Propargylic Ether Substrates

Continuing the organocobalt theme, two groups have reported using the Pauson-Khand reaction with carbohydrate templates to construct bis-annulated pyranosides. Propargylic ether substrates such as 148 and 150 provided the isomeric tricyclic systems 149 and 151, while the propargyl malonate substrates 152 and 154, cyclized to the isomeric tricyclic systems 153 and 155 (Scheme 38). ... 

As far as propargyl thioethers are concerned, the substrates in this section follow all the principles discussed for propargyl ethers and propargylamines in the two preceding sections. For alkyl propargyl thioethers typical bases used are sodium amide in liquid ammonia, alcoholate or alkali metal hydroxide [178, 186-189, 191, 287-291], and again some derivatives of carbohydrates have been used successfully [292, 293], If an ester group is also present in the molecule, the reaction can be accompanied by a hydrolysis to the carboxylate [294]. 

As mentioned in the Introduction, this chapter focuses on reactions that deliver allenes as the product. The principles discussed in Sections 1.2.1-1.2.9, of course, also allow the synthesis of allenes as reactive intermediates, which due to other functional groups that are present, undergo further reactions in situ. The most important examples here are base-catalyzed isomerizations to furans [347, 348] ring transfer reactions of propargylic ethers or amines [216, 349-371] and enyneallene cycliza-tion reactions starting from propargylic sulfones [372-375] and related substrates [376, 377]. Details are discussed, for example, in Chapters 16 and 20. 

Although the preparation of the substituted allene ether substrates for the Nazarov reaction is not the topic of this chapter, it is necessary to mention a few aspects of their synthesis. Lithioallene 1 (Eq. 13.13) can be trapped with chlorotri-methylsilane to give 35 [6]. Exposure of 35 to sec- or tert-butyllithium leads to allenyl-lithium 36, which can be trapped with alkyl halides or other electrophiles to give 37. Desilylation of 37 leads to 38. This is somewhat laborious, but it leads to allene 38 uncontaminated by propargyl ether 39. Exposure of 39 to n-butyllithium, followed by quenching with acid, typically produces mixtures of 38 and 39 that are difficult to separate. Fortunately, one need not prepare allenes 38 in order to access the C6-sub-... 

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. 

Yokozawa [44] also inverted the methodology and generated a-propargyl ethers 91 from carbonyls 6, alkoxysilanes 38 and allenylsilanes 90. Aromatic aldehydes remained the best substrates but aliphatic aldehydes or ketones could be induced to react, though the yields remained modest (Scheme 13.36). 

For both reactivity and regioselectivity, however, a compromise must be found between the bulkiness of the reagents (alkyne and carboxylic acid) and the steric hindrance of the diphosphine ligand, all of which are present in the coordination sphere of the ruthenium center during the catalytic process. Thus, with the more bulky trimethylsilylacetylene, the less hindered bis(diphenylphosphino)ethane ligand provides an efficient ruthenium catalyst (Ru(methallyl)2(dppe)) for producing silylated enol esters. Better reactivity is also observed with Ru(methal-lyl)2(dppe) as catalyst precursor when propargylic ethers are used as acetylenic substrates (Scheme 5) [10]. 

Aryloxymethylthiopyrano[3,2-c]pyran-5-ones, derived from a 4-mercaptopyran-2-one by thermal rearrangement of a propargyl ether, are suitable substrates for an aryl radical cyclisation. Only products arising from a 6-endo cyclisation are observed and in some instances one diastereomer of the annulated benzopyran is formed exclusively (Scheme 43) <06S2725>. 

No racemisation is observed during the Pt(IV)-catalysed cyclisation of chiral propargyl ethers to chromenes. The PtCU catalyst appears to activate selectively the triple bond to nucleophilic attack by the arene and enables this well-established route to chromenes to be carried out under mild, neutral conditions and with a variety of substrates (Scheme 12) <03T8859>. A Pt-catalysed 6-endo hydroarylation of an alkynone combined with an intramolecular Michael addition are the key steps in a synthesis of the rotenoid deguelin <030L4053>. 

Allyl propargyl ethers are also good substrates for the Wittig rearrangement. Deprotonation of the propargyl position is relatively facile. 

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. 

Substrate-induced 1,2 and 1,3 asymmetric induction are observed for the rearrangement of oxygenated propargyl ethers 1678,79. Simple diastereoselection follows previously established trends modest antijsyn ratios are ohtained for -olefinic substrates, while the corresponding Z-isomers yield exclusively sy -products. Levels of induced diastereoselection are excellent for both E- and Z-substrates. 

In a formal synthesis of brefeldin A, treatment of the allyl propargyl ether 305 with the base n-BuLi promoted deprotonation a- to the alkyne, followed by rearrangement to give predominantly the homoallylic alcohol 306 (3.199). " Likewise, deprotonation and rearrangement of the macrocyclic substrate 307 promoted rearrangement to the homoallylic alcohol 308, used in a synthesis of the diterpene kallolide B (3.200). Regioselective deprotonation of the diallyl ether 309 and... 

Regiocontrolled net hydroboration of terminal alkynes can also be realized due to the nature of NHC-Cu complex employed. Thus, with an iV-arylated NHC (e.g., IMes or IPr), a-vinylboronates are formed, while with a bulky 7V-alkyI NHC-Cu, the p-isomer prevails. Substrates such as propargyl ethers, amines, and a variety of aryl-substituted alkynes have all been studied. ... 

The substrate can be prepared by standard etherification reaction of a phenol derivative with a propargylic halide [lb]. Further carbon-carbon bond forming reactions of the terminal acetylenic carbon via metal acetylide provides a variety of substituted propargyl aryl ethers. Direct preparation using substituted propargyl ether is also possible. 

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