Six-Membered-Ring Formation

Azetidines under analogous reaction conditions to those above result in six-membered ring formation. However, diketene (472), an oxetan-2-one, offers considerable promise for five-membered heterocycle formation. With hydroxylamine the 3-methylisoxazolin-5-one (473) was formed. Phenylhydrazine gave the corresponding 3-methyl-l-phenylpyrazolin-5-one. 

Cyclopolymerizations of other 1,6-dienes afford varying ratios of five- and six-membered ring products depending on the substitution pattern of the starting diene. Substitution of the olefinic methine hydrogen (e.g. 11, R- CH3) causes a shift from five- to six-membered ring formation. More bulky R substituents can prevent efficient cvclization and cross-linked polymers may result. 

An alternative method of six-membered ring formation has been reported utilizing an SNAr mechanism (Equation 31) <2002J(P1)790>. Chlorine is set up to leave by the electron-withdrawing influence of a group 138. The... 

When sulfamate esters 114 are used as substrates, six-membered-ring formation is favored, and results in the selective formation of 1,2,3-oxathiazinane-2,2-dioxide heterocycles 115.251 Nevertheless, five-membered cyclic sulfamidates could be obtained when no alternative cyclization was possible. 1,3-Amino alcohols and related /2-amino acids are thus readily accessible from the same simple alcohols 113 by converting them into sulfamates 114 (Equation (90)). Furthermore, in comparison to the carbamate reaction (Scheme 9), the sulfamate substrates have... 

Most recently, reductive Michael cyclization catalyzed by In(OAc)3 in the presence of PhSiH3 was reported.50 As demonstrated by the reductive cyclization of the homologous bis(enones) 25a and 26a, both five- and six-membered ring formation occurs in good yield to afford cycloalkanes 25d and 26b as single trails-Aiastereorncrs (Scheme 20). 

Recently, the silane-mediated reductive cyclization of activated alkynes with tethered ketones using Stryker s reagent as a catalyst was reported.112,90b Alkynyl ketone substrate 84a was treated with a catalytic amount of Stryker s reagent in the presence of polymethylhydrosiloxane (PMHS) to afford the cA-fused hydrindane 84b as a single diastereomer. This method is applicable to both five- and six-membered ring formation, but often suffers from competitive over-reduction of the reaction products (Scheme 59). 

While the notion that the alkoxides derived from aliphatic alcohols are poor nucleophiles toward 7r-allylmetal complexes has prevailed over the years, much progress made in the recent past has rendered the transition metal-catalyzed allylic alkylation a powerful method for the O-allylation of aliphatic alcohols. In particular, owing to the facility of five- and six-membered ring formation, this process has found extensive utility in the synthesis of tetrahydrofurans (THFs) (Equation (29))150-156 and tetrahydropyrans (THPs).157-159 Of note was the simultaneous formation of two THP rings with high diastereoselectivity via a Pd-catalyzed double allylic etherification using 35 in a bidirectional synthetic approach to halichondrin B (Equation (30)).157 The related ligand 36 was used in the enantioselective cyclization of a Baylis-Hillman adduct with a primary alcohol (Equation (31)).159... 

The vinylcyclobutane rearrangement serves as a novel [3 + 3] or [4 + 2] strategy for six membered ring formation depending upon whether a nucleophilic (Eq. 96) or electrophilic (Eq. 97) conjunctive cyclopropyl reagent is employed. The use of the... 

The palladium catalysed conversion of alkenes to enols, also known as the Wacker reaction, has also been used in the formation of oxygen heterocycles. In the example shown in 3.68. the subsequent formation of two carbon-oxygen bonds leads to the desired dioxabicyclo[3.2.1]octane derivative. The first Wacker reaction gives selectively a six membered ring formation (other possible routes would lead to even larger rings), while in the second Wacker reaction the selective formation of the five membered ring is observed.86... 

This process nicely accounts for formation of product, but if we consider intermediate I, we see that there are several different a protons that could be removed by base, 1I , Hfe, and Hc. Furthermore the acidities of these various a protons should be comparable so all should be removed to similar extents under the reaction conditions. If we sequentially remove each proton and write the product from an intramolecular carbonyl addition, the following products could be produced. The fact is that only P is produced to any extent. This is due to the preference of six-membered ring formation over the formation of the more... 

Nitrogen Nucleophile Attacking sp2 Carbonyl Six-Membered Ring Formation... 

I) Five-membered ring formation, (2) Six-membered ring formation, (3) Seven- and eight-membered ring formation, and finally (4) Tandem cyclization. 

In order to prepare the bicyclic compound 9, an intramolecular Heck reaction under Grigg s conditions (Pd(OAc)2, K2CO3, Bu4NBr) is carried out (see Chapter 13).7 Starting from aryl iodide 8 a six-membered ring formation occurs providing intermediate 28, which reacts to alkene 29. Finally double bond isomerization to compound 9 is forced by the formation of a thermodynamically more stable enol ether. 

As an extension, carbocycles or heterocycles 35 are synthesized by intramolecular hydrocarbonation of alkyl- or alkoxyallenes 34 bearing active methyne groups at the terminus of the carbon chain, respectively (Scheme 7). With alkylallenes five-membered ring formation proceeds smoothly comparing to six-membered ring formation [6g] this problem is not encountered with alkoxyallenes [6h]. 

This reactivity proved to be a general process, providing the unique products in moderate yields following cyclopropanation and immediate treatment with silver tetrafluoroborate. These structures revealed that a cascade sequence was proceeding stereoselectively in every case to furnish a single product as the result of conrotatory 4jt electrocyclization, electrophilic aromatic substitution at the least hindered position on the arene moiety (para to the MeO) in favor of six-membered ring formation, and desilylation with protonation from the exo face of the bicyclic product. Dehydrochlorination to form a second cationic intermediate did not occur in this case, due to structural restrictions imposed by the bridged architecture of 81. 

Vim unit of the polymer side chain does not catalyze the hydrolysis of the ester of another polymer side chain [37] also supports intramolecular catalysis by the neighboring imidazole group via six-membered ring formation as shown in Scheme 4. 

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