Ó 2007 The Chemical Society of Japan Bull. Chem. Soc. Jpn. Vol. 80, No.

4, 595–607 (2007) 595

Vol. 80 Commemorative Accounts

Nitroso and Azo Compounds in Modern Organic Synthesis:

Late Blooming but Very Rich

Hisashi Yamamoto
and Masanori Kawasaki

Department of Chemistry, University of Chicago, Chicago, Illinois, 60637, U.S.A.

Received January 9, 2007; E-mail: [email protected]

The catalytic enantioselective oxidation is an extremely important process in organic synthesis and numbers of
effort to improve this process have been reported so far. Although nitroso and azo compounds are attractive tools for
hydroxylation and amination of organic compounds, no reports on a catalytic asymmetric version of these reactions
had been reported until recently. The main issues were their high and unique reactivities. In this review, we would like
to introduce the recent advances in this area.

1. Introduction O O
O O O cat. NaOH
The catalytic enantioselective oxidation, including hydroxy- + N EtO OEt
EtO OEt Ph EtOH
lation and amination, is an extremely important process for the N
Ph
pharmaceutical and agrochemical industry.1 This is clear be-
cause the most biologically active compounds have highly Scheme 1.
functionalized structure. Thus, it is not surprising to know that
O
despite enormous efforts to develop the asymmetric process,2 O OH O O
more efficient and practical oxidation of organic compounds O
N + N NHPh + NPh
N Ph +
are still strongly demanded. We recently focus our attention Ph PhH
0 °C to rt
on nitroso and azo compounds to introduce hydroxy and amino
groups directly into organic molecules. Nitroso and azo com-
pounds have unique reactivities and react with simple alkenes Scheme 2.
and carbonyl compounds as electrophiles.3 Despite their useful
1) Base
reactivity, the chemistry of nitroso and azo compounds have Cl
2)
not been intensively studied until recently.4–6 NO NH2
In this review, we would like to summarize our recent re- NHOH
HO
N N R
sults of enantioselective N-/O-nitroso aldol reactions and het- S
R 3) HCl aq.
S
R
O
O2 O O2 O
ero-Diels–Alder reactions using nitroso and azo compounds.

2. Nitroso Aldol Reaction Scheme 3.

The reactions of nitrosobenzene with 1,3-dicarbonyl OTMS O

compounds were reported to afford azomethine derivatives O cat. TESOTf
+ N O
(Scheme 1).7 The first synthesis of
-hydroxyamino ketones Ph 1,2-Dichloropropane NHPh
using nitrosobenzene as an electrophile was reported in 1972 94%
TESOTf : triethylsilyl trifluoromethansulfonate
(Scheme 2).8 In 1990, Oppolzer et al. described diastereoselec-
tive amination reaction with chiral enolates and
-chloro-
- Scheme 4.
nitroso derivative gave corresponding
-aminooxy ketones
which were further transformed (Scheme 3).9 tives (Scheme 4). This was a great surprise for us because this
In 2002, we reported a significant contribution in nitroso is a completely new method to introduce oxygen
- to carbon-
chemistry. The O-regioselective nitroso aldol (NA) reaction yl functionality.
with nitrosobenzene and silyl enol ethers promoted by Lewis After this important finding, we found that
-aminooxy
acids was first reported by us.10 The reaction was promoted ketones were also obtained using the enamine as a nucleophile
by Lewis acids to afford corresponding
-aminooxy deriva- (Scheme 5).11 The reaction of nitrosobenzene with pyrrolidine

Published on the web April 13, 2007; doi:10.1246/bcsj.80.595

596 Bull. Chem. Soc. Jpn. Vol. 80, No. 4 (2007) ACCOUNTS

O OH
N O Ph
N Ph
Ph P
AgOTf
P
O Ph
OSnMe3 Ph O
N PhH O
Ph O
0 °C to rt O NHPh
NHPh THF, -78 °C

N 99% ee

Scheme 7.
Scheme 5.

O O O
CuSO4 (0.3 mol. amt.)
O OH O OH
NHPh
O MeOH MeOH, 0 °C
N + N
N Ph
Ph toluene
-78 °C, 1 h
exclusively O NHPh
60% EuCl3
O O
NHPh
EtOH, MW, 105 °C

O
N O AcOH
+ O Scheme 8.
N NHPh
Ph toluene
-78 °C, 1 h
exclusively
52%
Ph
Ph
Scheme 6. P AgOTf
P AgOTf
Ph
enamine afforded
-aminooxy ketone almost exclusively. On OSnBu3 Ph O OH
the other hand, when morpholine enamine was used instead N
Ph
of pyrrolidine enamine, it gave hydroxyamino ketone exclu- EtOCH2CH2OEt, -78 °C
sively. The observed significant difference of the reaction
pathway is still unclear. However, we believe this comes from >99% ee
the different nucleophilicity of enamine and possibly the pres- Scheme 9.
ence of a small amount of the catalyst in the system. Thus, we
studied careful examinations of the effect of Brønsted acids catalyst of the silver–BINAP complex. The reaction of nitroso-
(Scheme 6).12 The N-NA reaction of morpholine enamine in benzene and tributylstannyl enolates with the 2:1 complex of
the presence of methanol at 78  C proceeded smoothly to silver–BINAP as a catalyst proceeded smoothly to give
-hy-
give hydroxyamino ketone. In sharp contrast, the O-NA reac- droxyamino ketones. The use of ethylene glycol diethyl ether
tion was accelerated significantly using acetic acid to furnish as a solvent was optimal to induce excellent regio- and enan-
aminooxy ketone. It is surprising to obtain either N- or O- tioselectivity.
NA product simply by changing the acid catalyst and enamine As we described earlier, the Brønsted acids promote NA re-
moiety. action of enamines regioselectively. On the basis of these ob-
servations, we attempted to develop an asymmetric NA reac-
3. Catalytic Enantioselective Nitroso Aldol Reaction tion catalyzed by a chiral Brønsted acid. After various chiral
Our previous observations have allowed us to develop a cat- carboxylic acids and chiral alcohols were assayed, we found
alytic enantioselective NA reaction for selective introduction that not only did the use of 1-(1-naphthyl)glycolic acid as a
of nitrogen or oxygen atoms at
-position of carbonyl groups. catalyst in Et2 O proceed O-NA reaction in excellent enantiose-
The asymmetric NA reaction of nitrosobenzene was initially lectivity (Scheme 10), but also the use of TADDOL derivative
tested using silver–BINAP catalyst. We found that the 1:1 promoted enantioselective N-NA reaction (Scheme 11).16
complex of silver–BINAP was optimal for O-NA reaction with Recent advances of the reactions using proline or its analogs
high enantioselectivity (Scheme 7).13 This is the first report of as a catalyst are highlighted in organic chemistry. The asym-
the catalytic enantio- and regioselective process of a nitroso metric O-NA reaction catalyzed by proline or its analogs has
electrophile. The key to this success is efficient generation of been reported by several groups. Various pyrrolidine-based
trimethylstannyl enolates. The corresponding
-aminooxy catalysts were used to give the corresponding
-aminooxy car-
ketone was converted to the corresponding
-hydroxy ketone bonyl compounds with excellent enantio- and regioselectivity
by using CuSO4 without any loss of enantioselectivity. We (Scheme 12).17 In contrast, the use of amino alcohols as cata-
have also found that
-aminooxy ketone was converted to lysts promoted N-NA reaction enantioselectively: For exam-

-amino enone in the presence of EuCl3 (Scheme 8).14 ple, Maruoka and co-workers reported that this catalyst with
Catalytic enantioselective amination of carbonyl com- a binaphthyl framework proceeded the reaction enantioselec-
pounds was achieved using nitrosobenzene as an aminating re- tively (Scheme 13).18 These results would be consistent with
agent (Scheme 9).15 This was accomplished by changing the our previous findings.
H. Yamamoto et al. Bull. Chem. Soc. Jpn. Vol. 80, No. 4 (2007) 597

O Nu
H O R
OH O A = RCO2H
OH N O O -NA
Ph A N H
O
O (0.30 mol. amt.)
N O O
+ N NHPh
Ph Et2O
-88 °C ~ -78 °C R
77% 92% ee A H O H
O A = ROH n N -NA
Scheme 10. N O R
Ph O
N H
Nu
Ar Ar Ar = 1-naphthyl anti
O
OH
Fig. 1.
O OH
Ar Ar
O OH N N
O (0.30 mol. amt.)
N N N
+ N Ph N
O R'
Ph toluene N H
O H R R R R
-88 °C ~ -78 °C + N O
O O N O O
O O 81% Ph N Ph
N
91% ee R R Ph

Scheme 11. Scheme 14.

X P
N AgOTf
O H O
O cat. OSnMe3 P O
+ O O (0.10 mol. amt.)
R N R NHPh O
Ph + NHPh
R' R' N
Ph THF, -78 °C
97~>99% ee
91%
RO O 93% ee
CO2H P AgOTf
CO2H NHR
N
H N N
H H OSnBu3 P AgOTf O OH
R = H, TBS R = Ms, Ts O (0.10 mol. amt.) N
N N + Ph
N
Ph EtOCH2CH2OEt
N NHR N
N N N -78 °C
N H H H 98% >99% ee
H TFA
R = Ts, Tf
Scheme 15.
Scheme 12.
ly studied the origin of regioselectivity on this reaction by us-
Ph Ph ing calculation and isotope effect. These results strongly sug-
OH gested o-hydrogen of nitrosobenzene coordinates the Lewis
basic site of catalyst by hydrogen bonding (Fig. 1). Thus, the
cat. NH proton of carboxylic acid activates nitrogen of nitrosobenzene
and carbonyl oxygen of that coordinates o-hydrogen to form 8-
O OH OH OH membered ring. In contrast, two molecules of alcohol partici-
O Ph Ph NaBH4
+ N pate the activation of nitroso group to form 9- or higher-mem-
H N Ph
Ph THF, 0 °C bered ring because proton of alcohol would coordinate anti-
R' R'
70~90% yield lone pair of nitroso group.
O Ph 96~99% ee
Based on these results of proline-catalyzed O-NA reaction,
Ph
N we developed the tandem O-NA/Michael reaction to afford
H
O
O
N
H
OH O OH cyclized products starting from enones (Scheme 14).20 The
R' cat. N
H + N O-NA reaction of nitrosobenzene with enones in the presence
H Ph
Ph
R R' R of pyrrolidine-based catalyst followed by intramolecular
~60% ee hetero-Michael reaction afforded cyclized products with high
Scheme 13. enantioselectivity and complete regioselectivity. This reaction
would proceed via a stepwise mechanism since the reaction of
After these reports of O-NA reaction catalyzed by proline or nitrosobenzene with stannyloxy diene in the presence of silver
its analogs, two mechanisms for the catalytic pathway of alde- catalyst gave N- or O-NA adduct without any cyclized product
hydes and ketones were reported.17g,19 In addition, we careful- (Scheme 15).21
598 Bull. Chem. Soc. Jpn. Vol. 80, No. 4 (2007) ACCOUNTS

After our report of O-NA reaction catalyzed by organocata- tion was first reported by Wichterle and Arbuzov in 1947.24
lyst, similar reaction catalyzed by different organocatalysts After this important finding, Kresze et al. and Kirby and
was reported by several groups. For example, Ley and co- Nazeer extended nitroso HDA reaction to an asymmetric ver-
workers reported the synthesis of chiral 3,6-dihydro-2H-ox- sion using chiral nitroso compounds or dienes.25 This powerful
azines starting from aldehydes or ketones by using O-NA tool was applied for a number of natural product syntheses.
and sequential Wittig reactions (Scheme 16).22 The reaction of The utilities of this method are summarized in several re-
ketones with nitrosobenzene in the presence of pyrrolidine- views.5,26 We would like to introduce several excellent appli-
based tetrazole catalyst afforded O-NA adducts. The resulting cations in this field.
solution was treated with Wittig reagents to give 3,6-dihydro-
2H-oxazines with excellent enantioselectivity. These com- 5. Diastereoselective Nitroso Hetero-Diels–Alder Reaction
pounds which are regarded as nitroso hetero-Diels–Alder Since nitroso HDA adducts are attractive building blocks
(HDA) adducts were converted to cis-1,4-amino alcohols. toward the synthesis of polyhydroxylated molecules, several
Barbas and Ramachary reported asymmetric
-hydroxylation excellent reports on nitroso HDA reactions using chiral nitroso
of meso-ketones in a single step (Scheme 17).23 The excess compounds were reported. Miller and Ritter reported that the
amount of PhNO was used as a reducing agent. Since the reac- reaction of chiral acylnitroso compounds derived from amino
tion was conducted with meso-ketones and PhNO in the pres- acids with 1,3-dienes afforded chiral cycloadducts.27 They also
ence of proline,
-hydroxy ketones were obtained with excel- demonstrated further manipulation of these adducts to useful
lent enantioselectivity. This is a fine example of desymmetri- building blocks such as 1,2- or 1,3-amino alcohols.28 For ex-
zation reaction. ample, the reaction was conducted with adducts and Grignard
reagent in the presence of copper catalyst to give 1,2-amino al-
4. Nitroso Hetero-Diels–Alder Reaction cohols. In addition, Kibayashi and co-workers reported total
The nitroso compounds also undergo hetero-Diels–Alder synthesis of ()-epibatidine using asymmetric nitroso HDA
(HDA) reaction with dienes. The nitroso HDA reaction pro- reaction as a key reaction (Scheme 18).29 They used a chiral
vides 1,4-aminoalcohols which are useful building blocks in acylnitroso compound which has a menthol derivative as a chi-
the synthesis of natural products and drugs. This useful reac- ral auxiliary and investigated the relationship between diaster-
eoselectivity and substituents of menthol derivatives. The
N N
Swern oxidation of chiral hydroxamic acids at low temperature
N generated chiral acylnitroso compounds which were trapped
N PPh3Br
O H , NaH R'' NPh
with 1,3-cyclohexadiene to give adducts with good diastereo-
O N
H R'' selectivity.
R + N O
Ph DMSO, rt R Intramolecular nitroso HDA reaction has been recognized
R' R'
as an efficient method to construct cyclic amino compounds
99% ee
with several stereocenters. Despite many synthetic efforts
Scheme 16. for diastereoselective intramolecular nitroso HDA reaction,
the diastereoselectivities are typically low.30 Kibayashi and
O O co-workers accomplished highly diastereoselective nitroso
HO HDA reaction in aqueous media. They found that intramolec-
O L-Proline
R R + R R ular nitroso HDA reaction of 4-substituted 5,7-alkadienohy-
N
O O Ph CH2Cl2 O O droxamic acid in aqueous media proceeded with high diaster-
O O O O eoselectivity. This interesting finding was applied for total syn-
thesis of ()-swainsonine,31 ()-pumiliotoxin C,32 (þ)-azi-
98~>99% ee
mine,33 (þ)-carpaine,33 and ()-lepadins30d (Scheme 19).
Scheme 17. To overcome these problems, Shea and co-workers applied

R ratio
O Swern O O H 1.2 : 1
oxidation O O C6H5- 8.9 : 1
OH +
O N O N O N 4-MeO-C6H4- 9.1 : 1
H 4-Br-C6H4- 13.2 : 1
R R R 4-NO2-C6H4- 22.7 : 1
2-naphthyl 14.0 : 1
major adduct

O
O Swern H Cl
oxidation Cl N
OH R' N
O N O N
H N
2-naphthyl (-)-epibatidine
42%
N Cl

Scheme 18.
H. Yamamoto et al. Bull. Chem. Soc. Jpn. Vol. 80, No. 4 (2007) 599

OR Me
RO RO H
n -Pr4NIO4 O N O
H
N
OH H N O H O N
O chair boat H H X
R =Bn, MOM (-)-pumiliotoxin C

H
OR
R solvent trans : cis yield (%) H
OR OR N Me
Bn CHCl3 1.3 : 1 76 H H
Bn H2O 4.1 : 1 87 N Me
H H
MOM CHCl3 1.7 : 1 75 N N O
(-)-lepadin A (X = H2, R = COCH2OH)
MOM H2O 4.4 : 1 93 O O n O B (X = H2, R = H)
O O O n C (X = O, R = COCH2OH)
O
cis-adduct trans-adduct

Me N
H
(+)-azimine (n = 1)
OH (+)-carpaine (n = 3)
H OH

OH
N
(-)-swainsonine

Scheme 19.

R
N
Oxid. O N O O
O R = Bn, Allyl
O N
H
N 1,4-adduct R O
OH A
NHOH
O 2 R
N O
Oxid. O N O
O O R = OBn, OTBDPS N
O
B 1,3-adduct O

Scheme 21.
O
N pounds. These compounds are quite reactive as electrophiles
O
O and smoothly proceed the HDA reaction with dienes without
1
N any promoters. Carboxamide N-oxide (acyl nitroso) com-
O pounds are particularly reactive nitroso compounds which
:

+
PhH, heat
60% 1 are usually generated and directly trapped by dienes.35
O
An intriguing concept for enantioselective nitroso HDA re-
N action was reported by Whiting and co-workers. They found
O that the oxidation of hydroxamic acids catalyzed by the oxo-
Scheme 20. ruthenium complex afforded corresponding acyl nitroso com-
pounds which reacted with dienes simultaneously. On the basis
their ‘‘type 2 intramolecular Diels–Alder reaction’’ methodol- of their observations, they expected that the use of a chiral li-
ogy for intramolecular nitroso HDA reaction.34 gand could lead to a chiral induction on an intermolecular ni-
The reaction of dienes for formation of bicyclo[4.3.1]ox- troso HDA reaction. They envisioned that the acyl nitroso spe-
azinolactams and bicyclo[5.3.1]oxazinolactams proceeded cies which are generated by oxidation of hydroxamic acids
with complete diastereoselectivity. These products would be would remain in the chiral environment of an oxoruthenium
formed from intermediate A. With dienes containing longer catalyst when they react with dienes (Scheme 22).36 However,
chains, the energetics for HDA reaction in conformation A the reaction of the acyl nitroso compound generated from tert-
and B are equivalent (Scheme 20).34b This would be consistent butyl N-hydroxycarbamate with 1,3-cyclohexadiene produced
with low selectivity of intramolecular nitroso HDA reaction the corresponding adduct in high yield without enantioselectiv-
with 2-substituted 1,3-dienes. Detailed studies on the relation- ity. This result indicates that dissociation of the acyl nitroso
ship between C2 substituents and -facial selectivity indicated compound from the catalyst proceeds rapidly before HDA re-
that diastereoselectivity of the reaction relies on steric and action on the catalyst take place and is supported by an intra-
electronic effects on C2 substituent (Scheme 21).34c molecular version of this reaction.
Chow and Shea reported an intramolecular version of this
6. Enantioselective Nitroso Hetero-Diels–Alder Reaction reaction. They expected that such a version of the reaction
Enantioselective nitroso HDA reaction has been regarded as would make acquisition of enantioselectivity easier, since the
a difficult process due to the unique reactivities of nitroso com- HDA reaction would take place while the acyl nitroso com-
600 Bull. Chem. Soc. Jpn. Vol. 80, No. 4 (2007) ACCOUNTS

N L N TBHP L'
Ru N N L' = OPPh3
Ru
O2N O L O NO2 O O
L'
t -BuOH
L = PPh3
L'
L
N N
Ru
O O
L
TBHP
O N N
Ru
O N O O
HDA Boc L'
NBoc t-BuOH
Racemic product
Catalytic cycle
O Boc
N O
O N N N N
Ru Ru
NBoc HDA O O O O
L' L'
Chiral product

H2O HO Boc
N
H

Scheme 22.

N L N TBHP L'
Ru N N L' = OPPh3
Ru
O2N O L O NO2 O O
L'
t -BuOH
NO2 O2N
L = PPh3 L'
L
N N
Ru
O O
L

TBHP
O N N
Ru
Racemic product N O O
HDA R L' t -BuOH

Catalytic cycle
O O R
O N O
N N N N
N Ru Ru
HDA O O O O
O L' L'
Chiral product

O
HO
H2O N O
H

Scheme 23.

pound still coordinates a catalyst. In fact, the reaction was con- nitroso compound coordinates the chiral catalyst while the
ducted with N-hydroxycarbamate derivative in the presence of HDA reaction proceeds.
the chiral ruthenium catalyst and afforded the product with In contrast to the acyl nitroso compounds, the aryl nitroso
75% ee (Scheme 23).37 This result was rationalized by the hy- compounds are more stable. Whiting and co-workers reported
pothesis of their group and Whiting’s group. Namely, the acyl that the reaction of nitrosobenzene or ortho-methoxynitroso-
H. Yamamoto et al. Bull. Chem. Soc. Jpn. Vol. 80, No. 4 (2007) 601

O Mtl
O O O
N Ar Mtl
O N Ar N N O N O
Ar Ar N Ar N
NAr O Ar Ar

Scheme 24.

complexation increases the reactivity of nitroso group, this

(R,R )-t-Butyl tartarate
(equimol. amt.) would be a nice tool for asymmetric synthesis. The choice of
OH i-Pr2Zn (equimol. amt.) OH moiety X has numerous possibilities as shown in Fig. 2. The
O n-PrZnBr (equimol. amt.)
+ N
O complex 4 would be the effective for asymmetric synthesis us-
Ph N ing nitroso compounds since this complex might not lead to
Ph
deactivate through resonance structure.
up to 92% ee
On the basis of this hypothesis, we developed the first cata-
Scheme 25. lytic enantioselective nitroso HDA reaction using 2-nitroso-
pyridine derivative as a dienophile and a chiral copper as a cat-
benzene with 1,3-cyclohexadiene in the presence of chiral alyst.41 The reaction of 2-nitrosopyridine and 1,3-cyclohexa-
Lewis acids afforded the product without any asymmetric diene gave the corresponding adduct with 59% ee. Gratifying-
induction.38 As we described earlier, this result is rationalized ly, the copper catalyst increases the reactivity of nitroso HDA
by a unique property of nitroso compounds. The dimers of reaction significantly and successfully minimizes the back
nitroso compounds act as bidentate ligands for transition met- ground non-catalyzed HDA reaction. The enantioselectivity
als (Scheme 24). Moreover, Whiting et al. also revealed that of the reaction is sensitive to the substituents of 6-position
this complex neither promotes nor inhibits the nitroso HDA re- and to the dihedral angle of the phosphine ligand (Scheme 26).
action. These results suggested that hard and/or bidentate The alkyl group at 6-position would force a bidentate coor-
Lewis acids would also not accelerate the reaction. dination between oxygen and pyridine. However, the much
The first highly enantioselective nitroso HDA reaction was bulkiness such as isopropyl group also would cause monoden-
reported by Ukaji, Inomata, et al. (Scheme 25).39 The reaction tate coordination for oxygen. The combination of 6-methyl-2-
was conducted with nitrosobenzene and diene having an alco- nitrosopyridine and CuPF6 (CH3 CN)4 -SEGPHOS was optimal,
hol group in the presence of stoichiometric amount of tert-butyl producing the HDA adducts with excellent enantioselectivity
tartarate to give the corresponding adduct with complete regio- and yield in a completely regioselective manner (Scheme 27).
selectivity and 92% ee. Key to the success is coordination of a The nitroso HDA adduct was easily converted to the pro-
hydroxy group of a diene to obtain a high enantioselectivity. tected amino alcohol (Scheme 28).41 The cleavage of N–O
As described earlier, we have developed catalytic enantio- bond followed by protection of the resulting amine and alcohol
and regioselective nitroso aldol reaction catalyzed by various afforded the protected amino alcohol. Quaternization of pyri-
silver–BINAP complexes.13,15 In these cases, silver might co- dine ring with MeOTf followed by hydrolysis with NaOH
ordinate nitrosobenzene via a monodentate mode. In spite of gave the protected amino alcohol without any loss of enantio-
the attraction of a monodentate coordination mode, the forma- selectivity.
tion of a stable dimer–metal complex is also possible. The bi- This reaction can be applied for acyclic dienes (Scheme 29).
dentate coordination with an additional site should afford a The reaction was conducted with 2-silyloxy-1,3-dienes and
more rigid and stable monomer–metal complex which should 6-methyl-2-nitrosopyridine in the presence of copper catalyst
be reactive. The complexes of metals and nitroso compounds to afford the corresponding adducts enantioselectively.42 The
via an oxygen atom or a nitrogen atom (1 and 2) are well bulkiness of the silyl group significantly impacted on the enan-
known.40 These complexes are attractive for asymmetric reac- tioselectivity. Their role is to force the diene to form an s-cis
tions while the resonance structures of these complexes could configuration which favors the concerted [4 þ 2] cycloaddition
lead to deactivate the nitroso compounds. However, if the reaction. In this case, compete back ground reaction is ene-
Monodentate coordination Bidentate coordination

Mtl 5-Membered ring 6-Membered ring

X X
N N Mtl X Mtl Mtl
Ar O Ar O Mtl
N O
1 2 N O
O N
3 4 5

X X X X
Mtl Mtl
Mtl Mtl
N O O
N N N
O O

Fig. 2.
602 Bull. Chem. Soc. Jpn. Vol. 80, No. 4 (2007) ACCOUNTS

(S )-BINAP O R ee (%)
CuPF6(CH3CN)4 N H 59
+ Me 86
R N N CH2Cl2, -85 °C to -20 °C N Et 87
O quant. i -Pr 77
R

H N N R N N i -Pr N N
P Cu O P Cu O O Cu P

P P P
R = Me, Et

Scheme 26.

O
Ligand O R
CuPF6(CH3CN)4 N R'
+
N N CH2Cl2, -85 °C to -20 °C
N TIPSOTf
O Si O
Ligand ee (%) Ligand
(R )-BINAP 87 OSi R R'
CuPF6(CH3CN)4
(R )-Tol-BINAP 86 + N O
R N N CH2Cl2
R'
(R )-H8-BINAP 67 O -85 °C to -20 °C N
(R )-MeO-BIPHEP 90
(S )-SEGPHOS 92

Scheme 27. Si ligand ee (%)

TMS (S )-SEGPHOS 16
TBS (S )-SEGPHOS 84 TBSO OTBS
TIPS (S )-SEGPHOS 98 R
R'
TIPS (S )-DIFLUORPHOS >99
NHTs

Scheme 29.

NHTs
O N NTs N NTs
N 3 steps MeOTf NaOHaq
Me
68% 74% 95%
N OTf
OTBS
OTBS OTBS

Scheme 28.

type reaction which is not enantioselective. The triisopropyl- dienes is an attractive route toward chiral 1,4-diamines.43 It
silyl (TIPS) group was optimal, obtaining excellent enantiose- is well known that the azodicarboxylate undergoes HDA reac-
lectivity. The reaction was conducted with 6-methyl-2-nitroso- tion (azo HDA reaction) to give 1,4-diamines in a single step.
pyridine and 2-TIPSO-1,3-diene in the presence of CuPF6 - Diastereoselective versions of this process are well studied;
(CH3 CN)4 -DIFLUORPHOS as a catalyst to give an adduct however, there are no reports of highly enantioselective azo
with excellent enantioselectivity in complete regioselectivity. HDA reaction. We recently reported catalytic highly enantio-
The adduct was transformed to the corresponding amino alco- selective azo HDA reaction using the designed azo compound
hol in the same manner as described earlier. This catalytic re- based on nitroso HDA reaction.44
action can be applied to a wide range of functionalized sub-
strates, proceeding the adduct with complete regioselectivity 8. Diastereoselective Azo Hetero-Diels–Alder Reaction
and good to excellent enantioselectivity. This method provides Several diastereoselective azo HDA reactions have been re-
an easy access to protected amino alcohols with three stereo- ported. They have mainly been accomplished using achiral
centers enantioselectively. azodicarboxylates with chiral dienes. In 1990, Breitmaier and
Rieger reported that the reaction of 4-phenyl-3H-1,2,4-tri-
7. Azo Hetero-Diels–Alder Reaction azole-3,5(4H)-dione (PTAD), which is one of the most reac-
The optically active 1,4-diamines are important building tive azo dienophile, with chiral dienes which have a chiral sec-
blocks in natural product synthesis and drug discovery. The ondary alcohol gave the corresponding adducts diastereoselec-
hetero-Diels–Alder (HDA) reaction of azo compounds with tively (Scheme 30).45 These adducts were converted to alco-
H. Yamamoto et al. Bull. Chem. Soc. Jpn. Vol. 80, No. 4 (2007) 603

CO2Me CO2Me
Ar O CO2Et CO2Et
N N
OH +
O N AcOEt, ca. 70 °C N
Ar O O EtO2C CO2Et
N 3 days
N NPh OR OR
+ THF or CH2Cl2 NPh N
-30 °C N R=
N N O OAc 82%
O O O single diastereomer
O N >95% de
Ph Ar = Ph (93% ee) OAc
PTAD 2-Naphthyl (86% ee)
OAc OAc
Scheme 30. Scheme 33.

O O
Ph N X Ph N X
H
O
O
CO2Et Ph N X
Ph N X N
+ CO2Et DEAD
N CH3CN N
EtO2C
reflux N
CO2Et O O
X = S: 50% de Ph X Ph X
N N
O: 24% de
CO2Et CO2Et
N N
N N
CO2Et CO2Et

Scheme 31.

Ph Ph O
PTAD N
NPh O O O O
N B PTAD B O
R R O
N
Bn NPh
H 40% de N
R= N O
P O
N single diastereomer
H Bn

Scheme 32.

hols with inversion of stereochemistry of alcohol. In addition, reaction proceeded slowly even at 70  C in ethyl acetate, since
the reaction of an amino alcohol derived chiral amino diene diene has a conjugated ester group which causes a lower
was conducted with DEAD as a dienophile to afford an adduct HOMO level of diene. Meanwhile, Adam and co-workers
(Scheme 31).46 The diastereoselectivity of thiooxazolidinone reported that the reaction of dienes with esters or an amide
derived diene was higher than that of oxazolidinone derived and PTAD gave adducts in good diastereoselectivity. These
diene. This selectivity would be explained by the syn conform- dienes were installed various chiral alcohols and an amine as
er of diene being less stable than the anti conformer, since the esters or an amide groups (Scheme 34).50 The reaction of a
syn conformer of oxazolidinone derived diene is stabilized by diene having an amide group with PTAD gave better selectiv-
hydrogen bonding. ity than those having ester groups.
Dienes which have diazaphospholidine or boronate as a chi- Moreover, tri-substituted diene can be used in this reaction.
ral auxiliary have been tried for diastereoselective azo HDA Sato and co-workers reported that the reaction of PTAD or
reactions (Scheme 32).47 While the reaction of chiral diene azodicarboxylate with chiral tri-substituted dienes gave ad-
with diazaphospholidine as a chiral auxiliary and PTAD gave ducts as a single diastereomer in high yield (Scheme 35).51
an adduct with 40% de, the reaction of a chiral boronate de- The use of a chiral azodicarboxylate was also reported in
rived diene and PTAD afforded an adduct as a single diaster- 2001 (Scheme 36).52 Di-()-menthyl azodicarboxylate reacted
eomer.48 with silyloxydiene in the presence of trimethyl phosphite and
The use of D-glucopyranose derivative as a chiral auxiliary TMSOTf to afford an adduct in quantitative yield. The diaster-
was reported by Stoodley et al. The reaction was conducted eoselectivity of this reaction was 66:34. These mixtures were
with DEAD and a chiral diene which has D-glucopyranose de- separated and were converted into pyrrolidine-2-phosphonic
rivative to afford an adduct in 82% yield (Scheme 33).49 This acid in several steps.
604 Bull. Chem. Soc. Jpn. Vol. 80, No. 4 (2007) ACCOUNTS

RO2C
PTAD N N
RO2C N N N N
O N O Mtl O Mtl N
CO2R
Ar Ph
R= 5-Membered coordination
Ar dr
PhOC6H4 74 : 26 Fig. 3.
Biphenyl 69 : 31
2-Naph 78 : 22
Table 1.
TIPSO
O OTIPS AgOTf (0.10 mol. amt.)
O ligand
+
PTAD N
N N N N N Troc -78 °C to -40 °C N N
N Py Troc
O O O
O Ph N
Ph
Ph Yield ee
Entry Ligand Solvent
dr = >95 : 5 /% /%
Scheme 34. 1 (R)-BINAP (0.10 mol. amt.) THF 73 55
2 (R)-BINAP (0.10 mol. amt.) Et2 O 74 56
Cy Cy 3 (R)-BINAP (0.10 mol. amt.) Toluene 63 67
O O
4 (R)-BINAP (0.10 mol. amt.) CH2 Cl2 72 80
N N 5aÞ (R)-BINAP (0.10 mol. amt.) CH3 CN 61 94
+ NPh NPh
N CH2Cl2 N
RO2C RO2C 6 (R)-BINAP (0.10 mol. amt.) EtCN 62 94
TMS O -30 °C TMS O 7 (R)-Difluorphos (0.10 mol. amt.) EtCN 76 30
Ph 80~90% 8 (R)-Segphos (0.10 mol. amt.) EtCN 71 20
Ph single diastereomer 9 (R)-BINAP (0.05 mol. amt.) EtCN 87 >99
RO = O or
O Ph 10 (R)-BINAP (0.20 mol. amt.) EtCN 26 0
a) Reaction was conducted at 40  C.
Scheme 35.

OTMS PO(OMe)2 tive. The key to this success is the formation of a rigid five-
CO2R P(OMe)3 PO(OH)2
N TMSOTf CO2R membered ring between pyridine and oxygen of a nitroso
+ N
RO2C
N CH2Cl2
N NH group. Based on this successful design, we envisioned that
CO2R the formation of the same rigid transition state in azo HDA
R = (-)-menthyl
66 : 34 reaction would lead to a high enantioselectivity (Fig. 3). How-
Scheme 36. ever, contrary to our expectation, the reaction of 2-azopyri-
dine with 3-TIPSO-2,4-hexadiene in the presence of CuPF6 -
(CH3 CN)4 -BINAP catalyst afforded the corresponding adduct
O O
without any chiral induction. Surprisingly, the reaction in the
N N presence of silver–BINAP catalyst proceeded smoothly to give
Cu
O Ph TfO OTf Ph O O an adduct with good enantioselectivity and complete regiose-
O
(0.10 mol. amt.) lectivity. The solvent and ratio of silver to ligand were check-
+ N N O N N O
N N ed, since we had found three types of silver–BINAP complex
Troc Troc (Table 1). The use of EtCN as a solvent and 2:1 of silver to
22% ee BINAP was optimal, producing an adduct with >99% ee. It
Scheme 37. is noted that the use of ligands with a narrow dihedral angle
led to lower enantioselectivity. Although the transition state
of this reaction is not clear, it seems that 2:1 complex of sil-
9. Enantioselective Azo Hetero-Diels–Alder Reaction ver–BINAP is an active catalyst, because ligands with a nar-
Despite the many reports of diastereoselective azo HDA re- row dihedral angle form 1:1 complex of silver–BINAP prefer-
action, only one paper on enantioselective azo HDA has been entially.
reported and that by Jørgensen and co-workers (Scheme 37).53 This reaction can be applied for various dienes including
They described that the use of an azodicarboxylate with an ester, ether, and protected amine, producing the corresponding
oxazolidinone moiety was as a chelation auxiliary for enan- adducts with high enantioselectivity (Scheme 38). However,
tioselective azo HDA reaction. The reaction of the azodicar- when silyloxydiene with a phenyl group was used, the enantio-
boxylate derivative with cyclopentadiene in the presence of selectivity was decreased dramatically. This result might be
chiral copper catalyst afforded the corresponding adduct with explained by the reaction having proceeded with low endo/
22% ee. exo selectivity.
We recently accomplished the first highly enantioselective In contrast to these results, when 2-TIPSO-1,3-cyclohexa-
azo HDA reaction using 2-azopyridine as a dienophile in the diene was used as a diene in the presence of chiral copper cat-
presence of a silver catalyst.44 As described earlier, we have alyst, the corresponding adduct was obtained with >99% ee
reported nitroso HDA reaction using 2-nitrosopyridine deriva- (Scheme 39).
H. Yamamoto et al. Bull. Chem. Soc. Jpn. Vol. 80, No. 4 (2007) 605

R
AgOTf (0.10 mol. amt.) TIPSO Needless to say, these functionalized molecules are important
OTIPS (R )-BINAP (0.05 mol. amt.) building blocks in organic synthesis. The demand for synthesis
+ R R'
N N
N
Troc EtCN N N of chiral-functionalized molecules from simple achiral mole-
R' -78 °C to -40 °C Py Troc cules is increasing day by day. Although the chiral technology
R = Me, Bn, 4-MOMO-CH2C6H4
CH2CH2CH2OTBS
55% ~ >99% ee has advanced greatly in past decade, the asymmetric reactions
CH2CH2CH2NNsBoc with nitroso and azo compounds are difficult issues due to their
R' = Me, n -C5H11, i -Bu, CH2OBn unique properties.
CH2CH2CH2CO2Me, Ph, 2-Furyl
We have summarized herein recent advances in catalytic
Scheme 38. enantioselective reactions with nitroso compounds and enan-
tioselective hetero-Diels–Alder reaction of an azo compound.
(R )-BINAP
In nitroso aldol reaction, the structurally defined silver–BINAP
(0.10 mol. amt.) complex has led to a clear solution of enantioselective nitroso
TIPSO CuPF6(CH3CN)4 aldol reaction with high N/O-selectivity. Moreover, the utility
(0.10 mol. amt.) TIPSO
+ N Py of chiral Brønsted acids and pyrrolidine-based organocatalyst
N CH2Cl2 N
N N Troc Troc in nitroso chemistry has been demonstrated. In nitroso HDA
-78 °C to -40 °C
>99% ee reaction, the appropriate and efficient design of the substrates
such as 2-nitrosopyridine derivatives has led to significant
Scheme 39.
solutions in this field. This substrate design has also been ap-
plied for development of catalytic enantioselective azo HDA
TIPSO TIPSO reaction.
1) TBAF, AcOH
2) NaBH4 MeOTf The door to catalytic enantioselective reactions with nitroso
N N 3) TIPSOTf, NEt3 N N and azo compounds has just been opened and we feel fortunate
Py Troc 65%, 3 steps Py Troc that we have contributed to this interesting and important field.
6 7 It is our hope that this fascinating chemistry will see strong
development and make the organic synthesis of chiral mole-
TIPSO
cules more facile.
TIPSO
TFAA
N N NaOH aq NEt3 We gratefully acknowledge the great contribution of Dr.
Troc MeOH HN N Norie Momiyama and Dr. Yuhei Yamamoto to our study of
N Me
CO2Me nitroso chemistry. We also appreciate the support of Dr. Ian
OTf 9 Steele in performing the X-ray crystallographic analysis.
8 M.K. thanks the support from the Uehara Memorial Founda-
tion. Funding for this research was provided by the SORST
TIPSO project of the Japanese Science and Technology Agency
SmI2 NHCOCF3
MeOH (JST), National Institute of Health (NIH) GM068433-01,
N N 71%
Merck Research Laboratories, and a grant from the University
TIPSO NHCO2Me of Chicago.
F3COC CO2Me
10 11
71%, 3 steps
References
Scheme 40.
1 S. Caron, R. W. Dugger, S. G. Ruggeri, J. A. Ragan,
The resulting adducts can be converted to diamino alcohols D. H. B. Ripin, Chem. Rev. 2006, 106, 2943.
(Scheme 40). For example, deprotection of TIPS group fol- 2 For recent reviews, see: a) C. Bonini, G. Righi, Tetra-
lowed by reduction and protection of the resulting alcohol hedron 2002, 58, 4981. b) J. M. Brunel, Chem. Rev. 2005, 105,
gave 7 as a single diastereomer. As described earlier, removal 857. c) C. Bolm, Coord. Chem. Rev. 2003, 237, 245. d) A. G. J.
Ligtenbarg, R. Hage, B. L. Feringa, Coord. Chem. Rev. 2003,
of the pyridine ring was cleanly achieved, accompanied
237, 89. e) T. Katsuki, Synlett 2003, 281. f) J. Eames, M.
by the conversion of 2,2,2-trichloroethoxycarbonyl group to
Watkinson, Angew. Chem., Int. Ed. 2001, 40, 3567. g) T. Katsuki,
methoxycarbonyl group. The reaction of 7 with MeOTf gave
Curr. Org. Chem. 2001, 5, 663. h) E. Erdik, Tetrahedron 2004,
pyridinium salt which was identified by 1 H NMR and LRMS.
60, 8747. i) C. Greck, B. Drouillat, C. Thomassigny, Eur. J.
Continuously, 8 was treated with NaOHaq in MeOH to afford Org. Chem. 2004, 1377.
an amine and to convert Troc group to methoxycarbonyl 3 For recent reviews, see: a) R. O. Duthaler, Angew. Chem.,
group. Protection of the resulting amine 9 with trifluoroacetyl Int. Ed. 2003, 42, 975. b) B. G. Gowenlock, G. B. Richter-Addo,
group followed by treatment with SmI2 afforded the diamino Chem. Rev. 2004, 104, 3315. c) J. Lee, L. Chen, A. H. West, G. B.
alcohol 11 in good yield. Thus, two amino groups were differ- Richter-Addo, Chem. Rev. 2002, 102, 1019.
entiated for further transformation. 4 For recent reviews, see: a) H. Yamamoto, N. Momiyama,
Chem. Commun. 2005, 3514. b) J. M. Janey, Angew. Chem., Int.
10. Conclusion Ed. 2005, 44, 4292.
The nitroso and azo compounds are attractive reagents to in- 5 Y. Yamamoto, H. Yamamoto, Eur. J. Org. Chem. 2006,
troduce hydroxy and amino groups into organic molecules. 2031.
606 Bull. Chem. Soc. Jpn. Vol. 80, No. 4 (2007) ACCOUNTS

6 W. Adam, O. Krebs, Chem. Rev. 2003, 103, 4131. Kresze, R. Prewo, A. Vasella, Helv. Chim. Acta 1986, 69, 1137.
7 H. Nohira, K. Sato, T. Mukaiyama, Bull. Chem. Soc. Jpn. c) G. W. Kirby, M. Nazeer, Tetrahedron Lett. 1988, 29, 6173.
1963, 36, 870. 26 a) J. Streith, A. Defoin, Synthesis 1994, 1107. b) C.
8 J. W. Lewis, P. L. Myers, J. A. Ormerod, J. Chem. Soc., Kibayashi, S. Aoyagi, Synlett 1995, 873. c) P. F. Vogt, M. J.
Perkin Trans. 1 1972, 2521. Miller, Tetrahedron 1998, 54, 1317. d) C. Kibayashi, Chem.
9 a) W. Oppolzer, O. Tamura, Tetrahedron Lett. 1990, 31, Pharm. Bull. 2005, 53, 1375.
991. b) W. Oppolzer, O. Tamura, G. Sundarababu, M. Signer, 27 A. R. Ritter, M. J. Miller, J. Org. Chem. 1994, 59, 4602.
J. Am. Chem. Soc. 1992, 114, 5900. 28 a) M. D. Surman, M. J. Miller, J. Org. Chem. 2001, 66,
10 a) N. Momiyama, H. Yamamoto, Angew. Chem., Int. Ed. 2466. b) M. D. Surman, M. J. Mulvihill, M. J. Miller, J. Org.
2002, 41, 2986. b) N. Momiyama, H. Yamamoto, Angew. Chem., Chem. 2002, 67, 4115.
Int. Ed. 2002, 41, 3313. 29 S. Aoyagi, R. Tanaka, M. Naruse, C. Kibayashi, J. Org.
11 N. Momiyama, H. Torii, S. Saito, H. Yamamoto, Proc. Chem. 1998, 63, 8397.
Natl. Acad. Sci. U.S.A. 2004, 101, 5374. 30 a) T. P. Burkholder, P. L. Fuchs, J. Am. Chem. Soc. 1990,
12 N. Momiyama, H. Yamamoto, J. Am. Chem. Soc. 2005, 112, 9601. b) S. Aoyagi, Y. Shishido, C. Kibayashi, Tetrahedron
127, 1080. Lett. 1991, 32, 4325. c) G. E. Keck, D. R. Romer, J. Org. Chem.
13 a) N. Momiyama, H. Yamamoto, J. Am. Chem. Soc. 2003, 1993, 58, 6083. d) T. Ozawa, S. Aoyagi, C. Kibayashi, J. Org.
125, 6038. b) N. Momiyama, H. Yamamoto, J. Am. Chem. Soc. Chem. 2001, 66, 3338. e) T. Sato, S. Aoyagi, C. Kibayashi,
2004, 126, 6498. Org. Lett. 2003, 5, 3839.
14 M. R. Morales, N. Momiyama, H. Yamamoto, Synlett 31 M. Naruse, S. Aoyagi, C. Kibayashi, J. Org. Chem. 1994,
2006, 705. 59, 1358.
15 N. Momiyama, H. Yamamoto, J. Am. Chem. Soc. 2004, 32 a) M. Naruse, S. Aoyagi, C. Kibayashi, Tetrahedron Lett.
126, 5360. 1994, 35, 9213. b) M. Naruse, S. Aoyagi, C. Kibayashi, J. Chem.
16 N. Momiyama, H. Yamamoto, J. Am. Chem. Soc. 2005, Soc., Perkin Trans. 1 1996, 1113.
127, 1080. 33 T. Sato, S. Aoyagi, C. Kibayashi, Org. Lett. 2003, 5, 3839.
17 For reviews, see: a) P. Merino, T. Tejero, Angew. Chem., 34 a) S. M. Sparks, J. D. Vargas, K. J. Shea, Org. Lett. 2000,
Int. Ed. 2004, 43, 2995. b) G. Zhong, Angew. Chem., Int. Ed. 2, 1473. b) C. P. Chow, K. J. Shea, S. M. Sparks, Org. Lett. 2002,
2003, 42, 4247. c) S. P. Brown, M. P. Brochu, C. J. Sinz, 4, 2637. c) S. M. Sparks, C. P. Chow, L. Zhu, K. J. Shea, J. Org.
D. W. C. MacMillan, J. Am. Chem. Soc. 2003, 125, 10808. Chem. 2004, 69, 3025.
d) Y. Hayashi, J. Yamaguchi, K. Hibino, M. Shoji, Tetrahedron 35 G. W. Kirby, J. G. Sweeny, J. Chem. Soc., Chem. Commun.
Lett. 2003, 44, 8293. e) A. Bøgevig, H. Sundén, A. Córdova, 1973, 704.
Angew. Chem., Int. Ed. 2004, 43, 1109. f) Y. Hayashi, J. 36 K. R. Flower, A. P. Lightfoot, H. Wan, A. Whiting, J.
Yamaguchi, T. Sumiya, M. Shoji, Angew. Chem., Int. Ed. 2004, Chem. Soc., Perkin Trans. 1 2002, 2058.
43, 1112. g) See Ref. 11. h) A. Córdova, H. Sundén, A. Bøgevig, 37 C. P. Chow, K. J. Shea, J. Am. Chem. Soc. 2005, 127, 3678.
M. Johansson, F. Himo, Chem. Eur. J. 2004, 10, 3673. i) Y. 38 A. P. Lightfoot, R. G. Pritchard, H. Wan, J. E. Warren, A.
Hayashi, J. Yamaguchi, T. Sumiya, K. Hibino, M. Shoji, J. Org. Whiting, Chem. Commun. 2002, 2072.
Chem. 2004, 69, 5966. j) W. Wang, J. Wang, H. Li, L. Liao, 39 X. Ding, Y. Ukaji, S. Fujinami, K. Inomata, Chem. Lett.
Tetrahedron Lett. 2004, 45, 7235. k) Y. Hayashi, J. Yamaguchi, 2003, 32, 582.
K. Hibino, T. Sumiya, T. Urushima, S. Mitsuru, D. Hashizume, 40 For reviews, see: a) M. Cameron, B. G. Gowenlock, Chem.
H. Koshino, Adv. Synth. Catal. 2004, 346, 1435. l) H. Sundén, Soc. Rev. 1990, 19, 355. b) J. Lee, L. Chen, A. H. West, G. B.
N. Dahlin, I. Ibrahem, H. Adolfsson, A. Córdova, Tetrahedron Richter-Addo, Chem. Rev. 2002, 102, 1019.
Lett. 2005, 46, 3385. 41 Y. Yamamoto, H. Yamamoto, J. Am. Chem. Soc. 2004,
18 a) T. Kano, M. Ueda, J. Takai, K. Maruoka, J. Am. Chem. 126, 4128.
Soc. 2006, 128, 6046. b) H.-M. Guo, L. Cheng, L.-F. Cun, L.-Z. 42 Y. Yamamoto, H. Yamamoto, Angew. Chem., Int. Ed.
Gong, A.-Q. Mi, Y.-Z. Jiang, Chem. Commun. 2006, 429. 2005, 44, 7082.
19 a) S. P. Mathew, H. Iwamura, D. G. Blackmond, Angew. 43 For examples, see: a) K. Izawa, T. Onishi, Chem. Rev.
Chem., Int. Ed. 2004, 43, 3317. b) H. Iwamura, D. H. Wells, 2006, 106, 2811. b) E. Specker, J. Böttcher, S. Brass, A. Heine,
S. P. Mathew, M. Klussmann, A. Amstrong, D. G. Blackmond, H. Lilie, A. Schoop, G. Müller, N. Griebenow, G. Klebe, Chem.
J. Am. Chem. Soc. 2004, 126, 16312. c) H. Wang, C. Yang, K. Med. Chem. 2006, 1, 106. c) K. Engstrom, R. Henry, L. S. Hollis,
Han, Struct. Chem. 2006, 17, 97. B. Kotecki, I. Marsden, Y.-M. Pu, S. Wagaw, W. Wang, J. Org.
20 Y. Yamamoto, N. Momiyama, H. Yamamoto, J. Am. Chem. 2006, 71, 5369. d) M. Ikunaka, Chem. Eur. J. 2003, 9,
Chem. Soc. 2004, 126, 5962. 378. e) A. K. Ghosh, G. Bilcer, G. Schiltz, Synthesis 2001, 2203.
21 N. Momiyama, Y. Yamamoto, H. Yamamoto, J. Am. 44 M. Kawasaki, H. Yamamoto, J. Am. Chem. Soc. 2006, 128,
Chem. Soc., in press. 16482.
22 a) S. Kumarn, D. M. Shaw, D. A. Longbottom, S. V. Ley, 45 R. Rieger, E. Breitmaier, Synthesis 1990, 697.
Org. Lett. 2005, 7, 4189. b) S. Kumarn, D. M. Shaw, S. V. Ley, 46 R. Robiette, K. Cheboub-Benchaba, D. Peeters, J.
Chem. Commun. 2006, 3211. Marchand-Brynaert, J. Org. Chem. 2003, 68, 9809.
23 D. B. Ramachary, C. F. Barbas, III, Org. Lett. 2005, 7, 47 P. B. Wyatt, C. Villalonga-Barber, M. Motevalli, Tetra-
1577. hedron Lett. 1999, 40, 149.
24 a) Wichterle, Collect. Czech. Chem. Commun. 1947, 12, 48 A. Zhang, Y. Kan, B. Jiang, Tetrahedron 2001, 57, 2305.
292. b) Y. A. Arbuzov, Dokl. Akad. Nauk SSSR 1948, 60, 993. 49 a) H. Aspinall, P. M. Cowley, G. Mitchell, R. J. Stoodley,
25 a) H. Nitsch, G. Kresze, Angew. Chem. 1976, 88, 801; J. Chem. Soc., Chem. Commun. 1993, 1179. b) I. H. Aspinall,
Angew. Chem., Int. Ed. Engl. 1976, 15, 760. b) H. Felber, G. P. M. Cowley, G. Mitchell, C. M. Raynor, R. J. Stoodley, J. Chem.
H. Yamamoto et al. Bull. Chem. Soc. Jpn. Vol. 80, No. 4 (2007) 607

Soc., Perkin Trans. 1 1999, 2591. 2002, 43, 285.

50 a) W. Adam, M. Guethlein, E.-M. Peters, K. Peters, 52 M. Kaname, Y. Arakawa, S. Yoshifuji, Tetrahedron Lett.
T. Wirth, J. Am. Chem. Soc. 1998, 120, 4091. b) W. Adam, S. G. 2001, 42, 2713.
Bosio, H.-G. Degen, O. Krebs, D. Stalke, D. Schumacher, Eur. J. 53 P. S. Aburel, W. Zhuang, R. G. Hazell, K. A. Jørgensen,
Org. Chem. 2002, 3944. Org. Biomol. Chem. 2005, 3, 2344.
51 H. Urabe, K. Kusaka, D. Suzuki, F. Sato, Tetrahedron Lett.

Hisashi Yamamoto received his B.Sc. from Kyoto University and his Ph.D. from Harvard Uni-
versity (Prof. E. J. Corey). He held academic positions at Kyoto University and at the University
of Hawaii, before he moved to Nagoya in 1980, where he became Professor (1983). In 2002, he
was appointed Professor at the University of Chicago. He has been honored with the Prelog Med-
al (1993), the Chemical Society of Japan Award (1995), the Max-Tishler Prize (1998), Le Grand
Prix de la Fondation Maison de la Chimie (2002), the National Prize of the Purple Medal (Japan)
(2002), the Yamada Prize (2004), and the Tetrahedron Prize (2006).

Masanori Kawasaki was born in Nara, Japan, in 1977. He received his B.Sc. in 2000, M.Sc. in
2001, and Ph.D. in 2005 from Osaka City University under the guidance of Professor Yasufumi
Ohfune. In 2005, he joined the research group of Professor Hisashi Yamamoto at University of
Chicago and is currently working to develop the catalytic asymmetric reaction using nitroso
and azo compounds. He awarded the Graduate Student Fellowship from Ono Pharmaceutical
Co., Ltd. (2002–2003), the Student Presentation Award from Japan Chemical Society (2004),
and Postdoctoral Fellowship from the Uehara Memorial Foundation (2007).