Cyclization heteroatom-substituted

Five-membered carbo- or heterocycles can be prepared with the aid of heteroatom-substituted carbene complexes in several different ways. In the following sections the focus will be on cyclization reactions in which the carbon-metal double bond plays a decisive role. 

Under optimized conditions, cycloisomerizations of a number of functionalized hept-l-en-6-ynes took place in good-to-excellent yields (Table 9.3). Heteroatom substitution was tolerated both within the tether and on its periphery. Alkynyl silanes and selenides underwent rearrangement to provide cyclized products in moderate yield (entries 6 and 7). One example of seven-membered ring formation was reported (entry 5). Surprisingly, though, substitution was not tolerated on the alkene moiety of the reacting enyne. The authors surmize that steric congestion retards the desired [2 + 2]-cycloaddition reaction to the point that side reactions, such as alkyne dimerization, become dominant. 

It is known that 3-aminobenzo[6]furan can be prepared from o-cyanophenols and a-halogenocarbonyl compounds with subsequent Thorpe cyclization (73JPR779). The extension of this synthesis to heteroatom substituted benzo[6]furans is straightforward (76JPR313). The reaction of potassium salts of 3-cyano-2-pyridones (e.g. 27) with a-halogenocarbonyl compounds (esters, ketones) yields 2-alkoxy-3-cyanopyridines which can be cyclized in the presence of sodium ethoxide to give 3-aminofuro[2,3-6]pyridines (Scheme 6). 

Some /J-heteroatom substituted a,/J-unsaturated acyl silanes react with methyl ketone enolates in a stepwise stereoselective cyclopentannelation process, formally a [3 + 2] annelation, which may proceed through aldol reaction followed by Brook rearrangement and cyclization (Scheme 111)223. 

B. Cyclization Reaction of Heteroatom-substituted Olefinic Alkyllithiums. 334... 

There are a few reports of hetero-Diels-Alder Reactions promoted by LPDE. Intriguing stereoselectivity is observed for the [4 + 2] cyclization between Danishefsky s diene 77 and a-heteroatom-substituted aldehydes. For example, reaction of 77 with N-Boc-protected a-aminoaldehyde with 76 gave the threo isomer selectively, a result in keeping with a chelation-controUed process. In contrast, the threo diastereoselectivity observed could be reversed by changing the amino protecting group from A-Boc to A,A(-dibenzyl. In this instance, the erythro isomer was generated exclusively via a non-chelation-controlled transition state (Sch. 38) [89]. 

The Mizoroki-Heck reaction promoted by microwave irradiation was first described by Laihed and Hallberg [205]. For easy catalyst recovery, solid-supported systems were often used. An a-heteroatom-substituted carbonyl linker has been utilized in solid-phase approaches to oxinolines by Pummerer cyclization [206]. The reaction performed with s/c = 20 in the presence of phosphine ligands (ratio ligand/palladium-precursor = 1 1) in 88-99% yield at 7 h reaction time. 

A one-pot coupling protocol of arynes with ortho-heteroatom-substituted benzoates to prepare xanthones, thioxanthones, and acridones has been reported by Zhao and Larock (Equation 12.30) [50]. The coupUng presumably proceeds by a tandem intermolecular electrophihc coupling of the aryne with the orthoheteroatom-substituted benzoates and subsequent intramolecular electrophilic cyclization. Proton abstraction by the aromatic carbanion intermediate is a major competing reaction in this cyclization. This side reaction is, however, largely suppressed by employing tetrahydrofuran (THF) as the solvent... 

Wilder and his co-workers have extensively used addition-cyclization reactions in the synthesis of heteroatom-substituted polycyclic systems. The reaction in Eq. (27) is an example. Bromination, as with 2-thia-l, 2-dihydro- ndo-dicyclopentadiene (79), has also been utilized. The polar bromination of (79) yields the isolable bromosulfonium bromide (80) by S-5, -6 participation." When (80) is treated with lithium carbonate in aqueous methanol, the exo-cis-dio (81) is formed, probably by the sequence of reactions shown in Eq. (28)." ... 

---