A General Stereoselective Synthesis of [4]Dendralenes

Abstract

The first general synthesis of branched tetraenes ([4]­dendralenes) involves two or three steps from inexpensive, commodity chemicals. It involves an unprecedented variation on Suzuki–Miyaura cross-coupling, generating two new C–C bonds in a one-flask operation with control of diastereoselectivity. The broad scope of the method is established through the synthesis of more than 60 diversely substituted [4]­dendralene molecules, along with substituted buta-1,3-dienes and other [n]­dendralenes. [4]­Dendralenes are demonstrated to be significantly more kinetically stable than their well-known [3]­dendralene counterparts. The first stereoselective synthesis of these compounds is also reported, through the catalyst-controlled generation of both E- and Z-diastereomeric products from the same precursor. Novel, through-conjugated/cross-conjugated hybrid molecules are introduced. The first selective dienophile cycloadditions to substituted [4]­dendralenes are reported, thus paving the way for applications in target-oriented synthesis.

Mild Stereoselective Synthesis of Densely Substituted [3]Dendralenes via Ru-Catalyzed Intermolecular Dimerization of 1,1-Disubstituted Allenes

“…Dendralenes are acyclic cross-conjugated polyenes that have recently been recognized as an important family of unsaturated hydrocarbons, despite being neglected for a long time . There have been increasing interests in the utilization of dendralenes in various fields, including the synthesis of useful natural molecules and polymer materials. − Among them, [3]­dendralenes, the simplest dendralenes with cross-conjugation, were first introduced in 1955 . Since then, they have received intensive interest from the synthetic community.…”

Reductive Metallation of Dendralenes and Myrcene Using Dimagnesium(I) Compounds: A Facile Route to Unsaturated Organomagnesium Compounds

“…[1] Over the past two decades this view has been dispelled, largely by Sherburn and co-workers, who have devised a variety of straightforward multi-gram synthetic routes to an extensive family of parent and substituted dendralenes, which they have shown to be considerably more stable than previously thought. [1][2][3] This has allowed the fascinating organic chemistry of dendralenes to be developed, most predominantly as building blocks in the synthesis of natural products and related complex polycyclic systems, by exploiting their buta-1,3diene like reactivity. [1][2][3] In contrast to the organic chemistry of dendralenes, their organometallic chemistry has been poorly investigated.…”

“…[1][2][3] This has allowed the fascinating organic chemistry of dendralenes to be developed, most predominantly as building blocks in the synthesis of natural products and related complex polycyclic systems, by exploiting their buta-1,3diene like reactivity. [1][2][3] In contrast to the organic chemistry of dendralenes, their organometallic chemistry has been poorly investigated. With that said, organometallic dendralenes have been prepared in situ and used as synthons for the construction of higher or substituted dendralenes.…”

“…For example, magnesium and zinc [3 or 4]dendralenyls have been accessed by the reductive dehalogenation of bromo-or chloro-dendralenes, then employed as precursors in homo-coupling reactions which yield [6]dendralene and [8]dendralene. [4] In another case, a η 4complex between [3]dendralene and the Fe(CO) 3 fragment undergoes a Hoveyda-Grubbs catalysed cross metathesis reaction with styrene to give 1-phenyl [3]dendralene. [5] One area of dendralene organometallic chemistry that appears not to have been explored is the reduction of their π-electronic systems by electropositive elemental metals or low-valent metal complexes.…”

A Rapid Aza-Bicycle Synthesis from Dendralenes and Imines

“…Dendralenes are now available in a wide range of different substitution patterns. , Historically, the most accessible structures are [3]­dendralenes substituted at the central CC bond, 15 . , Their successful deployment in DTDA sequences involving imines 16 is shown in Table .…”