Aldimines acyclic—

Another occasionally used method for the preparation of acyclic A-(l-alkoxyalkyl)amides (or carbamates) proceeds via addition of reactive carboxylic acid derivatives to aldimines. In a one-pot procedure, treatment of the imine with the acid chloride (or ethyl chloroformate) and subsequent (m)ethanolysisofthe intermediary a-chloroamide leads to the oc-alkoxyamide56-58. 

Table 1 Reaction of chromium alkoxycarbenes with acyclic aryl aldimines...

Depending on the steric bulk of the nitrogen bonded substituent, the reaction of 4 with pyridine-2-aldimines can also proceed by an intermolecular insertion of the silylene into the C-H bond of the acyclic CN group [19]. 

Akiyama applied Im in the inverse-demand aza-Diels-Alder reaction of various acyclic and cyclic vinyl ethers with N-aryl imines derived from o-hydroxyaniline to provide ophcally active tetrahydroquinoline derivatives (Scheme 5.16) [29]. Since aldimines derived from p-methoxyaniline gave no cycloaddition product, a nine-membered cyclic TS (akin to that proposed for the author s Mannich reachon) was invoked to rationalize the high levels of enantio-control. 

Shibasaki and co-workers applied (BINOL)Al(III)-derived catalyst 5a, previously developed for the cyanation of aldehydes [28], to the asymmetric Strecker reaction. This catalyst proved to be highly enantioselective for both aromatic and a,p-unsaturated acyclic aldimines (>86% ee for most substrates) (Scheme 8) [63-65]. Aliphatic aldimines underwent cyanide addition with lower levels of enantioselectivity (70-80% ee). A significant distinction of 5 relative to other catalysts is, undoubtedly, its successful application to the hydrocyanation of quinolines and isoquinolines, followed by in situ protection of the sensitive cx-amino nitrile formed (this variant of the Strecker reaction is also known as the Reissert reaction [66]). Thus, Shibasaki has shown that high enantioselectivities (>80% ee for most substrates) and good yields are generally obtainable in the Reissert reaction catalyzed by 5b [67,68]. When applied to 1-substituted... 

Crotyltins react regioselectively with a-alkylimines to give exclusively branched products with an excellent syn/anti selectivity up to 30 1, when the imine activation is conducted at —78 °C prior to the addition of the crotyltin. This selectivity which is consistent with an acyclic transition state is rapidly fading when operating at a higher temperature. This would be the result of an equilibrium between the two imine/Lewis acid complexes (equation 14). There are very few examples with a, /3-unsaturated aldimines, but it has to be noted that under TiCU activation, they are able to undergo a double nucleophilic addition of ketene silyl acetal and allyltributyltin to give the homoallylic amine in a reasonable yield . 

The chiral allylzinc complex also reacts with chiral aldimines to afford allylated secondary amines in high enantioselectivity. For the acyclic (E)-benzaldehyde IV-phenylimine, the amine was... 

A few natural product syntheses feature the use of both acyclic and cyclic aldimines of either enantiomer of f-leucine f-butyl ester. Kinetic resolution of racemic aldehydes has also been achieved using L-f-leucine f-butyl ester. ... 

Examples of highly stereoselective acyclic reactions include the Zr-mediated coupling of aldehydes with imines of (1) to produce chiral amino alcohol derivatives (eq 11), and the addition of cyanide to aldimines of (1) to yield intermediates that can be elaborated into enantiomerically pure a-amino acids (eq 12). ... 

Iminium salts bearing a labile trimethylsilyl group can be generated in situ and undergo nucleophilic addition (see Sections 1.12.4.2 and 1.12.7.3). Bis(trimethylsilyl)methoxymethylamine (75), for example, has been used as a formaldehyde equivalent for the preparation of primary amines. Cyclic imines, such as 3,4-dihydroquinolines, react with trimethylsilyl triflate (TMS-OTf) to provide reactive labile iminium salts (55), which condense with picoline anions. The addition of nonstabilized Grignard and organolithium reagents to acyclic aromatic ketimines and aldimines, however, is often not facilitated by the presence of TMS-OTf ... 

HNMR spectra of azirines which are unsubstituted at C-2 (69TL4073). The imine protons are commonly observed at ca. 10 p.p.m. whereas those of normal acyclic aldimines are observed in the vicinity of 8 p.p.m. imine (12), for example, displays a singlet at 7.63 p.p.m. (62CJC882). A similar but less pronounced shielding effect of ca. 0.4 p.p.m. hat been observed for the protons at C-3 compare, for example, the resonances assigned to the azirine (13)... 

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... 

Shono and coworkers have examined the electrochemical oxidation of sulfonamides [25], presumably with the intent of generating a-alkoxy sulfonamides. However, anodic oxidation of short chain acyclic sulfonamides, like 12, in the presence of halide ion surprisingly afforded the a-sulfonamido acetals 13 (Scheme 6) [25a]. It is believed that oxidation of 12 occurs to initially produce a-methoxy sulfonamide 14. Under the reaction conditions, however, 14 eliminates methanol to produce N-sulfonyl aldimine 15, which can tautomerize to ene sulfonamide 16. Reaction of 16 with a positive halogen species, generated elec-trochemically, probably leads to 17, which can rearrange via an intermediate aziridine to the observed acetal product 13. 

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