Palladium(0)-Catalyzed Synthesis of Medium-Sized Heterocycles by Using Bromoallenes as an Allyl Dication Equivalent

Abstract

We have developed a highly regio- and stereoselective synthesis of medium-sized heterocycles containing one or two heteroatoms via cyclization of bromoallenes bearing an oxygen, nitrogen, or carbon nucleophilic functionality in the presence of a palladium(0) catalyst and alcohol. In this reaction, bromoallenes act as an allyl dication equivalent, and the intramolecular nucleophilic attack takes place exclusively at the central carbon atom of the allene moiety. Interestingly, bromoallenes having a carbon nucleophile with a five-atom tether afford eight-membered rings with trans-configuration, while those having an oxygen or a nitrogen nucleophile give the corresponding cis-rings selectively. This is the first example that demonstrates the synthesis of medium-sized rings via cyclization of bromoallenes, and this reaction provides a very useful method for a catalytic synthesis of seven- and eight-membered heterocycles without using high dilution conditions.

Development of Useful Reactions Involving Tandem Cyclizations Based on the Novel Reactivities of Allenic Compounds

“…These results are in good agreement with the computational investigation by Prof. Ando. 130) [152][153][154] Medium-sized heterocycles are an extremely important class of compounds, the structural units of which are commonly found within the framework of a variety of natural products. 155) In particular, seven-and eightmembered heterocycles are constituents of a number of compounds with interesting pharmacological properties.…”

Highly substituted benzannulated cyclooctanol derivatives by samarium diiodide-induced cyclizations

“…Nevertheless, in recent years a range of interesting solutions for the efficient formation of eight-membered rings has been developed [1–2 4–18]. Successful approaches include ring-closing metathesis [4], rearrangements [5], and cycloadditions [6], transition metal-catalyzed cyclizations [7–8], nucleophilic and electrophilic substitution reactions [9] as well as ring expansion reactions [10]. Among these approaches to carbocyclic compounds, samarium diiodide-mediated reactions play an important role and have been described in a number of excellent review articles [19–21] and original publications [22–35].…”

[5+2] Cycloaddition of 2‐(2‐Aminoethyl)oxiranes with Alkynes via Epoxide Ring‐Opening: A Facile Access to Azepines

“…Accordingly,c onsiderable efforts has been devoted to the development of new efficient methods for assembling azepines. [4][5][6] Among them, cycloaddition reactions, [1,2,4] including the hetero-[5+ +2] cycloaddition reactions with alkynes, [5] are particularly fascinating for straightforward building the azepine frameworks.Despite the obvious synthetic utility,a pproaches through the hetero-[5+ +2] cycloaddition reactions with alkynes are less abundant and remain limited to the substrate scope with regard to both the five-atom units and the alkynes. [5] Pioneering work of the [5+ +2] cycloaddition reaction relied on the use of 2,3divinylaziridine as af ive-atom unit under metal-free conditions,b ut only two electron-poor alkynes were investigated for the synthesis of two azepines (Scheme 2a).…”

“…Ther eaction was successful when using FeCl 3 or BF 3 ·OEt 2 alone,a lbeit giving diminishing yields (entries 2a nd 3). As creen of the amount of both FeCl 3 and BF 3 ·OEt 2 revealed ac ombination of 10 mol %o fF eCl 3 and 1equiv of BF 3 ·OEt 2 as the best option (entries 1and [4][5][6][7]. A series of other Lewis acids,s uch as FeCl 2 ,F e(OTf) 3 ,C uCl 2 , InCl 3 and YbCl 3 ,were subsequently examined:each of which exhibited catalytic activity,b ut was less efficient than FeCl 3 (entries 1a nd [8][9][10][11].…”