Oximes reductive cleavage

Denmark and coworkers have found that methylaluminum bis (2,6-di-tert-butyl-4-methyl-phenoxide) (MAD) or methylaluminum bis(2,6-diphenylphenoxide) (MAPh) is effective as the Lewis acid promoter for cycloaddition of 2,2-disubstituted 1-nitroalkenes (Eq. 8.100).158 Other Lewis acids such as SnCl4, TiCl4, and TiCl2(Oi-Pr)2 fail to promote the cycloaddition of 2,2-disubstituted 1-nitroalkenes. The products are converted into 3,3-disubstituted pyrrolidines via hydrogenolysis.158 Reductive cleavage of N-0 bonds produces oxime hemiacetals, which are further reduced to amido aldehydes and finally to pyrrolidines. This reaction provides a useful synthetic method for pyrrolidines, which is discussed later. 

Reduction of imines cleavage of oximes.1 Na2S204 in aqueous DMF reduces imines to N-alkylamines at 110°. Yields are 40-73% (five examples). Carbonyl compounds are regenerated from oximes by cleavage with aqueous Na2S204 at 25°. Yields are 54-96% (four examples). 

A few examples of reductive cleavage followed by cyclization involving groups other than carbonyl or amino have been reported. They include oximes, Eq. (33),237 alcohols, Eq. (34),222 and enamines, Eq. (35).238... 

Trifluoropropcnc itself reacts regioselectively with various nitrile oxides, even nonaromatic nitrile oxides. The latter arc prepared in one step from oximes and A -chlorosuccin-imide, or in a two-step sequence with isolation of the hydroximoyl chlorides. Cycloadducts, obtained at room temperature in the presence of triethylamine, are then converted into trilluoro- 8-hydroxy ketones 9 by reductive cleavage. The reaction with a dipole substituted by a group derived from L-phcnylalanine allows the preparation of chiral ketones. ... 

Entry 9 in Table 15 illustrates another synthetically useful stereocontrolled reduction of cyclic oxime ethers (isoxazolines) to alicyclic amino alcohols using LAH. The stereoselectivity obtained is further enhanced by the incorporation of a 4a-hydroxy group which, upon reduction, affords almost entirely the erythro isomer (equation High diastereoselectivity in the reductive cleavage of isoxazolines has... 

The reductive cleavage of the N—O bond of oximes is a reaction which has been widely used by synthetic chemists. When accompanied by reduction of the C=N bond the reaction leads to the formation of primary amines. Reactions of this type are described in Chapters 1.2-1.8, this volume. The reductive cleavage of cyclic oximes, particularly isoxazoles and 4,5-dihydroisoxazoles, has been used as a key step in several target syntheses of natural products. These cleavage reactions are covered in Chapter 3.8, this volume however, some of the methods which clearly bring about cleavage of the N—O bond before reduction of the C=N bond are also described in this section. The products of these reactions are A-unsub-stituted imines. Unless the imines are sterically protected or unless special precautions are employed in the work-up, the isolated products are usually carbonyl compounds formed by hydrolysis (Scheme 19). Reductive hydrolysis reactions of this type are also included here. 

Low-valent metal salts have been used to bring about reductive cleavage of oximes. Corey and Rich-man used chromium(II) acetate to convert O-acetyl ketoximes into imines, which were hydrolyzed to ketones. " Aqueous titanium(III) chloride and vanadium(II) salts also reduce oximes again, the imines are usually hydrolyzed in situ, but some hindered imines, such as compound (37), are isolable." A method of preventing hydrolysis is to carry out the reduction in anhydrous conditions in the presence of an acylating agent. The products of such reactions, when applied to oximes of enolizable ketones, are en-amides. For example, these ketoximes are converted into A/-formylenamines when heated in acetonitrile with anhydrous titanium(III) acetate and acetic formic anhydride cyclohexanone oxime gives the en-amide (38 97% Scheme 22)." This type of reduction has been used by Barton and coworkers to prepare enamides from steroidal oximes. They reported that the reaction could be performed by acetic... 

Amines. Azobenzenes and oximes undergo reductive cleavage to give amines in the presence of Pd/C and HCOONH. ... 

Reductive cleavage of oximes.1 Vanadium(II) chloride in THF is a convenient reagent for deoximation (75-90% yield). 

A more direct route to 30 was also developed from the D-glucose derivative 15 (Scheme Reductive carbocyclization of the keto oxime derivative 31, obtained from 15, using an excess of Sml2, took place with subsequent N-0 reductive cleavage to afford the aminocyclopentitol 32 in 8 8 % yield. Hydrogenoly sis of 32 afforded trehazolamine analogue 30 in 57% overall yield from 15. 

Mild reduction converts azines and hydrazines into disubstituted hydrazines, but under vigorous conditions reductive cleavage of the N-N bond affords amines. Reduction of oximes thus affords a further but seldom used method of converting carbonyl compounds into amines. 

A polyamine synthesis depends on the reductive cleavage of 2,3-dihydropyrimidi-nes. The products have a ryn-1,3 configuration." 2-Aminocycloalkanone oximes give aliphatic amino nitriles, which are the reduction products from Beckmann fragmentation. 

Af-oxides back to the amine (see Fig. 31.25). The same is true for aromatic nitro compounds, aromatic nitroso compounds and hydroxylamines, and imines and oximes, which can ultimately be reduced to primary amines. Azo and azoxy compounds can be reduced to hydrazines. An important pathway of hydrazines is their reductive cleavage to primary amines. A toxicologically significant pathway thus exists for the reduction of some aromatic azo compounds to potentially toxic prUnary aromatic amines. 

In efforts to increase the reactivity of simple 1-aza-1,3-butadienes toward typical electron-deficient dienophiles, Ghosez and co-workers found that the a,/3-unsaturated hydrazone 1 behaves as a well-defined electron-rich diene in regioselective, normal (HOMOd,ene controlled) Diels-Alder reactions with a number of representative dienophiles. Reductive cleavage of the nitrogen-nitrogen bond concurrent with reduction of the carbon-carbon double bond has provided substituted piperidines, and aro-matization with elimination of dimethylamine has provided substituted pyridines (Scheme 9-1). Similar reactions of simple or functionalized a, -unsaturated oximes failed to provide an observable [4 -t- 2] cycloaddition. It remains to be determined whether this process is general for a,/3-unsaturated hydrazones capable of tautomerization. 

Reductive cleavage of oximes. The combination of M0OCI3 and zinc in II.2O THF cleaves oximes to carbonyl compounds (75-857o yield). ... 

DIBAL can also be used for the reductive cleavage of cyclic aminals and amidines (eq 19). Oximes can be reduced to amines. Due to the Lewis acidity of DIBAL, however, rearranged products are obtained (eq 20). This chemistry was used to prepare the alkaloid pumiliotoxin C via the Beckmann rearrange-ment/alkylation sequence shown in eq 21. ... 

A stereocontrolled total synthesis of (+)-vinblastine (329), a prominent alkaloid used in cancer chemotherapy, was reported by the Fukuyama/ Tokuyama team and features an INOC reaction for the preparation of a key reaction intermediate utilized in their synthesis (2010CR101). Thus, the oxidation of oxime 323 with sodium hypochlorite generated the expected nitrile oxide 324 which imderwent a subsequent 1,3-dipolar cycloaddition to produce isoxazoline 325 as a single isomer (Scheme 59). The INOC proceeded via a six-membered chairlike transition state (i.e., 324) to furnish 325 with the desired stereochemistry. After reductive cleavage of the N—O bond in isoxazoftne 325 with zinc dust in acetic acid, a... 

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