Ene-type cyclization

The chemistry and utility of zinc-based Lewis acids are similar to those of their magnesium analogs. Their mild Lewis acidity promotes several synthetic reactions, such as Diels-Alder reactions, hetero Diels-Alder reactions,229 radical-mediated reactions,230 ene-type cyclization, and Simmons-Smith reactions. 

The cyclization is quite general. The 1,6-enyne system of alkynyl /V-acylenamine 332 undergoes a similar ene-type cyclization using BBEDA (5%) to give 333 [137]. The bicyclic picrotoxane skeleton 335 has been constructed by this Pd-catalysed ene-type cyclization of 334. The cyclized product 335 was obtained in a satisfactory yield (70%) only by the combined use of the phosphine ligands 336 and 337 [138]. 

This ene-type cyclization has been extended to chiral unsaturated acyclic allylic acetates such as (S,E)-3 and (S,Z)-3.15 Pd-catalyzed cyclization of (S,E)-3 results in the (S)-pyrrolidine 4 in high optical purity by apparent displacement of the acetate... 

An efficient asymmetric synthesis of six-membered quinoline derivatives bearing a quaternary carbon center or a spiro-ring by an ene-type cyclization of 1,7-enynes catalyzed by the cationic BINAP-Pd(ll) complex was reported <03JA4704>. 

Entries 2 and 5 in Table 15 exonplify the use of a polymer-supported palladium(0)-phosphine catalyst which may offer practical advantages for carrying out p ladium-catalyz ene-type cycliz ons. As to the stereochemistry, dienes (229) containing a (Z)-enophile gave, under kinetic control, predominantly... 

The In(OTf)3-catalyzed (3,5) oxonium-ene type cyclization affords various multi-substituted tetrahydrofurans and tetrahydropyrans (Tab. 8.30). For tetrahydrofuran syntheses the reaction is temperature-dependent - increasing the reaction temperature converts the kinetic product 11 to the thermodynamic isomer 10 via a 1,3-shift (Scheme 8.124) [167]. 

Knierzinger, A., Grieder, A., and Schdnholzer, P, Palladium-catalyzed ene-type cyclizations of terpenoid 1,6-enynes, Helv. Chim. Acta, 74, 517, 1991. 

Scheme 26. Ene-type cyclization of triene system catalyzed by iron complex...

In some palladium-catalyzed cyclizations of enynes a [2 + 2] cycloaddition with subsequent metathesis-like rearrangement leads to other cyclic products50,51. The transition metal catalyzed Alder ene type cyclization reactions can also be applied to diynes52 and to enal-lenes53-55. The latter reaction is best performed using a polystyrene-supported nickel(II)/ chromium(II) catalyst. With the appropriate choice of substituents complete stereoselectivity can be achieved using this method55. 

Scheme 5 6-(2,4) Ene-type cyclization and anomalous carbocyclization of 1,6-enynes...

Ene-Type Cyclization with P,N Ligand via Five-Membered Ring Formation... 

Catalytic asymmetric alkaloid synthesis remains a challenge [114], in spite of the pharmaceutical importance of kainic acid [115,116] etc. Chiral transition metal complexes are the catalysts [117] of choice for cyclization of enynes, dienes [118, 119], or diynes [120]. With axially chiral P,N ligands having an achiral gem-dimethyloxazoline unit, alkaloid synthesis can be attained via ene-type cyclization [121]. 

Scheme 24 Spiro alkaloid synthesis by ene-type cyclization...

It has been proven that the chiral Pd(II) complexes as transition metal catalysts vs Lewis acid catalysts bring a breakthrough in the frontier of catalytic asymmetric organic synthesis. Here we discussed the key issues based on asymmetric carbon-carbon bond formations anomalous six-membered ring formation, ene-type cyclization leading to five-membered rings, spiro cycliza-tion, alkaloid and quinoline synthesis, Suzuki-Miyaura coupling, and C-H bond activation/C-C bond formation by transition metallic Pd(II) catalysts. On the other hand, the carbonyl-ene reaction, hetero Diels-Alder reaction, and... 

PalladiumfO) also catalyzed the 3-component reaction between unsaturated halides or triflates, propai gyl alcohols and the Michael acceptors alkylidenemalonates, leading to the formation of 3-alkylidenetetrahydrofurans <01JOC175>. Highly enantioselective formation of 2-alkylidenetetrahydrofurans was also realized by palladium-catalyzed ene-type cyclizations of 1,6-enynes <01AG(E)249, 01T5137> and l,2-dien-7-ynes <01JA8416>. 

Ene-type cyclization of the 1,6-enyne 158 to provide a five-membered ring is not possible. Instead, the cyclohexenes 159 and 160 were obtained using cationic Pd(n) and (/ )-BINAP. The reaction can be understood by two reaction paths. The rather unusual 6-endo cyclization of 161 to generate 162 is one possibility. The formation of the neopentyl-type palladium intermediate 163 by 5-exo cyclization is another possibility. Then the olefin insertion affords the cyclopropane 164, and subsequent -carbon elimination provides 165, from which 159 and 160 are formed by f-U elimination [50],... 

Shortly later, within 2 months, a similar reaction, the enantioselective cascade aza-ene-type cyclization reactions of a,p-unsaturated aldehydes 28 and enamide 154, was also reported by Wang et al. In addition, the reaction product hemiaminal 157 was converted to ketoaldehyde 158, pyridine 159 and enamide 160, Scheme 3.51 [67]. Similarity, the reaction mechanism started from a nucleophilic attack of enamide (an aza-ene-type reaction), followed by reversible enamine-iminium transformation and hydrolysis to provide the hemiaminal. 

The Pd-catalyzed ene reaction has widely been used combined with subsequent CO insertions. Indeed, the potential of Pd ene-type cyclization/carbonylation protocols for the synthesis of fused five-membered ring systems has amply been demonstrated by... 

W. Oppolzer, Pure Appl. Chem., 1990, 62, 1941-1948. Regio- and Stereocontrolled Catalytic Palladium- and Nickel ene-Type Cyclizations. 

W. Oppolzer, in OrganometalUc Reagents in Organic Synthesis, J. H. Batesson and M. B. Mitchell, Eds., Academic Press, London, 1994, 161-183. Stereocontrolled Catalytic Transition Metal-ene Type Cyclizations in Organic Synthesis. 

Mikami developed a highly enantioselective spiro cyclization of 1,6-enynes 37 with cyclic olefin catalyzed by cationic skewphos rhodium(I) complex. This is the first example of Rh(I)-mediated spiro-construction via an ene-type cyclization (Scheme 9.10) [19]. The ene cyclization provided two spiro isomers 38 and 39, and the selectivity was found to be dependent on the substitution and on the temperature of the reaction. Interestingly, the use of the less rigid chiral diphos-phane (5,S-skewphos) gave better results in term of enantioselectivity compared to atropisomeric diphosphanes, thereby demonstrating the interest of conformational flexibility of the active rhodium species. 

An array of multi-substituted tetrahydrofurans and tetrahy-dropyrans can be prepared through the indium-catalyzed ene-type cyclizations. "" In one example, the efficient formation of tetrahydropyran rings through the self-tandem carbonyl-ene, intramolecular (2,5) oxonium-ene cyclization of aldehydes and methylenecyclohexane is demonstrated. Methylenecyclohexane and benzaldehyde react initially to afford a homoallylic alcohol and subsequent (2,5) oxonium-ene cyclization involving a further molecule of aldehyde provides the tetrahydropyran in very good 3field and excellent diastereoselectivities, favoring the 2,3 anti, 2,6-syn isomers (eq 17). 

Fig. 8.89 (3,5) Oxonium-ene type cyclization of homoallylic alcohols catalyzed by ln(OTf)3.

Palladium-Catalysed Cycloisomerizations 10.2.1 Alder-Ene Type Cyclizations... 

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