Large ring heterocycles

Large ring heterocyclic radicals are not particularly well known as a class. Their behavior often resembles that of their alicyclic counterparts, except for transannular reactions, such as the intramolecular cyclization of 1-azacyclononan-l-yl (Scheme 1) (72CJCH67). As is the case with alicyclic ethers, oxepane in the reaction with r-butoxy radical suffers abstraction of a hydrogen atom from the 2-position in the first reaction step (Scheme 2) (76TL439). 

Electronic spectra of large-ring heterocyclic compounds... 

There are also few reports of the nitration of phenyl derivatives of large ring heterocycles. 7-Chloro-5-phenyl-l//-thieno[2,3- ]-l, 4-diazepin-2(3//)-one (92a) is nitrated to yield the 6-nitro derivative (92b) without phenyl substitution. 5-Phenyl-l-//-thieno[2,3-c]-l, 4-diazepin-2(3 )-one (91c) undergoes both nitration and chlorination to give 7-substituted products also without the formation of nitrophenyl derivatives (73M704, 73M709). 

Very few reports describe the use of radical methods in the construction of large ring heterocycles (>7). A peroxydicarbonate-mediated hydrogen atom abstraction from an aldimine followed by cyclization onto an aromatic ring has been applied to the synthesis of dibenzoxazepines 237 [95T12143]. The yield of the heterocyclic product is low. 

The ortho-substituted isothiocyanates are valuable intermediates for the preparation of a variety of heterocyclic compounds for example, o-isp-thiocyanato-( )-cinnamaldehyde with sodio diethyl malonate undergoes facile cyclization to 3-formylquinoline-2(l//)-thione,9 which in turn may be used for the preparation of tricyclic9,10 and large ring heterocyclic compounds."... 

In CHEC-II(1996), only very few metal complexes involving large ring heterocycles were reported. In the last decade, new information and studies have been conducted on selenium- and tellurium-containing large rings, especially crown ethers capitalizing on their very special features and characteristics. 

Alternative reactions leading to the formation of large ring heterocycles will probably require ring closure at sites remote from the heteroatom. Large-membered cycloalkenes containing silicon and germanium have been prepared by this approach. 

Insertion reactions provide elegant and easy syntheses of metal or metalloid complexes, some of which either are not accessible by alternative routes or are less conveniently so obtained, e.g., dithiocarbamates, especially of metalloids. Another example is provided by the synthesis of large-ring heterocycles, e.g., of the bisureidoborane 8 from 2-phenyl-1,3,2-diazaborolidine 9 and PhNCO, or compound 10 from As(NMe2)3 and S02(NC0)2. ... 

Large ring heterocycles have also been synthesized using the Ramberg-BScklund reaction. Preparation of [2.2]-(2,6)pyridinopha-l-ene (80) from bromo-sulfone 79 is one example,52 and rrans-olefin 83 from sulfide 81 is another via the intermediacy of chloro-sulfone 82.53... 

Scheme 4.60). This process is known as ring-closing metathesis and is particularly important in the formation of 5- and 6-membered rings, as well as large-ring heterocycles. 

Some interesting photo-NOCAS-type reaction (photochemical nucleophile-olefin combination, aromatic substitution) have been reported by three groups. Arnold has developed the photo-NOCAS reaction as three components photoaddition.Xu et al., reported the intramolecular photocyclization of A-(co-hydroxyalkyl)-tetrachlorophthalimide (138, 141) with alkenes to give medium- and large-ring heterocycles (140,143). These photoreactions proceeded via 1, n-biradicals generated from the nucleophilic attack of alcohols to alkenes between the radical anions of phthalimides and the radical cations of alkenes. 

Crown and Macrocyclic Ethers.—Interesting and important studies continue to emerge, particularly in preliminary form, in this area of large-ring heterocyclics. Two important reviews have appeared. ... 

Xue, J., Zhu, L., Fun, H-K., and Xu, J-H., Synthesis of medium and large ring heterocycles by photoinduced intermolecular and intramolecular electron transfer reactions of tetrachlorophthal-imides with alkenes. Tetrahedron Lett., 41, 8553, 2000. 

---