Iminium ions functionalization

Excited states of iminium ion functional groups have been shown to undergo one electron reduction readily from a number of unlikely one electron donors such as simple olefins, aromatic hydrocarbons, alcohols and ethers. PET reaction from these systems have led to the development of synthetically important carbon-carbon bond forming methodology. A number of studies... 

The Baldwin and Whitehead proposal [58] went on to suggest that the initial [4 + 2] adduct 119 can undergo redox exchange to give the pentacyclic intermediate 122 shown in Figure 3.6. Hydrolysis of the iminium ion functionality in 122 leads to a tetracyclic seco-skeleton containing an aldehyde functionality. The skeleton and aldehyde functionality present in the Baldwin and Whitehead tetracyclic intermediate 123 correspond exactly with the skeleton and aldehyde functional group placement in ircinals A (102) and B (103). Finally,... 

These pentacyclic products arise from aniline-derived iminium ions functioning as dienes rather than heterodienophiles in two sequential [4+2] cycloaddition reactions with cyclopentadiene. It is noteworthy that use of the preformed Schiff base under non-aqueous conditions leads to the formation of tricyclic tetrahydroquinoline derivatives wherein one cyclopentene unit is incorporated [5]. 

The aza-Cope/Mannich reaction takes advantage of the facility with which a y,<5-unsaturated itninium ion, such as 6, participates in a [3,3] sigmatropic rearrangement to give an isomeric species which is suitably functionalized for an intramolecular and irreversible Mannich cyclization (see intermediate 7). The aza-Cope rearrangement substrate 6 is simply an unsaturated iminium ion which can be fashioned in a number of ways from a homoallylic... 

Iminium ions bearing an electron-withdrawing group bonded to the sp carbon of the iminium function are very reactive dienophiles. Thus, iminium ions 26 generated from phenylglyoxal (Scheme 6.15, R = Ph) or pyruvic aldehyde (R = Me) with methylamine hydrochloride, react with cyclopenta-diene in water at room temperature with good diastereoselectivity [25] (Scheme 6.15). If glyoxylic acid is used, the formation of iminium salt requires the free amine rather than the amine hydrochloride. 

Moreover, Kim and coworkers have shown that a-amino-butyrolactones can be synthesized by a related process employing the amino acid homoserine with an unprotected hydroxy functionality [31]. In a more recent publication by the same research group, morpholin-2-one derivatives of type 9-37 have been prepared (Scheme 9.6) [32]. Herein, glycolaldehyde dimer 9-32 acts as a bifunctional compound, which first reacts with the a-amino acids 9-33 to give the iminium ions 9-34,... 

Addition of organocopper reagents to imine derivatives can readily afford functionalized amine derivatives. Three recent examples are shown below (Equations (129) and (130) Scheme 102).498,498a,498b In these cases, iminium ions are employed as an activated imine. 

Perhydrooxazolo[3,2- ]pyridines 338 are excellent precursors of iminium ions 339 obtained after treatment of the oxazolidine with either a Bronsted or Lewis acid. Trapping of these intermediate iminium ions with nucleophiles then allows for substitution at the C-8a position together with ring opening, yielding functionalized piperidines 340 (Scheme 93). 

The Catalysis Concept of Iminium Activation In 2000, the MacMillan laboratory disclosed a new strategy for asymmetric synthesis based on the capacity of chiral amines to function as enantioselective catalysts for a range of transformations that traditionally use Lewis acids. This catalytic concept was founded on the mechanistic postulate that the reversible formation of iminium ions from a,p-unsaturated aldehydes and amines [Eq. (11.10)] might emulate the equilibrium dynamics and 7i-orbital electronics that are inherent to Lewis acid catalysis [i.e., lowest unoccupied molecular orbital (LUMO)-lowering activation] [Eq. (11.9)] ... 

Formation of C-C bonds remains the ultimate challenge to the synthetic chemist. The employment of new synthetic methods in complex target synthesis can be frustrated by a lack of functional group tolerance and substrate specificity. These problems can be somewhat alleviated within conjugate addition reactions by the use of secondary amine catalysts where a number of important and highly selective methods have been developed. Two principle classes of nucleophile have been shown to be effective in the iminium ion activated conjugate addition of carbon nucleophiles to a,P-unsaturated carbonyl systems aryl, heteroaromatic and vinyl... 

The established activity of ethereal a-C-H bonds toward carbene and nitrene insertion has evoked new applications for sulfamate oxidation [76-78] In principle, a C-H center to which an alkoxy group is attached should be a preferred site for amination irrespec-hve of the addihonal functionality on the sulfamate ester backbone (Scheme 17.20). Such a group can thus be used to control the regiochemistry of product formation. The N,0-acetal products generated are iminium ion surrogates, which may be coupled to nucleophiles under Lewis acid-promoted conditions [79]. This strategy makes available substituted oxathiazinanes that are otherwise difficult to prepare in acceptable yields through direct C-H amination methods [80]. 

The epoxidation of olefins catalyzed by iminium salts and amines (or ammonium salts) is emerging as a new technique for the functionalization of simple aUcenes. These catalysts have relatively simple structures and hence are easily produced at scale they offer potential as green oxidation catalysts. These organic salts are effective oxygen transfer reagents towards electron-rich unfunctionalized olefins. For the iminium salt systems oxone oxidizes an iminium salt to the oxaziridi-nium intermediate, which then transfers oxygen to the olefin and as oxone reacts readily with iminium ions to regenerate the oxaziridinium species catalyti-cally, efficient oxidation is possible. 

Iminium ion-vinylsUane cyclization. This reaction can be used to control the configuration of exocyclic double bonds /i to the nitrogen function of alkaloids. Thus, reaction of the (Z)- and (E)-vinylsilanes 1 and 2 with paraformaldehyde (excess) and tf-camphor-10-sulfonic acid proceeds with >98% retention of configuration to give 3 and 4, respectively. The latter product is identical with the natural indoloquinolizidine alkaloid deplancheine. ... 

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