Forming five-membered heterocycles

A completely different, important type of synthesis, which was developed more recently, takes advantage of the electrophilicity of nitrogen-containing 1,3-dipolar compounds rather than the nucleophilicity of amines or enamines. Such compounds add to multiple bonds, e.g. C—C, C C, C—O, in a [2 + 3 -cycioaddition to form five-membered heterocycles. 

Aldehydes, ketones and cumulated double bonds react with oxiranes to form five-membered heterocycles (e.g. Schemes 31 and 32) (64HC(19-1)453). 

It is conceivable that, starting from a pre-formed, five-membered heterocycle of the tetrahydrofuranol type, or even a furanosyl derivative, a contraction or extension of a side chain, according to the situation, would permit synthesis of a 2,5-anhydride of a sugar. This method has been used effectively on several occasions. 

Allenes can also act as the -participant in electrophilic heteroatom cyclizations. Reviews of electrophilic additions to allenes discuss early examples of this type of cyclization.ld le-202 Numerous examples of cyclizations of a-functionalized allenes, including carboxylic acids, phosphonates, sulfinates and alcohols, to form five-membered heterocycles (equation 84) are cited in these reviews. The silver nitrate-mediated conversion of ot-allenic alcohols to 2,5-dihydrofurans203 has recently been applied to trimethylsilyl-substituted systems.204... 

Zhao [4] prepared pro-catalysts, (VI) and (VII), consisting of a transition metal and two nitrogen donor atoms forming five-membered heterocyclic intermediates. When the pro-catalysts were activated with trimethylaluminium, they were used to prepare ethylene dimers and oligomers. 

Nitrile oxides This acid is an effective catalyst for dehydration of primary nitro compounds (RCH,NO,) to nitrile oxides, which can be trapped with dipolarophiles to form five-membered heterocycles. The reaction is carried out in refluxing mesitylene. 

Recently, we reported that reactive trifluoroalkyl substituted 1.3-diazadienes in a formal [4+1] cycloaddition form five-membered heterocycles, eg., /BuN-C(Ph)=N-C(CF3)2-SiCl2 [2]. New investigations have shown that this strategy can be extended, with some decisive modifications, to other heterobutadienes, e g., l,4-diaza-l,3-butadienes I... 

Cyanoformamidines, exhibiting nucleophilic and electrophilic properties in the 1,3-positions, react with hexafluoroacetone forming five-membered heterocycles (86CB2127). This ability to form five-membered heterocycles is the major characteristic of hexafluoroacetone, which is also inherent in some perfluorinated and partially fluorinated ketones, aldehydes, and imines in their reactions with a-functional derivatives of carboxylic acids, as well as w-amino, a-N-alkylamino,... 

The reaction of terminal allyl alcohols proceeds in a 5-endo fashion to give five-membered ring compounds regioselectively and stereoselectively. Subsequent oxidation affords 2,3-5 y -l,3-diols preferentially, regardless of the nature of the catalyst (eq 1). The stereoselectivity increases with increased bulkiness of the al-lylic substituent and the nature of the alkene substituent (see below). 5-Exo type cyclization occurs with homoallyl alcohols to form five-membered heterocycles and 1,3-diols after oxidation. Two chiral centers are produced in this reaction. The 2,3-relationship (anti) is controlled by the allylic substituent, while the 3,4-relationship is determined by the stereochemistry of the alkene the hydrosilation occurs by cis addition of Si-H to the alkene (eq 2). ... 

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