Ketimines from hydrazones

Intramolecular addition of trialkylboranes to imines and related compounds have been reported and the main results are part of review articles [94, 95]. Addition of ethyl radicals generated from Et3B to aldimines affords the desired addition product in fair to good yield but low diaster control (Scheme 40, Eq. 40a) [96]. Similar reactions with aldoxime ethers [97], aldehyde hydrazones [97], and N-sulfonylaldimines [98] are reported. Radical addition to ketimines has been recently reported (Eq. 40b) [99]. Addition of triethylborane to 2H-azirine-3-carboxylate derivatives is reported [100]. Very recently, Somfai has extended this reaction to the addition of different alkyl radicals generated from trialkylboranes to a chiral ester of 2ff-azirine-3-carboxylate under Lewis acid activation with CuCl (Eq. 40c) [101]. 

The behaviour of compounds 49 where R = H and CH3 from is even more complicated. For example, 4-methylamino-3-(4-X-phenylazo)pent-3-ene-2-one (49) contains two isomers. The tautomeric form of both isomers was confirmed with the help of 2D H-15N GHMQC spectra. The minor isomer is very similar to the tautomeric form of azo-enamine ( j(15N, H) = 89.6 Hz) the major isomer possesses a somewhat stronger character of hydrazono-ketimine form ( /(15N,1H) = 74.5 Hz about 80% azo and 20% hydrazone). These conclusions are confirmed by the values of <5(15NH2) in the minor isomer it is 6(15N) = —269.0 ppm (i.e. almost the same as in the starting enaminone with... 

Section II,C Cyclization of a-acylamino ketimines or a-acylamino hydrazones gives rise to 34-87% yields of imidazoles or 1-aminoimidazoles. The starting materials are readily prepared from a-amino acids. Anhydro-mercaptoimidazolium hydroxides are available from JV-formylsarcosine-N-methylthioamide. ... 

Fortunately, the use of lithiated hydrazones derived from (S)- or ( )-l-amino-2-methoxymethylpyiro-lidine (SAMP or RAMP) as nucleophiles for asymmetric alkylations have provided a solution to the problems described above with metallated acyclic ketimines and aldimines. Lithiated SAMP or RAMP hydrazones of cyclic ketones are also alkylated in high yields. A major advantage of these chiral hydrazones is that their derivatives of aldehydes, acyclic and cyclic ketones all yield mainly ( )cc-. (Z)cN-Iithiated species on deprotonation with LDA in ethereal solvents under kinetic control. The ( )cc-configuration obtains as a result of the minimization of steric interactions in the usual closed transition... 

Extension of this work to the diastereoselective synthesis of y-lactams from N-sulfonyl aldimines [93] and ketimines [94] was subsequently reported. Scheldt and coworkers disclosed an enantioselective version (up to 98% ee) from reactive hydrazones in the initial demonstration of cooperative NHC/Lewis acid catalysis using a bulky, chiral triazolium salt and catalytic Mg(OBu )2 [95]. Rovis and coworkers synthesized y-lactams 109 enantioselectively using a chiral N-C Fs triazolium salt (Scheme 18.19). A weak carboxylate base was sufficient to partially deprotonate the precatalyst 108 in situ, and the carboxylic acid formed could activate the N-Ar imine acceptor 107 via protonation [lib]. In all these cases, a fine balance must exist between sufficient electrophilicity vis-a-vis the competing enal and reversible addition of the carbene to the imine/hydrazone/iminium or to the Lewis acid. 

---