Dendralene cross-coupling syntheses

The double alkenylation approach (Scheme 1.1) has only been exploited relatively recently, most probably because of the rise to prominence of cross-coupling methodologies in recent times. The first double cross-couplings between 1,1-dihaloalkenes and metalloalkenes were isolated examples appearing in 1998 [9] and 2000 [10]. In 2002, Oh and Lim [11] reported a series of double Suzuki-Miyaura reactions between a 1,1-dibromoalkene 6 and alkenyl boronic acids 7 (Scheme 1.2). In 2007 and 2008, the Sherburn research group reported syntheses of substituted [3] dendralenes [12] and the state-of-the-art synthesis of [5]dendralene [13] respectively, transforming a 1,1-dihaloalkene via double... 

A recent example is the synthesis by Ichikawa and coworkers [15] of a single tetra-fluoro[3]dendralene via double Negishi cross-coupling of 2,2-difluorovinylzinc bromide to a dibromoolefin. 

Higher dendralenes are accessible by double cross-coupling by including branched alkenes into the electrophile unit. For example, in their state-of-the-art synthesis of the parent dendralenes [23], Sherburn and coworkers prepared [6]dendralene (21) by the reaction between 2,3-dichloro-1,3-butadiene (20), and the Grignard reagent (9) prepared from chloroprene, another readily available unsaturated halide produced annually on a megaton scale (Scheme 1.4) [24]. The scope of this reaction in the synthesis of substituted higher dendralenes remains unexplored. 

Scheme 1.4 Synthesis of [6]dendralene via a double sp -sp cross-coupling reaction [23].

Recently, Tsuji and coworkers reported an isolated synthesis of a [3] dendralene 180 via a Suzuki-Miyaura cross-coupling reaction (Scheme 1.27) [126]. A variety of different 2-boryl-1,3-butadienes 178 were synthesized. While only one was coupled with an alkenyl halide 179, these butadien-2-yl coupling partners 178, in... 

Despite being a less obvious starting material than a l,3-butadiene-2-yl coupling partner, l,2-butadien-4-yl precursors (such as 166 in Suzuki s pioneering example in Scheme 1.26) have seen the most use in dendralene synthesis [118, 131-136]. A couple of more recent examples include the palladium-catalyzed cross-coupling reaction of alkenyl bromides 179 with, for example, the organoindium derived from allenyl bromide 181, or 1,1-dimethyl allene (183) (via a Mizoroki-Heckreaction) (Scheme 1.28) [132,135]. Palladium(0)-catalyzed dimerizations or homocouplings can also furnish the C2-C3 bond [138-142], as can nickel(O)- [143,144] and rhodium(I)-catalyzed ones [137]. 

Scheme 1.29 Chiral [3]dendralene synthesis via sp -sp cross-coupling as part of a total synthesis by Sherburn and coworkers [123].

Halodendralenes are valuable substrates for dendralene to dendralene transformations that preserve or extend the dendralene framework. They are intermediates in the synthesis of [7]- and [8]dendralene (Scheme 1.26) [23], as are their nucleophilic relatives, pinacolatoboryldendralenes, in the synthesis of substituted [4]-, [5]-, and [6] dendraienes [25, 27]. (Pseudo)halodendralenes have also been used in Stille [209] and Sonagashira cross-couplings [178, 210]. Dendralene dimers can be obtained via homocoupling of halodendralenes [211]. Dendralene frameworks can also be extended by uncatalyzed metathesis reactions on alkyne-containing dendraienes, and olefination reactions on carbonyl-containing ones [1, 211-214], each of which has been discussed. 

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