Aldoxime ethers

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]. 

Coordination of organometallic species has been used in studies of stereocontrol of the addition. These stereocontrolled addition reactions possess considerable preparative potential as outlined in the following examples. Addition of Grignard reagents to chiral aldoxime ethers such as 100 (equation 69) was found to proceed with a substantial stereoselectivity. ... 

Allylboronates of type 103 react with equivalent amounts of aldoximes 102 (equation 73) giving allylhydroxylamines 104 in good yields. Similar reactions of aldoximes and glyoxylate oxime ethers with allyl bromide and indium also provide hydroxylamines. Additions of substituted allyl boronates to oximes produce mixtures of stereoisomers with ratio highly dependent on the steric size of substituents in both molecules. Addition of allyltri-n-butyltin to aldoxime ether 105 (equation 74) was found to proceed with a considerable diastereoselectivity. 

Azetines 575, synthesized by the reaction of IV-acyl thiazolidinethione enolates with enolizable aldoxime ethers, have been successfully converted into the corresponding iV-acyl-substituted /3-aminocarbonyl compounds 576 by simple exposure to benzoyl chloride <2003JA3690>. The reactions presumably involved an acyliminium salt 577, which hydrolyzed to yield 576 (Scheme 74). 

A new reaction of iV-acyl thiazolidinethione enolates with enolizable aldoxime ethers has been reported to give 2-(thiazolidine-2-thione)-l-azetines 608 with excellent diastereoselectivity (Equation 235) <2003JA3690>. The absence of either a methoxy or a carbonyl group in the 1-azetines indicated a complex mechanism rather than a simple addition reaction. The formation of azetines has been rationalized by combination of the oxime and TiCh to give a highly electrophilic trichlorotitanium iminium intermediate 609, which adds onto enolate 610 to form intermediate 611, which cyclizes to azetidines 612 (Scheme 81). An irreversible elimination of bis-trichlorotitanium oxide provides the ultimate driving force to produce azetines. 

Radical addition-cyclization of substrate (115) bearing two different radical acceptor such as acrylate and aldoxime ether moieties generates (3-amino-y-butyrolactones (116a) and (116b) (eq. 4.40) [118-120],... 

A novel reaction of A-acyl thiazolidinethione enolates with enolizable aldoxime ethers produced thiazolidinethione azetines 1 with excellent diastereoselectivity <03JA3690>. Subsequent addition of an acyl chloride to these azacyclobutene derivatives leads to the formation of the corresponding A -acyl-a,p-disubstituted p-amino acid derivatives, via selective generation of a cyclic four-membered iminium salt. Azetine derivatives were obtained as minor products on irradiating aryl-substituted A-acyl-a-dehydroalanines <03H637>. 

Miyabe et al. developed a tandem addition/cycUzation reaction featuring an unprecedented addition of alkoxycarbonyl-stabihzed radicals on oxime ethers [117], and leading to the diastereoselective formation of /1-amino-y-lactone derivatives [118,119]. The reaction proceeds smoothly in the absence of toxic tin hydride and heavy metals via a route involving a triethylborane-mediated iodine atom-transfer process (Scheme 37). Decisive points for the success of this reaction are (1) the differentiation of the two electrophilic radical acceptors (the acrylate and the aldoxime ether moieties) towards the nucleophilic alkyl radical and (2) the high reactivity of triethylborane as a trapping reagent toward a key intermediate aminyl radical 125. The presence of the bulky substituent R proved to be important not only for the... 

Modification of the aldoxime ether group by introduction of an electron withdrawing moiety led to the finding (186) that the Z-N-methoxyimidoyl nitrile group serves as a stable methyl ester bioisostere. An example of this molecular modification, compound (148),... 

Trisuhstituted y-lactones (Scheme 138) [506] To a flask containing soHd-supported aldoxime ether and iPrI (30 equiv.) in toluene, a commercially available 1.0 m solution of triethylborane in hexane was added in three portions (3x3 equiv. total 9 equiv.) as a radical initiator at 100 °C. The reaction mixture was stirred at 100 °C for 2 h and then the resin was filtered off and successively washed with CH2CI2, EtOAc, and MeOH. Cleavage from the resin by treatment with NaOMe gave the desired azacycHc product in 69% isolated yield. 

An interesting extension of palladium-catalyzed arylation of directing-group containing arenes by aryl iodides has been recently described by Cheng [74], The arylation of aldoxime ethers under standard conditions (Pd(OAc)2 catalyst, CF3C02H solvent, stoichiometric Ag+ source at elevated T) affords fluorenones by tandem o-ary I at ion/pal ladium-catalyzed cyclization pathway (Scheme 20). 

---