis of 17e was not easy (Table 3, entry 5):
O
Me3SiO CF3
2a (5 mol%)
Me3SiCF3
+
Ph
THF, 0 °C, 1 h
Ph
11 >99%
(cf. 5 mol% of 1, 0 °C, 1 h: 47%)
10 (1.4 equiv)
ð3Þ
ð4Þ
3b
Me3SiO CN
2a (5 mol%)
Me3SiCN
+
3a
THF, 0 °C, 4 h
Ph
Ph
12 (1.2 equiv)
13 87%
Next, we examined the Lewis base-catalyzed silylphosphonyla-
tion of ketones with dimethyl trimethylsilyl phosphite (16) (Table
3). The thermal silylphosphonylation of carbonyl compounds was
first reported by Evans 30 years ago.13 However, to the best of
our knowledge, there has been no report on the catalytic silylphos-
phonylation of carbonyl compounds. The reaction between aceto-
phenone (3b) and 16 proceeded successfully with 5 mol % of 2a
at 0 °C for 15 min (entry 1, parentheses).14 Fortunately, the reac-
tion also proceeded smoothly with commercially available 2b (en-
try 1).15 With 5 mol % of 2b, other ketones, such as propiophenone
(entry 2), 3-acetylthiophene as a heteroaromatic ketone (entry 3),
acetone as a small aliphatic ketone (entry 4), and 2-adamantanone
as a bulky aliphatic ketone (entry 5), also reacted, and the corre-
sponding functionalized tertiary alcohols were obtained in good
OH
O
P
H
2b (5 mol%)
Ph
OMe
OMe
3b
+
+
3b
P
O
MeO
OMe
THF, 0 °C
15 min
ð6Þ
ð7Þ
19 (1.3 equiv)
20a 89%
11%
cf. 10 mol% of KO
t
-Bu, 0 °C, 15 min: 20a 20%
100 mol% of KO
t
-Bu, 0 °C, 15 min: 20a 26%
OH
O
OMe
OMe
2b (5 mol%)
P
O
+
19
THF, 0 °C, 2 h
(1.3 equiv)
20b 94%
3c

M. Hatano et al. / Tetrahedron Letters 50 (2009) 3171–3174
3173
Table 3
the TMS protection of tertiary alcohols is extremely effective for
stopping or minimizing the undesired retro-reactions (Figs. 1a and
c). Therefore, strong Lewis Base catalyst 2a or 2b could efficiently
promote the Mukaiyama aldol reaction and silylphosphonylation.
Finally, postulated catalytic cycles are shown in Figure 2.18 In
silylphosphonylation, 2a or 2b should be a Lewis base catalyst. A
naked counter anion ROꢀ (R = Ph or t-Bu) would activate 16 to gen-
erate hypervalent silicate (21). Next, after P–C bond formation, ROꢀ
could be regenerated from ROTMS as a possible catalytic cycle. In
direct hydrophosphonylation, 2b should be a Brønsted base cata-
lyst. After the deprotonation of 19 by naked t-BuOꢀ, a tautomeric
equilibrium would be formed between phosphonate 22 and phos-
phite 23.19 These intermediates could react with 3 to generate the
product via protonation by t-BuOH, accompanied by regeneration
of the active t-BuOꢀ moiety.
In summary, we have developed a highly efficient Mukaiyama
aldol reaction between ketones and trimethylsilyl enolates cata-
lyzed by potassium alkoxide–crown ether complex as a Lewis base.
The Lewis base catalyst could successfully promote other addition
reactions such as silyltrifluoromethylation, silylcyanation, and
silylphosphonylation. Catalytic direct hydrophosphonylation was
also promoted by the same complex as an effective Brønsted base.
In these reactions, the corresponding functionalized tertiary alco-
hols could be obtained in high to excellent yields. Further studies
on the application of this method to asymmetric catalyses are
now underway.
2b-catalyzed silylphosphonylation of ketones
OSiMe3
OSiMe3
O
2b (5 mol%)
R1
R2
OMe
OMe
+
P
P
R1
R2
THF, 0 °C, 15 min
MeO
OMe
O
3
17
16 (1.3 equiv)
Entry
1
Product (17)
Reaction time
Yield (%)
OSiMe3
Ph
OMe
15 min
>99
P
OMe
(15 min)a
(>99)a
O
(17a)
OSiMe3
Ph
Et
OMe
2
3
4
1 h
1 h
2 h
>99
>99
77
P
OMe
O
(17b)
OSiMe3
S
OMe
OMe
P
O
(17c)
OSiMe3
OMe
OMe
P
O
(17d)
OSiMe3
OMe
OMe
5
2 h
56
P
O
(17e)
a
The results of catalyst 2a in place of 2b are shown in parentheses.
(a) Silylphosphonylation
2a or 2b
We then turned our attention to mechanistic aspects of silyl-
phosphonylation and direct hydrophosphonylation in comparison
to the Mukaiyama aldol reaction and direct aldol reaction (Fig. 1).
The key to clarifying these reactions is the retro-reactions and their
equilibriums. In fact, the retro-reactions from tertiary alcohols 20
to ketones appeared to be slow.17 Therefore, we can conclude that
strong Brønsted base catalysts such as 2b promote deprotonation
of the reagent (19) and accelerate the desired direct hydrophos-
phonylation with essentially minimal retro-reactions ( Fig. 1d).
However, it is difficult to synthesize tertiary aldols from ketones
and carbonyl compounds because the equilibrium of direct aldol
reactions significantly shifts to the starting materials under basic
conditions (Fig. 1b).6 In sharp contrast to these direct reactions,
[K·18-Crown-6]
17
OR
16
ROSiMe3
O
Lewis base
R1
R2
OMe
OMe
P
O
OR
SiMe3
O
ROSiMe3
P
MeO
OMe
21
3
(R = Ph or t-Bu)
(a) Mukaiyama aldol reaction
(b) Direct hydrophosphonylation
2b
OSiMe3
R5
Me3SiO
O
O
R3
Lewis base
+
R1
R2
R5
R5
R1
R2
R4
R3 R4
OH
[K·18-Crown-6]
20
(b) Direct aldol reaction
O
t-Bu
Brønsted base
O
O
Brønsted base
19
O
R3
+
R1
R2
t-BuOH
R5
t-BuOH
R1
R2
R4
R3 R4
O
R1
OMe
OMe
(c) Silylphosphonylation
O
P
22
P
R2
OSiMe3
O
OSiMe3
R1
R2
OMe
OMe
Lewis base
O
+
MeO
MeO
OMe
P
P
R1
R2 MeO
OMe
O
(d) Direct hydrophosphonylation
O
3
OH
O
OH
P
P
Brønsted base
R1
R2
OMe
OMe
OMe
+
P
R1
R2 MeO
OMe
23
O
Figure 2. Possible catalytic cycles of silylphosphonylation (a) and direct hydro-
Figure 1. Retro-reactions and equilibriums in tertiary alcohol syntheses.
phosphonylation (b).

3174
M. Hatano et al. / Tetrahedron Letters 50 (2009) 3171–3174
Germany; (f) Farina, V.; Reeves, J. T.; Senanayake, C. H.; Song, J. J. Chem. Rev.
Acknowledgments
2006, 106, 2734.
6. TMS enolates with ketones: Hatano, M.; Takagi, E.; Ishihara, K. Org. Lett. 2007, 9,
4527; Very recently, Shibasaki and Matsunaga et al. used 1,2-
bis(diphenylphosphoryl)benzene as a Lewis base co-catalyst in the La(III)-
catalyzed diastereoselective Mannich-type reaction. Morimoto, H.; Yoshino, T.;
Yukawa, T.; Lu, G.; Matsunaga, S.; Shibasaki, M. Angew. Chem., Int. Ed. 2008, 47,
9125.
Financial support for this project was provided by JSPS. KAKENHI
(20245022), Grant-in-Aid for Young Scientists
B of MEXT
(19750072), the G-COE Program of MEXT, Toray Science Foundation.
S.S. acknowledges a JSPS Fellowship for Japanese Junior Scientists.
7. (a) Chuit, C. C.; Corriu, R. J. P.; Reye, C.; Young, J. C. Chem. Rev. 1993, 93, 1391;
(b) Rendler, S.; Oestreich, M. Synthesis 2005, 1727; (c) Orito, Y.; Nakajima, M.
Synthesis 2006, 1391.
Supplementary data
8. Phosphazene base-catalysis with TMS compounds: (a) Ueno, M.; Hori, C.;
Suzawa, K.; Ebisawa, M.; Kondo, Y. Eur. J. Org. Chem. 2005, 1965; (b) Kobayashi,
K.; Ueno, M.; Kondo, Y. Chem. Commun. 2006, 3128; (c) Suzawa, K.; Ueno, M.;
Wheatley, A. E. H.; Kondo, Y. Chem. Commun. 2006, 4850.
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2009.01.028.
9. Ring opening reaction of epoxides with KCN–18-crown-6 complex: Sassaman,
M. B.; Prakash, G. K. S.; Olah, G. A. J. Org. Chem. 1990, 55, 2016.
10. In this reaction, the possibility of self-catalysis by in situ generating aldolate
had been denied. See Ref. 6.
References and notes
1. For recent reviews: (a) García, C.; Martín, V. S. Curr. Org. Chem. 2006, 10, 1849;
(b) Riant, O.; Hannedouche, J. Org. Biomol. Chem. 2007, 5, 873; (c) Cozzi, P. G.;
Hilgraf, R.; Zimmermann, N. Eur. J. Org. Chem. 2007, 5969.
2. For reviews: (a) Hatano, M.; Miyamoto, T.; Ishihara, K. Curr. Org. Chem. 2007, 11,
127; (b) Hatano, M.; Ishihara, K. Synthesis 2008, 1647.
3. Pioneering Lewis acid or Lewis base catalysis with Si enolates with aldehydes:
(a) Mukaiyama, T.; Narasaka, K.; Banno, K. Chem. Lett. 1973, 1011; (b) Denmark,
S. E.; Winter, S. B. D.; Su, X.; Wong, K.-T. J. Am. Chem. Soc. 1996, 118, 7404; (c)
Matsukawa, S.; Okano, N.; Imamoto, T. Tetrahedron Lett. 2000, 41, 103; (d)
Fujisawa, H.; Mukaiyama, T. Chem. Lett. 2002, 31, 182; (e) Nakagawa, T.;
Fujisawa, H.; Nagata, Y.; Mukaiyama, T. Bull. Chem. Soc. Jpn. 2004, 77, 1555; (f)
Fujisawa, H.; Nakagawa, T.; Mukaiyama, T. Adv. Synth. Catal. 2004, 346, 1241;
(g) Nakagawa, T.; Fujisawa, H.; Nagata, Y.; Mukaiyama, T. Bull. Chem. Soc. Jpn.
2005, 78, 236; (h) Song, J. J.; Tan, Z.; Reeves, J. T.; Yee, N. K.; Senanayake, C. H.
Org. Lett. 2007, 9, 1013.
11. (a) Prakash, G. K. S.; Krishnamurti, R.; Olah, G. A. J. Am. Chem. Soc. 1989,
111, 393; (b) Krishnamurti, R.; Bellew, D. R.; Prakash, G. K. S. J. Org. Chem.
1991, 56, 984; (c) Zhu, S.-F.; Pang, W.; Xing, C.-H.; Zhu, S.-Z. Chin. J. Chem.
2007, 25, 233.
12. Diastereoselective cyanation of ketones with lithium alkoxide complexes:
Wilkinson, H. S.; Grover, P. T.; Vandenbossche, C. P.; Bakale, R. P.; Bhongle, N.
N.; Wald, S. A.; Senanayake, C. H. Org. Lett. 2001, 3, 553.
13. Evans, D. A.; Hurst, K. M.; Takacs, J. M. J. Am. Chem. Soc. 1978, 100, 3467.
14. Catalyst 1 was less active than 2a or 2b. In the reaction between 3b and 16,
both 17a and deprotected product 20a were obtained in 92% yield
(17a:20a = ca. 4:1).
15. This result was in sharp contrast to that with the Mukaiyama aldol reaction
(see Table 1). Other catalysts such as KOAc–18-crown-6 and KF–18-crown-6
showed almost no reactivity under the same reaction conditions. KOPh or KOt-
Bu without 18-crown-6 also showed no reactivity.
4. Examples of TMS enolates with ketones are limited. Also see Ref. 6, and the
references therein. Cl3Si- or in situ prepared (RO)3Si enolates with ketones: (a)
Denmark, S. E.; Fan, Y. J. Am. Chem. Soc. 2002, 124, 4233; (b) Oisaki, K.; Suto, Y.;
Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. 2003, 125, 5644; (c) Denmark, S. E.;
Fan, Y.; Eastgate, M. D. J. Org. Chem. 2005, 70, 5235; (d) Oisaki, K.; Zhao, D.;
Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. 2006, 128, 7164; N-Heterocyclic
carbene-catalysis: (e) Song, J. J.; Tan, Z.; Reeves, J. T.; Fandrick, D. R.; Yee, N. K.;
Senanayake, C. H. Org. Lett. 2008, 10, 877.
16. (a) Pudovik, A. N.; Konovalova, I. V. Synthesis 1979, 81; (b) Simoni, D.;
Invidiata, F. P.; Manferdini, M.; Lampronti, I.; Rondanin, R.; Roberti, M.;
Pollini, G. P. Tetrahedron Lett. 1998, 39, 7615; (c) Simoni, D.; Rondanin, R.;
Morini, M.; Baruchello, R.; Invidiata, F. P. Tetrahedron Lett. 2000, 41, 1607;
(d) Kuramshin, A. I.; Karpenko, E. A.; Cherkasov, R. A. Russ. J. Gen. Chem.
2001, 71, 191.
17. From 20a, 3b was obtained in yields of only 19–20% in THF at 0 °C for 2 h with
the use of 5 mol % of t-BuOK or 5 mol % of catalyst 2b.
5. (a) Nelson, S. G. Tetrahedron: Asymmetry 1998, 9, 357; (b) Mahrwald, R. Chem.
Rev. 1999, 99, 1095; (c) Machajewski, T. D.; Wong, C.-H. Angew. Chem., Int. Ed.
2000, 39, 1352; (d) Palomo, C.; Oiarbide, M.; García, J. M. Chem. Soc. Rev. 2004,
33, 65; (e) Mahrwald, R. Modern Aldol Reactions; Wiley-VCH: Weinheim,
18. With these preliminary results to date, we cannot exclude the possibility of
competitive self-catalysis by tertiary alkoxide intermediates.
19. (a) Doak, G. O.; Freedman, L. D. Chem. Rev. 1961, 61, 31; (b) Grayson, M.; Farley,
C. E.; Streuli, C. A. Tetrahedron 1967, 23, 1065.