Conjugate addition of nitroalkenes

In conjunction with the Knoevenegal reaction, a Michael addition (Figure 22) reaction was also described by Jaekson et al. using the same siliea supported tertiary amines for the catalysis of conjugate addition of nitroalkenes to a,y9-unsaturated carbonyl compounds. At a flow rate of 6.6 pL/min the eonversion rate was constant with a high yield for 7 hours reaction time. 

The conjugate addition of (R)- or fS -4-phenyl-2-oxa2oLidinone to nitroalkenes is catalyzed by r-BuOK at -78 C to give the addition product v/ith excellent diastereoselecdvity, the products are converted into vicinal diamines fEq 4 28 ... 

The products of the conjugate addition of (f )-4-phenyl-2-oxazolidinone to nitroalkenes are converted into D-a-amino acids with high enantiomeric purity (Eq. 4.30).36... 

Recently, very effective asymmetric conjugate addition of 1,3-dicarbonyl compounds to nitroalkenes has been reported, as shown in Scheme 4.10. The reaction of ethyl acetoacetate with nitrostyrene is carried out in the presence of 5 mol% of the preformed complex of magnesium triflate and chiral bis(oxazoline) ligands and a small amount ofW-methylmorpholine (NMM) to give the adduct with selectivity of 91%. The selectivity depends on ligands. The effect of ligands is presented in Scheme 4.10.63... 

A variety of carbanions have been employed forthe conjugate addition to nitroalkenes recent results are shown in Table 4.1. 

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). x a TADDOLs and their derivatives are excellent chiral auxiliaries.9611... 

The palladium-catalysed decarboxylative carbonylation of 5-vinyloxazolidin-2-ones 218 caused, unexpectedly, a ring enlargement process to 5-lactams 219 <00JA2944>. The conjugate addition of 4-phenyloxazolidin-2-one to a nitroalkene was used for the synthesis of diastereoisomers of dethiobiotin <00EJO3575>. Attempted deprotection of the O-TBDMS... 

Silylation of Products of Conjugated Addition of Nucleophiles to a-Nitroolefins Nitroalkane anions can be generated not only by deprotonation of nitroalkanes (various modifications of these process were considered above) but also by the conjugated addition of nucleophiles 56 to a-nitroalkenes (42) (Scheme 3.56, Table 3.2). 

In 1993, Alexakis et al. reported the first copper-catalyzed asymmetric conjugate addition of diethylzinc to 2-cyclohexenone using phosphorous ligand 28 (32% ee).36 An important breakthrough was achieved by Feringa et al. with chiral phosphoramidite (S,R,R)-29 (Figure 1), which showed excellent selectivity (over 98% ee) for the addition of 2-cyclohexenone.37 Since then, efficient protocols for the conversion of both cyclic and acyclic enones, as well as lactones and nitroalkenes, have been developed featuring excellent stereocontrol. 

The enantioselective conjugate addition of dialkylzinc to nitroalkenes using other phosphoramidite,79,79a 83a sulfonamide,84 and binaphthol-based thioether ligands65 has also been studied in the past few years. Particularly noteworthy are the efficient chiral monodentate phosphoramidite ligands (S,R,R)-29 and (A,A)-55 developed by Feringa et al. and Alexakis et al., respectively, for this reaction. (S,R,R)-29 provided excellent enantioselectivities (up to 98% ee) for acyclic nitroalkenes (Scheme 25).80 It also worked well for other nitroolefin substrates such as 3-nitrocoumarin 7068 and methyl 3-nitropropenoate 7185. 

Alexakis et al. showed that under optimized experimental conditions, the enantioselectivity of the Cu-catalyzed conjugate addition of dialkylzinc to cyclic nitroolefin was improved to 95% with both (A,A)-55 and (R,S,S)-29.79,79a Biphenol-based phosphoramidite ligand (S,S)-55 also provided acyclic nitroalkenes adducts with 95-96% ee.42... 

Ojima and co-workers found that chiral monodentate phosphoramidite (S,R,R)-35 was highly effective for the enantioselective conjugate addition of diethylzinc to acyclic nitroalkenes (up to 99% ee).86... 

Intramolecular nitrile oxide cycloaddition. The conjugate addition of t-butyl isocyanide to a nitroalkene can generate a nitrile oxide, which can be trapped intramolecularly by a double bond to form an isoxazoline. 

Conjugate alkylation of nitroalkenes. R3A1 or the etherate reacts rapidly with a,p-unsaturated nitro compounds to form products of 1,4-addition.1 Example ... 

Diastereoselective tandem conjugate addition of both oxygen- and nitrogen-centred nucleophiles (potassium phthalimide, TsNHK, MeONa, and MesSiOK) to the novel (IN)-lO-camphorsulfonic acid-derived nitroalkenes (139 R = Me, Pr, and... 

The first organocatalyzed conjugate addition of a-substituted p-ketoester to a,P-unsaturated ketones was presented by Deng et al. [42] (Scheme 3). Although traditional Cinchona alkaloids were efficient catalysts for conjugate addition of carbon nucleophiles to nitroalkenes and sulfones, replacement of the C(9)-OH with an ester group (Q-7b) showed great improvement in stereoselectivity. The reaction is applicable to a variety of cyclic and acyclic enones (16,18). 

The conjugate addition of phosphorus nucleophiles of various oxidation states and in neutral or metallated form constitutes an efficient and well-known method for C—P bond formation [30]. In the case of phosphanes as nucleophiles especially, the corresponding phosphane-borane adducts have been used in 1,4-additions to Michael acceptors. Following the idea to use a chirally modified phosphorus nucleophile in asymmetric Michael additions to aromatic nitroalkenes, we synthesized the new enantiopure phospite 45 starting from TADDOL (44) with nearly quantitative yield. Due to the C2 symmetry, of the... 

As a consequence of the strong electron-withdrawing properties of the nitro group, conjugated nitroalkenes behave as powerful Michael acceptors. An example of conjugate addition of Reformatsky reagents to (2-nitrovinyl)arenes 107 is given in equation 63150. 

Beak and co-workers have also produced the key alcohol intermediate 74 by the sparteine-mediated lithiation and conjugate addition of allylamines to nitroalkenes to give Z-enecarbamates in good yields with high enantio- and diastereoselectivty (Scheme 16). Thus treatment of the allylamine 87 with n-BuLi in the presence of (-)-sparteine followed by conjugate addition to nitroalkene 88 gave the desired enecarbamate 89 in... 

Nitroalkenes can serve as the two-carbon fragment of a [3 + 2] cyclization involving enamines as nucleophiles (equation 86) (81LA1534). This reaction is presumably initiated by a conjugate addition of the enamine to the nitroalkene (equation 87). The most attractive formulation of the cyclization is via an intramolecular nucleophilic addition to the aci-form of the nitronate anion. This provides a reduced nitrogen substituent which could be eliminated to complete aromatization. This procedure has provided quite satisfactory yields over a range of structural types. 

In contrast to the ester enolates, the a.O-carboxylic dianions are intrinsically more reactive and their use in conjugate reactions is thus limited. Typically, a-substituted-a.O-carboxylic dianions add exclusively to a,(3-unsaturated esters155a and nitroalkenes,155b while additions to ot,(3-enones are sensitive to the substitution pattern of the enones.155c>d Notable is the conjugate addition of dihydrobenzoic acid dianions (207), from Birch reduction of benzoic acids, to oi,3-unsaturated esters (Scheme 77).155e... 

As shown in Eq. (4), parallel screening of ligand libraries has allowed us to establish that a closely related peptide-based phosphine ligand promotes the catalytic asymmetric conjugate addition of alkylzincs to nitroalkenes [14]. Not only are the corresponding alkyl nitrones obtained efficiently and in high diaster-eo- and enantioselectivity, appropriate acid workup can deliver the derived ketone directly. 

The highly enantioselective direct conjugate addition of ketones to nitroalkenes has been promoted by a chiral primary amine-thiourea catalyst (7).31 The observed anti diastereoselectivity has suggested participation of a (Z)-enamine intermediate, given (g) the complementary diastereoselectivity obtained in analogous reactions involving (E)-enamines generated from secondary amine catalysts. 

A highly diastereo- and enantio-selective formal conjugate addition of nitroalkanes to nitroalkenes has been achieved using a chiral ammonium bifluoride catalyst (9)46 This strategy provides a reliable route to optically active 1,3-dinitro compounds. 

The chiral quaternary ammonium bifluoride (162) has been shown to catalyse a (g) highly diastereo- and enantio-selective conjugate addition of silyl nitronates (160) to nitroalkenes, giving rise to 1,3-dinitro compounds (161) (76-96% ee).213 ... 

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