Imines reactions with organometallics

One of the most studied imine precursors in the reaction with organometallic compounds is (3R,4R)-4-acetoxy-3-[(R)-l -((t-butyldimethylsilyl)oxy)ethyl]-2-azetidinone (31) (equation 23)97. 

The addition of aryl groups to C=N bonds can be achieved using cooper-catalyzed asymmetric reactions with organometallic reagents. The addition of alkylzinc and related reactions is quite common in literature [47] whereas copper-catalyzed asymmetric arylation of imines is somewhat harder to find. We wish to report some successful examples of this type of catalysts. 

Two other acid derivatives may also be converted to ketones by reaction with organometallic compounds. Grignard reagents add to nitriles to give imine salts (Section 14.4.3), which are hydrolyzed to ketones in the reaction work-up. In Figure 19.27, again the disconnected bond is highlighted in red. Remember than many aliphatic nitriles are readily prepared by displacement... 

Bell and Hall have incorporated an organometallic unit into a crown by using the ferrocenyl unit as part of the ring or as a third strand. The unit is incorporated either as the 1,1 -diformylferrocene or the corresponding acid. In the former case, the bis-imine is prepared and reduced to give the saturated crown (see structure 24). In the latter case, the acid is converted into its corresponding chloride and thence into the diamide by reaction with a diamine. Diborane reduction affords the saturated amino-crown. Structure 24 could be prepared by either of these methods but the dialdehyde approach was reported to be poor compared to the amide approach which afforded the product in ca. 60% yield . 

Reaction of Nitriles with Organometallic Reagents Grignard reagents add to a nitrile to give an intermediate imine anion that is hydrolyzed by addition of water to yield a ketone. 

Fluoral hydrate and hemiacetals are industrial products. They are stable liquids that are easy to handle, and they react as fluoral itself in many reactions. Thus, in the presence of Lewis acids, they react in Friedel-Crafts reactions. They also react very well with organometallics (indium and zinc derivatives) and with silyl enol ethers.Proline-catalyzed direct asymmetric aldol reaction of fluoral ethyl hemiac-etal with ketones produced jS-hydroxy-jS-trifluoromethylated ketones with good to excellent diastereo- (up to 96% de) and enantioselectivities. With imine reagents, the reaction proceeds without Lewis acid activation. The use of chiral imines affords the corresponding 8-hydroxy ketones with a 60-80% de (Figure 2.49). ° ... 

Although the diastereoselective addition of nucleophiles to imines offers an attractive route to chiral amine derivatives, most chiral nonracemic imines suffer from low reactivity (electrophilicity), resulting in no reaction or competitive reduction with organometallic reagents. Other problems include enolization of aliphatic imines, poor... 

Monoalkylation of primary amines.1 A two-step sequence for this reaction involves conversion of the amine to the N-(cyanomethyl)amine (2) by reaction with chloroaceto-nitrile or with formaldehyde and KCN. Reaction of 2 with an organolithium or a Grignard reagent generates an unstable formaldehyde imine (a) that reacts with a second equivalent of the organometallic reagent to form a secondary amine (3). 

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