Vinyl Dihydropyrans and Dihydrooxazines: Cyclizations of Catalytic Ruthenium Carbenes Derived from Alkynals and Alkynones

Abstract

A novel synthesis of 2-vinyldihydropyrans and dihydro-1,4-oxazines (morpholine derivatives) from alkynals and alkynones has been developed. The cyclizations require a mild generation of catalytic ruthenium carbenes from terminal alkynes and (trimethylsilyl)diazomethane followed by trapping with carbonyl nucleophiles. Mechanistic aspects of the new cyclizations are discussed.

Synthetic Applications of Vinyl Ruthenium Carbenes Derived from Diazoalkanes and Alkynes

“…It had been well‐established that the precatalyst [RuCl(COD)Cp*] could react with diazoalkane to form a ruthenium‐carbene species that activates the triple bond which could lead to the annulation reactions to form various heterocycles . Interestingly, the synthesis of 2‐vinyl‐3,4‐dihydropyrans 48 could be achieved by the coupling of alkynals 47 and trimethylsilyldiazomethane in the presence of precatalyst [RuCl(COD)Cp*] with excellent diastereoselectivities as reported by Saá and co‐workers …”

“…Therefore, several alkynals/alkynones have undergone ruthenium‐catalyzed cyclization to furnish dihydropyrans in good to moderate yield with good diastereoselectivity, as depicted in Scheme . Interestingly, the diastereoselectivity of this reaction with the enantiomerically pure silyloxyphenyl substrate was explained through the formation of the most stable conformer of the ruthenium intermediate with the least steric interaction …”

The chemistry of the carbon-transition metal double and triple bond: Annual survey covering the year 2014

“…682) catalyzed by ruthenium complex 683 afforded vinylated dihydropyrans (e.g. 687) [958]. Key steps in the proposed mechanism include coupling of the initially-formed carbene complex and the alkyne to form the vinylcarbene complex (e.g.…”

Nucleophilic Addition of Amines to Ruthenium Carbenes: ortho‐(Alkynyloxy)benzylamine Cyclizations towards 1,3‐Benzoxazines

“…[2] Recently, efficient syntheses of aza-heterocycles by direct rhodium-, copper-, and ruthenium-catalyzed intramolecular addition of amines to metal carbenes have been reported (Scheme 1). [6] To test our hypothesis, we began the study with the cyclization of the alkynyloxyamine 1 a in the presence of the precatalyst [Cp*RuCl(cod)] and TMSCHN 2 . [3] Nevertheless, the major drawback with these methods concerns the often troublesome installation of an activated diazoalkane (e.g., conjugated with a carbonyl group) within the starting material.…”

“…[4] We recently reported carbocyclizations involving the insertion of vinyl ruthenium carbenes into C(sp 3 )ÀH bonds [5] and we have now envisioned a new entry into azaheterocycles by intramolecular nucleophilic addition of amines to these electrophilic ruthenium carbenes. [6] To test our hypothesis, we began the study with the cyclization of the alkynyloxyamine 1 a in the presence of the precatalyst [Cp*RuCl(cod)] and TMSCHN 2 . To our surprise, the six-membered 2,2-disubstituted 1,3-benzoxazine 2 a was isolated in fairly good yield (Scheme 1 d).…”