Palladium-catalyzed spirocyclization

If the side chain with the nucleophile is situated in the 1-position of the conjugated diene, a palladium-catalyzed spirocyclization occurs. In this case stereoselective oxa-spirocyclizations were obtained from the diene alcohols 59 and 60 (equation 23 -25)58. The reaction worked well for the formation of a tetrahydrofuran and tetrahydropyran in the spirocyclization. In the absence of chloride ions 59 gave high yields of the acetoxy oxaspirocyclic compound 61 via a 1,4-anti addition across the diene (equation 23). In the presence of stoichiometric amounts of LiCl a 1,4-syn oxychlorination took place and allylic chloride 62 was obtained (equation 24). Under chloride-free conditions, cyclohep-tadiene alcohol 60 afforded oxaspirocyclic acetate 63 (equation 25). 

By using the same catalytic system, alkylations of 1,3-dimethylbarbituric acid with alcohols were also accomplished (Scheme 5.31) [68]. The Cp lr-catalyzed alkylation using 2-iodobenzyl alcohol, followed by palladium-catalyzed carbon-carbon bond formation with allene, gave spirocyclic barbituric acid derivatives in a one-pot process. 

Palladium-catalyzed reaction of bromo dienes 39 was complete after a few hours, and afforded spirocycles 40a and 40b as single regio- and stereoisomers (Scheme 12). The Heck spirocyclization reaction is regioselective, giving five-membered heterocycles. In addition, it is stereoselective because the Heck adducts were obtained as single geometric isomers [60]. 

The palladium-catalyzed cyclizative coupling reaction of a-allenols 41 with alkenyl halides was also explored. The transformation of allenols 41 into spirocyclic disubstituted dihydrofuran (3-lactams 43 was readily achieved in high yields, by treatment with allyl bromide or 2,3-dibromopropene in the presence of palladium (II) chloride (5 mol%) (Scheme 14) [60]. 

Palladium-catalyzed annulation reactions were involved in the syntheses of benzo[A furan-based spirocyclic compounds, 2-substituted-3-aroyl-benzo[A]furans, and 2-benzofuran-2-ylacetamides <07AGE7068 07JOC9278>. 

The ability to convert 2-piperidinones to the enaminotriflates allows the substitution of the 2-position through palladium-catalyzed coupling <97JOC3592, 97JOC4550, 97JOC8l31>. Intramolecular Heck reaction of a 2-substituted cyclic enamide of A-formy 1-1,4,5,6-tetrahydropiperidine affords spirocyclic piperidyl derivatives <97JOC595>. The preparation of... 

The Trost group has devised a strategy for stereoselective spirocyclic ring installation across 3-alkylidene oxindoles via palladium-catalyzed [3-1-2] cycloaddition with cyano-substituted trimethylenemethane (Scheme 33) [74, 75]. As illustrated, the opposite sense of diastereoselectivity was observed depending on the choice of chiral ligand 125 or 126. Preferential orientation of the benzenoid portion of the oxindole as dictated by the varied steric environments of the naphthyl ring systems on the catalysts has been put forth as a rationale for the observed difference in stereochemical outcomes. Spirooxindoles 127 and 128 were obtained in 92% ee and 99% ee, respectively. A variation of this methodology has been applied in the racemic synthesis of marcfortine B [75]. 

Ashimori, A. and Overman, L.E. (1992) Catalytic asymmetric synthesis of quaternary carbon centers. Palladium-catalyzed formation of either enantiomer of spirooxindoles and related spirocyclics using a single enantiomer of a chiral diphosphine ligand. J. Org. Chem., 57, 4571-2. 

The palladium-catalyzed cleavage of an allylic C-C bond forming cationic )t-allylpalladium intermediates is possible if the anionic counterpart is stabilized through charge delocalization on electron-deficient substituents [29]. Based on this concept, it has been shown that 3-vinylcyclopentenes undergo a two-carbon ring expansion to spirocyclic cyclopheptadienes in the presence of... 

The reaction of heterocumulenes or alkynes with ortho-iodoanilines under a carbon monoxide atmosphere has been shown to give4(3ff)-quinazolinones or 2-quinolones, respectively. A related cyclocarbonylation reaction has been used to synthesize new cardanol and cardol derivatives in a regioselective manner. Versatile and efficient routes to various spirocyclic compounds, including [5,5]-, [5,6]- and [5,7]-spiroindolines, have been established by exploiting a sequence of palladium-catalyzed cyclization processes (eq 105). ... 

Carbonylation Cascades. The norbornene enamide shown underwent a palladium-catalyzed 5-g o-trig cyclization followed by carbonylation (1 atm) to give a spirocyclic product as a single di-astereoisomer (eq 84). In this case ring strain prevents the competing /3-hydride elimination pathway. Similar diastereoselective three-component cascade processes proceed smoothly in excellent yield (eq 85). ... 

In 2010, Jaegli et al. reported a novel palladium-catalyzed intramolecular domino spirocyclization process for the preparation of biologically relevant spiropyrroUdine-3,3 -oxindoles 86 [32] (Scheme 6.19). Oxidative addition of the aryl halide to Pd(0) aminopalladation via the coordinated intermediate 84 leads to palladacycle 85 reductive elimination of complex 85 generates the final product. Both Heck reaction and aminopalladation processes were viable pathways from amide 83, and the route that occurs is dependent on the ligand chosen. The use of tBuMePhos as the ligand is required for the successful formation of spirooxindoles. 

SCHEME 6.81 Palladium-catalyzed aUene insertion toward spirocycles. 

The formation of spirolactams 47-49 could be rationalized in terms of a sequence domino cyclization of a-allenols-cross coupling reactions. A palladium (Il)-catalyzed mechanism for the domino sequence leading to spiranic adducts 47-49 is proposed in Scheme 17. It could be presumed that the initially formed allenepalladium complex 50 undergoes an intramolecular attack by the hydroxyl group (oxypalladation), giving rise to the spirocyclic vinylic palladium species 51. 

Apart from palladium and rhodium, copper(I) compounds have been shown to catalyze reactions of Fischer metal carbenes. As an example, the 7r-cyclization of tungsten carbene complex 103 to the spirocyclic vinylcyclopentadiene 104 has been found to be strongly enhanced in the presence of Cul and NEt3 (Scheme 45). [97c]... 

Cao, T., Linton, E. C., Deitch, J., Berritt, S., Kozlowski, M. C. (2012). Copper(ll)-and Palladium(ll)-catalyzed enantioselective Claisen Rearrangement of allyloxy- and propargyloxy-indoles to quaternary oxindoles and spirocyclic lactones. Journal of Organic Chemistry, 77, 11034-11055. 

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