Systems with nucleophilic trapping, intramolecular

The intramolecular reaction between carbenoids and amides is clearly emerging as a powerful tool for the synthesis of saturated oxazolo[3,2-tf]pyridine derivatives as shown by the cyclization of simple to extremely functionalized substrates 379 <2003CC440> and 381 <20050L47> (Scheme 100) trapping the intermediate isomtinchnone 1,3-dipoles by external (MeOH) or internal (indole) nucleophiles results in new heterocyclic fused systems with especially high efficiency. 

With 0,-y-unsaturated a -diazo ketones, the resulting [2.1.0]-bicyclic systems (40) were quite unstable and underwent a [2 + 2] cycloreversion to generate ketenes (41), which were then trapped by nucleophiles (Scheme 7). The overall scheme has been named a vinylogous Wolff rearrangement and offers a novel entry to products usually derived from a Claisen rearrangement.102 A recent report describes its application for functionalized angular alkylation in fused ring systems.103 In contrast, the intramolecular re-... 

Intramolecularity was the next issue to be probed within the context of alkynyliodonium salt/nucleophile addition reactions.53 1 No prior history was available to guide us, and so the prospects for success remained uncertain. Of primary concern was the potential for iodonium salt/base destructive interactions in competition with the desired N-H deprotonation reaction. A substrate that bore some resemblance to key portions of the agelastatin precursor 33 was prepared (Scheme 6), compound 39. This species duplicated the alkynyliodonium/"amide" pairing of the real system, but it lacked the complex piperazine carbene trap of 33. The tosylimide (pre)nucleophile was proposed as a compromise between what we really wanted (an N-methyl amide) and what would likely work (a tosylamide). Simple treatment of 39 with mild base effected the desired bicyclization to afford the tosylimide product 41 in decent yield. A transition state model 40 for C-H insertion that features an equatorial phenyl unit might rationalize the observed sense of diastereoselectivity. So, at least for 39, no evidence for possible interference by iodonium/base reactions was detected. 

Nucleophilic addition to organic radical-cations is one of the most common pathways to produce radicals. Irradiation of a wide variety of A-(2-alkenyl)- and N-(3-alkenyl)phthalimides and A-alkenylphthalimides [26] with a remote alkenyl double bond [27] afford new 5-, 6- and medium-size ring systems. Irradiation in methanol-acetonitrile triggers intramolecular electron transfer from the olefin double bond to the excited phthalimide carbonyl group. Because of the highly nucleophilic character of methanol, the olefin radical-cation can be trapped. The derived radical combines with the radical-anion to yield coupling products (Scheme 15). 

Previously, Ascic et al. [43] reported the same reaction with the Hoveyda-Grubbs II catalyst and trifluoroacetic acid as a bicatalytic system, but as a racemic version [43]. The intermediate acyliminium ion readily attacks also other tethered nucleophiles, such as trimethoxybenzene, benzothiophene, thiophene, 0,0-dimethyl catechol, and furan, intramolecularly. When tryptophane or the corresponding alanine derivatives are employed, reasonable levels of diastere-oselectivity can be observed for the terminal Pictet-Spengler acyhminium cyclization. Even a tethered alcohol functionahty diastereoselectively traps the chiral acyhminium intermediate, furnishing bicychc OAf-acetals. 

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