Ring-dosure

Cyclic structures Ring dosures are described by a bond to a previously defined atom which is specified by a unique ID number. The ID is a positive integer placed in square brackets behind the atom. An " " indicates a ring closure. 

Scheme 1. Various types of ring dosure for the thiazoles, thiazolines, and thiazolidines.

Intermediates such as 224 resulting from the nudeophilic addition of C,H-acidic compounds to allenyl ketones such as 222 do not only yield simple addition products such as 225 by proton transfer (Scheme 7.34) [259]. If the C,H-acidic compound contains at least one carbonyl group, a ring dosure is also possible to give pyran derivatives such as 226. The reaction of a similar allenyl ketone with dimethyl mal-onate, methyl acetoacetate or methyl cyanoacetate leads to a-pyrones by an analogous route however, the yields are low (20-32%) [260], The formation of oxaphos-pholenes 229 from ketones 227 and trivalent phosphorus compounds 228 can similarly be explained by nucleophilic attack at the central carbon atom of the allene followed by a second attack of the oxygen atom of the ketone at the phosphorus atom [261, 262], Treatment of the allenic ester 230 with copper(I) chloride and tributyltin hydride in N-methylpyrrolidone (NMP) affords the cephalosporin derivative 232 [263], The authors postulated a Michael addition of copper(I) hydride to the electron-... 

By treatment of allenic esters with N-benzylideneaniline and boron trifluoride, ring dosures to but-2-enolides with introduction of a carbon substituent at position 3 are also possible [306], However, both the number of examples and the yields are low. 

Radical cydizations onto allenes are feasible via the dig (addition to C ) or the exotrig mode of ring dosure (addition to QJ. The significance of the a-addition is more pronounced in the case of the intramolecular pathway than in its intermolecular counterpart owing to (i) the chain length between the reacting entities and (ii) the stereoelectronic prerequisites for a radical attack on a Jt-bond [4],... 

The most relevant results regarding the SRN1 substitutions have been extensively reviewed [1-5] consequently, in this chapter we indude only the most recent and major representative synthetic examples in the aromatic system, relating to C—C and C-heteroatom bond formation with sulfur and tin nudeophiles, and ring-dosure reactions. 

Vaillard, S.E., Postigo, A. and Rossi, R.A. (2002) Syntheses of 3-substituted 2,3-dihydrobenzofiiranes 1,2-dihydronaphtho [2,l-b]furanes, and 2,3-dihydro-l H-indoles by tandem ring dosure-SRNl reactions. Journal of Organic Chemistry, 67, 8500-8,506. 

So far, only the cydoaromatization of precursors possessing an acydic hexadienyne unit has been discussed. That this route probably also has considerable potential as a cydic variant has been shown by the thermal ring-dosure of the cydic dienynes 21 and 24 (Scheme 7). 

The manganese dioxide is added to convert the sulfurous acid formed in the ring dosure reaction to dithionate which is hanniess. Equally good results can be obtiiined by using 40 grams of copper sulfate which is converted in the reaction to insoluble CU2O. 

The first type of process is characterized by cydization reactions, which are found in a plethora of examples and hence can be considered as the flagship of the different classes being discussed in this section. In spite of the fact that this reaction type distinguishes a broad scope of subsections, the 5-exo-trig ring dosure can be regarded as the most frequent and productive one. Furthermore, 6-endo and 6-... 

Figure 1.7 Ring dosure to an imidazolium salt with triethyl-orthoformate.

Figure 6 illustrates clearly the significance of Tg concerning the free volume available for molecular motions and ring-dosure of the merocyanine side groups. Similar diagrams are obtained for azo chromophores present in several copolymers . 

This reaction can also be applied to the preparation of heterocydic organocopper reagents such as 77 from readily available secondary alkyl iodides. Ring-dosure in this case is catalyzed by Ni(acac)2 rather than by Pd(0), affording new heterocydic molecules such as 7S (Scheme 2.26) [55]. These cydization reactions are key steps in the preparation of such natural products as (-)-methylenolactocin 79 [57] and methyl epijasmonate SO [58] (Scheme 2.27). 

In an attempt to synthesize fused aromatic systems of a pentalene-like structure, Boekelheid and Fedoruk (332) submitted the dicyanomethyl ylide of thiazole (77) to the addition reaction with dimethyl acetylenedi-carboxylate (DMA). They unexpectedly observed the formation of a fused six-membered (80) rather than a five-membered-ring (78). This ylide (77) was readily afforded by the reaction of thiazole (73) with tetracyanoethylene oxide and then put into reaction with DMA. The initially formed thiazolopyrrole derivative (78) is strongly polarized by the gcm-dicyano group, and its pyrrole ring is spontaneously cleaved with proton elimination. The ring dosure of the intermediate (79) leads to the final stable derivative of 5-FT-thiazolo[3,2-a]pyridine (80). More recently. 

Application of the above method to chiral 2-en-7-ynoates derived from optically active 8-phenylmenthol led to asymmetric ring-dosure to give bicydic ketones bearing an angular substituent, with high ee values, as shown in Eq. 9.64, s.p. 349 [112]. 

Spiro qMfxidation of a, l-enoitrs. The conversion of kctones to spiro epoxides is usually carried out with dimetfaylsulfoniuni melhylide, but this reaction can proceed in tow and variable yields when extended to o. -enones. A generally u.sefitl route to these vinyl spiro epoxidc.s involves addition of 1. methylation. and ring dosure with base, as illustrated for cyclohcxenone. 

The mechanisms for the nonenzymatic formation of PQQ or any of its isomers are by no means obvious. These reactions must proceed from tyrosine, or partially oxidized tyrosines, and glutamic add or glutamine liberated from proteins. From tyrosine and glutamic add, a ring alkylation and two successive ring dosures are required together with a net 12-electron oxidation. 

In this approach proposed by Casassa, the linear polymer precursor to be cydized possesses two identical end groups and the ring dosure requires the use of a bifunctional coupling agent, as illustrated in Scheme 4. 

Ring dosure with isothiocyanates 3,4-Dihydroisoquinoline-l-thiones... 

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