Silylative Kinetic Resolution of Racemic 2,2-Dialkyl 5- and 6-Membered Cyclic Benzylic Alcohol Derivatives Catalyzed by Chiral Guanidine, (R)-N-Methylbenzoguanidine

Article abstract of DOI:10.1002/adsc.201900761

Efficient silylative kinetic resolution of racemic 2,2-dialkyl 5- and 6-membered cyclic benzylic alcohols was achieved using diphenylmethylchlorosilane (Ph₂MeSiCl) or phenyldimethylchlorosilane (PhMe₂SiCl) as a silyl source catalyzed by chiral guanidine. The reaction could be applied to a broad range of 2,2-dialkyl 1-indanols with good s-values, irrespective of the electronic nature of the substituent on the aromatic ring of the substrates and the type of substituent at the C2-position. In addition, several 2,2-dimethyl 6-membered cyclic and heterocyclic alcohols could be adopted in the reaction. (Figure presented.).

Full text of DOI:10.1002/adsc.201900761

Title: Silylative Kinetic Resolution of Racemic 2,2-Dialkyl 5- and 6-
Membered Cyclic Benzylic Alcohol Derivatives Catalyzed by
Chiral Guanidine, (<i>R</i>)-<i>N</i>-Methylbenzoguanidine
Authors: Shuhei Yoshimatsu and Kenya Nakata
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Adv. Synth. Catal. 10.1002/adsc.201900761
Link to VoR: http://dx.doi.org/10.1002/adsc.201900761

10.1002/adsc.201900761
Advanced Synthesis & Catalysis
COMMUNICATION
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Silylative Kinetic Resolution of Racemic 2,2-Dialkyl 5- and 6-
Membered Cyclic Benzylic Alcohol Derivatives Catalyzed by
Chiral Guanidine, (R)-N-Methylbenzoguanidine
Shuhei Yoshimatsu,a and Kenya Nakata,a,*
a
Department of Chemistry, Graduate School of Natural Science and Technology, Shimane University, 1060
Nishikawatsu Matsue, Shimane 690-8504, Japan, Fax: (+81) 852-32-6429; e-mail: nakata@riko.shimane-u.ac.jp
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
routes toward the chiral 2,2-dimethyl 1-indanol
2,2-dialkyl 5- and 6-membered cyclic benzylic alcohols moiety.
was achieved using diphenylmethylchlorosilane
Abstract. Efficient silylative kinetic resolution of racemic
(Ph2MeSiCl) or phenyldimethylchlorosilane (PhMe2SiCl)
as a silyl source catalyzed by chiral guanidine. The reaction
could be applied to a broad range of 2,2-dialkyl 1-indanols
with good s-values, irrespective of the electronic nature of
the substituent on the aromatic ring of the substrates and
the type of substituent at the C2-position. In addition,
several 2,2-dimethyl 6-membered cyclic and heterocyclic
alcohols could be adopted in the reaction.
Asymmetric catalyst
Ph
SePMB
O
I
OTBS
OBn
MeO
O
N
H
Ph
1[a]
2
Biologically active compound
O
OH
OH
Keywords: Guanidine; Indanols; Kinetic resolution;
Organocatalysis; Silylation
O
O
radulactone (4)
alcyopterosin I (3)
O
The optically active 2,2-dimethyl 1-indanol moiety
is frequently found in chiral catalysts such as the
electrophilic selenium catalyst 1[1] and organoiodine
catalyst 2[2] developed by Maruoka et al., as well as in
biologically active compounds such as alcyopterosin
I (3),[3] radulactone (4),[4] pterosin D (5),[5] and
pterolactone A (6)[6] (Figure 1). Diastereomeric
resolution techniques have been used obtain catalysts
1[1] and 2.[2] On the other hand, although Snyder et al.
reported the first asymmetric synthesis of ent-
alcyopterosin I ent-(3) by the asymmetric reduction
of the corresponding ketone at the final step, the
optical purity was only 57% ee (99% yield).[7,8] Two
other methods― enantioselective reduction of tert-
alkyl ketones using a chiral Ru complex as the
catalyst, developed by Noyori et al.,[9] and (ii) chiral
tartaric acid-derived borinic ester-catalyzed reduction
developed by Singaram et al.[10]―were adopted for
the same reaction, but the desired reaction did not
occur in both cases.[7] Similarly, the first asymmetric
synthesis of radulactone (4)[11] was achieved by the
asymmetric reduction of the corresponding ketone via
Corey-Bakshi-Shibata (CBS) reduction,[12] but the
chemical yield was only 38% (87.2% ee). Thus, there
are few options for practical asymmetric synthetic
OH
OH
O
HO
O
O
pterosin D (5)
pterolactone A (6)
Figure 1. Representative compounds containing the 2,2-
dimethyl 1-indanol moiety. [a] PMB: p-methoxybenzyl
On the other hand, kinetic resolution of racemic
alcohols is well known as one of the most reliable and
facile methods for providing optically active
compounds, and much effort has been undertaken in
this direction till date. The kinetic resolution of
racemic
-disubstituted
-hydroxy--
butyrolactones by asymmetric carbamoylation,[13]
acylation,[14] and silylation,[15] and the kinetic
resolution of -disubstituted -hydroxy esters by
asymmetric carbamoylation[16] have been reported. To
the best of our knowledge, however, there are no
examples of chemical or enzymatic methods for the
efficient kinetic resolution of racemic 2,2-dialkyl 1-
1
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900761
Advanced Synthesis & Catalysis
indanol derivatives in which there are no coordinating
functional groups adjacent to the reaction sites.
To optimize the reaction conditions, we first chose
the racemic 2,2-dimethyl-1-indanol ((±)-12) as a
model substrate and examined the combination of the
chiral guanidine catalysts 7 and 8 with silyl chlorides
11 (Table 1). Since the reaction of 12 did not proceed
when using a catalyst loading of 0.5 mol%,[25] we
decided to increase the catalyst loading up to 5 mol%
to improve the reactivity. No reaction occurred when
using 0.75 equiv of Ph3SiCl (11a) and iPr2NEt as a
co-base in the presence of 5 mol% of 7 in toluene at –
78 °C for 24 h under the previously established
conditions[25] (entry 1). Upon replacing a phenyl
group with a methyl group at one or two positions of
silyl chloride 11a, the reactions smoothly proceeded
to give good s-values (entries 2 and 4). On the
contrary, the reactions carried out using Et3SiCl (11d)
and Me3SiCl (11e) with tri-alkyl substituents did not
proceed or gave a moderate s-value (entries 8 and 9).
From these results, it was evident that at least one
phenyl substituent on the silyl chloride is essential for
achieving high selectivity. The same trend was
observed when using chiral guanidine catalyst 8
instead of 7. While the reactions using 11a and 11d
were unsuccessful (entries 10 and 14), those with 11b
and 11c (entries 11 and 12) proceeded to completion.
However, in all the cases, the selectivity was higher
when using catalyst 7 than when using catalyst 8. In
particular, the combination of catalyst 8 and silyl
chloride 11b gave poor selectivity (entry 11). When
the same reactions were carried out by changing the
solvent from toluene to THF, the selectivity was
improved in all cases (entries 2, 4, 12 versus 3, 5, 13).
In recent years, kinetic resolution and
desymmetrization by the catalytic asymmetric
silylation reaction of alcohols have attracted attention
as a new and powerful method for obtaining optically
active compounds. This strategy has been extended to
various substrates.[17–22] In our laboratory, chiral
guanidine catalysts[23] 7 and 8 were found to be
efficient for asymmetric silylation. We developed the
first general method for the non-enzymatic kinetic
resolution of racemic 1-indanol derivatives 9 with
Ph3SiCl (11) using 8 as the catalyst by asymmetric
silylation, with a high s-value[24] of up to 89 (Scheme
1, (a-1)).[25] During the course of the examination of
the substrate scope and limitations, we found that a
broad range of 1-indanol derivatives 9 could be used
in the reaction. However, no reaction occurred in the
case of 2,2-dialkyl 1-indanol 12 (Scheme 1, (a-2)).[25]
While the challenge with substrate 12 is the low
reactivity resulting from the steric hindrance of the
two substituents at C2, only a catalytic amount (0.5
mol%) is sufficient for the reaction of substrate 9,
which does not have any substituent at C2, as per our
previous study. Therefore, we decided to re-examine
the reaction to identify the suitable conditions for
substrate 12. Herein, we describe the first practical
kinetic resolution of a variety of racemic 2,2-dialkyl
5- and 6-membered cyclic benzylic alcohol
derivatives 13 with chlorosilanes by asymmetric
silylation using chiral guanidine catalysts (Scheme 1
(b)).
Table 1. Optimization of the combination of catalyst and
silyl chloride on reactivity and selectivity.
(a-1) Our previous study[ref 26]
Ph3SiCl (11; 0.65 eq.)
iPr2NEt (0.65 eq.)
cat. 8 (0.5 mol%)
OSiPh3
OH
OH
R1
R2
Ar
+
Ar
Ar
OH
Si
O
R3
toluene (0.2 M)
–78 °C, 24 h
(±)-9
(R)-10
(S)-9
s-value up to 89
iPr2NEt (0.75 equiv)
cat. 7 or 8 (5 mol%)
catalyst
Me
(±)-12
15
+
+
Me
N
OH
R1
N
N
N
toluene or THF (0.2 M)
R2
R3
Ph
Ph
–78 °C, 24 h
Si
N
N
Cl
(R)-NMBG 7
(a-2) Limitation
(R,R)-NbNpEtBG 8
(11; 0.75 equiv)
Entry Cat. Silyl reagent 11
12
ee [%]
Conva)
[%]
sa)
OH
(15; 12)
as above
1
2
3c)
4
5c)
6c,d)
7c,e)
8
7
7
7
7
7
7
7
7
7
8
8
8
8
8
Ph3SiCl (11a)
NRb)
–; –
–
no reaction
Ph2MeSiCl (11b) 62
11b 56
PhMe2SiCl (11c) 65
11c
11c
58; 96
71; 89
52; 98
49; >99
75; 87
87; 42
–; –
67; 55
–; –
53; 28
51; 95
67; 92
–; –
13.5
17.7
14.0
>14.5
19.5
21.3
–
8.7
–
4.2
10.3
16.1
–
(±)-12
R1
Si
(b) This study
R2
R3
67
54
32
NRb)
45
NRb)
O
OH
OH
silylative
kinetic resolution
R
R
R
R
R
11c
+
Ar
Ar
Ar
R
( )n
( )n
(±)-13
Et3SiCl (11d)
Me3SiCl (11e)
Ph3SiCl (11a)
Ph2MeSiCl (11b) 35
PhMe2SiCl (11c) 65
( )n
(R)-13
chiral guanidine cat.
(S)-14
9
10
11f)
12
13c)
14
Scheme 1. (a-1) Our previous study (a-2) limitation and
(b) this study.
11c
Et3SiCl (11d)
58
NRb)
2
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900761
Advanced Synthesis & Catalysis
a)
Conversions and s-values were calculated using Kagan’s
reactions of 4-substituted 2,2-dimethyl-1-indanols
16a and 16b with 11b and 11c in the presence of 7
proceeded smoothly, with higher selectivity obtained
when using 11b. On the other hand, the reactions of
5-, 6-, and 5,6-substituted 2,2-dimethyl-1-indanols
16c–16h gave better results when using 11c,
equation.[24] b) No reaction. THF was used as solvent.
c)
d)
e)
0.65 equiv of 11c was used. 0.48 equiv of 11c was used.
f) Average of two reactions.
In the reaction using 0.75 equiv of 11c with catalyst 7, irrespective of the electronic nature of the
the conversion was much more than 50% to afford
the corresponding (R)-12 with >99% ee; hence, the
exact s-value could not be evaluated (entry 5). Thus,
the same reaction was carried out by decreasing the
number of equivalents of 11c from 0.75 to 0.65 and
0.48 for adjusting the conversion to about 50% in
entries 6 and 7; high s-values were obtained in both
cases. The absolute configuration of the recovered
alcohol 12 was assigned (R)-configuration by
comparison with its previously reported experimental
optical rotation.[9]
To evaluate the scope and limitations of the
reaction, we investigated the substituents at the C2-
position and the effect of substituents on the aromatic
ring on 1-indanols using two combinations of catalyst
7 and silyl chlorides 11b or 11c (Scheme 2). The
substituents. Furthermore, in the case of 2,2-dialkyl
substituents 1-indanols 16i–16l, the suitable silyl
chloride depended on the structure of the substrate.
The reactions of 16i with 2,2-diethyl substituents and
16k with 2,2-dibenzyl ones afforded high s-values
when using 11c than when using 11b. In the reaction
of 16k with 11b, the conversion was low, probably
because of the steric hindrance between the dibenzyl
substituents and the two phenyl groups in the silyl
reagent. Good selectivity was observed in the
reactions of 16j with 2,2-dibutyl substituents and
spiro compound 17l using 11b.
R1
R2
Si
11b or 11c (0.75 equiv)
iPr2NEt (0.75 equiv)
OH
O
OH
R3
(R)-NMBG (7; 5 mol%)
R
R
R
R
R
R
Ar
Ar
Ar
+
THF (0.2 M)
–78 °C, 24 h
16
(±)-16
17; R1, R2 = Ph, R3 =Me
18; R1= Ph, R2, R3 =Me
OH
OH
OH
OH
OH
OH
Me
Cl
Br
MeO
Me
Br
16a → 17a +16a
17a; 76% ee
16b→17b +16b
17b; 75% ee
16c → 17c +16c
17c; 62% ee
16d → 17d +16d
17d; 56% ee
16e → 17e +16e
17e; 59% ee
16f → 17f +16f
17f; 70% ee
16a; 96% ee
16b; 90% ee
16c; 80% ee
16d; 86% ee
16e; 98% ee
16f; 83% ee
56% conv. s= 28
54% conv. s= 21
56% conv. s= 10
60% conv. s= 9
63% conv. s= 16
54% conv. s= 14
16a → 18a +16a
18a; 60% ee
16b→ 18b +16b
18b; 59% ee
16c → 18c +16c
18c; 48% ee
16d → 18d +16d
18d; 67% ee
16e → 18e +16e
18e; 57% ee
16f → 18f +16f
18f; 58% ee
16a; 98% ee
16b; 98% ee
16c; >99% ee
16d; 94% ee
16e; 99% ee
16f; 99% ee
62% conv. s= 18
62% conv. s= 17
67% conv. s> 14
58% conv. s= 17
64% conv. s= 17
63% conv. s= 17
OH
OH
OH
Et
OH
nBu
OH
OH
MeO
MeO
Ph
Ph
nBu
Et
MeO
16g→ 17g +16g
17g; 75% ee
16g; 79% ee
16h → 17h +16h
17h; 60% ee
16h; 99% ee
16i → 17i +16i
17i; 62% ee
16i; 92% ee
16a → 17j +16j
17j; 70% ee
16j; >99% ee
16k → 17k +16k
17k; 70% ee
16k; 8% ee
16l → 17l +16l
17l; 75% ee
16l; 96% ee
52% conv. s= 17
62% conv. s= 18
60% conv. s= 13
59% conv. s> 29
11% conv. s= 6
56% conv. s= 27
16g→ 18g +16g
18g; 61% ee
16a → 18h +16h
18h; 54% ee
16a → 18i +16i
18i; 55% ee
16a → 18j +16j
18j; 65% ee
16a → 18k +16k
18k; 88% ee
16a → 18l +16l
18l; 47% ee
16g; 98% ee
62% conv. s= 18
16h; 98% ee
64% conv. s= 14
16i; > 99% ee
65% conv. s> 17
16j; > 99% ee
61% conv. s> 23
16k; 81% ee
48% conv. s= 37
16l; 98% ee
68% conv. s= 12
Scheme 2. Silylative kinetic resolution of racemic 2,2-dialkyl 1-indanols.
3
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900761
Advanced Synthesis & Catalysis
We next applied the reaction system to other 2,2-
Scheme 3. Silylative kinetic resolution of racemic 2,2-
dimethyl-substituted benzylic alcohols.
dimethyl substituted benzylic alcohols, including 6-
and 7-membered cyclic and heterocyclic alcohols, as
well as acyclic benzylic alcohols, to further expand
the scope and limitations (Scheme 3). Since low
reactivity was observed for a series of examined
substrates, the reactions were carried out using
PhMe2SiCl (11c) with less sterically hindered
substituents as a silyl reagent. Under the optimized
reaction conditions, the reaction of 2,2-dimethyl-
substituted 6-membered cyclic and heterocyclic
benzylic alcohols 19a–19d proceeded to give 24%–
37% conversion with high s-values. To increase the
conversion, we carried out the same reactions by
increasing the catalyst loading from 5 to 20 mol%.
All the reactions showed improved conversion of up
to about 50% conversion with the same high s-values.
Unfortunately, the reactions of 7-membered cyclic
alcohol 19e and acyclic alcohol 19f did not proceed,
and the exact reason for this result is currently
unknown.
To demonstrate the scalability of the reaction, we
carried out the silylative kinetic resolution of (±)-12
using 11c on a 1 g scale, as shown in Scheme 4. The
reaction proceeded smoothly, irrespective of the scale,
to afford the silylated compound (S)-15c in 54% yield
with 71% ee, and the recovered alcohol (R)-12 in
44% yield with 94% ee, and high selectivity (s = 20).
This result indicated the good practicality of the
present reaction on a large scale.
PhMe2SiCl (11c; 0.65 equiv)
OH iPr2NEt (0.65 equiv)
cat. 7 (5 mol%)
OH
OSiMe2Ph
+
THF (0.2 M)
–78 °C, 24 h
(±)-12
1.0 g
(S)-15c
54%, 71% ee
(R)-12
44%, 94% ee
s= 20
OSiMe2Ph
Scheme 4. Gram-scale silylative kinetic resolution of (±)-
12 using PhMe2SiCl (11c).
PhMe2SiCl (11c; 0.75 equiv)
iPr2NEt (0.75 equiv)
(R)-NMBG
(cat. 7; 5 or 20 mol%)
OH
( )n
X
20
In conclusion, we have developed an efficient method
for the silylative kinetic resolution of racemic 2,2-
dialkyl 5- and 6-membered cyclic benzylic alcohols
using diphenylmethylchlorosilane (Ph2MeSiCl) or
phenyldimethylchlorosilane (PhMe2SiCl) in the
presence of chiral guanidine catalyst, (R)-N-
methylbenzoguanidine ((R)-NMBG), with good s-
values (up to 37). Although the kinetic resolution of
neopentyl alcohols is generally challenging task due
to their steric hindrance, we could overcome this
issue by using the present reaction system. Further
studies aimed at expanding the substrate scope of this
reaction are in progress in our laboratory.
+
OH
( )n
X
THF (0.2 M)
–78 °C, 24 h
(±)-19
( )n
X
19
OH
OH
OH
N
O
Boc
catalyst 5 mol%
catalyst 5 mol%
catalyst 5 mol%
19a → 20a +19a 19b → 20b +19b 19c → 20c +19c
20a; 86% ee
19a; 40% ee
20b; 88% ee
19b; 27% ee
20c; 85% ee
19c; 50% ee
32% conv. s= 19 24% conv. s = 20 37% conv. s= 20
Experimental Section
catalyst 20 mol% catalyst 20 mol% catalyst 20 mol%
19a → 20a +19a 19b → 20b +19b 19c → 20c +19c
Typical Procedure for the Silylative Kinetic Resolution
of Racemic 2,2-Dialkyl 1-Indanols (Scheme 2): To a
solution of racemic 4-methyl-2,3-dihydro-1H-indene-1-ol
(±)-16a (52.8 mg, 0.30 mmol) in THF (1.5 mL) at room
temperature were successively added (R)-NMBG 7 (3.7
20a; 78% ee
19a; 75% ee
20b; 81% ee
19b; 69% ee
20c; 81% ee
19c; 84% ee
49% conv. s= 18 46% conv. s= 20 51% conv. s= 25
HO
OH
OH
i
mg, 14.8 μmol) and Pr2NEt (39.2 μL, 0.23 mmol). After
cooling to –78 °C, Ph2MeSiCl (11b) (47.6 μL, 0.23 mmol)
was added to the mixture. The reaction mixture was stirred
for 24 h at the same temperature. Then it was quenched
with saturated aqueous NaHCO3 and diluted with EtOAc.
The organic layer was separated, and the aqueous layer
was extracted with EtOAc. The combined organic layer
was dried over Na2SO4. After filtration of the mixture, and
evaporated the solvent. The residue was purified by
preparative thin layer chromatography on silica
(hexane/EtOAc = 9/1) to afford the corresponding optically
active (–)-17a and the recovered optically active (–)-16a
[56% conversion, s = 28].
S
catalyst 5 mol%
19d → 20d +19d 19e → 20e +19e
20d; 88% ee
19d; 31% ee
26% conv. s= 22
catalyst 5 mol%
catalyst 5 mol%
19f → 20f +19f
20f; –% ee
19f; –% ee
no reaction
20e; –% ee
19e; –% ee
no reaction
catalyst 20 mol%
19d → 17d +19d
20d; 85% ee
19d; 65% ee
43% conv. s= 24
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900761
Advanced Synthesis & Catalysis
Enantiomeric excess of (–)-17a has been determined after
desilylation into (+)-16a as followed: To a solution of the
obtained silyl ether (–)-17a in THF (1.0 mL) at room
temperature was added tetrabutylammonium fluoride
(TBAF) (150 μL, 1.0 M in THF). The reaction mixture was
stirred for 2 h and then it was quenched with saturated
aqueous NH4Cl at 0 °C and diluted with EtOAc. The
organic layer was separated, and the aqueous layer was
extracted with EtOAc. The combined organic layer was
dried over Na2SO4. After filtration of the mixture, and
evaporated the solvent. The residue was purified by
preparative thin layer chromatography on silica gel
(hexane/EtOAc = 9/1) to afford the desilylated (+)-16a.
[12] a) E. J. Corey. R. K. Bakshi, S. Shibata, J. Am. Chem.
Soc. 1987, 109, 5551–5553; b) Elias J. Corey, C. J.
Helal, Angew. Chem. Int. Ed. 1998, 37, 1986–2012.
[13] N. Kurono, T. Kondo, M. Wakabayashi, H. Ooka, T.
Inoue, H. Tachikawa, T. Ohkuma, Chem. Asian J. 2008,
3, 1289–1297.
[14] K. Nakata, K. Gotoh, K. Ono, K. Futami, I. Shiina,
Org. Lett. 2013, 15, 1170–1173.
[15] R. W. Clark, T. M. Deaton, Y. Zhang, M. I. Moore, S.
L. Wiskur, Org. Lett. 2013, 15, 6132–6135.
[16] N. Kurono, K. Ohtsuga, M. Wakabayashi, T. Kondo,
H. Ooka, Takeshi Ohkuma, J. Org. Chem. 2011, 76,
10312–10318.
Acknowledgements
[17] For highlights and reviews, see: a) S. Rendler, M.
Oestreich, Angew. Chem. Int. Ed. 2008, 47, 248–250;
b) A. Weickgenannt, M. Mewald, M. Oestreich, Org.
Biomol. Chem. 2010, 8, 1497–1504; c) L.-W. Xu, Y.
Chen, Y. Lu, Angew. Chem. Int. Ed. 2015, 54, 9456–
9466; d) J. Seliger, M. Oestreich, Chem. Eur. J. 2019,
25, 9358–9365.
The authors thank Dr. Michiko Egawa, (Shimane
University, Japan), for her measurement of elemental
analysis.
References
[1] Y. Kawamata, T. Hashimoto, K. Maruoka, J. Am.
Chem. Soc. 2016, 138, 5206−5209.
[18] a) Y. Zhao, A. W. Mitra, A. H. Hoveyda, M. L.
Snapper, Angew. Chem. Int. Ed. 2007, 46, 8471–8474;
b) J. M. Rodrigo, Y. Zhao, A. H. Hoveyda, M. L.
Snapper, Org. Lett. 2011, 13, 3778–3781; c) N.
Manville, H. Alite, F. Haeffner, A. H. Hoveyda, M. L.
Snapper, Nat. Chem. 2013, 5, 768–774.
[2] T. Hashimoto, Y. Shimazaki, Y. Omatsu, K. Maruoka,
Angew. Chem. Int. Ed. 2018, 57, 7200–7204.
[3] J. A. Palermo, M. F. R. Brasco, C. Spagnuolo, A. M.
Seldes, J. Org. Chem. 2000, 65, 4482–4486.
[19] a) A. D. Worthy, X. Sun, K. L. Tan, J. Am. Chem.
Soc. 2012, 134, 7321−7324; b) X. Sun, A. D. Worthy,
K. L. Tan, J. Org. Chem. 2013, 78, 10494−10499.
[4] a) K. Fabian, K. Lorenzen, T. Anke, M. Johansson, O.
Sterner, J. Biosci. 1998, 53, 939–945; b) C. L. Nord, A.
Menkis, A. Broberg, Molecules 2014, 19, 14195–14203.
[20] a) C. I. Sheppard, J. L. Taylor, S. L. Wiskur, Org.
Lett. 2011, 13, 3794–3797; b) R. W. Clark, T. M.
Deaton, Y. Zhang, M. I. Moore, S. L. Wiskur, Org. Lett.
2013, 15, 6132–6135; c) L. Wang, R. K. Akhani, S. L.
Wiskur, Org. Lett. 2015, 17, 2408−2411; d) R. K.
Akhani, R. W. Clark, L. Yuan, L. Wang, C. Tang, S. L.
Wiskur, ChemCatChem 2015, 7, 1527–1530; e) R. K.
Akhani, M. I. Moore, J. G. Pribyl, S. L. Wiskur, J. Org.
Chem. 2014, 79, 2384−2396; f) L. Wang, T. Zhang, B.
K. Redden, C. I. Sheppard, R. W. Clark, M. D. Smith,
S. L. Wiskur, J. Org. Chem. 2016, 81, 8187−8193.
[5]a) M. Fukuoka, M. Kuroyanagi, K. Yoshihira, S. Natori,
Chem. Pharm. Bull. 1978, 26, 2365–2385; b) M.
Fukuoka, K. Yoshihira, S. Natori, K. Mihashi, M. Nishi,
Chem. Pharm. Bull. 1983, 31, 3113–3128; c) K.-M. E.
Ng, T. C. McMorris, Can. J. Chem. 1984, 62, 1945–
1953; d) X. Luo, C. Li, P. Luo, X. Lin, H. Ma, N. P.
Seeram, C. Song, J. Xu, Q. Gu, J. Nat. Prod. 2016, 79,
3014−3021.
[6] T. Murakami, H. Wada, N. Tanaka, Y. Saiki, C.-M.
Chen, Chem. Pharm. Bull. 1980, 28, 1869–1872.
[21] a) S. Y. Park, J.-W. Lee, C. E. Song, Nat. Commun.
2015, 6, 7512; b) H. Yan, H. B. Jang, Ji.-W. Lee, H. K.
Kim, S. W. Lee, J. W. Yang, C. E. Song, Angew. Chem.
Int. Ed. 2010, 49, 8915–8917.
[7] A. L. Jones, J. K. Snyder, J. Org. Chem. 2009, 74,
2907–2910.
[8] Enantiomerically enriched synthesis of 3 was reported
by the Rh-catalyzed [2+2+2] alkyne cyclotrimerization
reaction, see: T. Welsch, H.-A. Tran, B. Witulski, Org.
Lett. 2010, 12, 5644–5647.
[22] a) S. Rendler, G. Auer, M. Oestreich, Angew. Chem.
Int. Ed. 2005, 44, 7620–7624; b) H. F. T. Klare, M.
Oestreich, Angew. Chem. Int. Ed. 2007, 46, 9335–9338;
c) S. Rendler, O. Plefka, B. Karatas, G. Auer, R.
Frꢀhlich, C. Mꢁck-Lichtenfeld, S. Grimme, M.
Oestreich, Chem. Eur. J. 2008, 14, 11512–11528; d)
Weickgenannt, M. Mewald, T. W. T. Muesmann, M.
Oestreich, Angew. Chem. Int. Ed. 2010, 49, 2223–2226;
e) A. Weickgenannt, J. Mohr, M. Oestreich,
Tetrahedron 2012, 68, 3468–3479; f) X. Dong, A.
Weickgenannt, M. Oestreich, Nat. Commun. 2017, 8,
15547; g) X. Dong, Y. Kita, M. Oestreich, Angew.
Chem. Int. Ed. 2018, 57, 10728–10731; h) J. Seliger, X.
[9] T. Ohkuma, C. A. Sandoval, R. Srinivasan, Q. Lin, Y.
Wei, K. Muñiz, R. Noyori, J. Am. Chem. Soc. 2005,
127, 8288–8289.
[10] S. Eagon, J. Kim, K. Yan, D. Haddenham, B.
Singaram, Tetrahedron Lett. 2007, 48, 9025–9029.
[11] Z. Zeng, Y. Zhao, Y. Zhang, Chem. Commun. 2019,
55, 4250–4253.
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900761
Advanced Synthesis & Catalysis
Dong, M. Oestreich, Angew. Chem. Int. Ed. 2019, 58,
1970–1974.
[24] H. B. Kagan, J. C. Fiaud, Top. Stereochem. 1988, 18,
249–330.
[23] a) K. Nakata, I. Shiina, Org. Biomol. Chem. 2011, 9,
7092–7096; b) K. Nakata, T. Tokumaru, H. Iwamoto,
Y. Nishigaichi, I. Shiina, Asian J. Org. Chem. 2013, 2,
920–922; c) A. Yamada, K. Nakata, Tetrahedron Lett.
2016, 57, 4697–4701; d) A. Yamada and K. Nakata, I.
Shiina, Tetrahedron: Asymmetry 2017, 28, 516–521.
[25] S. Yoshimatsu, A. Yamada, K. Nakata, J. Org. Chem.
2018, 83, 452−458.
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900761
Advanced Synthesis & Catalysis
COMMUNICATION
Silylative Kinetic Resolution of Racemic 2,2-
Dialkyl 5- and 6-Membered Cyclic Benzylic
Alcohol Derivatives Catalyzed by Chiral
Guanidine, (R)-N-Methylbenzoguanidine
R1
R2
R3
Si
O
OH
R
R
R
iPr2NEt (0.75 eq.)
cat. (5 mol%)
Ar
Ar
Ar
Me
( )n
R
( )n
N
N
(R)
+
+
Adv. Synth. Catal. Year, Volume, Page – Page
Ph
THF (0.2 M)
–78 °C, 24 h
OH
R1
N
R2
R3
R
R
Si
s-valueup to37
Cl
cat. (R)-NMBG
( )n
R1, R2 = Ph, R3 =Me
Shuhei Yoshimatsu, and Kenya Nakata,*
(0.75 equiv)
R1= Ph, R2, R3 =Me
7
This article is protected by copyright. All rights reserved.