Ring systems cascade carbopalladation

The final option available to a u-alkylpalladium intermediate from Heck alkylation occurs if another alkene or alkyne function is situated properly to participate in a further Heck-type carbopalladation (equation 161)318,319. In properly constructed systems, more than one further carbopalladation is feasible, and many examples of these cascade car-bopalladations have been reported. Several have been quite spectacular (equation 162)320. Fused, spirocyclic and bridged bicyclic ring systems have been prepared in this manner. The process may also create as many as five rings in one step, with five-,six- and three-membered rings321 being the most suitable for preparation (equation 163). Alternatively, the proper orientation of double and triple bonds allows cyclotrimerization to highly functionalized arenes or fulvenes (equation 164)322,279. 

D.i.a. Formation of Cyclopropane Derivatives by Two Successive Intramolecular Carbopalladations. Intramolecular carbopalladation starting from 1,( —l)-dienes with a suitable leaving group at the 2-position and a substituent at the (n-l)-position of the alkene terminator leads to a neopentylpalladium intermediate, which can only continue the cascade by a 3-eJto-tng-carbopalladation to eventually form bicyclo[(n—2). 1.0]alkenes. This sequence works equally well for ring sizes five, six, and seven in the first formed ring (Scheme 22) and even heterocyclic systems can be constructed by this mode (Scheme 22). 

Three simpler ort/io-substituted iodobenzene derivatives with two alkene moieties in the side chains have been cascade cycUzed to give methylenespiroalkane-annelated indanes (Scheme 26) and bicyclic systems (Scheme 27). This outcome clearly demonstrates that the intramolecular carbopalladations are determined by entropic factors, which always favor the formation of the smaller possible ring sizes. 

A 2-bromotetradeca-l,13-dien-7-yne with a terminal phenyl group apparently also prefers to cascade-cyclize via a neopentylpalladium intermediate with attack on the proximal phenyl group to yield a pentacyclic system (Scheme 41) rather than following the carbopalladation sequence to yield a tetracycle with a bridging cyclopropane ring as observed for other 2-bromo-l,13-diene-7-ynes (see above, Scheme 33). 

Cascade reactions arising from sequential carbopalladations are especially valuable for the construction of various carbo- and heterooligocyclic systems with three, four, or even more annelated rings. The Heck reaction has successfully been employed in various inter-inter-, intra-inter-, as well as all-intramolecular reaction cascades (Sect. IV.3). In the carbopalladation step of the Heck reaction (Scheme 6) a new metal-carbon bond is formed, which, in principle, can undergo any of the typical reactions of a ct--M—C bond, when the /3-hydride elimination is not too fast. When the /3-hydride elimination is totally suppressed, the palladium species can undergo a number of reactions with the formation... 

As shown in Scheme 6.37, some transition-metal-assisted ring-closure reactions of 1,2-diethynylbenzenes afford dibenzopentalene derivatives unexpectedly. Diederich s group designed a carbopalladation cascade reaction of easily accessible ew-dibromoolefins 286 and alkynes to furnish monobenzo-287 and mononaphthopentalenes 288 (Scheme 6.72). This successful methodology allows the preparation of asymmetrically substituted pentalene derivatives with only one fused aromatic system [167]. 

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