Regioselective and Enantiospecific Synthesis of Dioxepines by (Cyclopentadienyl)ruthenium‐Catalyzed Condensations of Diazocarbonyls and Oxetanes

Abstract

1,4-Dioxepines result from the decomposition of a-diazo-b-keto estersi nt he presence of oxetanes using the catalytic combination of the (cyclopentadienyl)ruthenium complex [CpRu(CH 3 CN) 3 ][BAr F ]a nd 1,10-phenanthroline. Ther egioselective [4+ +3] insertions follow an S N 1like mechanism and occur yet enantiospecifically (es 74%). Ther etention of configuration was ascertained by vibrational circular dichroism (VCD) and solid state analyses.F urans,p roducts of [4+ +1] insertions,a re only observed as traces in the above protocol. To promote their formationu nder CpRu catalysis,i ti sn ecessary to use at wo-step process with g-halogenated alcohols as substrates.Seven-to eleven-membered cycles,a lso called medium-sized rings,a re importantb uilding blocks, being presenti nalarge variety of biologically relevant natural andm edicinal products. [1] Due to strain and entropy factors, [2] their synthesis is often challenging but it can be approachedw ith confidence through cycloaddition, ring-closing metathesis,c oupling or ring expansion reactions among others. [3] In the particular context of ring-expansions, [4] the use of reactive substratess uch as readily accessible oxetanes [5] can be advantageous. [6] In fact, the high nucleophilicity of oxygenl one pairs [7] and the important ring strain ( % 25 kcalmol À1 ) [8] permit the facile formation of reactive oxonium ylide intermediates that decompose spontaneously into higher ring systems regio-and stereoselectively. [9] Fori nstance,u nder Cu cataly-sis [9a,b,g,h,l] or photochemicalc onditions, [10] diazo reagents react with oxetanes in [4+ +1] processes to form substituted furans (Scheme 1a, [1,2]-shift mechanism). On the contrary,u nder Rh(II) [11] or Pd(II) [9i] catalysis, decompositions of a-diazo-carbonyls in the presence of oxetanes (solvent) afford 15-membered macrocycles by [3 + + 4 + + 4 + + 4] condensation (Scheme1b). Recently,i th as been shown that combinations of 1,10phenanthroline (phen) and [CpRu(CH 3 CN) 3 ][X] {X = PF 6 1a or X = BAr F ,t etrakis[3,5-bis(trifluoromethyl)phenyl]borate 1b}e fficiently catalyzet he decomposition of a-diazo-b-keto estersa nd promote selective 1,3-C-Hi nsertions into THF [12] and condensation reactions with ketones,lactones and cyclic carbonates. [13] With oxiranes (epoxides), [3+ +3] insertions lead to the formation of al arge variety of 1,4-dioxene moieties. [14] Herein, in an ew development, condensations of oxe-Scheme1.Oxoniumy lide formation by decompositiono f diazo reagents in the presence of oxetanes and subsequent reactivity (a, borc).

Three-Component Ring-Opening Reactions of Cyclic Ethers, α-Diazo Esters, and Weak Nucleophiles under Metal-Free Conditions

“…Ring-opening reactions of cyclic ethers can also be promoted by a pendant α-diazo ester moiety by means of a mechanism involving the generation of an oxonium ylide with a weakened C–O bond, which is then cleaved by intermolecular attack of a nucleophile (Scheme , eq 2). This transformation has been widely used in the construction of oxa-polycyclic compounds …”

Absolute Configurations of Synthetic Molecular Scaffolds from Vibrational CD Spectroscopy

“…Lacour and co-workers, for instance, reported the regioselective and enantiospecific synthesis of dioxepines like 4 by condensation of diazocarbonyls and chiral oxetanes. 37 In order to rationalize the mechanism of the reaction, which involved a (cyclopentadienyl)ruthenium complex and 1,10-phenanthroline, it was necessary to confirm the AC of the product. Using VCD spectroscopy, it was shown that the initial configuration of chiral oxetane starting material is retained in the final dioxepines.…”

“…Examples for such reactions and applications of VCD are manifold and can be found for both transition metal (TM) as well as organocatalytic reactions. Lacour and co-workers, for instance, reported the regioselective and enantiospecific synthesis of dioxepines like 4 by condensation of diazocarbonyls and chiral oxetanes . In order to rationalize the mechanism of the reaction, which involved a (cyclopentadienyl)ruthenium complex and 1,10-phenanthroline, it was necessary to confirm the AC of the product.…”

Preparation and Structural Characterization of [CpRu(1,10‐phenanthroline)(CH3CN)][X] and Precursor Complexes (X=PF6, BArF, TRISPHAT‐N)

“…(BAr F = tetrakis[3,5-bis(trifluoromethyl) phenyl]borate) specifically. [51,52] In view of the influence played by the BAr F or PF 6 anion nature onto the [CpRu] reactivity [44] but also, more generally, of the importance of negative counterions in catalysis, [53][54][55] care was then taken to determine the structural impact associated such counterions onto [CpRu(1,10-phenanthroline)(CH 3 CN)][X] and precursor complexes. 1…”

“…This catalytic system also promotes condensation reactions with nitriles, ketones, aldehydes and more recently with lactones and cyclic carbonates to generate the corresponding heterocycles ( Scheme 1). [49,50] Finally, in recent studies, regio and syn ‐stereoselective three‐atoms insertions into a large variety of epoxides and oxetanes were described leading to the formation of original 1,4‐dioxene and 1,4‐dioxepine motifs respectively with, as pre‐catalyst, the [CpRu(CH 3 CN) 3 ][BAr F ] (BAr F =tetrakis[3,5‐bis(trifluoromethyl)phenyl]borate) specifically [51,52] . In view of the influence played by the BAr F or PF 6 anion nature onto the [CpRu] reactivity [44] but also, more generally, of the importance of negative counterions in catalysis, [53–55] care was then taken to determine the structural impact associated such counterions onto [CpRu(1,10‐phenanthroline)(CH 3 CN)][X] and precursor complexes 1…”