Cyclization Lewis acid mediated

Trost and Ghadiri19 have found a Lewis-acid-mediated intramolecular cyclization of allyl sulfones. When the allyl sulfone 40 is treated with A1C13, polycondensed aromatic system 41 can be obtained in good yield (equation 24). The mechanism probably involves... 

A fourfold anionic sequence which is not initiated by a Michael but an aldol reaction has been reported by the group of Suginome and Ito (Scheme 2.129) [295]. In this approach, the borylallylsilane 2-573 reacts selectively in the presence of TiCl4 with two different aldehydes which are added sequentially to the reaction mixture. First, a Lewis acid-mediated allylation of the aldehyde with 2-573 takes place to form a homoallylic alcohol which reacts with the second aldehyde under formation of the oxenium ion 2-574. The sequence is terminated by a Prins-type cyclization of 2-574 and an intramolecular Friedel-Crafts alkylation of the intermediate 2-575 with formation of the fraws-1,2-be rizoxadeca lines 2-576 as single diastereomers. 

For a Lewis-acid-mediated cyclization reaction of a tryptamine-derived vinylogous amide that affords the Aspidosperma skeleton, see Huizenga RH, Pandit UK (1991) Tetrahedron 47 4155 1164... 

A Mitsunobu reaction then inverts the C-4 configuration to provide compound 151, and subsequent isomerization provides compound 152, which is ready for Lewis acid-mediated cyclization to construct the eight-membered firing. Using MeiAlOTf as a catalyst, intramolecular cyclization occurs, giving product 153 in which A, B, and C rings have been introduced with the desired stereochemistry (Scheme 7-45). 

Oxindole 89 was cleanly demethylated upon treatment with boron tribromide. The resulting oxindole 90 was subjected to the prenylation conditions, and the desired alkylated product 91 was obtained in 52% yield. The epoxidation/Lewis acid-mediated cyclization proved to be successful on this substrate. The epoxide product was directly treated with SnCl4 in THF to provided the desired 92. When oxindole 92 was treated with NaBHt (1.6 equivjand BF3 OEt2 (3.5 equiv) in THF, the desired 93 was obtained. The indole 93 was treated with TBDMSC1 and imidazole in DMF, to provide the required O-silylated indole, which was easily converted to the gramine 94 through the well known Mannich procedure. 

Alko xy ally 1)stannane aldehydes (57) can cyclize either thermally or with Lewis or protic acid catalysis to give cyclic ethers (58).85 The interrelationship of the reactant and product stereochemistries has been investigated, as have the methods used to promote the reaction. For both thermal and proton-promoted reactions, [(Z)-57 gave (cis-58), and [(E)-57] gave trans-58), whereas trans-58) was the predominant or exclusive product of Lewis acid mediation, regardless of the double bond geometry of... 

A stereoselective, Lewis acid-mediated cyclization of l-substituted-2-naphthols (41) has been reported to produce spirocyclic ketones (43). Evidence has been presented for the involvement of the cyclic aluminium intermediate (42).50... 

The synthesis of the 1,4-oxazepine 179 involved the formation of intermediate 178. The latter has been obtained by the three-component reaction of amine 175, aldehyde 176, and benzotriazole, leading to the intermediate 177, which underwent dehydrative cyclization to generate 178. Lewis acid-mediated cyclization with the loss of benzotriazole anion produced the interesting 1,4-oxazepine 179 (Scheme 29) <2001JOC5590>. A similar scandium or copper triflate-catalyzed reaction has been reported <1996SL871>. 

Lewis acid-mediated endo -cyclization of trimethylsilylmethylenecyclopropylimines provides a stereoselective route to indolizidines via a novel cascade sequence including (g) a [l,2]-hydride shift (Scheme 56).91... 

Vinylsilanes 236 undergo Lewis acid-mediated stereoselective cyclizations to afford 3,6-dihydropyrans. The stereochemistry of the dihydropyran product is dictated by the geometry of the vinyl silane with (Z)-236 and (E)-236 providing syn-237 and a -3,6-dihydropyrans 238, respectively (Scheme 67) <1997JOC3426>. 

A Lewis-acid-mediated intramolecular cyclization of allenyl stannane 344 furnishes 2,6- //-tetrahydropyran as the major product, the stereochemistry of which can be switched to syn with moderate effect if a propargylstannane 345 is used as a substrate (Equation 147, Table 16) <1996TL3059>. The stereoselectivity observed in an analogous system, the intramolecular cyclization of y-alkoxyallyl stannanes 346 with a tethered aldehyde, can be controlled by changing the geometry of the alkene (Scheme 83) <1997JOC7439>. y-Alkoxyallyl stannanes are also known to cyclize both diastereoselectively and enantioselectivity, by incorporation of both a chiral auxiliary and a chiral catalyst respectively into the reaction <1999JOC4901>. 

A diastereoselective synthesis of all. fy -2,3,6-trisubstitutcd tetrahydropyran-4-ones 1039 via an intramolecular Prins cyclization of enecarbamates 1038 with aldehydes is used during a formal synthesis of (+)-ratjadone (Equation 403) <2004JA12216>. Similarly, tetrahydropyran-4-ones bearing quaternary centres a-to the carbonyl are accessible via a Lewis acid-mediated Prins cyclization of silyl enol ether substrates <2004JA15662>. 

Indole N-substituted diyne tetracobalt complexes 1467 undergo a Lewis acid-mediated dimerization-cyclization reaction through the indole 3-position to afford indolophanetetrayne cobalt complexes 1468 (Scheme 280) <20030L1003>. 

Recently, a new multicomponent condensation strategy for the stereocontrolled synthesis of polysubstituted tetrahydropyran derivatives was re-published by the Marko group, employing an ene reaction combined with an intramolecular Sakurai cyclization (IMSC) (Scheme 1.14) [14]. The initial step is an Et2AlCl-promoted ene reaction between allylsilane 1-50 and an aldehyde to afford the (Z)-homoallylic alcohol 1-51, with good control of the geometry of the double bond. Subsequent Lewis acid-mediated condensation of 1-51 with another equivalent of an aldehyde provided the polysubstituted exo-methylene tetrahydropyran 1-53 stereoselectively and... 

A diastereoselective ewrfo-cyclization into an oxidatively generated oxocarbenium ion was a key step in a formal synthesis of leucascandrolide A. Exposing 56 to CAN provided cw-tetrahydropyran 57 in high yield and with excellent stereocontrol (Scheme 3.20). This transformation provides further evidence that oxidative electrophile formation is tolerant of several functional groups and can be applied to complex molecule synthesis. The synthetic sequence also utilized a Lewis acid mediated ionization reaction to form an oxocarbenium ion in the presence of the homobenzylic ether (58, 59), illustrating that two carbocation precursors that ionize through chemically orthogonal conditions can be incorporated into the same structure. 

In the laboratory of P.G. Steel, a five-step synthesis of ( )-epiasarinin from piperonal was developed. The key steps in the sequence involved the Darzens condensation, aikenyi epoxide-dihydrofuran rearrangement and a Lewis acid mediated cyclization. The desired vinyl epoxide intermediate was prepared by treating the solution of ( )-methyl-4-bromocrotonate and piperonal with LDA, then quenching the reaction mixture with mild acid (NH4CI). 

In an interesting application of Lewis acid-mediated oxirane ring openings, diazomethyl-chlorohydrins, formed from a,/ -epoxy diazomethylketones with SnCl4, cyclize to 3-oxetanones (Scheme 15) <92T9985>. 

A remarkable observation is the cyclization of biscarbamate (194) to y-lactone (195) mediated by methanesulfonic acid (equation 133). No trace of the expected 8-lactone is formed, presumably because of the unfavorable ester geometry in the transition state required for six-membered ring formation. Such problems with 8-lactone formation have been observed also in Diels-Alder chemistry. A nice example related to A-acyliminium chemistry is the thermal hetero Diels-Alder reaction of acylimine precursor (196) to bicyclic -y-lactone (197) in good yield. The corresponding intramolecular cycloaddition of (198) fails. Finally, Lewis acid mediated cyclization of allylsilane (199) is unsuccessful, although lactonization of (200) proceeds very well (equation 135, cf. equation 119). ... 

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