Reactions Leading to the Formation of Six-Membered Rings

Chlorodifluoromethylated derivatives represent good substrates for the preparation of gem-difluorinated heterocycles by means of electrochemical 

Szpilman et al. used his methodology to prepare yingzhaosu A, a natural endoperoxide isolated from extracts of Artabotrys uncinatus, a traditional remedy for treatment of malaria in China [148]. 

The imique reactivity of methylenecyclopropanes prompted Zhou to test on this substrate the manganese (Ill)-mediated free radical cychzation of alkenes with 1,3-dicarbonyl compoimds [149]. It was found that benzyh- 

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Reactions Leading to the Formation of Six-membered Rings with Three Nitrogen Atoms... 

The [4+2]-cycloaddition reactions lead to the formation of six-membered rings through interaction of conjugated 1,3-dienes (4jr system) with alkenes and acetylenes (dienophiles, 2 r system) [108] (Scheme 62). 

In addition to the benzannulation reactions discussed in Section 2.2.5, other reactions of heteroatom-substituted carbene complexes are known which lead to the formation of six-membered rings. Alkoxycarbene complexes have a reactivity... 

The Diels-Alder reaction is a well-established synthetic method that allows the creation of two new carbon-carbon bonds and leads to the formation of six-membered rings. Eventually, the photochemical reaction can advantageously compete with the thermal process. For instance, anthracene undergoes thermal and photochemical Diels-Alder reactions with alkenes, but the photoinduced addition of maleic anhydride to the homochiral anthracene, as depicted in Scheme 9.28, is faster than the thermal reaction and occurs with excellent diastereoselectivity (only one diastereoisomer) [42]. 

In almost all situations the reactions of Fischer carbene complexes of chromium with alkynes lead to the formation of six-membered ring products, but on several occasions five-membered ring annulated products have been observed as minor products or as major products if the formation of six-membered rings is blocked. In an early report by Ddtz, the reaction of the 2,6-dimethylphenyl complex (209) was observed to react with diphenylacetylene to give the complexed and uncomplexed indenes (210) and... 

By far the most cominon annulalion reactions of enamines lead to the formation of six-membered rings. Depending on the nature of the electrophilic reagent, the same enamine can act as either a two-carbon or a three-carbon component in the annulation process (Scheme 124). Furthermore, the same enamine and the same electrophilic reagent can give completely different products depending on the experimental conditions employed (Scheme 125). 

The Diels-Alder reaction is a [4 -h 2] cycloaddition between a diene and a dienophile (a substituted alkene or alkyne). It leads to the formation of six-membered rings. Trost has developed a related procedure for making five-membered rings. A trimethylenemethane, briefly trapped as its palladium complex, adds to an alkene, which is activated by an electron-withdrawing group. 

Type I is a radical reaction arising from chain rupture and leading to the formation of six-membered rings which occurs in the pyrolysis or depolymerization of polymers with double bonds in a 1,5- or 1,6-diene configuration. 

This tendency is especially significant in compounds containing functional groups capable of addition with the formation of both five- and six-membered rings. It has been shown that for amides and hydrazides of azolecarboxylic acids, selectively, and for the acids with any arrangement of a function and triple bond, heterocyclization always leads to the closure of the six-membered ring. Similar reactions in the benzoic series mainly lead to the formation of five-membered rings. 

This section describes the various reaction pathways that lead to the formation of five-membered ring cycloaurated complexes six-membered cycloaurated ring... 

Alkyl shift is evident in the Cope rearrangement. A Cope rearrangement is a [3,3] sigmatropic rearrangement of a 1,5-diene. This reaction leads to the formation of a six-membered ring transition state. As [3,3] sigmatropic rearrangements involve three pairs of electrons, they take place by a suprafacial pathway under thermal conditions. 

In the case of 6-yl radical energy minima always correspond to an approximately half-chair structure of the six membered ring, with the methyl group and the hydrogen atom occupying an equatorial and an axial position, respectively. It is noteworthy that these conformational features are identical to those found in 5,6-dihydrothymine [151] since the formation of the 6-yl radical corresponds to the initial step of the reaction leading to the formation of 5,6-dihydrothymine, the conformational features of the product could be already decided in the first reaction step. 

No reaction of the eight-membered ring compound (Me2SiNH4 with retention of the ring moiety is reported (before 1989). All attempts to carry out substitution reactions lead to the formation of isomeric six- and four-membered rings . 

We have seen that if a compound has two functional groups that can react with each other, an intramolecular reaction readily occurs if the reaction leads to the formation of a five-or a six-membered ring (Section 9.8). Consequently, a compound with two ester, aldehyde, or ketone groups can undergo an intramolecular reaction if a product with a five- or six-membered ring can be formed. 

Cyclopropanes can also be obtained by the reaction of vinyltrialkylborates with aldehydes followed by treatment with phosphoms pentachloride and base (300), and by the rearrangement of 5-substituted alkynyltrialkylborates (308). It is also possible to utilize this approach for the synthesis of five- and six-membered rings (3). Trans-1,4-elimination ia cycHc systems leads to the formation of stereodefined acycHc 1,5-dienes or medium-ring dienes, depending on the starting compound (309). 

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