Additions to Imines

Allenylation of N-tosylimines, such as 68, has been shown to effect the Kwon armulahon with the allene derivative 69 on catalysis with the axiaUy chiral 

Since alkenes are relatively impotent precursors to aziridines, especially with regard to stereoselective reactions, substantially greater advances have been made in this field by means of the addition reactions between imines and a range of car-bene equivalents. 

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Acyl isocyanates (13,X = O, S) have been shown to react as heterodienes ia most cycloadduct formations. Notable examples iaclude autodimerization and the addition to imines (46,47). Unlike aromatic isocyanates, it is not possible to predict the reaction pathway nor the stmcture of the products which may arise from a given approach or set of reaction conditions. 

Catalytic enantioselective addition to imines, in particular, aza-Diels-Alder reaction 99CRV1069. 

Auxiliary-Induced Diastereoselection I.4.3.3.I. Auxiliary Croup in the Enolate Addition to Imines or Iminium Salts... 

Table 1.2 gives a representative sampling of eqnilibrinm constants for additions to varions types of carbonyl compounds. Notice that there are nnmerons gaps in the table. This means that mnch remains to be done in the stndy of carbonyl addition reactions. In trying to devise schemes for predicting the eqnilibrinm constants for snch reactions, the scarcity of experimental data is a serions handicap. There are many fewer equilibrium constants for additions to imines, and even fewer cases where... 

Regarding the reagent control asymmetric addition to imines, there were three reports with aldo-imines. Based on our best knowledge, no asymmetric addition to ketimine was reported prior to our work (vide infra). 

Several reviews on the synthesis of aziridines have been published in the previous year. These publications include a review on the silver catalyzed addition of nitrenes (among other intermediates such as carbene) across a double bond <06EJOC4313> a review on sulfur ylide addition to imines to form aziridines <06SL181> a review on nitrogen addition across double bonds <06ACR194> a general review on functionalization of a,p-unsaturated esters with some discussion of aziridination <06TA1465>... 

Radical additions to imines, nitrones, and related compounds 401... 

Other examples of ZnR2-initiated radical additions to C=N bond-containing compounds can be found in a recent review by Miyabe et al 7 Overall, radical additions to imines and related derivatives may be considered as a valuable alternative to nucleophilic additions, particularly for the introduction of secondary and tertiary alkyl groups. In general, organozinc-mediated radical reactions are a new and significant direction with great potential.382,385... 

Lithium ester enolate addition to imines has been used for the construction of optically active p-lactams, e.g. 64 and the lithium enolates have been found to be superior to other metal derivatives for both yields and diastereoselectivity in some cases <00H(53)1479>. Immobilized lithium ester enolates have been utilized for the first time <00OL907> and soluble polymer supported imines were used to obtain N-unsubstituted azetidin-2-ones under mild conditions <00CEJ193>. Both lithium and titanium enolates have been employed to obtain cholesterol absorption inhibitors <99TA4841>. Lithium ynolates 65 add to imines to provide P-lactams in good to excellent yield <00TL5943>. 

Phosphorous acid has also been of use for additions to imines. Originally investigated by Moedritzer and Irani,241 who developed a Mannich-type procedure for the preparation of phosphorus-centered species, the approach was found later to be useful for both primary and secondary amines in reaction with formaldehyde and phosphorous acid. The approach was later used for the preparation of a cationic exchange resin using a polymer substrate.242... 

A variety of reaction conditions have been employed for Pudovik-type additions to imines, including the use of additional tertiary amines,323 324 sodium hydride,325 and sodium ethoxide,326/327 as well as monobasic trivalent phosphorus-containing acids.319/328-340... 

These authors also found that the addition of excess MgO during the in situ preparation of allyltantalum species improved reaction outcomes, even allowing for the first example of allylation of imines derived from aliphatic amines and aliphatic aldehydes (prepared in situ at room temperature in the presence of molecular sieves) (Equation (18)). The selective addition to imines permitted three-component reactions. 

Experimental procedure for acyl zirconocene generation and addition to imines [41] A... 

Zr-Catalyzed Enantioselective Cyanide Additions to Imines (Strecker Reactions)... 

Catalytic asymmetric cyanide addition to imines constitutes an important C—C bondforming reaction, as the product amino nitriles may be converted to non-proteogenic a-amino acids. Kobayashi and co-workers have developed two different versions of the Zr-catalyzed amino nitrile synthesis [73]. The first variant is summarized in Scheme 6.22. The bimetallic complex 65, formed from two molecules of 6-Br-binol and one molecule of 2-Br-binol in the presence of two molecules of Zr(OtBu)4 and N-methylimidazole, was proposed as the active catalytic species. This hypothesis was based on various NMR studies more rigorous kinetic data are not as yet available. Nonetheless, as depicted in Scheme 6.22, reaction of o-hydroxyl imine 66 with 5 mol% 65 and 1—1.5 equiv. Bu3SnCN (CH2C12, —45 °C) leads to the formation of amino nitrile 67 with 91 % ee and in 92 % isolated yield. As is also shown in Scheme 6.22, electron-withdrawing (— 68) and electron-rich (—> 69), as well as more sterically hindered aryl substituents (— 70) readily undergo asymmetric cyanide addition. 

Scheme 6.22. Zr-catalyzed enantioselective cyanide addition to imines in the presence of Bu3SnCN.

CO)sCr=CHNBzli- (cf. 11, 400-401). This carbene, like typical Fischer carbenes, undergoes a photolytic addition to imines to give mixtures of cis- and trans-3-dibenzylamino-p-lactams in fair to good yield. The products are convertible into 3-amino-2-azetidinones.1 2 4 5... 

The diastereoselective addition to imines proceeds well with aromatic enolsi-lanes (249). Propiophenone- and tetralone-derived enolsilanes provide good levels of diastereoselectivity (>95 5) and excellent enantioselectivity (>98% ee) with selective formation of the anti diastereomer. Nonaromatic enolsilanes are somewhat less selective although cyclohexanone enolsilane still provides useful levels of diastereoselectivity and enantioselectivity (92 8 anti/syn and 88% ee at -78°C). A one-pot procedure using glyoxylate, sulfonamide, and enolsilane as coupling partners was developed subsequently, leading to the product in comparable yields and selectivities (250, 251). 

Since then, optically active a-aminophosphonates have been obtained by a variety of methods including resolution, asymmetric phosphite additions to imine double bonds and sugar-based nitrones, condensation of optically active ureas with phosphites and aldehydes, catalytic asymmetric hydrogenation, and 1,3-dipolar cycloadditions. These approaches have been discussed in a comprehensive review by Dhawan and Redmore.9 More recent protocols involve electrophilic amination of homochiral dioxane acetals,10 alkylation of homochiral imines derived from pinanone11 and ketopinic acid,12 and alkylation of homochiral, bicyclic phosphonamides.13... 

Cycloaddition to give heterocycles IV. ADDITION TO IMINES AND CYANIDES... 

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