Acetylenic Schmidt reaction

Toste has reported a gold(I)-catalyzed protocol for the intramolecular addition of an alkyl azide to an alkyne with loss of dinitrogen (acetylenic Schmidt reaction) to form pyrrole derivatives [19]. For example, treatment of homopropargyl azide 16 with a catalytic 1 2 mixture of (dppm)Au2Cl2 (dppm = l,2-bis(diphenylphosphino)meth-ane) and AgSbFfi in methylene chloride at 35 °C led to isolation of2,5-dibutylpyrrole in 82% yield (Eq. (11.13)). The method was also effective for the cyclization of a-unsubstituted homopropargyl azides and tolerated both alkyl and aryl substitution of the alkyne. 

Li has reported a gold(I)-catalyzed procedure for the annulation of 2-tosylamino-benzaldehyde 19 with terminal aromatic alkynes to form aza-isoflavanones although extremely forcing conditions were required [22]. As an example, heating a toluene solution of 19 and phenylacetylene with a catalytic mixture of AuCN and PBU3 in a sealed tube at 150 °C for 2.5 days led to isolation of azaisoflavanone 20 in 65% yield (Eq. (11.14)). 

Che has reported the tandem hydroamination/hydroarylation of aromatic amines wirh terminal alkynes to form dihydroquinolines in which 1 equiv of aniline combines with 2 equiv of alkyne [23]. For example, reaction of 3-methoxyanilme with pheny-lacetylene (5 equiv) and a catalytic 1 1 mixture of the gold(I) N-heterocydic carbene complex (IPr)AuCl (IPr= l,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidine) and AgOTf at 150 °C under microwave irradiation led to isolation of dihydroquinoline 21 in 82 % yield (Eq. (11.15)). Alternatively, reaction of o-acetylaniline with pheny-lacetylene catalyzed by a mixture of (IPr)AuCl and AgOTf at 150 °C led to isolation of the quinoline derivative 22 in 93% yield via incorporation of a single equivalent of alkyne (Eq. (11.16)). Arcadi has reported the gold(IlI)-catalyzed hydroamination/ hydroarylation of 2-alkynylanilines with a,p-enones to form C3-alkyl indoles [24]. As an example of this transformation, treatment of 2-(phenylethynyl)aniline with 4-phenyl-3-buten-2-one and a catalytic amount of sodium tetrachloroaurate dihydrate in ethanol at 30°C formed 1,2,3-trisubstituted indole 23 in 88% yield (Eq. (11.17)). 

Kirsch has reported the conversion of propargyl vinyl ethers to form pyrroles via a multi-step transformation involving the silver-catalyzed propargyl Claisen rearrangement to form the a-allenyl P-keto ester, condensation with a primary aryl amine. 

Genet and Michelet have reported the gold(I)-catalyzed cydization/amination of 1,6-enynes with carboxamides and electron-deficient aromatic amines [27]. Reaction of 1,6-enyne 32 with o-cyanoaniline and a catalytic 1 1 mixture of (PPh3)AuCl and AgSbFg in dioxane at room temperature for 20 h led to isolation of methylene cyclopentane 33 in 93% yield as a single diastereomer (Eq. (11.19)). Gold(I)-catalyzed 

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A new one-pot tandem C-C coupling intramolecular acetylenic Schmidt reaction using Pd/C-Cu catalysis was developed to afford 3-substituted I (2/7)-isoquinolones 139 <07CC1966>. In this one-pot procedure, 2-iodobenzoyl azide 140 and the appropriate alkyne were reacted in the presence of Pd/C, PPh3, Cul and TEA to provide the products in good to high yields. 

Imines react with alkynes to give pyrroles (equation 29). " A related transformation of azides has been reported by the group of Toste to afford pyrroles by an acetylenic Schmidt reaction (equation 30). " In an intermolecular-related addition, gold triazolates are obtained. The intramolecnlar hydroamination of trichloroacetimidates derived from propar-gyl and homopropargyl alcohols also proceeds with cationic An(I) as catalysts. ... 

Toste and coworkers have discovered a gold(I)-catalyzed acetylenic Schmidt reaction for the synthesis of polysubstituted pyrroles 38 (SchemeAlB). In this reaction, it was suggested that the metal plays two roles. It both activates the alkyne bond (cf. 39) and also stabilizes the n-intermediate 40 by electron donation. This powerful reaction tolerates both alkyl and aryl groups, and alkyne chemoselectivity was complete starting from a 1,5-enyne. 

Scheme 4.13 Mechanism of Au(I) promoted acetylenic Schmidt reactions.

Variation 8 Gold(I)-catalyzed Intramolecular Acetylenic Schmidt Reaction (Toste )... 

It occurs with the alkyls, aryls or acetylides of metals more electropositive than magnesium, but including Grignard reagents, and is often carried out by adding a solution of the organometallic compound in an inert solvent to a large excess of powdered, solid C02 it is a particularly useful method for the preparation of acetylenic acids. The Kolbe-Schmidt reaction (p. 291) is another example of carbanion carbonation. 

Toste and coworkers have shown that intramolecular Schmidt reactions of acetylenic azides were possible through Au(I) catalysis. Thus, treatment of a series of acetylenic azides with (dppm)Au2Cl2 provides pyrroles in good yields (Table 7.6). These reactions were tolerant of varying substitution and chemoselective when a 1,5-enyne was present, the desired cyclization still proceeded, albeit with reduced efficiency (entry 5). 

Reaction (44a) is analogous to the 02-reaction of the vinyl radical leading to HCO and HCHO as reported by Gutman and co-workers [118,119], Evidence for the occurrence of reaction (44b) was based on the observation of a-dicarbonyl products in the absence of NO. Schmidt et al. [120] have recently observed the regeneration of HO from the HO + C2H2 reaction by means of a laser fluorescence technique. The branching ratios for the two unimolecular dissociation channels typified by reactions (44a) and (44b) were estimated to be 0.4 0.1 and 0.7 + 0.3 (acetylene), 0.12 + 0.02 and 0.53 0.03 (propyne), and 0.12 + 0.87 0.07 (2-butyne), respectively. In any case, the formation of acidic products as well as the a-dicarbonyl products from these reactions is of potential importance in the atmosphere. 

Although no total synthesis of kijanolide has ever been achieved, Yoshii managed to reach analog 26-0-methyl-28,29-bisnor-( )-kijanolide (244) 3 years before the synthesis of tetronolide [121]. For the spirotetronic part, Yoshii applied Schmidt s chemistry by performing a reaction between a p,Y-unsaturated cyclohexanone and Cl2CeC=CCOOMe followed by the base-catalyzed conversion of the resulting acetylenic carbinol 241 to spirotetronate 242 (Scheme 1.36). 

Mikhaleva, A.L and E.Yu. Schmidt. 2002. Two-step synthesis of pyrroles from ketones and acetylenes through the Trofimov reaction. In Selected Methods for Synthesis and Modification of Heterocycles, vol. 1, ed. V.G. Kartsev, pp. 334-352. Moscow, Russia IBS Press. 

Schmidt, E.Yu., A.I. Mikhaleva, A.M. VasU tsov et al. 2005. A straightforward synthesis of pyrroles from ketones and acetylene A one-pot version of the Trofimov reaction. Arkivoc vii 11-17. 

Mikhaleva, A.I., E.Yn. Schmidt, A.V. Ivanov et al. 2007. Selective synthesis of 1-vinyl-pyrroles directly from ketones and acetylene Modification of the Trofimov reaction. Zh Org Khim 43 (2) 236-238. 

Vasil tsov, A.M., A.B. Zaitsev, E.Yu. Schmidt et al. 2001. Unexpected foimation of l-vinyl-2-[2 -(6 -methylpyridyl)]pyrrole from dimethylglyoxime and acetylene in the Trofimov reaction. Mendeleev Commun 2 74—75. 

Trofimov, B.A., E.Yu. Schmidt, A.I. Mikhaleva et al. 2009. One-pot assembly of 4-methylene-3-oxa-l-azabicyclo[3.1.0]hexanes from alkyl aryl(hetaryl) ketoximes, acetylene, and aliphatic ketones A new three-component reaction. Tetrahedron Lett 50 3314-3317. 

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