Cyclization endo-selective

Electrophilic cyclizations are useful for closure of a variety of oxygen-, nitrogen-, and sulfur-containing rings. The product structure depends on the ring size and the exo-endo selectivity. The most common cases are formation of five- and six-membered... 

Intramolecular Diels-Alder cyclizations of (E)- -nitro-1,7.9-decatrienes under thermal conditions and Lewis acid conditions lead to the formation of decalin ring systems with excellent endo selectivity (Eq. 8.21). This strategy is used for preparing of the AB ring system of norzoanthamine.33... 

Increased ring strain in the C-4 ( = 2) and C-5 (n — 3) products may be a reason for lower yields (and longer irradiation times). The effect of strain on cyclizations is well-documented outside of cycloaromatization chemistry, as well. For example, annealing of a cyclopentene ring leads to a decrease in the cyclization rate and an inversion of the 5-exo/6-endo selectivity for all three patterns shown in Fig. 22. 

Diels-Alder catalysis.1 This radical cation can increase the endo-selectivity of Diels-Alder reactions when the dienophile is a styrene or electron-rich alkene. This endo-selectivity obtains even in intramolecular Diels-Alder reactions. Thus the triene 2, a mixture of (Z)- and (E)-isomers, cyclizes in the presence of 1 to 0° to the hydroindanes 3 and 4 in the ratio 97 3. Similar cyclization of (E)-2 results in 3 and 4 in the ratio 98 2 therefore, the catalyst can effect isomerization of (Z)-2 to (E)-2. Even higher stereoselectivity is observed when the styrene group of 2 is replaced by a vinyl sulfide group (SC6H5 in place of QHtOCT ). 

McDonald and coworkers studied a series of tandem endo-selective and stereospecific oxacyclization of polyepoxides by reaction with Lewis acid [92-95]. Polyepoxides, such as 50, can be obtained from the epoxidation of triene 49 with ketone 26 (Scheme 8). This cascade cyclization of polyepoxides provides an efficient method to synthesize substituted polycyclic ether structures, which are present in a number of biologically active marine natural products. 

Scheme 5.27 Solvent controlled exo and endo selective cyclization of various 7-siloxy-6-en-l-ynes.

Diels-Alder cyclization of IfiAO-undecatrienals.5 These unsaturated aldehydes undergo intramolecular Diels-Alder cyclization, particularly under Lewis acid catalysis. The reaction is highly endo-selective. Silyl-protected alcohol groups at C4 and Q can be present, and t-butyldimethylsilyl ethers show a strong axial preference. 

Chiral 4,4-dialkyl-l-cyclopentenones.1 The chiral bicyclic lactam 2, derived from levulinic acid and 1, on monoalkylation exhibits slight if any selectivity regardless of the electrophile. However, a second alkylation exhibits high endo-selectivity. This product (3), after reductive cleavage, furnishes a keto aldehyde that is cyclized by base to a chiral 4,4-disubstituted-2-cyclopentenone (4). Either antipode of 4 can be prepared by the sequence of alkylation. 

Recently, studies were carried out to explain the exo/endo selectivity the Patemo-Buchi reaction [30]. These studies were carried out mostly achiral or racemic substrates. Excited monocyclic aromatic aldehydes 33 re in their 3n,/rr state with cyclic enol ether derivatives like 2,3-dihydrofuran (Scheme 8) [31]. In these cases, the sterically disfavored endo isomer 35a obtained as major product. This result was explained by the fate of the trip biradical intermediate G. In order to favor cyclization to the oxetanes 35a,b, radical p-orbitals have to approach in a perpendicular fashion to increase spin-orbit coupling needed for the triplet to singlet intersystem crossing [32]. sterically most favored arrangement of this intermediate is depicted as G. encumbering Ar substituent is orientated upside and anti to the trihydrofur moiety. Cyclization from this conformation yields the major isomer 35a. 

The la-promoted imino Diels-Alder reaction is highly susceptible to the Lewis acid employed and to the structure of substrates. iV-Phenyl aromatic aldimine 34 readily cyclizes with the silyl enol ether of 35 under the influence of 10 mol % Ic to give exo adduct 36 exclusively (Sch. 26), whereas up to 98 % endo selectivity is observed when AICI3 is used at 20 °C [55a]. 

Among the wide range of cyclic ketone syntheses based on acyl radical cycliza-tions, the recently reported synthesis of 2-hydrazinocyclopentanones by Fallis and Brinza is noteworthy, since, unlike the corresponding cyclization onto a C-C double bond, the cyclization is selective in the 5-exo mode and no product arising from 6-endo cyclization was detected (Scheme 4-35) [61]. 

Intramolecular allylsilylation of alkynes is a convenient route to cyclic vinylsilanes. The HfCU-MesSiCl catalyst system effectively induces endo cyclization of al-kynylated allylsilanes to l-silyl-3-vinylcycloalkenes (Scheme 10.193) [515]. The endo selectivity is probably because the exo cyclization pathway via zwitterionic intermediate 144 is inhibited by a severe steric repulsion between the substituent R and the allylsilane moiety. 

Chiral secondary amines such as nonracemic imidazolidin-4-ones have been found to be effective asymmetric organocatalysts in the Diels-Alder cyclization of cyclopentadiene and a,p-unsaturated aldehydes [60]. A tyrosine-derived imidazoli-din-4-one was immobilized on PEG to provide a soluble, polymer-supported catalyst 110. In the presence of 110, Diels-Alder cycloaddition of acrolein 112 to 1,3-cyclohexadiene 111 proceeded smoothly to afford the corresponding cycloadduct 113 with high endo selectivity and enantioselectivity up to 92% ee (Scheme 3.31) [61]. 

The endo rule, formulated for the intermolecular Diels-Alder reaction, is not rigorously followed even in the intermolecular case (33). For intramolecular cyclizations, geometric factors (vide infra) tend to be more important. With highly activated dienophiles, and especially under acid catalysis, endo cyclization can predominate (34) [28, 29]. In the second example, the role of the acidic reaction medium in overcoming the geometric preference for an exo (chair-like) transition state is apparent. Other examples of improved endo selection on acid catalysis have been reported (7, 38). 

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