The Nitro group in organic sysnthesis - Feuer
.pdf7.2 R–H FROM R–NO2 199
example, the reaction of 1-deoxy-1-nitroaldoses with formaldehyde followed by denitration opens a new way to C-glycoside (see Eq. 7.63,71 Eq. 7.64,71 and Eq. 7.65.72
BnO |
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BnO |
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O |
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BnO |
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O |
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Bu3SnH, AIBN |
BnO |
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BnO |
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OAc |
benzene |
BnO |
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OBn |
OAc |
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BnONO2 |
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95% |
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O |
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O |
O |
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O |
O |
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O |
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O |
O |
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O |
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NO2 |
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O |
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H |
Bu3SnH, AIBN |
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H |
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O |
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O |
OAc |
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OAc |
benzene |
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O |
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O |
O |
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(7.64) |
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O |
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O |
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O |
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O |
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89% |
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Ph |
O |
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OH |
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Ph |
O |
O |
OH |
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O |
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AcO |
AcHN |
O Bu3SnH, AIBN |
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AcO |
AcHN |
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O |
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NO2 O |
benzene |
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H |
O |
(7.65) |
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97% |
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Martin has used this strategy for the preparation of β-(1,6) and β,β-(1,1) linked C-disaccha- rides, as shown in Scheme 7.7.73 Such C-disaccharides are a class of nonhydrolyzable mimics of disaccharide and potential glycosidase inhibitors in the treatment of metabolic diseases (Scheme 7.7).
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OAc |
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NO2 |
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O |
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O |
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OH |
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OAc |
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O O |
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O |
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AcO |
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OAc |
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O |
CH2NO2 |
+ |
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KF |
AcO |
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O O |
O |
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AcO |
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O |
CH3CN |
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OAc |
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AcO |
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O |
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52% |
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O |
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OAc |
NO2 |
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O O |
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O |
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AcO |
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OAc |
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Ac2O |
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NaBH4 |
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O |
AcO |
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OAc |
NO2 |
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O O |
O |
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pyridine |
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O |
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O |
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O |
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AcO |
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OAc |
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O |
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AcO |
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71% |
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O |
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91% |
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OAc |
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O |
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CH2OH |
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AcO |
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Bu3SnH |
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OAc |
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1) MeO– |
HO |
O |
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AcO |
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AIBN |
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O O |
O |
2) H3O |
+ |
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HO |
OH OH |
O |
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O |
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HO |
OH |
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OH |
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O |
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89% |
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57% |
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Scheme 7.7.
200 SUBSTITUTION AND ELIMINATION OF NO2 IN R–NO2
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OBn |
NO2 |
O |
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O |
O |
TMG |
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BnO |
+ |
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BnO |
BnOOH |
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O |
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O |
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OBn |
O |
Bu3SnH, AIBN |
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BnO |
O |
O |
toluene |
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BnO |
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BnOOH NO2 |
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O |
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OBn |
O |
1) BF3•Et2O, Et3SiH |
OAc |
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OAc |
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O |
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BnO |
O |
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2) L-Selectride |
AcO |
OAc |
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3) Pd(OH)2/C, H2 |
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O |
AcO |
OAc |
O |
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BnO |
BnO |
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4) Ac2O |
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OH |
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OAc |
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68% |
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Scheme 7.8.
The Michael addition of nitroalkanes followed by denitration is also a useful method for the preparation of C-disaccharide. The Michael addition of glucosyl nitromethane to the levoglucosenone proceeds stereoselectively, and subsequent denitration gives the C-disaccharide in 68% yield (Scheme 7.8).74
Elegant application of the Michael addition of nitroalkanes to enones followed by denitration is demonstrated in the synthesis of (+) dihydromevinol, (see Scheme 7.9).75
Si |
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NO2 |
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Si |
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O |
CHO |
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O |
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1) MeNO2, MeONa |
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Me |
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Me |
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2) CH3SO2Cl, Et3N |
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Me |
3) NaBH4 |
Me |
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70% |
O |
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1)HF
2)(S)-2-methyl butyric anhydride, DMAP
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O |
O |
Si |
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NO2 |
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Me |
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Me |
70% |
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O |
NO2 |
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O |
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Si O |
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Me |
amberlyst A-21 |
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Me |
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O |
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70% |
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Bu3SnH, AIBN |
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O |
O |
Si |
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toluene reflux |
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Me |
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Me |
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55% |
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Scheme 7.9.
7.2 R–H FROM R–NO2 201
Because the α-nitroketones are prepared by the acylation of nitroalkanes (see Section 5.2), by the oxidation of β-nitro alcohols (Section 3.2.3), or by the nitration of enol acetates (Section 2.2.5), denitration of α-nitro ketones provides a useful method for the preparation of ketones (Scheme 7.10). A simple synthesis of cyclopentenone derivatives is shown in Eq. 7.66.76
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O |
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MeO |
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NO2 |
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O |
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O2N |
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(CH2)7CO2Me |
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t-BuOK |
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+ |
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OMe |
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N |
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(CH2)7CO2Me |
DMSO |
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OMe |
N |
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OMe |
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O |
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80% |
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1) Bu3SnH, AIBN |
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(CH2)7CO2Me |
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O |
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MeONa |
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(CH2)6CO2Me |
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H |
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2) H+ |
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O |
(7.66) |
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73% |
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Magnus and coworker have presented a new strategy for the preparation of taxane diterpenes by using nitro-aldol reaction and denitration as key steps (see Scheme 7.11).77
The high acidity of α-nitroketones makes it possible to perform the Henry reactions or Michael additions under extremely mild conditions. The reaction proceeds in the presence of catalytic amounts of Ph3P to give the C–C bond formation products under nearly neutral conditions. Thus, 1,5-dicarbonyl compounds78 and α-methylenecarbonyl compounds79 are prepared by the denitration of α-nitroketones, as shown in Eqs. 7.67 and 7.68, respectively.
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O |
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O |
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H |
Ph3P |
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Me |
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n-C7H15 |
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Me + |
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n-C7H15 |
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H |
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NO2 |
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87% |
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Bu3SnH, AIBN |
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n-C7H15 |
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H |
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benzene |
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Me |
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87% |
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O |
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O |
1) HCHO, Ph3P |
O |
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2) Ac2O |
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Me |
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C6H13 |
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Me |
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C6H13 |
3) Bu3SnH, AIBN |
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(7.68) |
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NO2 |
4) DBU |
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70% (overall) |
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Ballini and coworkers have reported a simple synthesis of 1-phenylheptane-1,5-dione based on the strategy of the Michael addition and denitration as shown in Eq. 7.69).80 The product is a natural product that is isolated from fungus.
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O |
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1) Ph3P |
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+ |
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Ph |
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2) Bu3SnH, AIBN |
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O |
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(7.69) |
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50% (overall)
202 SUBSTITUTION AND ELIMINATION OF NO2 IN R–NO2 |
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R1CH NO |
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NO2 |
Bu3SnH |
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R1CH2NO2 |
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R2CHO |
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Oxidation |
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R2 |
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R2 |
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R1 |
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AIBN |
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O |
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R1 |
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R2 |
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NO2+ |
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OAc |
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NO2 |
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base |
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NO2 |
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Bu3SnH |
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E |
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1 |
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R2 |
+ |
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R2 |
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R |
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R |
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R |
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E |
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O |
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O |
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E = electrophiles |
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Scheme 7.10.
Biologically active natural products frequently contain medium or large rings, and many methods have been used in preparing of such compounds.81 Hesse and coworkers have exploited an elegant ring expansion reaction of α-nitroketones using the ability of the nitro group to stabilize a carbanion (retro-acylation of nitro compounds). Various macro cyclic compounds are now prepared by this route (see Section 5.3).82 The carbon-carbon bondforming reactions of α-nitroketones followed by an intramolecular addition of the alkoxide to the carbonyl group give the ring-expanded products. The nitro groups are finally removed on treatment with Bu3SnH. For example, tetradecano-14-lactone is prepared via palladiumcatalyzed allylation (Section 5.5) of 2-nitrocyclodecanone followed by ozonolysis, reduction, ring expansion, and denitration, as shown in Scheme 7.12.83 In a similar way,
(–)-15-hexadodecanolide (Scheme 7.13)84, (+)-13-tetradodecanolide (Scheme 7.14),85 and muscone (Scheme 7.15)86 are prepared.
H |
Me |
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Me |
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NC |
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O |
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NC |
O |
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MeNO2, DBU |
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DIBAL |
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CH2Cl2, –15 ºC |
O2N |
H |
O |
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CH2Cl2, –78 ºC |
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O |
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OTBS |
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OTBS |
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85% (α:β = 2:1) |
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Me |
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Me |
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OHC |
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O |
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TMG |
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HO |
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O |
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H |
O |
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CH2Cl2, 25 ºC |
O2N |
H |
O |
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O2N |
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OTBS |
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OTBS |
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90% |
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90% |
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Me |
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Me |
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Dess-Martin |
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O |
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O |
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O |
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O |
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Bu3SnH, AIBN |
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oxidation |
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CH2Cl2 |
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O2N |
H |
O |
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benzene, reflux |
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H |
O |
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OTBS |
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OTBS |
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79% |
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60% |
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Scheme 7.11.
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7.2 R–H FROM R–NO2 |
203 |
O |
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O |
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O |
CHO |
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NO2 |
O CO2Et |
NO2 |
O ,Zn |
NO2 |
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3 |
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Pd (0) |
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98% |
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91% |
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O |
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O |
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O |
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O |
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DIBAL |
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Bu3SnH |
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NO2 |
AIBN |
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85% |
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28% |
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Scheme 7.12. |
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|
Enantioselective nitro-aldol reaction (see Section 3.3) or Michael reaction (see Section 4.4) followed by radical denitration is useful as an alternative indirect method of enantioselective 1,2- or 1,4-addition of alkyl anions (see Eq. 7.7087 and Eq. 7.7188).
|
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OH |
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OH |
Me |
CHO |
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Me |
Me |
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Me |
Me |
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(R) |
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(R) |
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cat. |
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NO2 |
Bu3SnH |
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H |
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Me |
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Me |
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Me |
H |
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AIBN |
|
(7.70) |
OCOPh |
Me |
NO2 |
OCOPh |
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OCOPh |
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65% (88% ee) |
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70% |
cat.: La-K-(S)-6,6-bis(triethylsilyl)ethynyl BINOL (see Section 3.3)
|
O |
O |
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O |
NO2 |
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+ |
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Bu3SnH |
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AIBN |
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N |
CO2Rb |
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O2N |
(7.71) |
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H |
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84% (84% ee) |
84% (84% ee) |
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(5 mol%) |
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O |
O |
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O O Me |
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Me |
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H |
Me |
O |
O |
O |
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NO2 |
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NO |
+ |
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Ti |
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2 |
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Me Et2O, –30 ºC, 3 h |
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Me O |
O |
Me |
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63% |
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O O |
Me |
Bu3SnH, AIBN
toluene, reflux
47%
Scheme 7.13.
206 SUBSTITUTION AND ELIMINATION OF NO2 IN R–NO2 |
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O2N |
OH |
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OH |
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HO |
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OH |
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1) |
NO2 |
Bu3SnH, AIBN |
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OH |
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N |
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HN |
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2) Swern oxidation |
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N |
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toluene |
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(7.72) |
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Bn |
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Bn |
OTHP |
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Bn |
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70% |
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Dauzonne has reported a simple synthesis of flavanones by radical denitration and dehalogenation of 3-chloro-2,3-dihydro-3-nitro-2-aryl-4H-1-benzopyran-4-ones,92 which are readily prepared by the reaction of salicylaldehydes with 1-chloro-1-nitro-2-arylethenes (Eq. 7.73).93
O |
O |
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NO2 |
Bu3SnH, AIBN |
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Cl |
(7.73) |
||
benzene |
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Ph |
||
|
O |
O Ph
97%
Sequential Michael additions are versatile methods for the construction of cyclic compounds. Although a variety of these reactions have been developed, the use of alcohols as nucleophiles for the Michael addition to nitroalkenes has been little studied. Recently, Ikeda and coworkers have reported an elegant synthesis of octahydrobenzo[b]furans via the sequential Michael addition of 1-nitro-cyclohexene with methyl 4-hydroxy-2-butynoate in the presence of t-BuOK followed by radical denitration (Eq. 7.74).94
CO2Me |
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CO2Me |
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CO |
Me |
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O N |
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2 |
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NO2 |
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t-BuOK |
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2 |
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1) Bu3SnH, |
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+ |
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AIBN, toluene |
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(7.74) |
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THF, 0 ºC |
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O |
2) H+ |
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O |
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HO |
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100% |
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86% |
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The Diels-Alder reaction followed by radical denitration provides a useful strategy for construction of six-membered compounds, in which the nitro group accelerates the reaction and also controls the regio-chemistry of the addition (Eq. 7.75).95
O |
O |
O |
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+ |
|
Bu3SnH |
|
AIBN |
|
benzene |
|
|
reflux |
O2N |
Me |
NO2 |
Me |
|
|
83% |
86% (7.75) |
The intramolecular Diels-Alder reaction of nitrotrienes proceeds stereoselectively in the presence of LiClO4 in diethyl ether to give one stereoisomer from endo selectivity. The nitro group is removed from the adduct with Bu3SnH (Eq. 7.76).96
(7.76)
Thus, radical denitration has developed as a reliable tool in organic synthesis and has been mainly carried out using tin hydride in total syntheses of natural products. There is one report in which NaTeH was used for removing the nitro group. Norslanadione, a biologically active
208 SUBSTITUTION AND ELIMINATION OF NO2 IN R–NO2
Table 7.3. Radical denitration with Bu3SnH
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Yield (%) |
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Yield (%) |
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RNO2 |
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RH |
Ref. |
|
RNO2 |
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RH |
Ref. |
|||
Cl |
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S |
S |
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Me |
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NO2 |
87 |
100 |
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95 |
112 |
|||
Cl |
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NO2 |
Me |
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Cl |
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O |
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O |
O |
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O |
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OMe |
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78 |
104 |
O |
|
O |
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NO2 |
|
78 |
107 |
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Cl |
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ClNO2 |
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P(OEt)2 |
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O |
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NO2 |
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OAc |
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O O |
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O |
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CO2Me |
78 |
103 |
AcO |
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OMe |
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83 |
106 |
|||||
H |
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6 |
O2N |
AcO |
H |
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Me |
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NO2 |
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O2N O |
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O |
O |
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Me |
|
CO2Me |
75 |
103 |
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63 |
108 |
|||
O |
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6 |
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Ph |
O |
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O |
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AcO H |
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CH2Ph |
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O |
O |
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O |
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NO2 |
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O2N |
CO2Me |
80 |
102 |
O |
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O |
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58 |
72 |
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F |
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CN |
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Me |
|
NO2 |
31 |
101 |
O2N |
CO2Et |
|
O Si |
|
87 |
116 |
|||||
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O |
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F3C |
O |
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O |
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O |
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80 |
105 |
|
Et |
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85 |
115 |
||
N |
NO2 |
C4H9 |
C C CH2 CH CHPh |
|||||||||||||
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O |
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O NO2 |
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OH NO2 |
64 |
109 |
|
NO2 |
NHCbz |
|
65 |
117 |
||||||||
(S) |
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CO2Et |
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O |
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O |
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HN |
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Me |
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NO2 |
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HOCH2 |
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|||
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59 |
30 |
RO |
|
O |
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N |
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82 |
118 |
|||
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OH |
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O |
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MeO |
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NO2 |
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Me |
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Me |
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MeO |
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NO2 |
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N |
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|||
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O |
85 |
114 |
|
|
NO2 |
O |
|
91 |
120 |
||||||
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O |
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CO2Et |
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O |
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Ph |
NO |
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2 |
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|
|
|
|
|
|||
|
|
|
|
|
|
N |
|
|
|
|
|
|
|
|
|
|
|
|
NO2 |
26 |
111 |
|
O |
|
|
|
|
|
|
90 |
121 |
||
|
|
|
|
CPh |
|
|
|
|
||||||||
|
|
|
|
|
|
|
O |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
N |
|
|
|
|
|
|
|
||
|
|
Ph |
|
|
|
|
N Me |
|
|
|
|
|
||||
|
|
N |
91 |
113 |
|
Me |
|
|
|
85 |
122 |
|||||
|
|
|
|
|
|
|
C Me |
|
|
|
||||||
EtO2C ONO2 |
|
|
|
Me |
NO2 |
|
|
|
(continues) |
|||||||
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|