Propargylic amide, cyclization

A one-pot/two-reaction sequential ruthenium- and gold-catalyzed oxazole formation has been reported <2004CC2712>. The reaction of a propargylic alcohol and a primary amide in the presence of a Ru catalyst facilitates the formation of the intermediate propargyl amide which cyclizes upon treatment with AuCls (Scheme 61). 

The use of Zn(OTf)2 with a Ru complex, TpRuPPh3(MeCN)2PF6, proved useful for the cyclization of propargyl alcohols 99 with amides. The reaction proceeded through the intermediate 100 which was also isolated from the reaction mixture when only the Zn catalyst was used. Upon heating with the mixture of the two catalysts, compound 100 was completely converted into the final oxazole 101 <06JOC4951>. 

Cyclization reactions of a-acyliminium ions with allyl- and propargyl-silanes constitute a useful method for the preparation of various N-bridgehead bicyclic systems. Thus, from a reaction of hydroxylactams 107 and 108, the azaazulenes 109 and 110 were obtained in excellent yields (83TL1407). Similarly, the keto amide 112 was obtained from the imide 111 by reduction to the corresponding hydroxylactam and acid-catalyzed cyclization (84JCS(P1)2477). 

The rather unusual precatalyst silver(i) isocyanate was found to efficiently catalyze the cyclization of propargyl carbamates 420 to 4-alkylideneoxazolidin-2-ones 421 in good to high yields (Scheme 123).348 The presence of a base such as potassium /-butoxide or triethylamine is required for formation of the amide nucleophile which undergoes a stereoselective intramolecular attack at the activated triple bond (/rstereo-isomer 421 exclusively. Likewise, homopropargyl carbamates are converted into six-membered (Z)-4-alkylidene-l,3-oxazinane-2-ones under the same conditions. 

In terms of functional group compatibility, ethers, alcohols, tertiary amines, acetals, esters, amides and heterocycles are compatible with the Pauson-Khand reaction. In the intramolecular version, relatively few carbon skeletons undergo the cyclization. Most intramolecular PKRs use systems derived from hept-l-en-6-yne (6) or propargyl allyl ethers (7) or amines (8). Other interesting and more recent substrates are enynes connected through aromatic rings like 9-11, which have allowed us and other groups to obtain aromatic polycycles (Fig. 1) [28-31]. 

Base-catalyzed cyclization of propargyl amides is an expeditious approach to a variety of substituted oxazoles. In addition, propargyl amides can serve as... 

Nilsson and Hacksell isolated 2,5-dimethyl-4-phenyloxazole 245 (Ri = CH3, R2 = CeHs) as the only product from methylation of N-(l-phenyl-2-propynyl)acet-amide 244 (Ri = CH3, R2 = CeHs). The authors found that propargyl amides could be cyclized to 2,5-disubstituted and 2,4,5-trisubstituted oxazoles (Scheme 1.67). Thus a propargyl alcohol 243 was converted to the corresponding amide 244 in... 

It is interesting to note that early work on ferrocene derivatives of nucleosides uses Sonogashira coupling of ethynylferrocene to 5-iodouridine or 8-bromoadenosine. This reaction was later used to synthesize ferrocenylated ODNs by solid-phase synthesis techniques. Depending on the conditions, a cyclization reaction occurs with uracil derivatives. Instead of ethynylferrocene, Grinstaff et al. used ferrocene carboxylic acid propargyl amide. 

In the cyclization of A-propargyl amides, whether the exo-cyclic double bond of the initial product migrates into the ring or not could be controlled by the choice of catalyst (Scheme 6.75). The same substrate 6.193, with a gold(III) catalyst gave the oxazole 6.194 after double-bond migration. With the milder gold(I) triflamide... 

A review of the rearrangement reaction of anthranilic acid esters, thioesters, or amides under acidic conditions to 2-aryl-3-substituted 4(l//)-quinolinone has been reported and summarizes limits and scope of the reaction in the synthesis of flavonoids. " Theoretical studies of the addition-cyclization-isomerization reaction of propargyl cyanamides with thiol and methanol have been reported to occur via five steps ... 

L=AZARYPHOS, see Scheme 7) [86], to synthesize indoles from homo-propargylic amines/amides in good yields [105]. The use of doubly ethynylated substrates in the presence of water gave rise to the product derived from cyclization to the indole plus anti-Markovnikov hydration of the second terminal alkyne (Scheme 21). 

A similar ruthenacyclopentene intermediate can be proposed for the coupling of alkynes and allylic alcohols to lead to Y,8-unsaturated aldehydes and ketones. When [Cp Ru(CH3CN)3]PFg was used as a catalyst, the catalytic coupling between propargylic amides and allylic alcohols selectively provided piperidine derivatives by cyclization of the highly reactive aminoaldehyde intermediate [65] [Eq. (27)]. Only the branched isomer was formed by oxidative coupling, allowing the intramolecular condensation. 

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