Ethers isoureas

Inversion of configuration.1 The configuration of a secondary alcohol (2) can be inverted by reaction with dicyclohexylcarbodiimide (1) to form an isourea ether (3), which is allowed to react, without isolation, with formic acid with formation of the ester 4 with inverted configuration. 

Moreover during the reaction, decomposition of DMSO to dimethylsulfide occurs resulting in a pungent odour. The treatment with DCC may also lead to the formation of isourea ethers according to reaction shown in Fig. 26. 

Fig. 26 Formation of isourea ethers as a side reaction during conversion of dextran using DCC as coupling reagent...

O-tert-Butyl trichloroacetimidate, prepared in 70% yield by reacting potassium rerr-butoxide with trichloroacetonitrile, reacts with carboxylic acids and alcohols in the presence of a catalytic amount of boron trifluoride etherate at room temperature in cyclohexane-dichloromethane [Scheme 6.35], 7 The method also converts alcohols to ferr-butyl ethers (see section 4.3.2). A very similar reaction that allows /erf-butylation under essentially neutral conditions on a large scale involves reaction of a carboxylic acid with 3-4 equivalents of JV,N -di-isopropyl-Orerf-butylisourea88 [Scheme 6,36].56S9 The reaction proceeds via a tertiary carbocation ion intermediate and since capture of the cation is inefficient, excess isourea is required. The presence of alcohols is tolerated but not thiols or unhindered amines. The reaction conditions are compatible with a range of acid sensitive groups such as AMrityl derivatives and cydopentylidene acetals.90... 

The low solubility of 2 in alkanes or ethers and its crystallinity allowed us to carry out a crystal structure analysis. Previous H NMR studies [7] of 2 1 adducts between R-NCO molecules and l,4-bis(trialkylsilyl)-l,4-dihydropyrazines have indicated the formation of both urea and isourea ftinctionalities (Scheme 3). 

Triphenyllead(IV) methoxide forms a similar stable adduct with di-l-naphthyl-carbodiimide and catalyzes the addition of methanol to the carbodiimide. Two of the four Ti-0 bonds in titanium(IV) tetraisopropoxide add to di-p-tolylcarbodiimide to give the bis(isourea) ether . 

Oxazolidines are obtained in good to excellent yields by the palladium(II)-catalyzed cyclization of A-Boc protected iV-allyl-A -hydroxymethylamines (191) <94CC357>. The palladium species is regenerated by molecular oxygen in DMSO (Scheme 94). Allyl carbamoylmethyl ethers cyclize to oxazolidines by reaction with mercuric acetate <89H(28)663>. Silver triflate catalyzes the cyclization of (9-propargyl isoureas to 4-alkylidene-oxazolidines with high diastereoselectivity <88CC1175>. 

Inoue and co-workers have also reported a variant of the Wittig-type reaction described in Scheme 64 based on isourea ethers. " ... 

A study examined the formation of ethers by substitution at secondary alcohols by the isourea method. (25)-Octan-2-ol provides (7R)-l-methylheptyl phenyl ether by this chemistry. The formation of olefinic by-products suggests the involvement of carbocation intermediates and a mixed 1/5 2 mechanism. 

Spectroscopic and X-ray crystal structure analysis has shown that (/ )- -methylheptyl phenyl ether formed in the reaction between phenol and the isourea derivative of (2S)-octan-2-ol proceeds via the carbenium ion intermediate (9). It is suggested that only 0 the (IJ)-l-methylheptyl phenyl ether (99.4% ee) is formed because attack by the phenol nucleophile on the carbenium ion intermediate can only occur from one direction because of strong shielding by the two bulky cyclohexylamino groups. 

Guanylureas. Diisopropylcarbobidiimide in methylene chloride added dropwise at room temp, during 1 hr. to ethereal fluoroboric acid and ter -butanol in the same solvent, and the product isolated after 2 additional hrs. 1,2,3-triisopropyl-1-isopropylcarbamylguanidine. Y 85%. F. e., also formation of isoureas, s. K. Hartke and M. Radau, Ardi. Pharm. 305, 654 (1972) f. reactions s. ibid. 305, 665, 702, 708, 737. 

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