The Nitro group in organic sysnthesis - Feuer

PMe

71%

Scheme 10.15.

The Michael addition of lithium enolates to nitroalkenes followed by reaction with acetic anhydride gives acetic nitronic anhydrides, which are good precursors for 1,4-diketones, pyrroles, and pyrrolidines (Eq. 10.73).113

N

H

34–53%

(10.73)

Nitroalkenes are shown to be effective Michael acceptor B units in three sequential reactions (A + B + C coupling) in one reaction vessel. The sequence is initiated by enolate nucleophiles

(A) and is terminated by aldehydes or acrylate electrophiles (C). The utility of this protocol is for rapid assembly of complex structures from simple and readily available components. A short total synthesis of a pyrrolizidine alkaloid is presented in Scheme 10.16.114

LDA, –78 ºC

Scheme 10.21.

developed an efficient approach for the preparation of them. Enzyme-catalyzed reduction of 5-nitro-2-oxopentanoic acid to the corresponding (S)- and (R)-2-hydroxy acids. Subsequent esterification, catalytic hydrogenation of the nitro group using Pt2O catalyst, and spontaneous

intramolecular cyclization give enantio-pure 3-hydroxy-piperidin-2-one, as shown in Scheme 10.22.128

Asymmetric Michael addition of nitromethane to a crotonyl camphorsultam gives access to

the enantio-pure 2-oxoesters, which may be converted into the 3-hydroxy-5-methylpiperidin- 2-one (Eq. 10.77).129

The reaction of γ-nitrobutenoate with aldehydes and ketones in the presence of ammonium acetate gives 3-nitropiperidines.130 This reaction is used for synthesis of CP-99,994, a highly potent substance P antagonist (Scheme 10.23).131

A novel synthetic approach toward the AB-ring system of 9-azasteroids using the Diels-Alder reaction of nitroalkene and subsequent reductive cyclization has been shown (Scheme 10.24).132

Scheme 10.25.

Palladium-mediated methylencyclopentane annelation of nitrostyrene is used for a total synthesis of cephalotaxine, which is the predominant alkaloid of the cephalataxus species (Scheme 10.25).133

10.3.3 Miscellaneous

The reduction of aromatic nitro compounds to amino derivatives and cyclizations to various heterocyclic compounds are presented in Chapter 9. Recent advances are presented here. Reaction of 2-nitrobenzaldehyde with vinyl carbonyl compounds in the presence of 1,4-diazbi- cyclo[2.2.2]octane affords Baylis-Hillman products, the catalytic reduction of which results in direct cyclization to quinoline derivatives (Eq. 10.78).134

OH O

H2, Pd/C

NO2 O

78%

Tandem reduction-Michael addition using suitably substituted nitroarenes provides a general route to aryl-fused nitrogen heterocycles (Eq. 10.79).135

Reductive cyclization of 2-formyl-2′-nitrobiaryl compounds gives phenanthridine derivatives.136 The Stille coupling of nitroarylstannanes with 2-bromobenzaldehyde are used for the preparation of the requisite 2-formyl-2′-nitrobiaryls. Subsequent treatment of biphenyl derivatives with zinc dust in acetic acid gives the phenanthridine derivatives as shown in Eq. 10.80.137

CHO

MeO N

90%

The carbinolamine-containing pyrrolo[2,1-c][1,4]benzodiazepine family of antitumor antibiotics is produced by various Streptomyces species; well-known members include abthramycine, tomaymycine, and DC-81.138 Various approaches to the synthesis of these compounds have been investigated over past years; reductive cyclization of suitably substituted nitroaldehydes is the frequently used method (Eq. 10.81).139

O

68%

Nitroenamines and related compounds have been used for synthesis of a variety of heterocyclic compounds. Rajappa has summarized the chemistry of nitroenamines (see Section 4.2).140 Ariga and coworkers have developed the synthesis of heterocycles based on the reaction of nitropyridones or nitropyrimidinone with nucleophiles. For example, 2-substituted 3-nitro- pyridines are obtained by the reaction of 1-methyl-3,5-dinitro-2-pyridones with ketones in the presence of ammonia (Eq. 10.82).141

3-Methyl-5-nitropyrimidin-4(3H)-one reacts with ketones in the presence of ammonium salts to give 4,5-disubstituted pyrimidines or 5,6-disubstituted 3-nitro-2-pyridones depending on reaction conditions (Eq. 10.83).142

2,2-Dithio-1-nitroalkenes are prepared by the reaction of nitromethane with CS2 and KOH followed by alkylation with alkyl halides (Eq. 10.84).43 They are important reagents for synthesis

Reaction of nitroketene aminals with enaminoketones provides a route for the derivatives of 2-amino-3-nitropyridines (Eq. 10.87).147

Reaction of diphenylcyclopropanone with nitroketene aminals gives 6-amino-2-pyridones (Eq. 10.88).148

Reaction of 1-diethylamino-2-nitroalkenes with ethyl isocyanoacetate in the presence of DBU at room temperature, followed by quenching with HCl, leads to 1-hydroxypyrazoles in good yield (Eq. 10.89).149

REFERENCES

1a. Gossauer, A. In Houben-Weyl, Methoden der Organischen Chemie, Thieme Verlag, Stuttgart, 1994, Vol. E 6a, Part 1, p. 556–798.

1b. Sundberg, R. J. Comprehensive Heterocyclic Chemistry; ed. by A. Katritzky and C. W. Rees, Pergamon, Oxford, Vol. 4, p. 313.

1c. Bean, G. P. Pyrroles; ed. by A. Jones, Wiley, New York, 1990, Vol. 1, p. 105.

2.Smith, K. M. Porphyrins and Metalloporphyrins, Elsevier, Amsterdam, 1975.

3.Miyashita, M., B. Z. E. Awen, and A. Yoshikoshi. J. Chem. Soc., Chem. Commun., 841 (1989).

224(1986).

5.Sire, B. Q., I. Thevenot, and S. Z. Zard. Tetrahedron Lett., !$, 9469 (1995). 6a. Crob, C. A., and K. Camenisch. Helv. Chim. Acta, !$, 49 (1953).

6b. Tratwein, A. W., and G. Jung. Tetrahedron Lett., !', 8263 (1998).

7.Sanchez, A. G., B. M. Stiefel, R. F. Fernandez, C. Pascual, and J. Bellanato. J. Chem. Soc., Perkin Trans 1, 441 (1982).

8.Sanchez, A. G., M. Mancera, and F. Rosado. J. Chem. Soc., Perkin Trans 1, 1199 (1980).

9.Meier, H. Liebigs Ann. Chem., 1534 (1981).