Gold-Catalyzed Cyclization of N-Alkynyl Carbamates

Abstract

Six different N-alkynyl carbamates containing Boc groups were prepared. Their gold(I)-catalyzed cyclization to oxazolinones proceeded radily at room temperature or even lower temperatures.Among gold-catalyzed reactions 2 the intramolecular oxyauration of C-C multiple bonds is an excellent tool for the formation of oxygen-containing heterocycles. The first example was the cycloisomerization of allenyl ketones or propargyl ketones, 3 similar results were obtained with 2-alkynyl-2-alken-1-ones. 4 Subsequently, the isomerization of N-propargylcarboxamides to oxazoles or even the rare alkylidene oxazolines was investigated. 5 Propargylic and homopropargylic trichloroacetimidates react analogously. 6 Carboxylates and tert-butyl carboxylates also react. 7 A study of the cyclization of tert-butyl allenoates showed that the tert-butyl group is eliminated and a butenolide is formed. 8 This principle was then extended to tert-butyl carbonates, 9 where for example a propargylic carbonate was shown to cyclize faster than a homopropargylic one. 9a A similar behavior was reported for propargylic and homopropargylic tert-butyl carbamates. 9c,dWe now wanted to investigate N-alkynylcarbamates as substrates, where instead of a 5-exo-dig or 6-exo-dig, a 5-endo-dig cyclization would lead to oxazolinones. To the best of our knowledge, so far only one reference has described the use of derivatives of alkynylamines in goldcatalyzed reactions. 10The synthesis of the substrates started from the Boc-protected amines 1, using the phenyliodonium salts 2, 11 the tert-butyl N-alkynylcarbamates 3 and 4 were obtained (Table 1). For the ynamine synthesis two acceptors are needed on the amine, the Boc group is either accompanied by a second Boc group, a Ts group, or a pivaloyl group. When the terminal position of the alkyne was occupied by the TMS group, partial desilylation was observed. Changing to the more robust TBDMS group avoided this problem. Overall, the yields of these substrates were not high, but still allowed the investigation of the cyclization of 3 and 4.Gold catalysis with Gagosz's catalyst 12 [Ph 3 PAu]NTf 2 readily delivered the corresponding oxazolinones 5 in 65-93% yield. As shown in Table 2, the terminal (entries 1 and 3), the TMS (entries 2, 4, and 6), and the TBDMS (entry 5) carbamates all react well. With the combination Ts/ Boc it was very clear that the Boc carbonyl oxygen atom is the more nucleophilic partner (entries 1 and 2), but in the combination Piv/Boc also a high selectivity towards Table 1 Alkynyl Carbamates Entry Carbamate Iodonium salt Product Yield (%) 1 1a; R 1 = Ts 2a; R 2 = TMS 3a/4a 24/46 2 1b; R 1 = Boc 2a 4b 23 a 3 1b 2a 3b 51 4 1b 2b; R 2 = TBDMS 3c 27 5 1c; R 1 = Piv 2a 3d 27 a Cs 2 CO 3 (1.3 equiv) instead of KHMDS; DMF instead of toluene.Table 2 Gold-Catalyzed Oxazolinone Synthesis Entry Alkynyl carbamate Product Yield (%) 1 4a; R 1 = Ts, a R 2 = H 5a 71 2 3a; R 1 = Ts, a R 2 = TMS 5b 67 3 4b; R 1 = Boc, R 2 = H 5c 65 4 3b; R 1 = Boc, R 2 = TMS 5d 90 5 3c; R 1 = Boc, R 2 = TBDMS 5e 93 6 3d; R 1 = Piv,...

Gold Catalysis: Isolation of Vinylgold Complexes Derived from Alkynes

“…[2] In 2004, we reported the use of N-propargyl carboxamides 1, having terminal alkynyl groups (Scheme 1, R 2 = H), for 5-exo-dig cyclizations, [3] and in 2007 we reported the 5-endo-dig cyclization of N-alkynyl carbamates. [4] These first two papers have initiated the development of an entire family of gold-catalyzed cyclizations involving carbonyl groups as nucleophiles to deliver different types of heterocycles. [5][6][7] Herein we report new findings on the cyclization of N-propargyl carboxamides having internal alkynyl groups.…”

Gold‐Katalyse: Isolierung von Vinylgold‐Komplexen ausgehend von Alkinen

“…[2] 2004 berichteten wir über die Verwendung von N-Propargylcarboxamiden 1 mit endständigen C-C-Dreifachbindungen (Schema 1; R 2 = H) für 5-exo-dig-Cyclisierungen [3] und 2007 über die 5-endo-dig-Cyclisierung von N-Alkinylcarbamaten. [4] Besonders diese ersten beiden Publikationen haben die Entwicklung einer ganzen Reihe von Gold-katalysierten Cyclisierungen ausgelöst, die auf Carbonylgruppen als Nucleophilen beruhen und verschiedenste Typen von Heterocyclen liefern. [5][6][7] Hier berichten wir über neue Beobachtungen zur Cyclisierung von N-Propargylcarboxamiden mit inneren C-C-Dreifachbindungen.…”

Gold(I)-catalyzed [4+2] cycloaddition of N-(hex-5-enynyl) tert-butyloxycarbamates

“…It is also noteworthy that the previously reported 5-endo cyclization of the tert-butyloxycarbamate on the alkyne (Scheme 1) [7,8] did not significantly compete with this new transformation. The nucleophilic addition of the alkene moiety on the activated gold-alkyne complex seems to be a more favored process and only traces of oxazolones 14 could be observed when a gold complex was used as the catalyst.…”

“…The first study in this domain was made by Cossy and coworkers who described the gold(I)-catalyzed cycloisomerization of ene-ynamides into 2-azabicylco[3.1.0]hexanes [6]. Later on, the group of Hashmi [7] and our group [8] independently reported that N-alkynyl tert-butyloxycarbamates 1 could be converted in the presence of a gold(I) complex into a range of functionalized oxazolones 2 (Scheme 1). More recently, Hashmi and coworkers reported the elegant synthesis of dihydroindole and tetrahydroquinoline derivatives using electron-deficient ynamides as the substrates [9].…”