Oxiranes propargyl

Terminal alkynes react with propargylic carbonates at room temperature to afford the alka-l, 2-dien-4-yne 14 (allenylalkyne) in good yield with catalysis by Pd(0) and Cul[5], The reaction can be explained by the transmetallation of the (7-allenylpailadium methoxide 4 with copper acetylides to form the allenyKalk-ynyl)palladium 13, which undergoes reductive elimination to form the allenyl alkyne 14. In addition to propargylic carbonates, propargylic chlorides and acetates (in the presence of ZnCb) also react with terminal alkynes to afford allenylalkynes[6], Allenylalkynes are prepared by the reaction of the alkynyl-oxiranes 15 with zinc acetylides[7]. 

The stereochemistry of the first step was ascertained by an X-ray analysis [8] of an isolated oxazaphospholidine 3 (R = Ph). The overall sequence from oxi-rane to aziridine takes place with an excellent retention of chiral integrity. As the stereochemistry of the oxirane esters is determined by the chiral inductor during the Sharpless epoxidation, both enantiomers of aziridine esters can be readily obtained by choosing the desired antipodal tartrate inductor during the epoxidation reaction. It is relevant to note that the required starting allylic alcohols are conveniently prepared by chain elongation of propargyl alcohol as a C3 synthon followed by an appropriate reduction of the triple bond, e. g., with lithium aluminum hydride [6b]. 

Scheme 2.7 Influence of dimethyl sulfide on the Sn2 substitution of propargyl oxirane 20.

Scheme 2.8 Mechanistic model for the formation of the reduction product 26 from propargyl oxirane 23 and lithium cuprates.

The beneficial effect of added phosphine on the chemo- and stereoselectivity of the Sn2 substitution of propargyl oxiranes is demonstrated in the reaction of substrate 27 with lithium dimethylcyanocuprate in diethyl ether (Scheme 2.9). In the absence of the phosphine ligand, reduction of the substrate prevailed and attempts to shift the product ratio in favor of 29 by addition of methyl iodide (which should alkylate the presumable intermediate 24 [8k]) had almost no effect. In contrast, the desired substitution product 29 was formed with good chemo- and anti-stereoselectivity when tri-n-butylphosphine was present in the reaction mixture [25, 31]. Interestingly, this effect is strongly solvent dependent, since a complex product mixture was formed when THF was used instead of diethyl ether. With sulfur-containing copper sources such as copper bromide-dimethyl sulfide complex or copper 2-thiophenecarboxylate, however, addition of the phosphine caused the opposite effect, i.e. exclusive formation of the reduced allene 28. Hence the course and outcome of the SN2 substitution show a rather complex dependence on the reaction partners and conditions, which needs to be further elucidated. 

Scheme 2.9 Influence of copper salt and additives on the SN2 substitution of propargyl oxirane 27 with lithium cuprates. TBS = Si(tBu)Me2.

Scheme 2.10 Sn2 substitution of propargyl oxirane 27 with magnesium cuprates.

The related zinc cuprates formed from diorganozinc reagents and copper(I) cyanide also undergo smooth SN2 substitution reactions with propargyl oxiranes in the presence of phosphines or phosphites (Scheme 2.12). These transformations can also be performed with catalytic amounts of the copper salt since no direct reaction between the organozinc reagent and the substrate interferes [31, 34], and therefore should also be applicable to functionalized organozinc compounds. 

Scheme 2.49 SN2 substitution of propargyl oxirane 23 with a silylaluminum reagent.

Moreover, propargyl oxiranes 202 were found to react with samarium diiodide and ketones to form a,a -dihydroxyallenes 203 with moderate to high anti-diastereo-selectivities (Scheme 2.62). Aurrecoechea and co-workers [99] reported this reductive coupling to proceed smoothly in the absence of a palladium catalyst, i.e. a direct electron transfer from the samarium(II) to the substrate has to take place in order to generate an allenyl/propargyl samarium intermediate of type 184/185, which is then regioselectively trapped by the electrophile. 

Scheme 2.62 Samarium-mediated reductive coupling of propargyl oxiranes with ketones.

Copper-catalyzed enantioselective SN2 substitution of propargyl oxiranes in the presence of chiral phosphoramidites F. Bertozzi, P. Crotti, F. Macchia, M. Pineschi, A. Arnold, B. L. Feringa, Tetrahedron Lett. 1999, 40, 4893—4896. 

To link the two half moieties of the molecule, a Julia-Kocienski olefmation was carried out between the C19 building block 59 (again prepared by syn-SN2 -substitu-tion of a propargylic oxirane with DIBAH) and the C20 building block 60, formed via oxidation of 58 with Mn02 (Scheme 18.19). Although this reaction initially led to the formation of the Z-isomer as the major product, the latter was readily isomerized at room temperature to the desired all-trans-polyene peridinin (6). 

The effect of the BF3 activation on the regioselectivity of the ring opening of vinylic and acetylenic oxiranes is dramatic, as in these conditions the reaction occurs exclusively on the allylic " or the propargylic " position, and still with inversion (Scheme 40). This excellent regioselectivity allows the direct stereospecific preparation of homoallylic and homopropargylic alcohols in excellent yields. In the case of acetylenic oxiranes, a remarkable difference in the reactivity of cis and trans oxiranes has been evidenced, the former being more reactive. 

Although the reaction of alkali acetylides with oxirane proceeds slowly in liquid ammonia 15], it is an excellent method for preparing "homo-propargylic alcohols in quantities of 1 mol or more [2). Since oxirane is very volatile, considerable losses could occur if it is allowed to be swept along with the escaping ammonia vapour. One solution is to carry out the reaction under reflux, using a special condenser filled with dry ice and acetone. This would require regular addition of dry ice over a period of at least 12 h. It is much simpler to mix the acetylide... 

Various metal acetylides are used for smooth coupling with propargylic halides and acetates. 2,3-Alkadien-5-yn-l -ols are obtained by the reaction of 2-(l -alkynyl)oxiranes [28,29], As a synthetic application, the unstable 2,3-octadiene-5,7-diyn-l-ol (136), a fungus metabolite, has been synthesized by the coupling of 4-trimethylsilylbutadiy-nylzinc chloride (134) with 2-ethynyloxirane (135) followed by desilylation [31]. 

Normant, J. F. Preparation of propargylic carbenoids and reactions with carbonyl compounds. A stereoselective synthesis of propargylic halohydrins and oxiranes. Eur. J. Org. Chem. 2001, 3295-3300. 

Z)-Phenol-substituted alkenes (67) can be produced by the palladium(0)-catalysed reaction of propargylic oxiranes (66) with phenols. This regio- and stereo-selective (g) addition is believed to occur via the formation of 7t-propargyl- and Tr-allylpalladium complexes. The phenoxy-substituted enones were obtained as by-products and their proportion depended on the reaction conditions.75... 

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