Directing groups imine

Intramolecular process with rhodium catalyst has been described for the syntheses of indane, dihydroindoles, dihydrofurans, tetralins, and other polycyclic compounds. Wilkinson catalyst is efficient for the cyclization of aromatic ketimines and aldimines containing alkenyl groups tethered to the K z-position of the imine-directing group. 

It is just about possible to ortholithiate imines, but in nearly all cases, the side reaction of nucleophilic attack at C=N is at least as important. Ortholithiation can overcome this side-reaction if it is assisted by an additional directing group (Scheme 58) . ... 

This chelation-assisted C-H/olefin and C-H/acetylene coupling can be applied to a variety of aromatic compounds with a directing group such as ester, aldehyde, imine, azo, oxazolyl, pyridyl, and nitrile [7]. In this section, we describe the coupling reactions of aromatic carbonyl compounds with olefins using a transition metal catalyst. 

Some other directing groups which involve the sp2 nitrogen can also function as a directing group in place of the pyridine ring. The reaction of aromatic imines with CO and ethylene in the presence of Ru3(CO)12 did not stop at the carbonylation step, but rather indenone derivatives were the final products and were formed via an intramolecular aldol-type reaction of the expected carbonylation products in situ (Eq. 27) [44]. The treatment of the reaction mixture with silica gel selectively afforded indenones in good yields. 

Unactivated C-H bonds can be functionalized if a suitable directing group can be incorporated into a substrate. For example, an on/io-t-butylaniline derivative will react with a substituted benzaldehyde to give an imine. This imine nitrogen then directs cyclometalation of the t —butyl methyl group (equation 71). The resulting Pd-C bond is then able to undergo further functionahzation. 

Treatment of imine 331 with KHSOs (Oxone) in the presence of NaHC03 afforded A -alkyl oxaziridines 332 in 67-85% yields (Table 26) <2005JOC301>. Optically active oxaziridines of this type could be obtained using phenyl ethylamine as the chiral directing group (Table 26, entries 3 and 4). 

The reduction of imines such as 3,4-dihydroisoquinolines with chiral sodium triacyloxyborohydrides [NaB(0acyl)3H] has been effected in optical yields of up to 1 % Two new methods for the preparation of 1-substituted tetrahydroisoquinolines have been reported. These both involve directed 1-lithiation and subsequent reaction with electrophiles. The directing groups on nitrogen are CH=N-R and P(0)(NMe2)2 (see above) respectively, both of which are readily removable. 

Carbonyl electrophiles can suffer competing enolization (Table 1). With the methoxymethyl directing group, reactive carbonyl compounds including aldehydes [24, 28, 49, 56, 69-72], acid chlorides [17, 24, 34, 44, 56, 57, 73-76], anhydrides [77,78], esters [22,24,79-81], amides [22,28,82-84] and several ketones [19, 22, 28, 70, 85, 86] were reported (Eq. 7). Others include phenyl isocyanate [54,78,87],benzonitrile [55], and imine derivatives [28]. 

Sames also found that palladium(ii) was effective for intermolecular functionalizations. Using an imine directing group, bonds could be activated and coupled with boron reagents to give elaborated organic products... 

Iridium has been found to be a very robust late transition metal which can mediate or catalyze C—H bond activation reactions very efficiently. However, the highly enantioselective Ir-catalyzed C—H bond functionalization via a transient C—Ir species for the construction of C—C or C—X bonds only emerged recently. Mechanistically, the catalytic cycle starts with oxidative addition of the Ii catalyst to the inert C—H bonds (such as aromatic, olefinic, or aliphatic C—H bonds), which are usually assisted with an ortho directing group. Subsequently, the formed C—Ir species inserts into an unsaturated functionality such as alkene, alkyne, or imine, delivering a new C—Ir speeies. Finally, the reductive elimination releases the products and regenerates the Ir catalyst. 

Addition of p-tolyl magnesium bromide to o-benzyl benzonitrile (156), followed by copper-catalysed benzylic oxidation, yields dione (157), via unsubstituted imine (158), in one pot. The imine acts as an intramolecular directing group the formation of the benzoyl is suggested to be triggered by a 1,5-hydrogen transfer with a transient iminyl-copper species. 

DG = directing group ketone, aldehyde, amide, phenol, imine, oxazoles, imidazoles, etc. 

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