Dendralene synthesis reaction

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

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]. 

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. 

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... 

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]. 

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... 

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... 

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].

Uncatalyzed metathesis can also be performed on substrates that contain two reactive alkyne sites, for the rapid synthesis of highly substituted [4]dendralenes. Diederich and coworkers recently reported double [2+2] cycloaddition/retro-4n-electrocychzation cascades to yield a number of fully substituted [4]dendralenes 68 featuring push-pull chromophores (Scheme 1.10) [46, 48]. Using a similar double alkyne substrate 67, Diederich has also used different alkenes to incorporate varied functional groups into the product dendralene, a strategy recently also adopted by Morita and coworkers [47], who in 2012 reported stepwise or one-pot reactions to incorporate both TCNE (55) and TTF (60) into the structure of [4]dendralenes 69, via double uncatalyzed metathesis. 

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... 

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. 

Electrocyclization reactions are powerful synthetic tools to prepare compounds of great molecular diversity. These reactions allow for the formation of many substituted cyclic and polycychc compounds important in medicine, materials science, cosmetics, and so on. The well-established mechanisms and predictable outcomes of electrocyclization reactions permit the elaboration of logical blueprints for the synthesis of important molecules. Among these, the Nazarov cyclization is a salient member of the family. Reported first in 1941 by Ivan Nikolaevich Nazarov [1], this reaction has been studied extensively and many variations and applications have been developed over the years. In this chapter, we will present selected examples highlighting the versatility and synthetic power of this transformation [2]. In its simplest form, the Nazarov employs a divinyl ketone as the starting material, a cross-conjugated compound which can be regarded as a 3 -oxa-[3]dendralene. 

Synthesis of Dithiafulvene-Dendralene Oligomers by Cascade Reactions... 

The focus of this chapter has so far not been so much on synthesis, but one very nice cascade reaction to dendralenes incorporating DTF donor groups and dicyanomethylene acceptor groups deserves mention. While TCNE can undergo a thermal [2+2] cycloaddition with electron-rich alkynes followed by electrocyclic ring opening [21, 39], TTF can undergo a similar reaction with electron-poor alkynes [40]. These observations were employed to construct a... 

The first successful natural product synthesis incorporating a DTDA reaction sequence was published by Sherburn and coworkers in 2008, and constitutes a formal synthesis of triptolide (165) (Scheme 12.34) [46]. The carbon framework of this natural product was rapidly assembled from silyl protected [3]dendralene 161, beginning with a DA reaction between the free alcohol and methyl acrylate. In situ lactonization provided semicyclic diene 162, which was subjected to a high-pressure DA reaction with quinone 163. Tetracycle 164 was functionalized further to intercept an intermediate from Berchtold s 1982 total synthesis of triptolide [47]. 

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