Azides, alkyl reactions

A variety of triazole-based monophosphines (ClickPhos) 141 have been prepared via efficient 1,3-dipolar cycloaddition of readily available azides and acetylenes and their palladium complexes provided excellent yields in the amination reactions and Suzuki-Miyaura coupling reactions of unactivated aryl chlorides <06JOC3928>. A novel P,N-type ligand family (ClickPhine) is easily accessible using the Cu(I)-catalyzed azide-alkyne cycloaddition reaction and was tested in palladium-catalyzed allylic alkylation reactions <06OL3227>. Novel chiral ligands, (S)-(+)-l-substituted aryl-4-(l-phenyl) ethylformamido-5-amino-1,2,3-triazoles 142,... 

Cs azide were active catalysts in the alkylation reaction, whereas alkali metal oxide clusters showed no activity at all. 

This reaction may involve stepwise addition of the two equivalents of PhNCS via a 3-membered ring intermediate, RN—S—C=NPh.66 A thia-ziridine was also suggested by Borsche67 to explain the formation of 4-phenyl-5-phenylimino-l,2,4-dithiazolidine-3-thione from the aluminum chloride-catalyzed decomposition of phenyl azide in carbon disulfide. If a 4-substituted thiatriazoline is formed from phenyl isothiocyanate and the alkyl azide, the reaction may then be formulated as indicated in Eq. (21). This scheme is supported by the recent findings of Neidlein and... 

Stable triazolines are obtained from aryl azides and V-alkyl and N-aryl maleimides (Scheme 81 )307-309a the reaction succeeds with silyl azides310 and is utilized in the synthesis of polymers from bisazides and bismaleimides.311 312 Unlike maleimides, maleic anhydrides do not yield stable triazolines with trimethylsilyl azide the reaction products are oxazinediones (Section IV,A).310,313,314... 

Pyrrolidines are an important class of five-membered heterocycles with noteworthy biological properties [46]. In addition to pharmaceutical applications, the pyrrolidine moiety has also been widely used as a chiral auxiliary for asymmetric synthesis [47]. Although many elegant syntheses of chiral nonracemic pyrrolidines have been reported within the past decade or so [48-50], an alternative approach based on the intramolecular reaction of an azide and organoborane has been developed very recently [51-53], This approach utilizes the hydroboration-azide alkylation tandem reaction as a key sequence, taking advantage of the efficient stereocon-trolled steps. Scheme 20 shows an application of the synthesis of 3-substituted 5-(2-pyrrolidinyl)isoxazole which has been found to have nanomolar activity, comparable to (5)-nicotine, against whole rat brain [54]. 

The reaction of trialkylboranes with iV-chloroalkylamines can be used to synthesize a wide variety of functionally substituted dialkylamines in good yields [66,67], and it complements the synthesis of secondary amines via the reaction of trialkylboranes with organic azides. The reaction is analogous to the reaction of chloramine with organoboranes, and presumably occurs via an anionotropic migration of an alkyl group from boron to nitrogen (Scheme 24). 

The lower stereoselectivity compared with the azidation of the imide enolate 6 (see Section 7.1.1.) is surprising in view of the much higher selectivity (>96%) observed in the alkylation reactions of 610. 

A typical rearrangement of an alkyl azide is reaction (71) to form... 

Sulfonyl Azides. Alkyl- and arylmagnesium halides,305 306 as well as alkyl-307, aryl- (see Eq. 70),308-312 and heteroaryllithium313 reagents add to sulfonyl azides to give triazene salts which may be reduced to amines 305 310 312 Gr converted into azides. The latter reaction has been accomplished by an aqueous workup with the highly hindered 2,6-dimesitylphenyl azide,314 whereas quenching with aqueous potassium hydroxide (see Eq. 72)305,315 sodium bicarbonate,313 or sodium pyrophosphate305,316 (see Eqs. 67 and 74) is necessary with other arenesulfonyl azide adducts. Thermolysis of the dry triazene salts also leads to azides,307,308 but because of the hazards involved, this procedure is not recommended. 

The development of the chemistry of the tetrazoles up to the end of 1965 has been reviewed in two papers by Benson.1 2 Shorter reviews of specific aspects of tetrazole chemistry include alkylation reactions of tetrazoles,3 synthesis of tetrazoles from aminoguanidines,4 influence of solvents on tetrazole synthesis from 1,3-cycloadditions of azides,3 general aspects of tetrazole chemistry,6 azidoazomethine tetrazole isomerism,7,8 tetrazolinyl radicals,9 and complexes of 1,5-disubstituted tetrazoles.10... 

Thermal decomposition of sulfonyl azides produces variable amounts of alkylazides presumably through a radical mechanism [75, 76]. The first preparative and attractive tin-free procedure for the azidation of radicals was recently reported. Secondary and tertiary alkyl iodides and dithiocabonates are easily transformed into the corresponding azides by reaction with ethanesulfonylazide in the presence of di-lauryl peroxide (DLP) as radical initiator (Scheme 27, Eq. 27.2). Interestingly, this... 

The alkylation reaction in a two-phase system was also extended to various heteronucleophiles [11]. Secondary amines (morpholine, benzyhnethylamine, etc.) as well as primary amines (n-butylamine, 2,2-diethylpropargylamine, cyclohexyl-amine, a-methylbenzylamine, etc.) react for example with ( )-cinnamyl acetate to give only the monoaUylated product in quite good yields [Eq. (2)]. The water-soluble nucleophiles sodium azide and sodium p-toluene sulfinate react also under these conditions, giving the corresponding aUyl azide and allyl p-toluene sulfone in 92 and 95% yield, respectively. 

Alkyl isocyanates, like n-butyl isocyanate, do not react with different alkyl azides and aryl azides respectively. In contrast, aryl isocyanates 131 react with alkyl azides 130 like n-butyl azide or cyclohexyl azide to yield 1-alkyl-4-aryl-A -tetrazoline-5-ones 132, however, aryl isocyanates do not react with aryl azides. The reactions take place within some hours and up to several days at elevated temperatures, ranging from 55 to 130 °C, and are performed in benzene or without solvent (Scheme 29A). The addition of aryl azides to acyl isocyanates, such as benzoyl isocyanate or carboalkoxy isocyanates like chloroacetyl isocyanate and trichloroacetyl isocyanate, was unsuccessfully attempted at different reaction conditions [107]. 

It is important to understand that alkyl azides may be thermally or photochemically unstable, and sometimes explosive, so great care is always exercised when this chemistry is used. If one exercises the proper caution, however, azide substitution reactions are a reasonable method for making primary amines from primary and secondary alkyl halides. 

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