Propargyl ethers, rearrangement

A reliable predictive model for simple diastereosclcction and high levels of chiral transmission have contributed to the utility of the propargyl ether rearrangement as an important tool for the elaboration of remote stereochemical relationships in steroidal systems52 >4. The stereochemical trends observed for acyclic substrates arc maintained in these rigid systems of note is the reversal of simple diastereoselectivity and 1,4 chirality transfer for trimcthylsilylpropynyl ethers 59 and 61, which parallels the behavior of similarly functionalized acyclic substrates52 53. 

Bisphenol A propargyl ethers rearrange to chromenes (I) on heating in the range from 150°-220°C [35]. This is normally carried out in a solvent such as diethylbenzene (Dowtherm J). These chromene-propargyl ether monomer mixtures are of the structure... 

Cleavage of propargyl ethers by Grignard reagents 12-2 Rearrangement of alkynes... 

The cyclisation of naphthyl propargyl ethers occurs efficiently under microwave irradiation leading to naphthopyrans, but naphthofurans are formed in the presence of base <96JCR(S)338>. The thermal rearrangement of naphthyl 3-trimethylsilylprop-2-ynyl ethers yields the 4-trimethylsilyl derivatives of naphthopyrans <96H(43)751>. 

Shortly after Trost s works, two investigations demonstrated the high reactivity of platinum halide salts for this type of reactions. Blum reported a PtCU-catalyzed rearrangement of allyl propargyl ethers to 3-oxabicyclo[4.1.0]-heptenes (Scheme 79).294 This series of reactions also represented the premiere entry into the versatile formation of cyclopropyl products based on skeletal rearrangements of enynes.295 This intriguing aspect is discussed further. 

Another abnormal Claisen rearrangement is the product formed on heating phenyl propargyl ether. The normal product O-allenyl phenol rearranges by a [1, 5] hydrogen shift and then there is an electrocylic ring closure to give chromene which is the observed product. 

Two groups independently demonstrated that the strategy for the preparation of 55 could be used for the synthesis of 2-substituted-3-allenylbenzo[b]furans 59 (Scheme 3.31). The synthesis of 59 was achieved by intermolecular cyclization between alkynylphenols 56 and propargyl carbonates 57 [67] or by intramolecular rearrangement of (2-alkynylphenyl)propargyl ethers 58 [67, 68]. 

The bis(oxazoline) S, 5)-(115) has been used as an external chiral ligand to induce asymmetric diastereoselective lithiation by r-BuLi during [2,3]-Wittig rearrangement of achiral substrates, (fj-crotyl propargylic ethers.It is believed that the enantios-electivity is determined predominantly at the lithiation step. 

Norpseudoephedrine-derived amino ether 81 was also used as a chiral coordinating agent for the enantioselective [2,3]-Wittig rearrangement. The rearrangement of propargyl ether 82 induced by n-BuLi/81 provided allenyl alcohol (5 )-83 in 62% ee (equation 45). In contrast, a similar reaction with (-)-24 provided only 9% ee of (S)-S3. 

It is noteworthy that the rearrangement of crotyl propargyl ether 86 with f-BuLi/f, )-27 at —95 °C carried out in pentane provided [2,3]-shift product 87 in high enantiopurity (89% ee, 47% yield) with high (>95%) anf/-selectivity (equation 48). 

TABLE 4. [1,4]-Wittig rearrangement of propargyl ether systems... 

Attempts to isolate 1,3-dilithiated propargylic ethers with two equivalents of BuLi at temperatures above -20 give unsatisfactory results, because the dilithio compounds are unstable. In the case of HCsCCH2Or-Bu, HCsCCH(-f-Bu)OH is found after aqueous hydrolysis, possibly as a result of a Wittig-rearrangement [2]. At temperatures below -20 C the dilithiation is too sluggish to be of practical interest. With the super-basic reagent BuLi.t-BuOK in a THF-hexane mixture dipotassiation can be effected in a relatively short time at low temperatures. 

Ether was a better solvent in cases where the propargylic position was unsubstituted (methylene group) since, in THF, a competitive [1,2] -Wittig rearrangement took place and led to diminished yields. When applied to the secondary homoallylic propargyl ethers 388, the zinc-ene-allene cyclization afforded the c -2,3,5-trisubstituted tetrahydrofurans 389 with moderate to satisfactory levels of diastereoselectivity, which could be rationalized by the preferential pseudo-equatorial positioning of the homoallylic substituent in the cyclic... 

THF if CuBr is present.1393 The reaction takes place either with or without allylic rearrangement.1394 Propargylic ethers give allenes.1395 Vinylic ethers can also be cleaved by Grignard reagents in the presence of a catalyst, in this case, a nickel complex.1396 Silyl enol ethers R2G=CROSiMe3 behave similarly.1397... 

A particularly useful chromene synthesis involves the thermal rearrangement in an inert solvent of aryl propargyl ethers (33) (62CPB926,63CPB1042) which are conveniently prepared from a phenol and a chloroalkyne. An indication of the ease of cyclization is apparent from the presence of chromene in the ethers prepared in this manner. 

Electron-withdrawing m-substituents will decrease the electron density at the aromatic terminus of the [3,3]-rearrangement, thereby retarding the reaction. This allows polymerization of the terminal alkyne to compete successfully with the cyclization. However, the presence of a m -substituent has a much more significant effect the cyclization of m-substituted aryl propargyl ethers can lead to two isomeric products (46a and b). 

The pyrolytic reactions of pentafluorophenyl and heptafluoro-2-naphthyl propargyl ethers give product mixtures containing benzo- and naphtho[6]furan derivatives, resulting from initial Claisen rearrangement followed by further intra- and intermolecular reactions.31 34... 

The propargyl ether 1 was heated in refluxing dimethylaniline for 5 hours in the expectation that Claisen rearrangement followed by cyclisation would lead to the linear tricyclic system. The only product - isolated in only 12.5% yield - was, however, the angular tricyclic ketone 2. 

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