Discovery and Computational Rationalization of Diminishing Alternation in [n]Dendralenes

Abstract

The [n]dendralenes are a family of acyclic hydrocarbons which, by virtue of their ability to rapidly generate structural complexity, have attracted significant recent synthetic attention. [3]Dendralene through [8]dendralene have been previously prepared but no higher member of the family has been reported to date. Here, we describe the first chemical syntheses of the "higher" dendralenes, [9]dendralene through [12]dendralene. We also report a detailed investigation into the spectroscopic properties and chemical reactivity of the complete family of fundamental hydrocarbons, [3]dendralene to [12]dendralene. These studies reveal the first case of diminishing alternation in behavior in a series of related structures. We also report a comprehensive series of computational studies, which trace this dampening oscillatory effect in both spectroscopic measurements and chemical reactivity to conformational preferences.

Synthesis of Functionalized [3], [4], [5] and [6]Dendralenes through Palladium‐Catalyzed Cross‐Couplings of Substituted Allenoates

“…In this regard, they are well configured to maximize "step economy" en route to both natural and unnatural materials that contain polycyclic arrays. Notwithstanding the remarkable advances made in preparing higher homologs that now have reached [12]dendralene, [4] recent papers from the Sherburn group highlight the need for additional inroads to both the parent and especially substituted systems, as well as new chemistry that extends the repertoire of reactions of dendralenes beyond [4+2] cycloadditions. Indeed, in a recent Account, [5] Sherburn concludes: "Regarding our deployment of the dendralenes and related unsaturated hydrocarbons in the rapid generation of structural complexity, again, we have deployed only known reactions (and in the main, just one: the venerable Diels-Alder reaction)."…”

“…Other reactions of functionalized dendralenes, especially those associated with higher homologs that are regioselective, are few in number. [2d, 5] Since most published routes to dendralenes involve double cross-couplings from dihalo-and diborylated intermediates (Figure 2, top) [4,6] selective mono-functionalized and unsymmetrical patterns, which are likely to prove more valuable in total synthesis, remain few in number. In this report, therefore, we describe rapid access to both functionalized symmetrical and unsymmetrical [3]-[6]dendralenes from a common allenic precursor, using Pd-catalyzed crosscouplings under micellar catalysis conditions; i.e., in water and typically at ambient temperature (Figure 2, bottom).…”

“…Although the full scope and utility of our modified approach to related 1,3-butadienes will be described at a later date, use of alkenylboronates as coupling partners in place of related aryl derivatives successfully provided a range of functionalized [3]dendralenes (Scheme 1, A). The presence of substituents on the cross-conjugated triene framework imparted sufficient stability to the products, [4] thereby leading to their facile isolation in neat form.…”

“…This multi-catalytic system applied to the synthesis of functionalized dendralenes shows broad substrate compatibility, as well as functional group tolerance. Furthermore, these mild conditions compare very favorably with existing methods, [1,2,4,6] in terms of simplicity, amounts of reagents involved, and environmental concerns (such as organic waste in the form of solvents, and energy invested in the form of low temperatures).…”

“…Altering the electrophilic coupling partner to a vinyl allenoate (19, Scheme 3) provided rapid entry to substituted [3], [4], [5] and [6]dendralenes utilizing any of the four pathways, A-D (Schemes 1 and 2). Furthermore, the SuzukiMiyaura approach (Scheme 1, A) could be extended beyond 2 -sp 2 couplings to include sp-sp 2 and sp 2 -sp 3 bond formations.…”