Promoted Cyclization Cascades

Balme G, Bouyssi D, Monteiro N (2006) The Virtue of Michael-Type Addition Processes in the Design of Transition Metal-Promoted Cyclizative Cascade Reactions. 19 115-148 Barluenga J, Rodriguez F, Fanands FJ, Fldrez J (2004) Cycloaddition Reaction of Group 6 Fischer Carbene Complexes. 23 59-121 Basset J-M, see Candy J-P (2005) 16 151-210... 

The Virtue of Michael-Type Addition Processes in the Design of Transition Metal-Promoted Cyclizative Cascade Reactions... 

Closely related to the polyepoxide cascade procedure for the synthesis of polycyclic systems is Corey s biomimetic-type, nonenzymatic, oxirane-initiated (Lewis acid-promoted) cation-olefin polyannulation. By this strategy, compound 96, containing the tetracyclic core of scalarenedial, was constructed by exposure of the acyclic epoxy triene precursor 95 to MeAlCl2-promoted cyclization reaction conditions (Scheme 8.25) [45]. 

In an alternative approach to annulation across the indole 2,3-tt system, Padwa and coworkers have reported approaches to the pentacyclic and hexacyclic frameworks of the aspidosperma and kopsifoline alkaloids respectively that involve as the key step a Rh(II)-promoted cyclization-cycloaddition cascade <06OL3275, 06OL5141>. As illustrated in their approach to ( )-aspidophytine 150, Rh2(OAc)4-catalyzed cyclization of a diazo ketoester 148 affords a carbonyl ylide dipole that undergoes [3+2]-cycloaddition across the indole 2,3-tt bond to generate 149 <06OL3275>. 

Cyclization reactions of allylic 3-imidazolinonyl-P-ketoesters 454, 456 were carried out in a Mn(lll)-promoted radical cascade. The reaction pathway (S-exojfi-endo or 5-exol5-exo) can be directed to construct the cyclohexenyl 455 and central cyclopentyl 457 core skeletons with regioselectivity. In the cyclization, two C-C bonds and three or four contiguous stereogenic centers are established in one step, as shown in products 462 and 464. A plausible mechanism is depicted in Scheme 107 <2006AGE4345>. 

One of the first attempts in this field refers to a multicomponent intermolecular sulfa-Michael/amination cascade process in which an a,p-unsatu-rated aldehyde and a thiol were reacted in the presence of a dialkyl azodicarboxylate reagent, giving access to p-amino-y-thioalcohol derivatives with excellent yields and enantioselectivities. Isolation of the final products was accomplished by in situ reduction followed by base-promoted cyclization (Scheme 7.48). 0-Trimethylsilyl diarylprolinol 31c was identified as the best... 

The pentacyclic alkaloid ( )-meloscine (134) was prepared by Feldman and Antohne using a clever allenyl azide cycloaddition/cyclization cascade to deliver the core azabicyclo[3.3.0]octadiene substructure (2012OL934). Strain-driven release of nitrogen from the dipolar cycloadduct 129 derived from 128 promotes formation of the azatrimethyl-enemethane diradical 130 en route to the bicyclic product 131 (Scheme 30). For the synthesis ofmelo-scine 134, the thermolysis of a dilute solution of allene 132 in toluene gave the desired bicycle 133 whose structure was estabfrshed by single crystal X-ray analysis. Subsequent manipulation of the peripheral functionality in 133 then delivered ( )-meloscine 134. 

The conversion of the (Z)-phenylhydrazone of 5-amino-3-benzoyl-l,2,4-oxadiazole into the relevant 1,2,3-triazole in the presence of several haloacetic acids and the kinetics of the rearrangement of (Z)-arylhydrazones of 5-amino-3-benzoyl-l,2,4-oxadiazole to (2-aryl-5-phenyl-2//-l,2,3-triazol-4-yl)ureas have been reported. Treatment of benzannulated enediynyl alcohols with trifluoroacetic acid promoted a cascade sequence of cyclization reactions leading to 1,4-naphthoquinone methides (Scheme 37)7 ... 

Scheme 11 Iron trichloride-promoted cyclization of acetamide 37 and cascade-sequence leading to oxazoline 38 and dihydropyran 43. Reagents and conditions a) i) NMBA, Pd(PPh3)4 (2 mol%), CH2CI2, 35 "C, 12 h. iD AcjO (1.2 equiv), NaHCOj (8 equiv), MeOH, rt, 2 h, 85% from 24a b) FeCl3 -6H20 (2 equiv), CH2CI2, 45 "C, 2 h 87% c) FeClj. 6H2O (3 equiv), H2O (4 equiv), CH2Cl2/Me2CO (4 1), rt, 24 h, 82%. NMBA = N,N-dimethylbarbituric acid.

Wang et aL [34] have also described an organocatalyzed enantioselective FC alkylation/cyclization cascade reaction of 1-naphthols 217 and a,p-unsaturated aldehydes 218 promoted by a diphenylproli-nol ether 219 as a catalyst (Scheme 2.31). This method affords one-pot access to chiral and synthetically useful chromanes and dihydrobenzopyranes 220 in high yields and enantioselectivities. 

Nitrones have been widely exploited in various cycloaddition reactions. Intriguingly, these electrophilic species can also serve as the hydride acceptors. Sun and Xu et al. reported an expeditious access to structurally diverse oxadiazepines 108 via 1,5-hydride shift/cyclization of pyrrolidine- or tetrahydroiso-quinoline-containing nitrones 107 with nitrones as hydride acceptors and AICI3 was exploited as Lewis to promote the cascade process (Scheme 42) [121]. Furthermore, the nitrone 107 could be furnished in situ, which underwent subsequent 1,5-hydride shift, and ring cyclization through a one-pot process to afford 108 in good yields. 

All these results seemed to indicate that this reaction was ideal for the con-stmction of the (—)-berkelic acid skeleton. However, a serious problem was still unresolved at this point how to constmct the additional pyran ring contained in the natural product. Nevertheless, our experience on cycloisomerization reactions led us to speculate on the possibility that a unique metal complex could promote the cycloisomerization of alkynol 15 to give the exo-cyclic enol ether 19 and also that the cycloisomerization of an alkynyl-substituted salicylaldehyde 23 would give 25. Thus, activation of the alkyne of 15 should promote a hydroalkoxylation reaction to give the exocyclic enol ether 19. On the other hand, activation of the alkyne in 23 should promote a cascade cyclization process to finally give the 8//-isochromen-8-one derivative 25. The formal [4-F 2]-cycloaddition reaction between intermediates 19 and 25 would result in the formation of the core structure of (—)-berkehc acid 24 in a very simple way (Scheme 7). 

Along the same lines, Kilburn and coworkers have shown that BF3 AcOH, a mild Lewis acid, is able to promote the cascade cyclization of trimethylsilyl-substituted methylene cyclopropyl ketone (146) to afford the oxabicyclic compound (147) through the intermediacy of the allyl cation (148) (Equation 88) [90]. 

Beside aldehydes and active ketones, imines can also be used to construct chiral N-heterocycles with a-isothiocyanato imides in the promotion of either Cinchona alkaloid derivatives [101a,b] or tertiary amine thiourea [101c]. For example, in the presence of 5mol% 185a, the a-isothiocyanato imides 265 and Ts-protected imines 148 reacted via Mannich-cyclization cascade to afford methylthioimidazolines 270 with high optical purity (Scheme 2.71) [101c]. 

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