Cascade reactions asymmetric polycyclizations

Furthermore, the asymmetric PS reaction has been applied as a key step in the cascade reaction to build up chiral polycyclic compounds. In 2009, Dixon and coworkers [71] developed a chiral phosphoric acid 8f-catalyzed cyclization cascade between tryptamines and enol lactones, leading to the products in good yields and with good to excellent enantioselectivities. This was further extended to the reaction of tryptamines and ketoacids, which were more readily available than enol lactones [72]. By using diarylprolinol silyl ether as catalyst, the other cascade transformations involving Michael addition, iminium formation and PS cyclization were also efficiently realized [73]. 

In this review, we have shown the major advances in the growing field of cascade chemistry that have led to regio-, chemo-, and stereoselective formation of several new carbon-carbon and carbon-heteroatom bonds in a stepwise economical fashion by using transition metal-catalyzed reactions. These approaches have already allowed very impressive and rapid construction of unnatural and natural polycyclic compounds of very high molecular complexity. These initial achievements should stimulate the synthetic community to pursue further works notably to develop more efficient and selective strategies that involve new generations of versatile catalysts. Next endeavors will have to focus on green processes as well as asymmetric catalysis. 

The identification of novel ways to incorporate an asymmetric intramolecular Mizoroki-Heck reaction as part of a cascade cyclization sequence has led to attractive approaches for assembling complex polycyclic molecules. Keay and coworkers [54] reported the use of a double Mizoroki-Heck cyclization as the pivotal step in the asymmetric total synthesis of xestoquinone (93), a reduced congener of halenaquinone (Scheme 16.20). In this step, naphthyl triflate 90 was cyclized with Pd2(dba)3 (dba = dibenzylideneace-tone), (5 )-BINAP and 1,2,2,6,6-pentamethylpiperidine (PMP) in toluene at 110°C to give pentacyclic product 92 with impressive efficiency and moderate enantioselectivity. This conversion proceeds by initial asymmetric 6-exo Mizoroki-Heck cyclization to form the central six-membered carbocycle and install the benzylic quaternary stereocentre. The first cyclization event is followed by a second Mizoroki-Heck reaction in which neopentyl... 

In the years since the first reports in 1989 [4,5], the scope of the asymmetric intramolecular Mizoroki-Heck reactions has been substantially increased. This transformation has now been employed as a key strategic step in total syntheses of a wide variety of polycyclic natural products. Among the features that contribute to the broad utility of asymmetric Mizoroki-Heck cyclizations are the high functional group tolerance of palladium(O)-catalysed reactions, the remarkable capacity of this transformation to forge C—C bonds in situations of considerable steric congestion and the ability to orchestrate cascade or tandem processes that form multiple rings. 

Enantiopure polycyclic chromans arise from an asymmetric cascade annulation reaction of 2-hydroxystyrenes with o-alkynyl benzaldehydes or ketones (Scheme 34) (13JA11402). 

A synthetically powerful variant of the asymmetric FCA reaction via Michael addition involves cascade processes in which multiple catalytic events occur subsequentially. The approach has been efficiently employed in the synthesis of chromanes and polycyclic analogues via enantioselective annulation reactions. 

In 2012, a further evaluation of the gold(I)/chiral Brpnsted acid binary catalytic systems was carried out by the same research group [134]. In this report, the well-designed enynes 375 can be efficiently converted into 1,3-silyloxydienes 378 via Au(I) 377-catalyzed hydrosiloxylation, thus enabling subsequent asymmetric Diels-Alder reaction in the promotion of a phosphoramide 70b, affording polycyclic compounds 379 in high optical purties (Scheme 2.100). This relay catalytic cascade intramolecular hydrosiloxylation/asymmetric Diels-Alder reaction provides an unprecedented alternative to traditional Diels-Alder reactions. 

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