Silicon electrofuge

Due to their ready isomerization simple cyclopentenones present a particular challenge in the Nazarov cyclization. In all of the cases studied in a- and -monosubstituted and a, -disubstituted systems the cy-clopentenone product contained the double bond in the less substituted position, as required by loss of the silicon electrofuge (Scheme 17). The relative conBguration of substituents in disubstituted cases is controlled by kinetic protonation and weakly favors the cis isomers. Substituent effects in rate were particularly noted in these cases where substitution with a- and -alkyl groups greatly accelerated and decelerated the reactions, respectively. 

The Lewis acid-promoted cyclization of the deuterium-labeled model 13 is found to give products corresponding to an anti Sp reaction. All of the cycliza-tions with Lewis acids are greater than 95% selective for the anti Sp reaction. The high selectivity observed demonstrates that in a sterically unbiased S/- reaction an anti orientation of the electrophile with respect to silicon is preferred. The products from both the synclinal and antiperiplanar transition structures are found to be anti selective. The arrangement of double bonds in the transition structure does not affect the relative disposition of the silicon electrofuge, which must be disposed away from the approaching electrophile. 

A interesting variation on this theme employing the isomeric enynol acetates (Scheme 24) has been developed by Rautenstrauch. The cyclizations are induced by a Pd" catalyst in warm acetonitrile. The proposed mechanism is intriguing. Reaction is initiated by an anchimerically assisted palladation to (35) followed by opening the dioxolenium ion to a pentadienylic cation (36). The closure of (36) is analogous to the silicon-directed Nazarov cyclization in the ejection of the Pd" electrofuge from (37). Both secondary and tertiary acetates can be employed as well as both acyclic and monocyclic systems. 

In several instances, Mannich-type cyclizations can be carried out expeditiously under photochemical conditions. The photochemistry of iminium ions is dominated by pathways in which the excited state im-inium ion serves as a one-electron acceptor. The photophysical and photochemical ramifications of such single-electron transfer (SET) processes as applied to excited state iminium ions have been expertly reviewed. In short, one-electron transfer to excited state iminium ions occurs rapidly from one of several electron donors electron rich alkenes, aromatic hydrocarbons, alcohols and ethers. Alternatively, an excited state donor, usually aromatic, can transfer an electron to a ground state iminium ion to afford the same reactive intermediates. Scheme 46 adumbrates the two pathways that have found most application in intramolecular cyclizations. Simple alkenes and aromatic hydrocarbons will typically suffer addition processes (pathway A). However, alkenic and aromatic systems with allylic or benzylic groups more electrofugal than hydrogen e.g. silicon, tin) commonly undergo elimination reactions (pathway B) to generate the reactive radical pair. 

The electrofugal benzylic trimethylsilyl group will also admirably direct photocyclizations. This directing effect is enunciated in the cyclizations of A -xylylpyrrolinium perchlorates (133) and (135). Upon irradiation in acetonitrile, salt (133) is converted to the dimethylbenzopyrrolizidine (134) in 90% yield. In comparison, silicon analog (135) cleanly photocyclizes at the benzylic site in acetonitrile to yield the benzoindolizidine (136 Scheme 49). ... 

It should be pointed out that this reaction has been carried out photochemically (i.e., the photo-Nazarov cyclization Fi2) or under near-critical water conditions. More importantly, it has been improved to occur in a controllable fashion, through a directed Nazarov cyclization or an interrupted Nazarov reaction. It is worth noting that two practically directed Nazarov cyclizations have been developed, one by Denmark by using the jS-cation stabilizing effect and electrofuge of silicon (Scheme 2),2 > 2tt,6,i3 and the other from Ichikawa by application of a /3-cation destabilizing effect and the... 

Rautenstrauch reported another mechanistically intriguing example. Treatment of enynol acetate 111 with a palladium(II) catalyst in warm acetonitrile resulted in the formation of cyclopentenone 115. The proposed mechanism involves generation of divinyl cationic species 113, followed by electrocyclization, and elimination of the palladium(ll) electrofuge in a manner comparable to the silicon-directed Nazarov cyclization (see Section 3.4.5.1). 

---