Intramolecular reaction ring-opening

Extension of these studies to benzologues of tetrazolo[l,5- ]pyridine, that is, for tetrazolo[l,5- ]quinoline 21 and tetrazolo[5,l- ]isoquinoline 22, led to interesting results <2003JOC1470> as shown in Scheme 7. Both of these fused tetrazoles resulted in formation of a nitrene 23 and 24, respectively, which could be interconverted via formation of the fused cyclic carbodiimide derivative 25. Isoquinolylnitrene 24, furthermore, was found to undergo subsequent reactions ring opening afforded the vinylnitrene 26, which was transformed to o-cyanophe-nylacetonitrile 27 by a 1,2-H shift and to 4-cyanoindole 28 by an intramolecular cyclization in 40% and 25% yields, respectively. 

Exposure of 3-(tetrahydro-2-furyl)-3-trimethylsilylpropanoic acids 178 to trifluoroacetic anhydride allows intramolecular acylative ring-opening reaction to give the corresponding eight-membered lactones 180 in moderate to good yields (Scheme 46) <1999SL1757>. However, when R1 = R2 = Me, lactones 180 are not formed. The acyloxonium ion 179 is a probable intermediate in these reactions. Similarly, acids 182 afford lactones 183 (Scheme 47). 

In a very clever reaction sequence, A-methylaziridines have been shown to be useful directing groups for ort o-metallation <2005OL3749>. Reaction of 170 with r-BuLi followed by trapping with a carbonyl compound provides alcohol 172. Subsequent intramolecular aziridine ring opening provides isobenzofuran derivative 173 (Scheme 45). 

Intramolecular nucleophilic ring-opening reactions of oxazolines are also known. Hydrozirconation of A -allylox-azolidine 141 gave a zirconocene intermediate 142, which reacted with TiCh to afford the corresponding 2-substituted pyrrolidine 143 in good yield and diastereoselectivity (Scheme 36) <2005OL4887>. 

An intramolecular oxirane ring-opening reaction can likewise be seen in Eq. 295. ... 

A transition metal catalyzed synthesis of ethers by carbene insertion into the O—bond has been reported. Not only saturated but also unsaturated alcohols can be utilized in this catalytic process. ° Intermolecular and intramolecular oxirane ring opening reactions by alkoxides and phenoxides also provide efficient and stereospecific preparations of acyclic and cyclic ethers. The procedures have been surveyed in detail. ... 

Regioselective C-2 amination of 2,3-epoxy alcohols can be realized by intramolecular oxirane ring opening of the carbamates prepared by the reaction of the epoxy alcohols with isocyanates." -" In some cases, however, acyl transfer is a serious side reaction (Scheme 59)." ... 

This entailed the lengthy and difficult successive constraction of the three missing rings F, G, and C. The synthesis of the F ring is the least troublesome, as it succeeds in only three steps and with 67 % yield (rac-45 rac-47) (Scheme 7). The key step is the intramolecular nucleophilic ring-opening of the unisolated epoxide rac-45 the thermodynamically controlled reaction yields rac-46 exclusively. 

When the attacking nucleophile is carbon-centered, intramolecular epoxide ring-opening reactions provide an entry intocarbocyclic systems. For example, epoxy allylsilane 70 cyclizes in an overwhelmingly 5-exo fashion under Lewis acid catalysis to form a putative silyl-stabilized carbocation intermediate (71) which then undergoes... 

Intermolecular and intramolecular oxirane ring opening reactions by alkoxides and phenoxides also provide efficient and stereospecific preparations of acyclic and cyclic ethers. The procedures have been surveyed in detail. ... 

The intramolecular nucleophihc ring opening of the epoxide 165 of the penteno-nitrile [260] is less academic, and gives the hydroxynitrile 166 (Reaction scheme 105). 

Nocquet, P.-A., Hazelard, D., Compain, P. (2011). Synthesis of spirocyclo-propyl yl ctams by a highly stereoselective tandem intramolecular azetidine ring-opening/closing cascade reaction. European Journal of Organic Chemistry, 2011,6619-6623. 

Asymmetric intramolecular addition/ring opening reaction of 3-(2-borylphenyljcyclobutanones afforded 1-indanones having chiral benzylic quaternary carbon centers by enantioselective P-carbon elimination (Scheme 3.18) [30]. 

In addition to the activity, the selectivity of the two zincates was also different in some cases [12]. In a representative example, addition of LiZnMes to aryl iodide 17 resulted in intramolecular epoxide ring-opening reaction in 86% yield with 96% en o-selectivity. In sharp contrast, when Li2Zn(SCN)Me3 was used, the selectivity changed and the exo-product became the major one (Eq. 12). Dihydroindole 18 and tetrahydroquinoline 19 stmctures exist widely in natural products and pharmaceuticals. Hence, combining the complementary results obtained with zincate-wa and zincate-i a would provide an efficient and practically useful protocol for preparation of aryl zincates as well as for further derivatization ... 

An efficient carboannulation proceeds by the reaction of vinylcyclopropane (135) or vinylcyclobutane with aryl halides. The multi-step reaction is explained by insertion of alkene, ring opening, diene formation, formation of the TT-allylpalladium 136 by the readdition of H—Pd—I, and its intramolecular reaction with the nucleophile to give the cyclized product 137[I08]. 

The reaction is very slow in neutral solution, but the equiUbrium shifts toward the lactam rather than glutamic acid. Under strongly acidic or alkaline conditions, the ring-opening reaction requires a very short time (10). Therefore, neutralization of L-glutamic acid should be performed cautiously because intramolecular dehydration is noticeable even below 190°C. 

The ring opening of 2//-azirines to yield vinylnitrenes on thermolysis, or nitrile ylides on photolysis, also leads to pyrrole formation (B-82MI30301). Some examples proceeding via nitrile ylides are shown in Scheme 92. The consequences of attempts to carry out such reactions in an intramolecular fashion depend not only upon the spatial relationship of the double bond and the nitrile ylide, but also upon the substituents of the azirine moiety since these can determine whether the resulting ylide is linear or bent. The HOMO and second LUMO of a bent nitrile ylide bear a strong resemblance to the HOMO and LUMO of a singlet carbene so that 1,1-cycloadditions occur to carbon-carbon double bonds rather than the 1,3-cycloadditions needed for pyrrole formation. The examples in Scheme 93 provide an indication of the sensitivity of these reactions to structural variations. 

Ring opening by intramolecular attack by an electron source located on a /3-carbon is represented by the Wharton reaction (Scheme 62) (8UCS(P1)2363) and the Eschenmoser fragmentation (Scheme 63) (81S276). 

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