Enantioselective O- and N-Nitroso Aldol Synthesis of Tin Enolates. Isolation of Three BINAP-Silver Complexes and Their Role in Regio- and Enantioselectivity

Article abstract of DOI:10.1021/ja039103i

The selective generation of three different silver-BINAP catalysts has been achieved via the proper combination of metal/ligand ratio and/or choice of silver salt. Indeed, the X-ray crystallographic study has been used to gain insight into the structure of the catalyst. After the evaluation of each species, 1:1 (AgX·(R)-BINAP) complex was found to be the real active species in the O-selective nitroso aldol reaction. On the other hand, a systematic survey of solvent has shown that the optimal 2:1 (AgX·(R)-BINAP) complex is the effective catalyst in the N-selective pathway. Thus, a new method of generation of the silver-BINAP catalyst and the synthetic transformations provide not only new insights into the developing area of catalytic enantioselective nitroso aldol synthesis but also clear guidance for the design of an effective catalyst. Copyright

Full text of DOI:10.1021/ja039103i

Published on Web 04/13/2004
Enantioselective O- and N-Nitroso Aldol Synthesis of Tin Enolates. Isolation
of Three BINAP-Silver Complexes and Their Role in Regio- and
Enantioselectivity
Norie Momiyama and Hisashi Yamamoto*
Department of Chemistry, The UniVersity of Chicago, 5735 South Ellis AVenue, Chicago, Illinois 60637
Received October 17, 2003; E-mail: yamamoto@uchicago.edu
Scheme 1
One of the most intensely studied areas in chemical synthesis at
present is the development of new catalytic and highly enantiose-
lective processes, especially for the efficient synthetic construction
of R-oxy and R-amino carbonyl compounds.1 After our early study
of nitroso aldol synthesis,2 we had demonstrated that the BINAP-
silver complex is an effective catalyst for the O-nitroso aldol
synthesis of tin enolates.3 In this Communication, we describe the
isolation of three structures of BINAP-silver complexes identified
by NMR study and X-ray analysis.4 Furthermore, each of the three
complexes plays a different role in regio- and enantioselectivity in
the nitroso aldol synthesis (Scheme 1).
In an effort to investigate the coordination of BINAP-silver
metal, low-temperature NMR studies were undertaken. In the
preparation of 1 equiv of AgOTf for (R)-BINAP in THF, the catalyst
was unambiguously discerned as a mixture of three species, 1:2
Table 1. 1:1 (AgX‚(R)-BINAP) Complexes in O-Nitroso Aldol
(A), 1:1 (B), 2:1 (C) (AgOTf‚(R)-BINAP) complexes, in the 31P
NMR spectrum at -78 °C (molar ratio of three complexes: A/B/C
) 21/63/16).5 We were very pleased to learn that, during a
systematic survey of the metal-to-ligand ratio, either the A or the
C complex was selectively generated from 2 equiv of (R)-BINAP
or 0.4 equiv of (R)-BINAP for AgOTf, respectively. The generation
of the 1:1 complex was highly dependent on the choice of silver
anion, but, fortunately, this complex was also obtained almost
exclusively by switching the silver salt from AgOTf or AgClO4 to
AgOAc or AgOCOCF3. Furthermore, we were able to isolate each
metal species, and the X-ray crystallographic study provided us a
clear view of the structure of each catalyst.6 The tetragonal geometry
of complex A (X ) OTf) conformed to that of the proposed
structure previously reported by our lab.7 The tetragonal geometry
of complex B (X ) OCOCF3) is likewise similar to that of a closely
related X-ray structure of BINAP‚AgOAc reported by Yamagishi
et al., with silver coordinated to two oxygen atoms. The crystal-
lographic data for complex C (X ) OTf) revealed a trigonal
geometry, but with a metal center coordinated to one phosphine
and triflate on another silver salt.8
Synthesisa
b
c
entry
mol %
AgX
yield, %
ee, %
1d
2
3
10
2
2
AgOTf
AgOAc
AgOCOCF3
88
93
94
99
97
95
a Reactions were conducted with a catalytic amount of (R)-BINAP‚AgX,
1.0 equiv of nitrosobenzene, and 1.0 equiv of trimethyltin enolate in THF
at -78 °C for 2 h. b Isolated yield. c Determined by HPLC (Supporting
Information). d Reactions were conducted with a catalytic amount of (R)-
TolBINAP‚AgOTf, 1.0 equiv of nitrosobenzene, and 1.0 equiv of trimeth-
yltin enolate in THF at -78 °C for 2 h.
N selective) with <1% ee and thus did not contribute to the nitroso
aldol reaction. Taken into account all of the above results, it appears
that 1:1 complex B should be the responsible catalyst for the silver
catalyzed O-nitroso aldol process as evidenced by the enantiose-
lectivity/regioselectivity profile.
Given each of the silver-BINAP complexes, A, B, C via the
proper combination of metal/ligand ratio and/or choice of metal
salt, a representative selection of tin enolates was evaluated in the
O-nitroso aldol process. The reaction with the trimethyltin enolate
of cyclohexanone in the presence of 10 mol % of catalyst derived
from (R)-TolBINAP and AgOTf (THF, 1 h, -78 °C) afforded
O-adduct with exceptional regio- and stereoselectivity (O-/N- )
>99:1, >99% ee). The AgOAc- or AgOCOCF3-derived 1:1
complexes B should also be efficient catalysts that exhibit the
capacity to participate in the activation as a Lewis acid uniformly
to give high enantioselectivities and efficiencies (95-97% ee, 93-
94% yield) under the relatively low catalyst loading (Table 1). In
contrast to these results, reaction with complex C afforded the
O-adduct in low enantioselectivity (O-/N- ) 95:5, 9% ee). Further,
complex A was totally ineffective in producing the O-adduct (>99%
Turning now to the hydroxyamination issue, due to relatively
high N-selectivity in the reaction catalyzed by the 10 mol % of
AgOTf and (R)-BINAP system in THF (O-/N- ) 8:92, 54% ee of
N-adduct), tributyltin enolate of cycloheptanone was chosen for
evaluation of these complexes in the N-selective pathway.9 Complex
A resulted in complete N-selectivity but without any enantioselec-
tivity (O-/N- ) 1:>99, 2% ee of N-adduct). The enantioselectivity
of N-adduct was also very low using complex B derived from
AgOAc (∼20% ee). A dramatic increase of enantio- and regiose-
lectivities was observed by using complex C in THF, to give the
N-adduct in 87% ee with 96% regioselectivity.
The high enantioselectivity in the use of tin enolate of cyclo-
heptanone associated with the use of complex C prompted us to
select catalyst C for the development of R-hydroxyamino ketone
9
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J. AM. CHEM. SOC. 2004, 126, 5360-5361
10.1021/ja039103i CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Solvent Effect in N-Nitroso Aldol Synthesisa
The synthetic transformations described herein provide new
insights into the developing area of catalytic enantioselective nitroso
aldol synthesis and new methodology for the construction of a
variety of chiral building blocks. Further, the new method of
selective generation of three different silver-BINAP complexes
opens a new entry into various unknown synthetic reactions. These
catalysts are easily generated and provide clear guidance for the
design of an even more effective catalyst.
b
c
entry
solvent
yield, %
N-/O-
eeof N-adduct, %
1
2
3
4
5
6
7
THF
DMF
Et2O
94
90
92
97
93
94
92
5/95
94/6
73/27
92/8
92/8
96/4
93/7
9
5
90
59
40
MeOCH2OMe
Acknowledgment. We thank Dr. Ian M. Steele for the X-ray
crystallographic analysis. Support for this research was provided
by the SORST project of the Japan Science and Technology Agency
(JST), National Institutes of Health (NIH) GM068433-01, and a
grant from the University of Chicago.
MeOCH2CH2OMe
EtOCH2CH2OEt
MeOCH2CH2OtBu
>99
87
a Reactions were conducted with 4 mol % of complex C (X ) OTf),
1.0 equiv of nitrosobenzene, and 1.0 equiv of tributyltin enolate in
corresponding solvent at -78 °C for 2 h. b Isolated yield. c Determined by
HPLC (Supporting Information).
Supporting Information Available: Experimental procedures,
spectral data for all new compounds, and crystallographic data (PDF
and CIF). This material is available free of charge via the Internet at
http://pubs.acs.org.
Table 3. Reaction Scope in N-Nitroso Aldol Synthesisa
References
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(5) See the Supporting Information for a list regarding a survey of the metal-
to-ligand ratio.
a Reactions were conducted with 4 mol % of complex C (X ) OTf),
1.0 equiv of nitrosobenzene, and 1.0 equiv of tributyltin enolate in ethylene
glycol diethyl ether at -78 °C for 2 h. b Isolated yield. c Determined by
HPLC (Supporting Information).
(6) The crystallographic analysis for each species has been described in the
Supporting Information.
(7) (a) Yanagisawa, A.; Nakatsuka, Y.; Asakawa, K.; Wadamoto, M.;
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synthesis.10 Variation of the solvent has a pronounced effect on
regio- and enantioselectivity, and some of our results are sum-
marized in Table 2. Generally, the complex C-catalyzed N-nitroso
aldol reaction performs well in a number of ether solvents with
moderate-to-high enantioselectivities. Excellent levels of enantio-
and regioselectivities were observed when the reaction was carried
out in ethylene glycol diethyl ether (Table 2, entry 6).
The benefits of complex C extend over a wide range of cyclic
substrates, and those experiments that probed the scope of tin
enolates in ethylene glycol diethyl ether are summarized in Table
3.11 Extremely high enantioselectivities were observed during the
examination, an indication that complex C is indeed very effective
and that these reactions proceed via a highly organized transition
state.
(9) It should be noted that the N-nitroso aldol synthesis proceeds smoothly
without catalyst.
(10) For the asymmetric reaction catalyzed by the bimetallic-BINAP complex,
see: (a) El-Qisairi, A.; Hamed, O.; Henry, P. M. J. Org. Chem. 1998, 63,
2790. (b) El-Qisairi, A.; Henry, P. M. J. Organomet. Chem. 2000, 603,
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2002, 656, 168. (d) El-Qisiari, A. K.; Qaseer, H.; Lorenzi, P.; Trivendi,
U.; Tracz, S.; Hartman, A.; Miller, J. A.; Henry, P. M. Org. Lett. 2003,
5, 439.
(11) Unfortunately, the tin enolate of 3-pentanone could not produce significant
enantioselectivity.
JA039103I
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