The Nitro group in organic sysnthesis - Feuer
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4.1 |
ADDITION TO NITROALKENES |
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NO2 |
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PhS |
Cu(CN)ZnI |
DME |
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–78 ºC to 0 ºC |
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NO2 |
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83% |
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Dialkylzincs react efficiently with nitroalkenes in a mixture of THF and N-methylpyrrolid- inone (NMP) to give the addition products in good yield (Eq. 4.88).110
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THF-NMP |
Ph |
(CH2)5OAc |
NO2 |
+ [AcO(CH2)5]2Zn |
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Ph |
–30 ºC, 3 h |
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84% |
Organoaluminum compounds are also good nucleophiles for 1,4-addition to nitroalkenes as shown in Eq. 4.89.111
NO2
NO2
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AlEt2 |
(4.89) |
–15 ºC
86% (ds = 93/7)
Seebach and coworkers have developed enantioselective conjugate additions of primary dialkylzinc reagents to 2-aryl- and 2-heteroaryl-nitroalkenes mediated by titanium-TADDO- Lates (Eq. 4.90).96a TADDOLs and their derivatives are excellent chiral auxiliaries.96b
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Ti-TADDOL: |
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–90 ºC |
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Ti-TADDOL |
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TiCl2•( PrOH)2 |
Et2Zn |
(1.2 equiv) |
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93% (74% ee) |
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(4.90) Feringa and coworkers have used copper (I) phosphoramidite as a catalyst for asymmetric conjugate addition of dialkyl zinc reagents to α,β-unsaturated nitroacetates. The reaction of E,Z-mixtures of α,β-unsaturated nitroacetates provides 1,4-addition products in excellent yields but with low ee (Eq. 4.91). High enantioselectivities (ee up to 92%) are obtained with structurally
rigid 3-nitrocumarins (Eq. 4.92).112
NO2 |
Cu(OTf)2 |
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CO2Et |
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cat. (2.4 mol%) |
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CO2Et |
cat. |
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Et2Zn |
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64% (25% ee) |
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NO2 |
Cu(OTf)2 |
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O O |
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cat. (2.4 mol%) |
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O O |
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Et2Zn |
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95% (92% ee) |
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(4.92)
100 MICHAEL ADDITION
A radical approach to asymmetric aldol synthesis, which is based on the radical addition of a chiral hydroxyalkyl radical equivalent to a nitroalkene, has been reported, as shown in Eq. 4.93.113 The radical precursor is prepared from the corresponding carboxylic acid by the Barton reaction,114 which has been used for synthesis of new β-lactams.115
BnO |
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BnO |
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BnO |
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BnO |
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BnO |
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O O2N |
SPyr |
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Me |
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Me * |
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77% (ds:5/1) |
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BnO |
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15% aq TiCl3 |
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BnO |
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NH4OAc, THF |
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pH 5–6, 48 ºC |
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4.2 ADDITION AND ELIMINATION REACTION OF >-HETEROSUBSTITUTED
NITROALKENES
Nitroalkenes with potential leaving groups in β-position such as a dialkylamino, an alkylthio, or a phenylsulfonyl group undergo addition-elimination reactions with nucleophiles. The
chemistry of nitroenamines has been extensively investigated, and their potential utility in organic synthesis has been well established.26b,116 Severin and coworkers have developed the
addition of elimination reactions of nitroenamines with carbon nucleophiles in 1960–1970, as exemplified in Eq. 4.94.117
MgBr |
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NO2 |
THF |
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Me2N |
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80% |
Node and Fuji have developed stereoselective nitroolefination of various carbonyl compounds using β-nitroenamines (Eq. 4.95).118
OSiMe3 |
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Me |
MeLi |
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77% |
They have developed direct asymmetric synthesis of quaternary carbon centers via additionelimination process. The reactions of chiral nitroenamines with zinc enolates of α-substituted- δ-lactones afford α,α-disubstituted-δ-lactones with a high ee through addition-elimination process, in which (S)-(+)-2-(methoxymethyl)pyrrolidine (SMP) is used as a chiral leaving group (Eq. 4.96).119 Application of this method to other substrates such as α-substituted ketones, esters, and amides has failed to yield high ee.
4.2 ADDITION AND ELIMINATION REACTION OF β-HETEROSUBSTITUTED NITROALKENES 101
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OMe |
OZnCl |
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–78 ºC |
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89% (96% ee) |
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If the chiral auxiliary in Eq. 4.96 is modified by changing MeO into more bulky groups such as trityl (Tr) or t-butyldimethylsilyl (TBS) group, an improved asymmetric nitro-olefination of α-alkyl-γ- and δ-lactones is possible (Eq. 4.97).120
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OZnCl |
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Yield (%) |
ee (%) |
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Me |
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THF |
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Me |
Tr |
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NO2 |
TBS |
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Chiral nitroolefins prepared in Eqs. 4.96 and 4.97 are converted into various natural products as summarized in Scheme 4.16.121–123
The modification of chiral enamines enables the asymmetric nitro-olefination of oxyindoles, as shown in Eq. 4.98.124 An enantioselective synthesis of (–)-psudophyrnaminol is accomplished using this reaction.
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OMe |
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1) n-BuLi |
NO2 |
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N O |
2) ZnCl2 |
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NO2 |
SiMe2But |
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N O |
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OH |
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85% (95% ee) |
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(4.98)
N N
H H Me
The strategy based on asymmetric nitro-olefination is further applied to a total synthesis of
(–)-horsfiline (Eq. 4.99).125
MeO |
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1) n-BuLi |
MeO |
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N |
+OMe
N O |
2) ZnCl2 |
NO2 |
SiMe But |
NO |
N O |
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2 |
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SiMe2Bu |
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NMe |
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MeO |
84% |
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(4.99)
N O H
102 MICHAEL ADDITION |
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NO2 |
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OH |
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MeHN |
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(Ref. 122) |
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MeH Me |
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HO2C |
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OMe |
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CO2H |
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Scheme 4.16.
Nitroalkenes are generally prepared by the substitution reaction of β-nitro sulfides and sulfoxides with a variety of carbon nucleophiles via an addition-elimination sequence. This method is particularly useful for the preparation of cyclic nitroalkenes (Eq. 4.100).126
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O2N O |
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1) LDA |
S Et |
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2) ZnCl2 |
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NO2 |
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87% |
A chiral sulfoxide can be used as a leaving group for the asymmetric induction via addition-elimination process. δ-Lactam enolates are converted into the corresponding nitroalkenes substituted with lactams (Eq. 4.101).127
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91% (84% ee)
A total synthesis of (–)-physostigmine is accomplished from a chiral nitroolefin of Eq. 4.101 (Scheme 4.17).128
The addition-elimination reaction of copper-zinc organometallics RCu(CN)ZnX with (E)- 1-nitro-2-phenylsulfonylethylene gives highly functionalized (E)-nitroalkenes in excellent yields.129
Organometallics bearing esters (Eq. 4.102),13015 dienes (Eq. 4.103),131 or oxygen functions (Eq. 4.104)132 give nitroalkenes functionalized by these groups.
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4.3 MICHAEL ADDITION OF NITROALKANES |
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75% |
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29% (3 steps) |
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NaOMe, CuI |
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35% |
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Scheme 4.17. |
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Et2OC(CH2)3I |
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Zn, CuCN |
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SO2Ph |
EtO2C(CH2)3CH=CHNO2 |
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81% |
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THF, –60 ºC |
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hexane, RT |
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85% |
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(overall yield) |
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OAc |
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OAc |
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SO2Ph |
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Pri |
|
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|||||||
Pri |
Cu(CN)ZnBr |
|
|
THF, –60 ºC, 2 h |
|
NO2 |
|
|
|
|
|
(4.104) |
||||||||||||||||||
|
|
|
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|
|
74% |
|
|
|
|
|
|
|
|
|
|
|
4.3 MICHAEL ADDITION OF NITROALKANES
4.3.1 Intermolecular Addition
The Michael addition of nitroalkanes to electron-deficient alkenes provides a powerful synthetic tool in which it is perceived that the nitro group can be transformed into various functionalities. Various kinds of bases have been used for this transformation in homogeneous solutions, or, alternatively, some heterogeneous catalysts have been employed. In general, bases used in the Henry reaction are also effective for these additions (Scheme 4.18).133
R |
NO2 |
|
|
2 |
|
base |
R2 |
|
|
+ |
R |
Y |
R |
Y |
|||||
R1 |
H |
|
|
||||||
|
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|
|
R1 NO2 |
|
||||
|
|
|
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|
|
Y = CO2Et, C(O)R3, CN, S(O)Ph, SO2Ph, etc.
base = RO-, F-, R3N, R3P, tetramethylguanidine (TMG), DBU, etc.
Scheme 4.18.
104 MICHAEL ADDITION
When electron-deficient alkenes are very reactive, weak bases such as triethylamine or triphenylphosphine (Eq. 4.105)134 are reactive enough as base. On the other hand, stronger bases
O |
|
O |
O |
|
Me |
PPh3 |
NO2 |
|
|
NO2 |
Me |
|
||
+ |
(4.105) |
O |
THF |
|
RT, 24 h |
|
|
|
94% |
|
|
|
such as DBU or tetramethylguanidine (TMG) are necessary when less reactive alkenes such as vinyl sulfoxides (Eq. 4.106)135 or α-substituted α,β-unsaturated carbonyl compounds are used
(Eq. 4.107).136 TMG has been widely used for the Michael addition of nitroalkanes to various electron-deficient alkenes since the first report in 1972.137–140 High-pressure accelerates the
reaction to induce the Michael addition with less reactive alkenes.141
|
Me |
NO2 |
+ |
|
|
SOPh |
|
Base |
Yield (%) |
||
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Me |
H |
|
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Et3N |
0 |
||||
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||
|
|
base (1.0 equiv) |
O2N |
SOPh |
(2) |
TMG |
60 |
||||
|
|
MeCN |
|
|
|
Me |
Me |
DBU |
(4.106) |
||
|
|
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|
|
||||||
|
|
RT, 24 h |
|
|
|
|
95 |
||||
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||||
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|
Me |
NO2 |
+ |
|
|
Me |
|
|
Base |
Yield (%) |
|
|
|
|
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|
CO2Me |
|
||||
|
Me |
H |
|
|
|
|
|
Et3N |
0 |
||
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|
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|
|||||
|
|
|
|
|
|
|
|
Me |
|
||
|
|
base (1.0 equiv) |
|
|
TMG |
19 |
|||||
|
|
O2N |
CO2Me |
(3) |
|||||||
|
|
|
|
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|
|
|||||
|
|
|
MeCN |
|
|
|
DBU |
(4.107) |
|||
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|
|
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|||
|
|
|
RT, 24 h |
Me |
Me |
|
61 |
The reaction of conjugated nitroalkenes with α,β-unsaturated esters, ketones, nitriles, and
sulfones is catalyzed by TMG to give the Michael adduct of allylic nitro compounds (Eq. 4.108).142
Me |
|
|
TMG (0.1 equiv) |
NO2 |
CN |
||
|
|
|
|||||
Me |
+ |
CN |
|
|
|
(4.108) |
|
NO2 |
MeCN |
Me |
|||||
|
|
||||||
|
|
|
|||||
|
|
|
|
72% |
|
||
|
|
|
|
|
|
Tetraalkylammonium fluorides or metal fluorides are also effective as catalysts for the Michael addition of nitroalkanes (see, Table 4.2).143–145
In recent years, there has been increased recognition that water is an attractive medium for organic reactions from the environmental point of view. The Michael addition of various nitroalkanes to conjugated enones can be performed in NaOH (0.025 M) and in the presence of cetyltrimethylammonium chloride (CTACl) as cationic surfactant in the absence of organic solvents (Eq. 4.109).146 The Michael addition of nitromethane to methyl acrylate is carried out in water using NaOH as a base to give the mono adduct (Table 4.2).147
|
|
|
|
|
|
|
O |
Me |
NO2 |
|
|
Me NaOH (0.025 M) |
O2N |
(4.109) |
|
|
|
+ |
|
|
|
|
Me |
Me |
H |
|
|
CTACl, RT, 1 h |
|
||
|
O |
|
Me |
Me |
|||
|
|
|
4.3 MICHAEL ADDITION OF NITROALKANES |
105 |
Table 4.2. Michael Addition to nitro compounds
Nitro compound |
|
Alkenes |
|
Base/conditions |
Product (yield, %) |
|
Ref. |
||||||||
|
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O |
|
|
|
|
|
O |
|
|
|
|
|
|
CH |
NO |
2 |
(CH ) CO |
Me |
TMG/RT, 2 days |
|
(CH |
) CO |
Me |
(83) |
137 |
||||
3 |
|
|
2 6 |
2 |
|
|
|
|
|
2 6 |
2 |
|
|
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|
|
CH2NO2 |
|
|
|
|
||
|
|
|
|
|
|
|
|
|
|
|
NO2 |
|
|
|
|
CH3(CH2)4NO2 |
O O |
O |
|
|
TMG |
|
|
|
|
|
(64) |
139 |
|||
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O |
O |
O |
|
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|
|
|
|
|
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|
|
|
|
|
|
|
||
CH3NO2 |
O |
|
|
|
TMG |
O |
|
NO2 |
|
(77) |
140 |
||||
|
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|
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|
|
||||||||
|
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|
|
|
|
|
|
|
(CH3)2CHNO2 |
PhCH=CHC(O)Ph |
Bu4NF SiO2/DMF, |
Ph |
Ph |
|
(65) |
143 |
||||||||
Me |
|
O |
|
|
|||||||||||
|
|
|
|
|
|
|
20 °C, 3 h |
|
|
|
|
|
|||
|
|
|
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|
|
Me NO2 |
|
|
|
|
||||
|
|
|
|
|
|
|
|
|
|
|
|
|
|||
C7H13NO2 |
|
Me |
|
|
CsF-Al2O3/20 °C, 1 h |
|
NO2 |
Me |
(85) |
144 |
|||||
|
|
|
|
C6H13 |
|
||||||||||
|
|
|
|
O |
|
|
|
|
|
|
|
||||
|
|
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|
|
|
|
|
|
O |
|
|
|
|||
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
C2H5NO2 |
|
|
O |
CsF-Si(OR)4/80 °C, |
Me |
|
N |
O |
|
(74) |
145 |
||||
Me |
N |
|
|
|
|||||||||||
|
|
|
|
|
|||||||||||
|
|
|
|
|
74 h |
|
|
|
|
|
|
|
|||
|
|
|
|
O |
|
|
Me |
O |
|
|
|
|
|||
|
|
|
|
|
|
|
|
|
|
|
|
||||
|
|
|
|
|
|
|
|
NO2 |
|
|
|
|
|||
|
|
|
|
|
|
|
|
|
|
|
|
|
|
||
CH3NO2 |
|
CO2Me |
|
|
NaOH, H2O/20 °C |
|
O2N |
|
|
|
(57) |
147 |
|||
|
|
|
|
|
|
|
|
MeO2C |
|
|
|
|
|||
|
|
|
|
|
|
|
|
|
|
|
|
|
|||
|
|
|
|
O |
|
|
|
|
O |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
C2H5NO2 |
|
|
|
|
KF-basic |
|
|
NO2 |
|
(100) |
148 |
||||
|
|
|
|
|
|
|
Al |
O /THF, RT, 24 h |
|
|
|
|
|
||
|
|
|
|
|
|
|
2 |
3 |
|
|
|
|
|
|
|
|
|
|
MeMe |
|
|
|
|
Me Me |
|
|
|
|
|
||
CH3NO2 |
|
|
DBU |
Me |
|
CO2Et |
(40) |
180 |
|||||||
Me |
CO2Et |
|
|||||||||||||
|
|
|
|
|
|
|
|
||||||||
|
|
|
|
|
O2N |
|
|
|
|
|
|||||
|
|
|
|
|
|
|
|
|
|
|
|
|
|
||
CH3NO2 |
|
S |
|
|
DBU |
O2N |
|
S |
|
|
(85) |
181 |
|||
Ph |
N |
|
|
Ph |
|
N |
|
||||||||
|
|
|
|
|
|
|
|
|
|
|
|||||
|
|
|
|
H CO2Me |
|
|
O |
CO |
Me |
|
|
||||
CH3NO2 |
Me3SiO |
|
|
Triton B |
|
|
|
2 |
|
(75) |
182 |
||||
|
|
|
|
|
|
|
|||||||||
|
|
|
|
|
|
|
|
NO2 |
|
|
|
||||
|
|
|
|
|
|
|
|
|
|
|
|
|
|||
[NC(H2C)2]3 |
|
|
|
|
|
|
|
|
NC |
|
|
|
|||
|
|
|
|
DBU |
[NC(H2C)2]3 |
|
|
(40) |
183 |
||||||
|
|
NO2 |
|
CN |
|
|
|
|
|||||||
|
|
|
|
|
|
|
|
|
|
NO2 |
|
|
|||
|
|
|
|
|
|
|
|
|
|
|
|
|
|
||
|
CF |
|
|
|
|
|
|
|
F3C NO2 |
|
|
|
|
||
|
3 |
|
Me |
|
|
Al2O3 |
|
|
|
Me |
|
(85) |
184 |
||
H3C |
NO2 |
|
|
|
Me |
|
|
|
|||||||
|
O |
|
|
|
|
|
O |
|
|
|
|||||
|
|
|
|
|
|
|
|
|
|
|
|
|
|||
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
106 MICHAEL ADDITION
Ytterbium triflate is an extremely effective catalyst for the Michael addition of α-nitro esters to enones in water (Eq. 4.110).149
|
|
|
O |
Me CO2Et |
Me |
Yb(OTf) |
O2N |
+ |
|
3 |
Me (4.110) |
|
|
||
NO2 |
O |
H2O, RT |
Me CO2Et |
|
|
|
98% |
The heterogeneous catalytic systems have some advantages over homogeneous reactions. Chemical transformations under heterogeneous conditions can occur with better efficiencies, higher purity of products, and easier work-up. Ballini and coworkers have found that commercial amberlyst A-27 is the best choice for the Michael addition of nitroalkanes with β-substituted alkene acceptors (Eq. 4.111).150 The reaction is also carried out by potassium carbonate in the presence of Aliquat 336 under ultrasonic irradiation (Eq. 4.112).151
|
|
|
|
|
|
|
|
|
|
O |
|
Me |
NO2 |
+ |
|
Me Amberlyst A-21 |
O2N |
Me |
(4.111) |
||||
Me |
H |
|
|
Solvent Free |
|
|
|||||
|
O |
|
Me |
Me |
|
||||||
|
|
|
RT, 25 h |
|
|||||||
|
|
|
|
|
|
|
75% |
|
|||
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
K2CO3 |
|
Ph |
|
|
Me |
NO2 |
|
|
|
|
|
O2N |
CO2Me |
|
||
+ |
Ph |
|
|
|
Aliquat 336 |
(4.112) |
|||||
|
|
CO2Me |
|
|
|
|
|
||||
Me |
H |
|
)))), 90 h |
Me Me |
|||||||
|
|
|
|
||||||||
|
|
|
|
|
|
|
|
|
|
70% |
|
Recently very reactive solid bases have been devised, which are prepared by derivatization
of amorphous silica and hexagonal mesoporous silica (HMS) with the dimethylaminopropyl group (Eq. 4.113).151b
|
Me |
O |
O |
|
|
N |
|
|
Me |
Si(OMe) |
|
|
|
3 |
+ |
NO2 |
|
(4.113) |
|
|||
|
|
HMS, RT, 2.5 h |
|
|
|
|
NO2 |
|
|
93% |
In Table 4.1, the Michael addition of nitro compounds to various electron deficient alkenes is shown.
The Michael addition of nitro compounds is a useful method for the preparation of various natural products. The Michael addition of nitroalkanes to dehydroalanines gives γ-nitro-α- amino acids, which provides a convenient synthesis of side-chain modified α-amino acids (Eq. 4.114).152 Transformations of γ-nitro-α-amino acid derivatives into α-amino acids occur by reductive denitration (see Section 7.2) into γ-oxygenated α-amino acids by the Nef reaction (Eq.
Me |
Me |
CO2Me |
|
Bu4NF |
O2N |
CO2Me |
|
||
|
|
+ |
|
|
|
|
Me |
Me NHCbz |
(4.114) |
O2N |
H |
|
|
RT, 22 h |
|||||
NHCbz |
|
|
85% |
|
|||||
|
|
|
|
|
|
|
|
|
|
O2N |
CO2Me |
Bu SnH |
H |
CO2Me |
|
||||
|
|
|
|||||||
|
|
|
|
3 |
|
Me Me NHCbz |
(4.115) |
||
|
Me |
Me NHCbz |
|
AIBN |
|||||
|
|
|
|||||||
|
|
67% |
|
||||||
|
|
|
|
|
|
|
|
|
|
|
4.3 |
MICHAEL ADDITION OF NITROALKANES |
107 |
|||
|
|
|
|
|
|
NH |
+ |
|
|
|
|
|
|
|
|
3 |
|
|
|
Me |
Me |
KOH-H2O |
O2N |
CO2- |
|
|
OHC CO H + NH |
|
+ |
|
(4.116) |
||||
3 |
|
|
|
|||||
2 |
O2N |
H |
|
Me |
Me |
|
|
|
|
|
|
|
|
||||
|
|
|
|
|
|
50% |
|
|
4.115).153 Condensation of glyoxalic acid, nitroalkanes, and amines provides a simple method for β-nitro-α-amino acids (Eq. 4.116).154
The base-catalyzed reaction of nitromethane with α-amidoalkyl sulfones gives the nitro compounds as in Eq. 4.117; the nitromethyl group is converted into a carboxylic group to give α-amino acids by the Nef reaction using KMnO4.155
O |
SO2Ph |
NaH-CH3NO2 |
|
|
|
|
|
|
|
|
|
|
|
(4.117) |
|||
Ph N |
Ph |
THF, RT, 1 h |
|
|
|
|||
|
|
|
|
|||||
H |
|
|
|
|
|
|
|
|
|
O |
|
NO2 |
|
O |
CO2H |
|
|
|
|
|
|
|
|
|||
|
|
|
|
|
KMnO4 |
|
|
|
|
Ph |
N |
Ph |
|
Ph |
N |
Ph |
|
|
|
H |
|
|
|
|
H |
|
|
|
88% |
|
|
|
|
90% |
|
The Michael addition of nitroalkanes to α,β-unsaturated ketones followed by the Nef reaction has been extensively used as a method for the conjugated addition of acyl anions to enones (see
Section 6.1, Nef Reaction). This strategy is one of the best methods for the preparation of 1,4-dicarbonyl compounds.156a–h Various natural products have been prepared via this route.157 For
example, cis-jasmone is prepared from readily available materials, as shown in Scheme 4.19.156f
CHO |
|
|
O |
|
O |
O |
|
|
|
|
|
|
|
1) Bu3P |
|
|
O |
O |
|
O |
+ |
|
|
|
|
|
|
2) H+, HO |
OH |
|
NO2 |
TMG |
|
NO2 |
CH3NO2 |
|
|
62% |
|
|
95% |
O |
|
O |
|
O |
|
|
H2O2 |
|
|
O |
H+ |
|
CHO |
K2CO3 |
|
|
|
|
|
|
|
O |
|
|
|
O |
|
|
|
|
|
|
||
|
|
85% |
|
|
90% |
|
|
|
O |
|
|
O |
|
|
|
|
–OH |
|
|
|
Ph3P=CHCH2CH3 |
|
|
|
|
|
|
|
O |
|
|
|
|
|
|
|
|
60% |
|
|
83% |
|
|
|
Scheme 4.19. |
|
|
|
O |
|
|
|
O |
|
|
|
|
CH3NO2 |
|
|
|
|
|
CO2Me |
|
CO |
Me |
||
|
TMG |
|
2 |
|
||
|
|
|
NO2 |
|
|
|
|
|
|
|
O |
|
|
O |
|
|
|
70% |
|
|
|
|
|
|
|
CO2Me |
|
(Nef) |
|
|
CO2Me |
Wittig |
|
|
|
|
|
|
|
|
|
1. NaOMe, MeOH |
|
|
|
|
|
|
2. H2SO4 |
CHO |
71% |
|
O |
|
|
|
|
|
|
|
|
|
CH2NO2 |
|
CHO |
|
|
|
Scheme 4.20.
108 MICHAEL ADDITION
The Michael addition of nitromethane to cyclopentenone derivatives is used for synthesis of prostaglandins (Scheme 4.20).158 Here, the anion of nitromethane is used as a formyl anion synthon.
Ballini and coworkers have used the Michael addition of nitro compounds followed by the Nef reaction for the synthesis of various spiroketalic pheromones (Scheme 4.21).159
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MeNO2 + |
Al2O3 |
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O |
NO2 |
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NO |
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62% |
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53% |
OH |
OH |
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NaBH4 |
TiCl3 |
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53% |
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Scheme 4.21. |
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Asymmetric synthesis of spiroketalic pheromones is also reported, in which the asymmetric reduction of carbonyl group is carried out with baker’s yeast (Scheme 4.22).160
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amberlyst A-21 |
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baker's yeast |
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NO2 |
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nitromethane |
NO2 |
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3 days |
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(2S, 8S) |
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58% |
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OH |
OH |
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O |
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O |
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1) NaOH, EtOH |
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(2S, 5R, 7S) |
(2S, 5S, 7S) |
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2) H2SO4, n-hexane, |
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H2O, 0 ºC,1 h |
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(Z, Z) |
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(E, E) |
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41% (1:3) |
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Scheme 4.22.
The Michael addition of nitro compounds to electron-deficient alkynes affords allylic nitro
compounds in good yields, in which KF-n-Bu4NCl in DMSO is used as a base and solvent (Eq. 4.118).161
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NO2 O |
NO2 |
1) KF, n-Bu4NCl |
(4.118) |
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2) CO2Me
3) H2C=CHC(O)Me
53%
A short enantioselective synthesis of (–)-(R,R)-pyrenophorin, a naturally occurring anti-fun- gal 16-membered macrolide dilactone, is prepared from (S)-5-nitropentan-2-ol via the Michael addition and Nef reaction (Scheme 4.23).162 The choice of base is important to get the E-alkene in the Michael addition, for other bases give a mixture of E and Z-alkenes. The requisite chiral (S)-5-nitropentan-2-ol is prepared by enantioselective reduction of 5-nitropentan-2-one with baker’s yeast.163