Ritter reaction, with

The Ritter reaction with unsaturated carbenium ions under either silver-assisted solvolysis or photolytic conditions leads to excellent yields of isoquiaolines (173). The ease of preparation of the requited vinyl bromides makes an attractive route to highly substituted isoquiaolines. 

Davies and Reider (1996) have given some details of the HIV protease inhibitor CRDCIVAN (INDINAVIR) for which (lS,2R)-c -amino indanol is required. Indene is epoxidized enantioselectively, using the lacobsen strategy (SS-salen Mn catalyst, aqueous NaOH and PiNO), to (lS,2/ )-indene oxide in a two-phase system, in which the OH concentration is controlled. Indene oxide was subjected to the Ritter reaction with MeCN, in the presence of oleum, and subsequent hydrolysis and crystallization in the presence of tartaric acid gives the desired amino indanol. 

By analogy with their behavior in mass spectrometry, branched hydrocarbons are cleaved when oxidized in CH3 CN/TEABF4 at —45 °C. The resulting acetamides of the fragments (Table 6) are formed by cleavage of the initial radical cation at the C,C bond between the secondary and tertiary C atom, to afford after a second electron transfer, carbocations, which react in a Ritter reaction with acetonitrile [29]. 

Epoxides also participate in the Ritter reaction with nitriles. An investigation of the ring opening of several alkyl-substituted glycidic esters and amides 181 showed that this transformation occurs with inversion and is completely regiospecific. ° Esters appeared to be somewhat more reactive than amides. However, phenyl-substituted glycidic esters and amides 184 are almost totally nonstereoselective. In addition, the oxazolines 186 are isolated in low yield due to the propensity of intermediate 185 to generate an aldehyde byproduct 187 (Scheme 8.53). 

Olefins also undergo the Ritter reaction with nitriles in the presence of diphenyl diselenide, ammonium persulfate, and trifluoromethanesulfonic acid to produce oxazolines.When cyanamide is used, 2-aminooxazolines are obtained. The active electrophilic agent is phenylselenyl sulfate formed by oxidation of diphenylselenide with ammonium persulfate. The reaction is trans-stereospecific. 

A preliminary experiment indicates the usefulness of similar complexation for Ritter reactions with a propargyl alcohol (equation II). 

Alkyl iodides are cleaved in acetonitrile/lithium perchlorate to iodine and al-kyl.cations. These react prior to or after rearrangement in a Ritter reaction with acetonitrile to form N-alkylacetamides in 21% to 75%yield (Eq. (217) ) 4S8). 

In the Ritter reaction a rather different kind of evidence for the cation is the fact that families of isomeric alcohols all give the same product. In all these cases, rearrangements of the first formed carbocation (Chapter 37) can easily account for the products. Another example in the decalin series is this Ritter reaction with KCN as the nitrile in acidic solution so that HCN is the reagent. The starting material is a spirocyclic tertiary alcohol but the product is a frans-decalin formed by... 

The reaction is akin to the Ritter reaction, with activation achieved by nitration, rather than proton-ation, and the products accordingly retain the nitro group. Additions to 1-phenylcyclohexene (59%) and to franr-stilbene (72%) are stereospecific (trans) cfr-stilbene gives the expected tfireo product (39%) plus some erythro (6%). Reactions of nitrogen dioxide with alkenes are very complex and rarely use-ful. A recent mechanistic paper gives many key references. " Addition of NjOs is occasionally usefiil, as with dicyclopentadiene (Scheme 49). ... 

The anodic oxidation of trimethylacetic acid in acetonitrile, however, leads to t-butylacetamide owing to further oxidation of the intermediate t-butyl radical to the t-butyl cation and its Ritter reaction with MeCN [Eq (3)] [36]. 

The anodic oxidation of substituted (4-hydroxy-3-coumarinyl) phenylthiomethanes in MeCN-LiC104 on a Pt electrode results in a C-S bond cleavage to give N-substituted acetamides by a Ritter reaction with MeCN [123] ... 

Reaction of sugar lactone with ester enolate (the Claisen condensation) gives -keto ester, the resulting 1,3-dicarbonyl compound immediately reacts with the hydroxyl group present in the same molecule to afford a lactol with an axial hydroxyl group. In a recent example shown in O Scheme 4 [8], the product of the reaction was further transformed to the corresponding nitrile or amide by addition of cyanide or a Ritter reaction with benzonitrile in the presence of TMSOTf as a Lewis acid. 

Both nitronium and nitrosonium salts are effective initiators but with quite different results. Thus, propene and nitronium fluoroborate react to produce the secondary a-nitrocarbenium ion which undergoes Ritter reaction with acetonitrile to yield amide (118). Under similar conditions, nitrosonium fluoroborate leads to heterocyclic products. Intramolecular reaction of the nitroso and nitrilium groups, followed by prototropic shifts, affords the iV-hydroxy imidazolium salt (119). This may be either neutralized to produce the iV-oxide or reduced to the imidazole (120 Scheme SS). 

Jirgensons, A., Kauss, V., Kalvinsh, I., Gold, M. R. A practical synthesis of tert-alkylamines via the Ritter reaction with chloroacetonitrile. Synthesis 2000,1709-1712. 

S Cascade reactions implementing the Ritter reaction Recent examples of the Ritter reaction have combined this useful synthetic tool with other reactions and rearrangements to produce complex reaction sequences. For example, Bishop has reported the combination of the Ritter reaction with the Wagner-Meerwein rearrangement, which can result in complex and sometimes unpredictable reaction sequences.17 The use of the Ritter reaction to trap cationic intermediates in the CAN-mediated dimerization of alkoxystyrenes has recently allowed the synthesis of a-aminotetralin derivatives by Nair.18... 

Explain why in the Ritter reaction with hydrogen cyanide and t-butyl alcohol, the product is t-butylamine and not t-butyl cyanide (or trimethylacetic acid). 

The development of carbocations of organometallic complexes of transition metals offers an alternative method of carrying out the Ritter reaction with primary and secondary alcohols, which normally give poor yields. Reaction of the complex 114 with concentrated sulphuric acid at -15 °C in the presence of acetonitrile gives the amide complex in good yield. ... 

The Ritter reaction (with a nitrile and acid) converts either a 6j3-hydroxy-3a,5a-cyclo-steroid or a 3jS-mesyloxy-A -steroid into the 3/ -acylamino-A -derivative... 

If the nitration of olefins by nitronium salts is carried out in acetonitrile, the nitrocarbenium ion intermediates undergo Ritter reaction with the solvent to form nitroacetamides [87]. 

An appealing alternative to the substitution with azide is provided by the Ritter reaction with benzonitrUe, from which the oxazolines can be isolated as well. [324, 330] It is interesting that the Ritter reaction produces a high (18 1) diastereo-meric ratio. It may be assumed that the configuration of the benzyl cation is stabilised by the neighbouring hydroxy-group in the a-position. 

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