Stereocontrolled domino reactions

Pellissier, H. (2012). Stereocontrolled domino reactions. Chemical Reviews, 113, 442-524. 

In spite of the explosive development of asymmetric domino processes including multicomponent reactions, domino reactions involving chiral carbohydrate derivatives still remain rare in the literature. It is particularly true with regard to carbohydrate-derived organocatalysts. This section highlights several important works dealing with stereocontrolled domino reactions of chiral carbohydrate derivatives in a first part, and a rare enantioselective domino reaction catalyzed by a chiral carbohydrate derivative in a second part. It must be noted that all the discussed domino reactions are multicomponent ones. 

Stereocontrolled Domino Reactions of Chiral Carbohydrate Derivatives... 

The first example of an intermolecular radical addihon/intermolecular trapping domino reactions of an acyclic system in a stereocontrolled fashion to build stereo-genic centers at the a- and 3-carbons was described by Sibi and coworkers [59]. Enantioselective addition of in-sitw-prepared alkyl radical to crotonate or cinnamate,... 

Domino reactions usually show a good stereocontrol and good overall yields. Also very important is the fact that novel pathways can be developed, which cannot be followed in a stepwise approach, as in domino reactions intermediates can be unstable compounds, which are consumed as they are formed in a further step. 

Menendez and coworkers [75] developed a domino reaction of a-nitrocycloalkanones 128 with a-alkyl a,P-unsaturated aldehydes 129 in water, which led to functionalized bridged bicydic lactones 130 containing 10-, 11-, 13-, and 15-membered rings with complete stereocontrol depending on the ring size (Scheme 12.51). The structures of the products were determined by X-ray diffraction analysis. 

Finally, multicomponent reactions (MCRs) are a subclass of domino reactions and can be defined as processes in which three or more starting materials react to form a product, where basically all or most of the atoms contribute to the newly formed product [10]. A recent example reported by our group (Scheme 1.4c) involves the reaction between p-ketoamides, acrolein, and aminophenols, allowing the preparation of an enantioenriched diazabicyclo[2.2.2]octanone (2,6-DABCO) scaffold [11]. The chemoselective reaction sequence installs five new bonds and three stereocenters, with excellent yields and high levels of stereocontrol. 

A cascade carbopalladation-carbonylation sequence for substrates possessing P-hydrogens was explored by Seashore-Ludlow and Somfai [19] (Scheme 6.10). This allows for the construction of complex architectures with vicinal stereocenters in a concise and rapid fashion via the stereocontrolled formation of two carbon-carbon bonds. An integral aspect of this domino reaction is the ability to control P-hydride elimination of the organopalladium intermediate and instead form the carbonylation product. 

If nitroalkenes are employed as heterodienes in hetero Diels-Alder reactions instead of nitrosoalkenes, cyclic nitrones are formed. These cycloadducts undergo numerous subsequent reactions, and especially the combination of this hetero Diels-Alder reaction with a 1,3-dipolar cycloaddition is an extremely powerful tool for the synthesis of polycyclic alkaloids. This domino [4+ 2]/[3+ 2] cycloaddition chemistry has been comprehensively reviewed by Denmark and Thorarensen very recently, and this review also covers many hetero Diels-Alder reactions of nitroalkenes being not part of this sequential transformation [5]. Therefore the present article will focus on some selected examples which might highlight the advanced state of the art concerning stereocontrol of these reactions. On the other hand, an insight shall be given into the multitude of polycyclic structures accessible by means of nitroalkene cycloaddition chemistry. 

Scheme 4.15 Regio and stereocontrolled synthesis of substituted 2,3,4,5-tetrahydro-l, 5-benzothiazepines through domino S. reaction.

The precursor dihydroxyacetone dimer 223 and aldehyde 27.7. underwent a domino sequence to afford the interesting hexahydrofuro[3,4-c]furane in excellent yields [114]. In this example by Vicario, in the oxa-Michael/aldol/hemiacetalization process, an iminium ion species formed between organocatalyst 1 and enal 222 reacts with the structurally interesting dihydroxyacetone dimer 223, providing the intermediate enamine which undergoes an intramolecular aldol reaction (Scheme 7-47). The high stereocontrol of the reaction (about 90-99% ee and 10 1 dr) was proposed to involve the reversibility of oxa-Michael addition and a predicted fast aldol condensation and/or dynamic kinetic resolution process where the chiral catalyst 1 accelerates the aldol reaction for one diastereoisomer over the other. For a mechanistic rationale of this reaction please, see Chapter 8. 

In the course of a total synthesis of the diterpenoic tetraol (+)-aphidicolin, Des-longchamps and coworkers developed a domino transannular Diels-Alder/aldol reaction of macrocyclic trienyl oxo aldehyde 88, which closed four rings and assembled the entire skeleton of the natural product in one transformation. Heating 88 in a sealed tube in toluene at 230 °C for 24 h in the presence of triethylamine as proton scavenger first initiated the transannular Diels-Alder reaction, which was followed by the intramolecular aldol reaction to deliver tetracycle 90 in excellent yield and as a single diastereomer (Scheme 8.26) [47]. Three new carbon-carbon a-bonds and four new stereogenic centers were established with complete stereocontrol. 

Welle, A., Petrignet, J., Tinanf B., Wonters, J. Riant, O. (2010). Copper-catalysed domino silylative aldol reaction leading to stereocontrolled chiral quaternary carbons. Chemistry - A European Journal, 16, 10980-10983. 

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