The Nitro Group in Organic Synthesis

7.3 ALKENES FROM R–NO2 215

X Reagent

+ X–

O2N

X = NO2, SO2Ar, SAr, OC(S)R

Reagent: Na2S, Ca/Hg, NaTeH, Bu3SnH + AIBN

Y = CO2R, CHO, C(O)R, SO2R

Scheme 7.21.

oxidation of the anion derived from nitroalkanes. Unsymmetrical dinitro compounds are

prepared by the reaction of geminal dinitro compounds with nitroalkane salts (see Eqs. 7.103 and 7.104).143

Because sodium sulfide is a strong nucleophile, other non nucleophilic reagents such as Ca/Hg 144 or Bu3SnH145 are more suitable than Na2S in the synthesis of functionalized olefins (see Eq. 7.105). NaTeH is also effective to induce the elimination reaction presented in Eqs. 7.103 and 7.104.146

Vasella and coworkers have used this radical elimination for the chain elongation of 1-C-nitroglycosyl halides.147 The requisite 1-C-nitroglycosyl chlorides and bromides are easily available from sugar oximes.148 Treatment of 1-C-nitromannosyl chloride with the potassium salt of 2-nitropropane gives the vicinal dinitro sugar in 81% yield. Reduction of this dinitro sugar with Na2S gives the enol ether in 96% yield (see Eq. 7.106).

Because anions of nitro compounds are good electron-transfer reagents, they can serve as reducing agents in radical type eliminations of vicinal dinitro compounds. In fact, N-azolyl-sub-

216 SUBSTITUTION AND ELIMINATION OF NO2 IN R–NO2

stituted olefin is spontaneously formed by an SRN1 reaction of the anion derived from gemnitroimidazolylethane with gem-chloronitropropane (Eq. 7.107).149 Similar sequential SN1 reaction followed by radical elimination is observed in the reaction of 1-methyl-2-trichlo- romethyl-5-nitroimidazole with the anion of 2-nitropropane (see Eq. 7.108),150a or difluoromethyl quinone (see Eq. 7.109).150b The main product of Eq. 7.109 is substitution product, but it can be converted to 2,3,5-trimethyl-6-(2-methyl-1-propenyl)benzo-1,4-quinone on treatment with the anion of 2-nitropropane.

Ono and coworkers have extended the radical elimination of vic-dinitro compounds to β-nitro sulfones151 and β-nitro sulfides.138,152 As β-nitro sulfides are readily prepared by the Michael

addition of thiols to nitroalkenes, radical elimination of β-nitrosulfides provides a useful method for olefin synthesis. For example, cyclohexanone is converted into allyl alcohol by the reaction shown in Eq. 7.110. Treatment of cyclohexanone with a mixture of nitromethane, PhSH, 35%-HCHO, TMG (0.1 equiv) in acetonitrile gives a hydroxymethylated-β-nitro sulfide in 68% yield, which is converted into the corresponding allyl alcohol in 86% yield by the reaction with Bu3SnH.138 Nitro-aldol and the Michael addition reactions take place sequentially to give the required β-nitro sulfides in one pot.

Tin radical-induced elimination from β-nitro sulfones or β-nitro sulfides proceeds in a stereoselective way to give anti elimination products.153 When diastereomers of β-nitro sulfones can be separated, each diastereomer gives (E)- and (Z)-alkenes selectively (Eq. 7.111). Such

7.3 ALKENES FROM R–NO2 217

stereo-specific radical elimination is rather unusual because usually radical reactions proceed in a nonspecific way.

Stereoselective preparation of (E)-allyl alcohols via radical elimination from anti-γ- phenylthio-β-nitro alcohols has been reported.154 The requisite anti-β-nitro sulfides are prepared by protonation of nitronates at low temperature (see Chapter 4), and subsequent treatment with Bu3SnH induces anti elimination to give (E)-alkenes selectively (see Eq. 7.112). Unfortunately, it is difficult to get the pure syn-β-nitro sulfides. Treatment of a mixture of synand anti-β- nitrosulfides with Bu3SnH results in formation of a mixture of (E)- and (Z)-alkenes.

Ono and coworkers have devised a new acetylene equivalent for the Diels-Alder reaction; namely, 1-phenylsulfony-2-nitroethylene is a very reactive dienophile, and the radical elimination from the adduct gives the Diels-Alder adduct of acetylene, as exemplified in Eq. 7.113.155 Other acetylene equivalents are summarized in a review.156

Acetylene equivalent of β-sulfonylnitroalkene in the Diels-Alder reaction is used in part for total synthesis of pancratistatin (Eq. 7.114). Pancratistatin is isolated from the root of the plant Pancratium littorale Jacq., native to Hawaii, which exhibits anti-cancer activity.157

96%

Nitro-aldols, which are readily available (see Henry reaction Section 3.1), are converted into olefins via conversion of the hydroxyl group to the corresponding phenyl thiocarbonate ester and treatment with tin radical.158 The yield was not reported. Because the radical deoxygenation via thiocarbonate (Barton reaction) proceeds in good yield, the elimination of Eq. 7.115 might be good choice for olefin synthesis.159

Due to the toxicity of tin reagents, a new radical elimination without using Bu3SnH is highly desirable. Barton has reported that nitro olefins are converted into olefins via radical elimination of β-nitro trithiocarbonates (Eq. 7.116).160 The Michael addition of trithiocarbonate to nitroalkenes is carried out in CS2 to avoid the addition of EtSH.

(7.116)

7.3.2 Ionic Elimination of Nitro Compounds

In a previous review dealing with β-elimination reactions of nitrous acid, the literature is covered up to 1985.161 The basic concept is very simple: the nitro group at the β-position of the electron-withdrawing groups is eliminated to give alkenes on treatment with base. A typical example is shown in Scheme 7.22; electrophiles can be introduced to ethyl β-nitropropionate at both α- and β-positions, and subsequent elimination of HNO2 gives various alkenes. The Henry reaction or Michael reaction of ethyl β-nitropropionate followed by elimination of HNO2 gives β-substituted acrylate.162 On the other hand, alkylation of the dianion derived from the

same compound followed by elimination of HNO2 gives α-substituted acrylate (Eqs. 7.117 and 7.118).163

55%

(7.122)

Another approach is the Michael addition to ethyl β-nitroacrylate, as shown in Eq. 7.123, which has been used in the synthesis of α-methylenebutyrolactone, a moiety characteristic of many sesquiterpenes.169

(7.123)

The Michael addition of nitroalkanes to alkenes substituted with two electron-withdrawing groups at the α- and β-positions provides a new method for the preparation of functionalized alkenes. Although reactions are not new,170 Ballini and coworkers have used this strategy in the synthesis of polyfunctionalized unsaturated carbonyl derivatives by Michael addition of nitroalkanes to enediones as shown in Eqs. 7.124–7.126.171 Success of this type of reaction depends on the base and solvent. They have found that DBU in acetonitrile is the method of choice for this purpose. This base-solvent system has been used widely in Michael additions of nitroalkanes to electron-deficient alkenes (see Section 4.3, which discusses the Michael addition).172

(7.124)

(7.125)