Ring formation systems

The application of this type of ring formation to ene-l,4-dione systems necessitates either a formal internal oxidation, as in the examples in Scheme 52d (69CC420), or the use of a reducing agent (Schemes 52e (73TL5185) and 52f (65CC272)). 

Formation of ring-fused systems by this procedure is not as common. If the vicinally substituted hydroxyamino derivative is available, then Pb(OAc)4 treatment will lead to a ring-fused oxazole as in the conversion of (272) into (273) (71JCS(C)1482). In a different approach the CH=N— functional group is generated in situ. The 2-(l-pyrrolidinyl)ethanol... 

Ring-fused systems have also been prepared using this bond formation approach. Treat-ent of the /3-aminoketone (281) with lead tetraacetate gave the isoxazole system (282 ... 

The addition of nucleophiles to double and triple bond systems is often a convenient way of effecting an intramolecular ring closure. Addition to cyano groups has received considerable attention, as in addition to ring formation it provides a convenient method for the introduction of an amino group. Reaction of methyl Af-cyanodithiocarbimidate with Af-methylaminoacetonitrile resulted in displacement of methanethiol and formation of (314). Sodium ethoxide treatment in DMF converted (314) into a 4-amino-5-cyanoimidazole... 

Formation of ring-fused systems by reactions of this type can be achieved in two ways in one the heterocycle to which ring annulation is to occur acts as the dipolarophile the alternative mode utilizes incorporation of the 1,3-dipole into the heterocyclic ring for reaction with the dipolarophile. Both approaches have been investigated intensively. 

With an appropriately substituted precursor, photochemical carbon-carbon bond formation is a convenient method for the synthesis of ring-fused systems of the type under discussion. 

This group has also developed two ring-contraction systems of potential use in crown synthesis. In the first of these, extrusion of a phenylphosphine oxide unit results from treatment with alkoxide ion. In the second, similar conditions initiated decarbonyla-tion of a bis-pyridyl ketone Despite the apparent potential of these methods for crown synthesis, direct formation of crowns by processes which involve them do not appear to have enjoyed great success thus far. 

By reaction of 2-alkyl-4,6-dichloro-l,3,5-trimethylborazines (alkyl = methyl, ethyl, i-propyl) with bis(trimethylsilyl)amine the tetrameric borazine ring systems 4-6 are produced (Fig. 2) they can be purified by several successive vacuum sublimations (yields 4-60%). If the borazines carry n-propyl and tert-butyl groups in the 2-position or if methylbis(trimethylsilyl)amine is used to bridge the borazine molecules, the macrocyclic ring formation is inhibited [17, 18]. 

The synthesis takes advantage of the well-documented sulfoxide - sulfenate rearrangement , as well as of its retro-process, leading to cyclization and formation of the desired four-membered ring sulfoxide system (i.e. 211, 212). A closely related ring enlargement is based on the reversibility of this rearrangement and has found wide use in penicillin chemistry . 

To explain the formation of non-crosslinked polymers from the diallyl quaternary ammonium system, Butler and Angelo proposed a chain growth mechanism which involved a series of intra- and inter-molecular propagation steps (15). This type of polymerization was subsequently shown to occur in a wide variety of symmetrical diene systems which cyclize to form five or six-membered ring structures. This mode of propagation of a non-conjugated diene with subsequent ring formation was later called cyclopolymerization. 

In the reaction of diazofluorene with PTAD the dipolar intermediate (87) is isolable.136 Collapse to a five-membered ring is prevented by the steric constraints of the cyclic system, and although three-membered ring formation is possible, dimerization is the only process observed on heating. However, the dipole reacts with a variety of dipolarophiles (a=b, PhN=CO, Me02CC CC02Me, etc.) to give the expected adducts as shown in Scheme 11. 

Chelate ring formation may be rate-limiting for polydentate (and especially macrocyclic) ligand complexes. Further, the rates of formation of macrocyclic complexes are sometimes somewhat slower than occur for related open-chain polydentate ligand systems. The additional steric constraints in the cyclic ligand case may restrict the mechanistic pathways available relative to the open-chain case and may even alter the location of the rate-determining step. Indeed, the rate-determining step is not necessarily restricted to the formation of the first or second metal-macrocycle bond but may occur later in the coordination sequence. 

An interesting example of oxadiazole ring formation from formally O-C-N-N-C-O component 109 is the synthesis of tricyclic system (pyridooxadiazolpyridine) depicted in Scheme 26 <1998MI655>. 

A further application of ring-closing metathesis in seven-membered heterocyclic ring formation is in the synthesis of the trans-fused oxpane systems. This process involved tandem RCM/allylstannane-aldehyde cyclizations and interaction of the process provides access to trans-fused polyoxepanes <00S883>. 

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