Dendralenes, synthesis

In the 1970s and 1980s, it was discovered that electron-deficient alkenes, such as tetracyanoethylene (TCNE, 55) reacted with metallated alkynes 54 to furnish a metallated hexasubstituted 1,3-diene unit 56, an overall transformation akin to enyne metathesis (Scheme 1.8) [37, 39]. In a recent (2012) addition to this work, the Bruce group reported the synthesis of a ruthenated [3]dendralene 58 via insertion of phenylacetylene (57) into 56 (Scheme 1.8) [38]. The metallated dendralene synthesis is low yielding and, as yet, an isolated example, but presents an interesting avenue for future investigations. 

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 1.27 Recent [3]dendralene synthesis by Tsuji and coworkers using a metallated butadiene [126].

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

C-H activation is an important and rapidly developing area of dendralene synthesis. In very recent years, several C2-C3 bond forming approaches to dendralenes involving C-H activation have been reported. In 2013, Glorius and coworkers developed a Rh(III)-catalyzed, Heck-type alkenyl C-H activation and coupling reaction with allenyl carbinol carbonates 205 and acrylamides 206 (Scheme 1.33) [157]. This new reaction performs well for the synthesis of highly substituted [3]dendralenes. 

The first example of a dendralene synthesis via C3-C3 bond formation (Scheme 1.37) dates back to 1904, when Fellenberg reported an addition/elimination sequence between methyl magnesium bromide (224) and phorone (223) (Scheme... 

Other variants of olefination have also been applied to dendralene synthesis [186-188]. In 2004, Dixon and Halton [189] prepared a variety of cyclic [3]dendralenes using Peterson-type olefination reactions (Scheme 1.39). These... 

Scheme 1.40 [3]Dendralene synthesis using (a) a trivinyi methide anion [190] and (b) an indium pentadienyl nudeophile [191, 192].

Dendralenes From a Neglected Class of Polyenes to Versatile Starting Materials in Organic Synthesis... 

The masked dendralenes 36 are crystalline compounds, stable at room temperature, from which, as hoped, the hydrocarbons 37 could be released on demand in good yields by high-temperature pyrolysis. No solvent is required in these cheletropic reactions which facilitates the work-up. The dendralenes 37 obtained, up to [8]dendralene, have been completely characterized by the usual spectroscopic and analytical methods and can, although they tend to polymerize, be handled under the usual laboratory conditions (see below). The sulfolene decomposition route has recently been applied to the synthesis of many other cross-conjugated compounds, among them the hydrocarbons 39-42 (Scheme 7) [12]. 

Sy 1 -phenylethyltrifluorosilane 439 1-phenylethylzinc chloride 27, 29 1 -phenyl-3-methyl-1,2-butadiene 475 (1Z,3E)-1-phenyl-1,3-octadiene, synthesis 84-5 phenylpalladium iodide complex 137 l-phenylpent-4-en-l-yne 196-7 (Z)-phenyl-substituted dendralene 117 ( -(-)-1 -phenyl-1 -trifluoroacetoxy-2-propyne 475 l-phenyl-4-triinethylsilyl but-2-ene 351... 

Stille coupling An expedient synthesis of [6]dendralene involves coupling of 2,3-bis(trimethylstannyl)-l,3-butadiene with 3-iodosulfolene and pyrolysis. A lesser amount of [8]dendralene is also produced. 

Scheme 2.44 Domino dienyne metathesis in the synthesis of [4]dendralene 122.

Sherbum reported a robust synthesis of the fascinating diene [4]dendralene (97) and its behavior in Diels-Alder reaetions with N-methylmaleimide (89, NMM). Dendralene 97 is available in one step from chloroprene and combines with three equivalents of an A-methylmaleimide-methyl aluminium diehloride complex to provide a diastereomeric mixture of 98 after three Diels-Alder reactions. ... 

Dendralenes [24] (acyclic cross-conjugated polyenes) have been used as dienes in tandem Diels-Alder reactions, and a methodology for the synthesis of highly functionalized angularly anel-lated aromatic compounds has been developed (Scheme 16.23) [25]. A tandem double Diels-Alder reaction of DMAD with [3]dendralene followed by oxidation with DDQ gave the tetramethyl ester... 

Synthesis of a hexasubstituted phenanthrene derivative from [4]dendralene is illustrated in Scheme 16.24 [25]. The poor yields observed in the cycloaddition steps might be due to the thermal instability of [4]dendralene and the initially formed cycloadduct. 

SCHEME 16.24 Synthesis of hexasubstituted phenanthrene derivative from [4]dendralene. 

The Kumada reaction was employed for the synthesis of dendralenes, cross-conjugated alkenes, which show interesting reactivity (Scheme 2.20). The products even include the labile [3]dendralene 2.56 which has a half-life of just 10 h at 25 °C. 

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].

Scheme 1.6 Possibilities for the synthesis of dendralenes via reactions forming two or more alkene groups.

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