Elimination substituents, ring closure

Hydroxy-THISs add to the C-C bond of diphenylcyclopropenethione (181. Inner salts without substituents in 5-posnion react similarly with diphenylcyclopropenone (Scheme 10) (4, 18). Pwolysis of the stable adducts (9) leads to rupture of the R-C-CY bond. Subsequent ring closure yields 10. When Y = O. 10 eliminates COS. producing 2-pyridone. When Y = S. 10 is isolated together with its isocyanate extrusion product, a thiopyran-2-thione (18). 

In some cases involving dicyano-substituted thiocarbonyl ylides of type 9, ring closure to a thiirane and spontaneous desulfurization results in the formation of dicyano alkenes of type 68 (19,20). As a rule, the presence of electron-withdrawing substituents facilitates sulfur elimination. On the other hand, with alkyl and aryl substituents, desulfurization requires elevated temperature or the use of phosphanes (42,99,105,109,124-127). 

By ring closure of the acrylates (73), 3-substitu ted 4-oxo-4//-py rido [ 1,2-a] -pyrimidines with chloroacetyl, 2-ethoxycarbonylvinyl, and nitro- and 4-chlorophenylsufonyl substituents have been prepared.22145-147 Reaction of 2-aminopyridine and the enamine (84) led to the 3-phenyl derivative (85), which is presumably formed by an addition-elimination mechanism.153... 

Looking for a suitable preparation of dihydrobenzofuran derivatives by carbolithiation reactions, we have recently described how allyl 2-bromophenyl ethers 358 with a substituent at the a-position afford, after treatment with r-BuLi, addition of TMEDA and further quenching with electrophiles, functionalized fraws-2,3-dihydrobenzofuran derivatives 359 in a totally diastereoselective manner (Scheme 94)155. The key for the success of this reaction is the fact that intermediate organolithium 360 is not prone to undergo the 1,3-elimination process, probably due to the steric effect of the R substituent. The high diastereoselectivity of the ring closure could be explained by a transition state that accommodates the R group in a pseudoequatorial position. Moreover, simple allyl... 

Treatment of 1,3-dicarbonyl compounds with DBP in a methoxide/methanol system affords 2-alkyl-4-[(phenylsulfonyl)methyl]furans, where reaction proceeds by Initial addition-elimination on the vinyl sulfone moiety. In contrast, silyl enol ethers in the presence of silver tetrafluoroborate resulted in products derived from Sn2 displacement at the allylic site.11 Anions derived from 1,3-dicarbonyls substituted at the C-2 position are found to induce a complete reversal in the mode of ring closure.12 The major products obtained are 3-[(phenylsulfonyl)methyl]-substituted cyclopentenones. The internal displacement reaction leading to the furan ring apparently encounters an unfavorable Ai -interaction in the transition state when a substituent group is present at the 2-position ol the dicarbonyl compound. This steric Interaction is not present in the transition state leading to the cyclopentenone ring. 

Three-membered cyclic compounds can generally be prepared from difunctional compounds by 1,3-elimination. In the formation of oxiranes from 2-substituted alkanols, the alkoxide produced in the basic medium participates in an internal nucleophilic attack, which promotes the departure of the substituent on the adjacent carbon atom leading to ring-closure. A stereochemical condition for the reaction is that the reacting groups should be in an antiperiplanar conformation relative to each other (Eq. 51). 

The mechanism proposed by Ddtz involves the insertion of a carbon monoxide into the vinyl carbene complex intermediate with the formation of the vinyl ketene complex (255). °° Electrocyclic ring closure of (255) leads to the cyclohexadienone complex (252), which is related to the final benzannulation product by a tautomerization when R is hydrogen. The mechanism proposed by Casey differs from that of Ddtz in that the order of the steps involving carbon monoxide insertion and cyclization to the aryl or alkenyl substituent is reversed.Specifically, the vinyl carbene complex intermediate (248) first undergoes cyclization to the metallacyclohexadiene (249), followed by carbon monoxide insertion to give the intermediate (251), and finally reductive elimination to give cyclohexadienone intermediate (252). At this time the circumstantial evidence favors the intermediacy of vinyl ketene intermediates since they can be trapped from these reactions and isolated where the metal is dispaced from the vinyl ketene functionality however, there is not any evidence which can rule out the alternative mechanism. 

Cyclobutenones are fairly common side-products in the reaction of chromium arylalkoxy-carbenes with internal alkynes. As indicated in Scheme 5-1, the branch point in the formation of cyclobutenone versus naphthol products is believed to be vinylketene intermediate 4, which may undergo electrocyclic ring closure to 9, followed by reductive elimination to the product [7 a]. Cyclobutenone formation occurs only in the presence of internal or external ligands that can coordinate to unsaturated chromium species sufficiently well to prevent complexation to an internal n-system and thus divert the system toward 9. Depending on the alkyne and aryl substitution patterns and the reaction conditions, cyclobutenone formation can be made to predominate. Thus, solvents of good coordinating ability such as acetonitrile, o-OMe aryl substitution (which allows internal coordination to chromium), and bulky alkynyl substituents all favor cyclobutenone formation [Eq. (23)] [13]. In fact, the effect of solvent alone can be even more dramatic for the reaction partners in Eq. (21), a 0.5 M concentration of the carbene complex in acetonitrile gives instead a 78 % yield of cyclobutenone and only a combined 17 yield of quinone and indene products [9]. 

Ring closure across substituents of 1,4-disubstituted p-lactams is a convenient route to both bicyclic and tricyclic systems. For instance, cyclization of 81 gives the carbacephem 82 in high yield in the presence of benzylidenebis(tricyclohexylphosphine)ruthenium dichloride through an enyne metathesis process <97CCI375>. The 4-formyloxy-P-lactam 83 gives the oxacephem 84 by the action of Lewis acids but here the 4-substituent is eliminated to form the intermediate cation 85 <97TA2553>. 

Alkaline hydrolysis of the acetoxy or phthalimido substituents in several derivatives of (16) affords pyrazole derivatives in ca. 60-75 /o yield, apparently via transannular ring closure, followed by alcoholysis and elimination, as shown for the acetoxy derivatives (16 Ar = Ar = Ph, X = OAc, Y = Cl, SPh). Isolation of the intermediate bicyclic enone upon acidic hydrolysis of the SPh derivative provides strong support for this mechanistic proposal (Scheme 7) <87CL157>. 

Scheme 10. Orthoester formation via 1,2-phenylseleno migration followed by glycosylation and ring closure after syn elimination. PG - protecting group. Note substituents on carbohydrate rings have been deleted for clarity.

Ring closure of cyclic enacylamines with elimination of substituents... 

The capture of the palladium complex formed in the intramolecular insertion of A-acryloyl-2-haloanilines has also been exploited by Grigg. The addition of aryl-, and vinylboron reagents to the mixture of N-(2 methylacryloyl)-2-iodoaniline and a palladium catalyst led, after the closure of the five membered ring, to the transfer of the organic moiety to the formal terminal carbon atom of the acryloyl chain (3.16.). The role of the substituent in the 2 -position is presumably to block / -hydride elimination and so prolong the lifetime of the palladium complex formed in the insertion step.21... 

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