With the huge variety of reactions today available the real question for chemists is not what they can synthesize, but how they can do it fulfilling green chemistry guidelines. Great emphasis is given to the design of novel processes aimed at waste prevention (1st principle), little toxicity of reagents and products for human health and environment (third, fourth and tenth principles), reduced energy requirements (sixth principle) and risks of chemical accidents as releases, explosions and fires (twelveth principle). Besides the intensive research of more environmentally benign and recyclable solvent and catalysts, the development of safer reagents is strongly demanded and in this context novel biomimetic oxidant systems based on molecular oxygen or hydrogen peroxide could provide high atom economy and negligible toxicity since water is the only by-product [56-58]. Advances in osmium-free hydroxylations  are also greatly expected whereas transfer hydrogenation has yet became a well-established alternative to the reaction with gaseous hydrogen for the conversion of ketones to alcohols at ambient pressure.
The design of new chemical processes addressed to achieve high atom economy, avoidance of derivatization steps and purification of intermediates as well as substantial decreases in time, labor and waste generation can be viewed as the ultimate goal of green chemistry. Therefore, great interest is reserved to multi-component reactions (MCRs) [60, 61], defined as reactions in which more than two compounds react to form a product in such a way that the product retains the majority of atoms of starting material through the formation of many covalent bonds. In this context, the term cascade (or domino) reactions has been specifically introduced to underline that multiple formation of C-C bonds occurs under the same reaction conditions, without additional reagents or catalysts, through sequential and inseparable transformations of reactive intermediates whose chemical functionalities have been formed in the previous step . Further classification according the mechanism involved in the formation of intermediates has been proposed  and one-pot combinations of reactions that could be executed independently (tandem reactions) have been also reported .
As very exciting and at the same time challenging research field, MCRs have attracted interest of organic chemists for long time and fundamental examples as Strecker, Mannich, Biginelli, Passerini and Ugi reactions were dated between the end of nineteenth and the half of twentieth century. Since then several cascade processes have been developed and applied for synthesis of complex molecules and natural products [64-66]. Final product stereochemistry has been in many cases diastereoselectively controlled using one of the substrates in enantiopure form, but multicomponent catalytic asymmetric transformations of achiral precursors have been successfully developed  and some examples of enan-tioselective Strecker, Mannich or Passerini reactions have been yet discussed in the previous sections.
One-pot sequences of enantioselective reactions, directed at construction of multiple stereogenic centres, can be performed using a single catalyst able to promote different asymmetric transformation or a multicatalytic system, following an approach resembling biological cascades in which several enzymes in the cell convert simple precursors in complex molecules through a serie of coupled reactions. As concern the first strategy, secondary amine organocatalysts play a central role since they are able to promote either functionalization of aldehydes and ketone with electrophiles (through enamine intermediate) either addition
(a) + Nucleophile
67-97%, >99% ee syn:ant/ from 9:1 up to >25:1
O HVH O
IBu^rSi O t-Bu
Me N Me
hydride as nucleophile
Me N Me
hydride as nucleophile oO
Scheme 4.7 Iminium-enamine cascade sequences (a-b) and proposed mechanism (c)
of nucleophiles to a, b-unsaturated compounds (through imininium intermediate) and different combinations of these activation modes have provided effective cascade processes .
Using imidazolinone catalysts 10 or 11, MacMillan's group developed a cascade sequence for consecutive addition of a variety of nucleophiles and chlorine (or fluorine) on double bond of enals with simultaneous and stereocon-trolled generation of two chiral carbons  (Scheme 4.7a-b). According the proposed mechanism (Scheme 4.7c) for such iminium-enamine sequence, the substrate was firstly coordinated to catalyst giving an iminium specie that underwent nucleophilic attack leading to a saturated aldehyde whose enamine, formed in the second catalytic cycle, suffered a-halogenation. Final products were obtained in excellent yields and optical purities.
67-97%, >99% ee syn:anti from 9:1 up to >25:1
enamine activation of aldehyde
iminium activation ofenal h2°
R2^ R3 NO2
R2^ R3 NO2
^ h rchoh3
35-56%, >99% ee, cte>10:1 R2 = Ph, 2-Cl-Ph; R3 = H, Ph
Scheme 4.8 Cascade sequences for synthesis of cyclohex-1-ene carbaldehydes (a) or tricyclic frameworks (b)
The J0rgenson catalyst 12 was active in triple Michael-Michael-aldol sequences leading to the synthesis of cyclohex-1-ene carbaldehydes 13 with up four new stereogenic centres from an aldheyde, an enal and nitrostyrenes through enamine-iminium-enamine catalytic cascade  (Scheme 4.8a). Remarkably, from 16 possible stereoisomers of 13 only two epimers differing for nitrogroup configuration were formed in a ratio ranging from 2:1 to 99:1 and an additional intramolecular Diels-Alder reaction occurred with aldehydes bearing suitable diene substituent, so allowing the synthesis of complex tricyclic derivatives 14 with new eight chiral carbons in a one-pot operation  (Scheme 4.8b).
The same prolinol catalyst 12 displayed high efficiency in the synthesis of other substituted cyclohexane derivatives and cyclopentane carbaldehydes bearing a stereogenic quaternary carbon through combination of Michael additions with aldol , nitroaldol  or a-alkylation  reactions in cascade fashion (Scheme 4.9a-c).
R = Ph, naphthyl,2-furyl c-C6H„, 4-NO2-Ph 4-Br-Ph, 4-OMe-Ph
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