Zn-catalyzed asymmetric allylation for the synthesis of optically active allylglycine derivatives. Regio- and stereoselective formal α-addition of allylboronates to hydrazono esters

Article abstract of DOI:10.1021/ja710627x

We have developed Zn-catalyzed asymmetric allylation of hydrazono esters with allylboronates. The reactions proceeded smoothly in high yields and high stereoselectivities. Remarkably, formal α-addition occurred for α-substituted allylboronates exclusively, and excellent stereoselectivities were observed. This is the first example of catalytic regio- and stereoselective allylations with formal α-addition. In addition, the reaction proceeded in aqueous media, and the use of water is essential. Zn(OH)₂ might be a catalyst in this asymmetric allylation, and the catalytic activity of Zn(OH)₂ was confirmed. This is also the first case of chiral metal hydroxide-catalyzed asymmetric reactions. Copyright

Full text of DOI:10.1021/ja710627x

Published on Web 02/16/2008
Zn-Catalyzed Asymmetric Allylation for the Synthesis of Optically Active
Allylglycine Derivatives. Regio- and Stereoselective Formal r-Addition of
Allylboronates to Hydrazono Esters
Mari Fujita, Takashi Nagano, Uwe Schneider, Tomoaki Hamada, Chikako Ogawa, and
Shuj Kobayashi*
Department of Chemistry, School of Science and Graduate School of Pharmaceutical Sciences,
The UniVersity of Tokyo, The HFRE DiVision, ERATO, Japan Science Technology Agency (JST),
Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Received November 27, 2007; E-mail: shu_kobayashi@chem.s.u-tokyo.ac.jp
Table 1. Zn-Catalyzed Asymmetric Allylation of Hydrazono Esters
1 with Allylboronates 2a-c
Enantioselective addition to iminoester and equivalents provides
an efficient route to optically active R-amino acids.1 While catalytic
asymmetric Mannich-type reactions of iminoester derivatives have
been reported,2 less progress has been made for the corresponding
allylations.3 We now report catalytic asymmetric allylation of
hydrazono esters with allylboronates; the remarkable regio- and
stereoselective formal R-addition of allylboronates is also described.
Recently we reported catalytic asymmetric allylation of hydra-
zono esters with allyltrimethoxysilane.3h While the reactions pro-
ceeded smoothly in aqueous media (water/THF ) 1/9) in the pres-
ence of ZnF2-chiral diamine to afford the corresponding allylated
products in high yields with good selectivities, they suffered from
the requirement to employ an excess (3 equiv) of allyltrimethoxy-
silane, a relatively low reactivity, and a narrow substrate scope.
To address these issues we decided to investigate allylboronates
as allylating agents instead of allyltrimethoxysilane.
It was found that the desired reactions proceeded well when
hydrazono ester 1a4 was treated with allylboronic acid pinacol ester
(2a) in the presence of catalytic amounts of ZnF25 and chiral diamine
4a in water/organic solvent mixtures, affording the allylated prod-
ucts in high yields with good enantioselectivities (Table 1). It is
noted that the reactions proceeded faster than those using allyltri-
methoxysilane and that high yields were obtained using a slight
excess of the allylating agent (1.2 equiv). Among organic co-sol-
vents tested, acetone gave the best results (Table 1, entries 1-5).
Interestingly, the reaction did not proceed at all in the absence of
water (entry 1). Moreover, other allylboronates 2b and 2c gave the
same levels of yield and enantioselectivity (entries 12, 13). After
optimization of the reaction conditions, the desired allylated product
3h was obtained quantitatively with 90% ee from hydrazono ester
1h and allylboronate 2a in water/acetone (3/5) at 0 °C in the
presence of 5 mol% of ZnF2 and 12 mol% of chiral diamine 4a
(entry 14).
Table 2. Zn-Catalyzed Asymmetric Allylation of Hydrazono Ester
1h with R-Substituted Allylboronates 2
We then investigated the reactions using substituted allylboro-
nates. When (E)-crotylboronate 2d was treated with hydrazono ester
1a under the optimal conditions, the reaction proceeded diastereo-
selectively (syn/anti ) 96/4) but very slowly in low yield (19%
after 110 h at 0 °C), and the enantiomeric excess of the major dia-
stereomer was also low (7% ee). Similarly, (Z)-crotylboronate 2e
reacted with 1a to afford the crotylated product diastereoselectively
(syn/anti ) 1/99), but again the yield and the enantioselectivity of
the major product were very low (25% yield, 14% ee). These results
were unexpected since high reactivity was observed in the reactions
using unsubstituted allylboronates 2a-c. We next studied the reac-
tions of R-substituted allylboronates (Table 2). When R-methyl-
substituted allylboronate 2f6 was reacted with hydrazono ester 1h
under the optimal conditions, the reaction proceeded faster, and
unexpected crotylated product 3i was isolated in high yield; remark-
ably, no γ-addition product was obtained. Only an anti-adduct was
produced in high enantiomeric excess. The reaction proceeded at
-20 °C to afford the crotylated product quantitatively with perfect
anti-selectivity and 88% ee (entry 1). We tested other R-substituted
allylboronates (entries 2-5), and in all cases only formal R-addition
products were obtained. In addition, anti-adducts were obtained
exclusively in high yields with high enantioselectivities in all cases.
These results are especially remarkable because stereoselective
reactions of various allylating agents with carbonyl and related
compounds have been well investigated, and to the best of our
knowledge no catalytic regio- and stereoselective formal R-addition
reactions have been reported to date.7,8
9
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J. AM. CHEM. SOC. 2008, 130, 2914-2915
10.1021/ja710627x CCC: $40.75 © 2008 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1. Assumed Reaction Pathway and Catalytic Cycle
for R-substituted allylboronates exclusively, and excellent stereo-
selectivities were observed. This is the first example of catalytic
regio- and stereoselective allylations with formal R-addition. (3)
The reaction proceeded in aqueous media. The use of water is
essential. (4) Zn(OH)2 might be a catalyst in this asymmetric
allylation. The catalytic activity of Zn(OH)2 was confirmed, and
this is also the first case of chiral metal hydroxide catalyzed
asymmetric reactions. Further investigations to clarify the precise
mechanism of the formal R-addition as well as catalytic cycle of
Zn species and to use metal hydroxides in organic reactions in
aqueous media are now in progress in our laboratories.
Acknowledgment. This work was partially supported by a
Grant-in-Aid for Science Research from the Japan Society for the
Promotion of Science (JSPS).
Scheme 2. Zn(OH)2-Catalyzed Asymmetric Allylation in Aqueous
Media
Supporting Information Available: Procedures and characteriza-
tion. This material is available free of charge via the Internet at http://
pubs.acs.org.
Scheme 3. Synthesis of Allylglycine Derivatives
References
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At present we assume this unprecedented reaction pathway and
catalytic cycle as shown in Scheme 1. In an initial stage,
allylboronate 2 may react with ZnF2 to form allylzincate. While
this process was confirmed by NMR analysis using allylboronate
2a and ZnF2, similar experiments using R-methyl-substituted
allylboronate 2f and ZnF2 have so far proved unsuccessful. We
assume that 2f may react with ZnF2 via a six-membered chairlike
transition state (γ-addition of 2f toward ZnF2) to afford Z-crotylzinc
species, which may react with hydrazono ester 1 stereoselectively
via γ-addition, giving the crotylated product with anti-selectivity.9
Another interesting point regarding this proposed pathway and
catalytic cycle is regarding the regeneration of ZnF2 or other active
Zn species. Since water is necessary in this reaction, hydrolysis of
intermediate 5 may proceed smoothly to afford the product along
with generation of Zn(OH)F. Since after the second turnover
Zn(OH)2 may be formed, we then conducted the reaction employing
catalytic Zn(OH)2 instead of ZnF2 to test its efficacy as a catalyst
and probe the mechanism. Interestingly, the allylation reaction of
1h with 2a proceeded using Zn(OH)2 as a catalyst to afford the
desired allylated product in 80% yield with 85% ee (Scheme 2). It
should be noted that, to the best of our knowledge, this is the first
example of a chiral metal hydroxide-catalyzed asymmetric reaction
and that metal hydroxides are ideal catalysts for organic reactions
in aqueous media.10
(8) R-Addition, of allylbarium is known. (a) Yanagisawa, A.; Habaue, S.;
Yamamoto, H. J. Am. Chem. Soc. 1991, 113, 8955. (b) Yanagisawa, A.;
Habaue, S.; Yasue, K.; Yamamoto, H. J. Am. Chem. Soc. 1994, 116, 6130.
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1564. (d) Miyabe, H.; Yamaoka, Y.; Naito, T.; Takemoto, Y. J. Org.
Chem. 2003, 68, 6745.
To demonstrate the utility of this asymmetric allylation and
determine the relative and absolute configurations of the products,
several transformations of the products were conducted. Allylated
adduct 3h was treated with Cbz-Cl, followed by SmI2 to afford
allylglycine derivative 6;11 similarly, 3i was converted to 7.12 3m
was also converted to the previously reported allylglycine derivative
8 bearing a hydroxy group in good yield (Scheme 3).13
(9) Ogawa, C.; Sugiura, M.; Kobayashi, S. Angew. Chem., Int. Ed. 2004, 43,
6491.
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many chiral catalysts are not stable in the presence of water. See: (a)
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S.; Ogawa, C. Chem.sEur. J. 2006, 12, 5954. (c) Kobayashi, S.; Ogawa,
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S., Eds.; Wiley-VCH: Weinheim, 2007; p 117.
(11) Abbott, S. D.; Lane-Bell, P.; Sidhu, K. P. S.; Vederas, J. C. J. Am. Chem.
Soc. 1994, 116, 6513.
In summary, we have developed Zn-catalyzed asymmetric
allylation of hydrazono esters with allylboronates. Several charac-
teristic features of these reactions have been revealed. (1) Catalytic
asymmetric allylation of imine derivatives was attained in high
yields and high stereoselectivities. (2) Formal R-addition occurred
(12) Kazmaier, U.; Mues, H.; Krebs, A. Chem.sEur. J. 2002, 8, 1850.
(13) (a) Kandula, S. R. V.; Kumar, P. Tetrahedron: Asymmetry 2005, 16, 3268.
(b) Delle Monache, G.; Giovanni, M. C. D.; Misiti, D.; Zappia, G.
Tetrahedron: Asymmetry 1997, 8, 231. Some values of optical rotations
in ref 13a are fatally incorrect. See Supporting Information.
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