Cyclization Lewis acid-catalyzed

Figure 11-16. Thermal ether cyclizations Lewis acid catalyzed ether cyclizations,...

The Lewis acid-catalyzed cyclization of 3-anaino-2-alkerLirnines (21) leads to a wide variety of alkyl- and aryl-substituted quinolines (59). The high regiospecificity and the excellent yields obtained make this process promising. 

An analogous Lewis acid catalyzed cyclization of the oi-acctoxy derivatives 3 gives rise to one pair of diastereomers of 4 in the case of the ( )-alkenc, while the (Z)-alkene affords a diastereomeric mixture of (2S, 3/J, 4/J )-4 (major product) and (2,S, 3,S, 4/ )-4 (minor product)90. 

Kobayashi has found that scandium triflate, Sc(OTf)3,36 and lanthanide triflate, Ln(OTf)3, are stable and can be used as Lewis catalysts under aqueous conditions. Many other Lewis acids have also been reported to catalyze Diels-Alder reactions in aqueous media. For example, Engberts reported37 that the cyclization reaction in Eq. 12.7 in an aqueous solution containing 0.010 M Cu(N03)2 is 250,000 times faster than that in acetonitrile and about 1,000 times faster than that in water alone. Other salts, such as Co2+, Ni2+, and Zn2+, also catalyze the reaction, but not as effectively as Cu2+. However, water has no effect on the endo-exo selectivity for the Lewis-acid catalyzed reaction. 

It was proposed that a Diels-Alder cyclization occurred during a polyketide synthase assembly of the bicyclic core of Lovastatin by Aspergillus terreus MF 4845." In vitro Diels-Alder cyclization of the corresponding model compounds generated two analogous diastere-omers in each case, under either thermal or Lewis-acid-catalyzed conditions (Eq. 12.37). As expected, the Diels-Alder reaction occurred faster in aqueous media. The cyclization half-life in chloroform at room temperature is 10 days while in aqueous media at either pH 5 or 7, the half-life drops to two days. 

Scheme 1.24. Lewis acid-catalyzed cationic domino cyclization to give bicyclo[2.2.1]heptane derivatives.

Another Lewis acid-catalyzed atom-transfer domino radical cyclization, to produce various bicyclic and tricyclic ring skeletons, has been developed by Yang and coworkers [54]. Reactions of the a-bromo-(3-keto ester 3-125 with Yb(OTf)3 and Et3B/02 led to the bicycle 3-126 in 85 % yield (Scheme 3.33). The reaction proceeds via a (>-endo-Irig and 5-exo-trig cyclization after initial abstraction of the bromine... 

The Nazarov cyclization of vinyl aryl ketones involves a disruption of the aromaticity, and therefore, the activation barrier is significantly higher than that of the divinyl ketones. Not surprisingly, the Lewis acid-catalyzed protocols [30] resulted only in decomposition to the enone derived from 46,47, and CO. Pleasingly, however, photolysis [31] readily delivered the desired annulation product 48 in 60 % yield. The photo-Nazarov cyclization reaction of aryl vinyl ketones was first reported by Smith and Agosta. Subsequent mechanistic studies by Leitich and Schaffner revealed the reaction mechanism to be a thermal electrocyclization induced by photolytic enone isomerization. The mildness of these reaction conditions and the selective activation of the enone functional group were key to the success of this reaction. 

The scheme below depicts the novel use of a carbonyl ene cyclization (A, Lewis acid-catalyzed) and a closely related Prins cyclization (B, Brpnsted acid-catalyzed) to generate predominantly trans (cyclization condition A) or cis (cyclization condition B), di and tri substituted piperidines 160 and 161 <06JOC2460 06OBC51>. Of note, in the formation of di-substituted derivatives, R1 = H and R2 = Ph, no reaction occurs under cyclization condition B and the cis isomer 160 is obtained exclusively under cyclization condition A. In the case of tri-substituted derivatives, when bulky substituents at the 2-position (R1 = f-Bu or Ph) are present the trans diastereomer 161 is obtained almost exclusively under cyclization condition A, while no diastereoselectivity is seen under cyclization condition B. 

The Skraup cyclization is another reaction principle that provides rapid access to the quinoline moiety. Theoclitou and Robinson have published the preparation of a 44-member library based on the 2,2,4-trisubstituted 1,2-dihydroquinoline scaffold by the Lewis acid-catalyzed cyclization of substituted anilines or aminoheterocyc-les with appropriate ketones (Scheme 6.237) [420], The best results were obtained using 10 mol% of scandium(III) triflate as a catalyst in acetonitrile as solvent at... 

The product possesses a homoallylic stannane moiety, which can be utilized as a useful synthon for cyclopropane formation (Scheme 68). Upon treatment of the homoallylstannane with HI, destannative cyclization takes place to give cyclopropylmethylsilane.271,272 A Lewis acid-catalyzed reaction with benzaldehyde dimethyl acetal affords vinylcyclopropane.273... 

Particularly interesting is the reaction of enynes with catalytic amounts of carbene complexes (Figure 3.50). If the chain-length between olefin and alkyne enables the formation of a five-membered or larger ring, then RCM can lead to the formation of vinyl-substituted cycloalkenes [866] or heterocycles. Examples of such reactions are given in Tables 3.18-3.20. It should, though, be taken into account that this reaction can also proceed by non-carbene-mediated pathways. Also Fischer-type carbene complexes and other complexes [867] can catalyze enyne cyclizations [267]. Trost [868] proposed that palladium-catalyzed enyne cyclizations proceed via metallacyclopentenes, which upon reductive elimination yield an intermediate cyclobutene. Also a Lewis acid-catalyzed, intramolecular [2 + 2] cycloaddition of, e.g., acceptor-substituted alkynes to an alkene to yield a cyclobutene can be considered as a possible mechanism of enyne cyclization. 

Lewis acid-catalyzed cyclization of unsaturated aldehydes is also an effective reaction. Stannic chloride is the usual reagent for this cyclization. 

Pattenden and Teague have prepared tricyclic diol 684 which is epimeric to the naturally occurring A < -capnellene-8p,10a-diol (68S) Their strategy, which is summarized in Scheme LXXI, encompasses two critical cyclization steps. The first is the Lewis acid-catalyzed ring closure of enol acetate 686 and the second involves reductive closure of acetylenic ketone 687. It is of interest that the oxidation of 688 proved to be stereospecific. 

The second method of forming the oxazin-3-one ring is illustrated by reaction of 363 with diketene 364 followed by diazo exchange, base hydrolysis, and Lewis acid-catalyzed cyclization to give 365 as shown in Scheme 43. This method has been used in fewer reports <1983JOC2675, 1983EPP80117, 1984USP4431167>. 

Methylenetetrahydrofurans and 4-methylenepyrrolidines.1 The adducts formed by Lewis acid-catalyzed reaction of 1 with an aldehyde or ketone undergo cyclization to 4-methylenetetrahydrofurans in the presence of a Pd(0) catalyst prepared from Pd(OAc)2, P(C6H5)3, and BuLi, and a base, DBU or N(C2H5)3 (1.5 equiv.). 

Intramolecular Sakurai reaction. Allylic and propargylic silanes can undergo a Lewis acid catalyzed intramolecular Sakurai reaction.1 In cyclization to hydrin-danones, the stereochemical outcome can differ from that obtained by fluoride ion catalysis (presumably kinetically controlled cyclization), equation (I).2... 

Majetich reports a general intramolecular Lewis acid allylation protocol for the synthesis of bicy-clo[5.4.0]undecen-3-ones (168) and bicyclo[4.4.0]decen-3-ones (170), which are 1,6-addition products (Scheme 27). The same precursors, (167) and (169), when submitted to the fluoride ion cyclization protocol, also afford 1,2- and 1,4-addition products.73 Typically, ethylaluminum dichloride, a proton sponge Lewis acid, is used in order to minimize adventitious protonic desilylation. Other 0,y-unsatu-rated silanes also undergo similar intramolecular Lewis acid catalyzed additions for example, the si-lylpropargylic enones (171) undergo intramolecular cyclization to the allenylspiro system (172).74... 

As described in Section II, Lewis acid catalyzed desilylative carbon-carbon bond formation with an electrophile has been shown to be very versatile in organic synthesis. Occasionally, depending on the nature of the substrates (e.g. the presence of appropriate functional groups), the carbon-silicon bond may remain intact. For example, treatment of 132 with a Lewis acid affords a mixture of cyclization products 133-135 (equation 113). The isolation of 133 indicates that the carbocation intermediate thus formed is trapped by the oxygen nucleophile before elimination of the silyl moiety occurs204. 

A Lewis acid-catalyzed cyclization of 2-aza-3-trimethylsilyloxybuta-l,3-diene has been reported in 2003 and the stereochemical differences with the uncatalyzed... 

Similarly, Lewis acid-catalyzed rearrangement of epoxy alcohols 84 (Scheme 37) gives in most cases the exo-cyclized tetrahydropyrans 85 as the main products (80-97%) however, with La(OTf)3 as the catalyst, the main products (80-90%) are endo-cyclized oxepanes 86 <1998TL393>. 

The Nazarov Cyclization is a rare example of a Lewis acid-catalyzed 4-7t conrotatory electrocyclic reaction. Asymmetric... 

---