Propargyl-allenyl isomerization

This system was described in one report and has been synthesized by a copper-assisted cycloisomerization of alkynyl imines. The authors proposed the following mechanism at first, 372 could undergo a base-induced propargyl-allenyl isomerization to form 373 next, coordination of copper to the terminal double bond of the allene (intermediate 374) would make it subjected to intramolecular nucleophilic attack to produce a zwitterion 375. The latter would isomerize into the more stable zwitterionic intermediate 376, which would be transformed to the thiazole 377 (Scheme 55) <2001JA2074>. 

A dipolar route of heterocyclization of a monocyclic enallenyl nitrone (from precursor 126 by base-catalyzed propargyl-allenyl isomerization) leads to lactam 127 (05EJO2715) that is an analog of astrocasine (8). 

Several thiopropargylimines 32 underwent ring-closure to the pyrroles 33 upon treatment with Cul in hot A V-dimethylacetamide (DMA). This process involves a propargyl-allenyl isomerization followed by a 1,2-migration of the thio-group in the intermediate allenes <03AG(E)98>. 

It was hypothesized that propargyl allenyl isomerization produces an allenic intermediate 246 first which cycloisome-rized to the major product 246 (path a, Scheme 68). Alternatively, an intermolecular nucleophilic attack of the sulfur atom at the central carbon atom of the allene can transform it into the thiirenium ion 247, which then is transformed into the minor product 245 via Ad -E 247 —> 248 or through a direct SN2-Vin-type of process (path b. Scheme 68). This reaction was successfully applied for synthesis of furans and pyrroles (from thiopropargylimines) (Scheme 69 Table 10). 

Kel in et al. reported that the copper-assisted cycloisomerization of the alkynyl imines 320 gave the pyrroles 321 in high yields (Scheme 101).169 Mechanistic studies revealed that this reaction proceeded via the propargyl-allenyl isomerization of 320 to the... 

The syntheses of thiophenes (as well as pyrroles and cyclopentenes) were developed via a sequence consisting of a propargyl-allenyl isomerization, a Michael addition, and an intramolecular Wittig reaction shown below (14JOC10867). 

A sequence involving propargyl-allenyl isomerization and aza-electrocyclization have been reported for the synthesis of polyfunctionalized quinolines (Scheme 31). ... 

The treatment of 6-methyl-3-(prop-2-ynylsulfanyl)-1,2,4-triazin-5(2f/)-one with a catal)4ic amount of Pd(PhCN)2Cl2 in HMPT afforded 2,6-dimethyl-7/f-thiazolo- [3,2-fc][l,2,4]triazin-7-one via propargyl-allenyl-[3,3] sigmatropic rearrangement, intramolecular hydrothiolation, and C=C bond isomerization (eq 195).i" ... 

Note 2. Traces of unreacted triethylamine might cause partial isomerization of the allenyl sulfoxide into the propargyl sulfoxide. The methyl iodide is added to ensure that no triethylamine remains. 

In the Pd-catalyzed cross-coupling reactions of acylzirconocene chlorides with allylic halides and/or acetates (Section 5.4.4.4), the isolation of the expected p,y-unsaturated ketone is hampered by the formation of the a, P-un saturated ketone, which arises from isomerization of the p,y-double bond. This undesirable formation of the unsaturated ketone can be avoided by the use of a Cu(I) catalyst instead of a Pd catalyst [35], Most Cu(I) salts, with the exception of CuBr - SMe2, can be used as efficient catalysts Thus the reactions of acylzirconocene chlorides with allyl compounds (Table 5 8 and Scheme 5 30) or propargyl halides (Table 5.9) in the presence of a catalytic amount (10 mol%) of Cu(I) in DMF or THF are completed within 1 h at 0°C to give ffie acyl--allyl or acyl-allenyl coupled products, respectively, in good yields. ill... 

These allenes are very important for organic synthesis and their use is discussed in Chapter 8. For their synthesis usually a strong base is needed, typically KOtBu. There are many examples most of them cover the isomerization of a propargylic ether to the corresponding allenyl ether. 

Because of the usually high temperatures required to rearrange propargyl sulfi-nates to allenyl sulfones, a report about such palladium-catalyzed transformations seems to be promising [106], Even at low temperatures the synthesis and isomerization of trifluoromethanesulfinate 51 are possible if, during the reaction of the ter-... 

The isomeric propargylic stannylated aldehyde intermediate, on the other hand, could be prepared from the alcohol precursor without competing cyclization to an seven-membered enol ether product (Eq. 9.105). Treatment of this stannane with SnCl4 afforded the cis-disubstituted tetrahydrofuran stereoselectively. Presumably, this reaction proceeds through an allenyl trichlorostannane intermediate. 

Intramolecular [4+2]-cycloaddition reactions, which involve base-induced isomerization of a propargyl ether to an allenyl ether, have been extensively studied. Treatment of 157 with a base caused an intramolecular Diels-Alder reaction of the intermediate allenyl ether to give tricyclic compounds 158 [131]. An asymmetric synthesis of benzofuran lactone 159 was achieved by an analogous procedure [132],... 

A very unusual Nazarov cyclization of propargyl vinyl ketones has been reported by Hashmi et al. (Eq. 13.16) [18]. Propargyl alcohol 50 was oxidized to ketone 51 with the Dess-Martin periodinane. Attempts to purify 51 by column chromatography on silica gel led to cyclopentenone 53 in 59% isolated yield. This suggests that the solid support catalyzed the isomerization of 51 to allenyl vinyl ketone 52, which was not isolated, but which underwent spontaneous cyclization to 53. This result is consistent with earlier observations of the great ease with which allenyl vinyl ketones undergo the Nazarov reaction (cf. 8, Eq. 13.2). 

A similar isomerization of an allenyl ketone, catalyzed by a Cr(CO)sL complex, is most probably the mechanistic key step of the palladium-catalyzed conversion of chromium carbene complexes and propargyl bromide to furans. In control experiments different aryl and alkyl allenyl ketones 96 isomerized to the furans 99 in the presence of 10 mol% of Cr(CO)5(NEt3) in good yields (Scheme 15.31) [70],... 

Ketones and aldehydes possess the highest a-acidity, many examples being known. In fact, it is usually very difficult to keep a terminal propargyl ketone from isomerizing to the allenyl ketone. Thus the oxidation of a homopropargylic alcohol 54, a typical precursor, in most of these cases directly delivers the allenyl ketones 56 rather than the propargyl ketones 55 in high yields [92-109] (Scheme 1.23). 

To elucidate the reaction pathway, deuterium-labeled allenyl pinacol boronate 10 was prepared, and the addition reaction with hydrazonoester 6 was conducted in the presence of Bi(OH)3 and Cu(OH)2 (Scheme 4). In both Bi- and Cu-catalyzed cases, the reactions proceeded smoothly (in quantitative yields in both cases). In the Bi(OH)3-catalyzed reaction, a major product was allenyl compound 11, in which the internal position was deuterized. It was assumed that a propargyl bismuth was formed via transmetalation from boron to bismuth, followed by addition to hydrazonoester via y-addition to afford allenyl compound 11. Thus, two y-additions could selectively provide a-addition products [75, 76, 105, 106]. It was confirmed that isomerization of 10 did not occur. Recently, we reported Ag20-catalyzed anti-selective a-addition of a-substituted allyltributyltin with aldehydes in aqueous media [107], On the other hand, in the Cu(OH)2-catalyzed reaction, a major product was propargyl compound 12, in which the terminal position was deuterized. A possible mechanism is that Cu(OH)2 worked as a Lewis acid catalyst to activate hydrazonoester 6 and that allenyl boronate 10 [83-85] reacted with activated 6 via y-addition to afford 12. 

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