Heterogeneous Catalysts for the One-Pot Synthesis of Chemicals and Fine Chemicals

Conjugate addition of carbon nucleophiles to electron-poor alkenes is of paramount importance among the large body of synthetic processes devoted to carbon-carbon bond formation.1 The first nucleophilic systems used for this purpose, more than a century ago, were stabilized carbanions that can be prepared in polar solvents from malonates and â-dicarbonyl derivatives in relatively mild conditions using bases of moderate strength.2 This process is usually referred to as Michael addition, and ever since the number of carbanionic species that have been used for conjugate additions has considerably increased to include various enolate systems and strong nucleophilic species such as organometallic reagents. The utilization of these carbon nucleophiles has allowed the accomplishment of many synthetic processes with an outstanding degree of selectivity even though the related experimental procedures are often elaborated and not amenable to scale-up at the industrial level. Conjugate additions using highly stabilized carbanions are still of interest since a growing number of these procedures can be carried out in environmentally benign solvents such as water and using catalytic amounts of the basic promoter. In addition, the achievement of diastereoand enantioselective processes is no longer an exclusive domain of highly reactive carbanionic systems working in carefully controlled conditions3 but can be nowadays conducted even at room temperature using easily available substrates and suitable base/solvent combinations. Nitroalkanes are a valuable source of stabilized carbanions since the high electron-withdrawing power of the nitro group provides an outstanding enhancement of the hydrogen acidity at the R-position (cf. pka MeNO2 ) 10).4-8 Nitronate anions 2 that can be generated from nitroalkanes 1 using a wide range of bases act as carbon nucleophiles with common electrophiles including haloalkanes,9 aldehydes,10,11 and Michael acceptors,1 leading to carbon-carbon bond formation (Scheme 1). The obtained adducts 3-5 still retain the nitro function, and therefore, a suitable transformation of the nitro group very often follows the main addition process. Reduction of the nitro group to a primary amine 7 can be easily carried out providing a modification of the oxidation state of the nitrogen atom (Scheme 2). Alternatively, the nitro group can be removed from the molecule using two distinct synthetic strategies. Replacement of the nitro group with hydrogen gives the corresponding denitrated product 8 so that the whole process (nucleophilic addition-denitration) closely resembles the addition of an organometallic reagent to an electrophilic substrate.5,12 The presence at the â-position of an electron-withdrawing group allows a base-assisted elimination of nitrous acid with consequent introduction of a double bond in the molecular framework 9. A further option is represented by conversion of the nitro group into a carbonyl group 10, a transformation widely known as the Nef reaction, which ultimately leads to a reversal in the polarity of the neighboring carbon atom from nucleophilic to electrophilic.13,14 This review is focused on the utilization of nitroalkanes as nucleophiles in conjugate additions with electron-poor alkenes and covers the new procedures and related applications appearing in the literature after 1990. Emphasis will be given to asymmetric additions carried out using optically active alkenes or with the aid of chiral catalysts. * To whom correspondence should be addressed. Phone: +39 0737 402270. Fax: +39 0737 402297. E-mail: roberto.ballini@unicam.it; marino.petrini@unicam.it. 933 Chem. Rev. 2005, 105, 933−971

Conjugate Additions of Nitroalkanes to Electron-Poor Alkenes: Recent Results

Alcohols have been employed as substrates for C–C bond-forming reactions which involve initial activation by the temporary removal of hydrogen to form an aldehyde. The intermediate aldehyde is converted into an alkene via a Horner–Wadsworth–Emmons reaction, nitroaldol and aldol reactions. The ‘borrowed hydrogen’ is then returned to the alkene to form a C–C bond.

Borrowing hydrogen: iridium-catalysed reactions for the formation of C–C bonds from alcohols

The conjugate addition of carbon nucleophiles to nitroalkenes is an important synthetic process in organic synthesis mainly because of the large range of subsequent possible transformations of the nitro group. The generation of optically active 1,3-dinitro compounds is an attractive facet of this research area because they are precursors of enantioenriched 1,3-diamines, which can serve as versatile building blocks for pharmaceutical compounds. However, enantioselective versions of these processes have only just started to emerge. In 2006, Du and co-workers reported the direct asymmetric Michael addition of nitroalkanes to nitroalkenes by using zinc(II)bis(oxazoline) and -bis(thiazoline) complexes as catalysts. Wang et al. showed that a modified cinchona alkaloid was a useful asymmetric catalyst for the synthesis of 1,3-dinitroalkanes. Subsequently, the Maruoka research group revealed that N-spiro chiral ammonium bifluorides could efficiently catalyze the asymmetric Michael addition with silyl nitronates. Despite these important contributions, the development of new and efficient asymmetric catalytic systems is still an interesting challenge. N,N’Dioxides have been successfully applied as excellent chiral scaffolds in many asymmetric reactions. Moreover, the electropositive properties and high coordination ability of lanthanide ions has resulted in them attracting significant attention in organic synthesis. Herein, we describe the direct asymmetric Michael addition of unmodified nitroalkanes to nitroalkenes by using lanthanum(III) triflate in combination with an N,N’-dioxide ligand. Initially, N,N’-dioxide L1 (Scheme 1) was complexed in situ with various metal salts to catalyze the Michael addition in the presence of iPr2NEt. [14] The metal source had a decisive effect on the enantioslectivity of the reaction. As shown in Table 1, the Cu, In, and Sc complexes of N,N’-dioxides successfully employed in other asymmetric reactions only gave extremely poor results in the Michael reaction (Table 1, entries 1–3). Furthermore, although the Cu and Ni complexes showed excellent activating ability for the nitroolefins, their N,N’-dioxide complexes catalyzed the

Highly Enantioselective Direct Michael Addition of Nitroalkanes to Nitroolefins Catalyzed by La(OTf)3/N,N′‐Dioxide Complexes

Highly efficient one or two-step sequences for the synthesis of fine chemicals from versatile nitroalkanes

In the title compound, C5H14N3+·H2PO4−, the cation has a central guanidinium fragment with a planar geometry, as expected for a central Csp2 atom with a small charge delocalization along the three C—N bonds. The crystal packing is governed by hydrogen bonds so that the phosphate anions are linked head to tail, forming chains running parallel to the c direction. These chains in turn are interconnected by hydrogen bonds to intermediate tetra­methyl­guanidinium cations forming hydrogen-bonded molecular layers stacked parallel to the bc crystal planes.

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S. Perez-Garrido

Papers

1,1,3,3-Tetramethylguanidinium dihydrogenorthophosphate

Synthesis of aliphatic 1,3-dinitro compounds

Synthesis of Aliphatic 1,3-Dinitro Compounds.