Lewis acids imine additions

Carbon monoxide rapidly inserts into the carbon—zirconium bond of alkyl- and alkenyl-zirconocene chlorides at low temperature with retention of configuration at carbon to give acylzirconocene chlorides 17 (Scheme 3.5). Acylzirconocene chlorides have found utility in synthesis, as described elsewhere in this volume [17]. Lewis acid catalyzed additions to enones, aldehydes, and imines, yielding a-keto allylic alcohols, a-hydroxy ketones, and a-amino ketones, respectively [18], and palladium-catalyzed addition to alkyl/aryl halides and a,[5-ynones [19] are examples. The acyl complex 18 formed by the insertion of carbon monoxide into dialkyl, alkylaryl, or diaryl zirconocenes may rearrange to a r 2-ketone complex 19 either thermally (particularly when R1 = R2 = Ph) or on addition of a Lewis acid [5,20,21]. The rearrangement proceeds through the less stable... 

Compared with aldehydes and ketones, aldimines and ketimines are less reactive towards nucleophilic addition. Furthermore, imine additions are subject to steric constraints, and rapid deprotonation proceeds with imines bearing ot-hydrogen atoms. The Lewis acid promoted addition methodology has provided a solution to these problems. 

In a related example, Hegedus has incorporated chirality into the functionalization of the allenylstannane. Lewis acid-promoted additions of stannylallenamide 359 to simple aldehydes and imines are high i yn-selective processes (Scheme 5.2.76)." The reaction is presumed to occur via antiperiplanar 362, illustrating the anti-SE characteristics of stannyl substitution with a minimization of non-bonding interactions. 

Guanti and coworkers have reported that catalytic amounts (0.1 equiv.) of TMS-OTf can be used in place of stoichiometric amounts of TiCU in silyl ketene acetal-imine additions.When conducted at the optimal temperature of -65 C, 3-amino esters enriched in the anti diastereomer are obtained in 45-85% yields. Use so far has been limited to nonenolizable imines. Interestingly, the observed anti stereoselectivity is independent of the geometry of the silyl ketene acetal, further evidence that a nonpericyclic mechanism is involved in the Lewis acid catalyzed addition of silyl ketene acetals to imines. An applies-... 

Ketene silyl acetals undergo Lewis acid catalyzed addition to imines to give /3-amino esters, which can then be cyclized in a second step to give /3-lactams. Chiral substituents, which might control the configuration of the product, can be introduced into R1, R2, R3 or R4. 

Starting from commercially available Merrifield resin, silyl enol ether 57 was generated in two steps. Lewis acid catalysed addition of 57 to a variety of imines gave amino thioesters 58 which upon reduction with LiBH afforded amino alcohols 59 in moderate to good yields (50-80%). After reduction, the resin was recovered in its thiol form and could be further acylated and re-used. 

Lewis Acid. In addition to the numerous examples of the type throughout this article, several specific examples of TMSCl as a Lewis acid are given here. Addition of diethylzinc to various imines is promoted by different Lewis acids, such as TMSCl, BF3 Et20, and ZnCh, to offer a variety of secondary... 

Lewis Acid Promoted Addition Reactions of Organometallic Compounds Nucleophilic Addition to Imines and Imine Derivatives Nucleophilic Addition to Carboxylic Acid Derivatives... 

In general, Lewis acid-catalyzed addition reactions ofimines require highly sophisticated reaction systems because basicity of the starting imine and the product (amine) may lead to deactivation of the Lewis acid even in organic solvents, needless to say in water. It is noted that this study has addressed this issue for the first time in water. 

Two papers have appeared on carbohydrate approaches to polyhydroxylated quinolizidines. The key step in the synthesis of 165 was a diastereoselective Lewis acid-mediated addition to imine 164 derived from D-arabinose (Scheme 34). ... 

Reduction Conversion of Nitriles into Amines Reduction of a nitrile with LiAIH4 gives a primary amine, RNH . The reaction occurs by nucleophilic addition of hydride ion to the polar C=N bond, yielding an imine anion, which still contains a C=N bond and therefore undergoes a second nucleophilic addition of hydride to give a dianion. Both monoanion and dianion intermediates are undoubtedly stabilized by Lewis acid-base complexafion to an aluminum species, facilitating the second addition that would otherwise be difficult Protonation of the dianion by addition of water in a subsequent step gives the amine. 

The most successful approach in this reaction category has been the use of chiral boron Lewis acid catalysts, in the addition of ethyl diazoacetate to imines reported by Wulff (Scheme 1.33) [59-60]. 

The condensation of nitro compounds and imines, the so-called aza-Henry or nitro-Mannich reaction, has recently emerged as a powerful tool for the enantioselective synthesis of 1,2-diamines through the intermediate /3-amino nitro compounds. The method is based on the addition of a nitronate ion (a-nitro carbanion), generated from nitroalkanes, to an imine. The addition of a nitronate ion to an imine is thermodynamically disfavored, so that the presence of a protic species or a Lewis acid is required, to activate the imine and/or to quench the adduct. The acidic medium is compatible with the existence of the nitronate anion, as acetic acid and nitromethane have comparable acidities. Moreover, the products are often unstable, either for the reversibility of the addition or for the possible /3-elimination of the nitro group, and the crude products are generally reduced, avoiding purification to give the desired 1,2-diamines. Hence, the nitronate ion is an equivalent of an a-amino carbanion. 

Based on the experimental results above and together with Wang s previous work a tentative mechanism was proposed (Scheme 20) [33]. Thus, intermediate A is formed initially through coordination of imine and alkyne to the Lewis acid. This coordination sets the stage for an addition of the alkyne to the imine leading to the propargylamine intermediate B, which then undergoes an intramolecular... 

The addition of alkyl nitronate anions to imines in the presence of a Lewis acid proceeds in high yield with up to 10 1 diastereoselection favoring the anti isomer. This reaction is used for the stereoselective synthesis of 1,2-diamines (Eq. 4.121).167 Scandium triflate catalyzes the addition of 1-trimethylsilyl nitropropanoate to imines with a similar selectivity.35... 

Ally 1-tin compounds are employed as more reactive allylating agents. Because of their high reactivity, less active catalysts (TX species having mild Lewis acidity) or less reactive substrates are often required (Scheme 23).88,89 In addition to carbonyl compounds as substrates, allylation reactions of imines have been also reported.90 Also, a binuclear TiIV Lewis acid has been developed (compound (C) in Scheme 23), which shows higher catalytic activity than the mononuclear analogue (D) because of bidentate coordination to the carbonyl moiety of the substrate.91... 

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