Lactams, preparation from oximes

In an interesting fragmentation reaction, the hexahydroazocine (23) is formed by solvolysis of (22) in the presence of NaBHt in 94% yield (75TL2613). A related compound (24) can be prepared from 4-cycloheptenone oxime tosylate via the unsaturated lactam (25) (79JOC287). Whereas (25) adds bromine to the double bond, (24) undergoes a transannular reaction to give a 1-substituted pyrrolizidine (26). The latter type of reaction also occurs... 

BC13 convert 0=0 groups of ketones, lactones, and lactams to G=S groups119 and H2S-Me3SiCl-i-Pr2NLi converts carboxylic esters to thiono esters.120 Carboxylic acids RCOOH can be converted directly to dithiocarboxylic esters RCSSR, 120a in moderate yield, with P4S, and a primary alcohol R OH.121 Thioketones can also be prepared by treatment of ketones with P4SI0,122 and from oximes or various types of hydrazone (overall conversion C=N------> C=S).123... 

Since oximes are obtained from condensation reactions of ketones with hydroxylamine, the single-pot preparation of amides and lactams directly from ketones and H2NOH.HCI was achieved via in situ generated oximes, by using the above catalyst in nitromethane under azeotropic conditions. 

The major ring expansion route to the dibenzazocines is via a Beckmann or Beckmann-type rearrangement of the oxime. Lactams 160313 and 161314 were prepared by ring expansion of the corresponding dibenzosuberones. Other dibenz[b,/]azocines have been similarly made.315 320 The fully unsaturated dibenzazocine 162 has also been prepared from the corresponding lactam in a manner similar to that used for 118 (Scheme 3).260... 

The synthesis of lactames has interest for the production of chemicals and fine chemicals. In the case of more bulky lactames derived from cyclodedecanone-oxime and cyclooctanone-oxime, they are used for producing nylon-12 and for the preparation of the precursor of azacycloalkanediphosphonic derivates which have pharmaceutical interest for the treatment of Ca metabolism disorders, respectively. 

Spontaneous Beckmann rearrangement has been observed upon 0-tosylation of oximes. Lactams can therefore be conveniently prepared from cyclic oximes, as shown in eq 23. The rearrangement has long been known to proceed with retention of configuration of the migrating group.This is complementary to the reaction of oximes with Sulfuric Acid (eq 24). ... 

Starting from 5-gluconolactone the sugar-derived thioamide (81) can be obtained via thionation of the corresponding amide with LR. The related thiolactam (82) was prepared from the lactam because a higher yield of the desired oxime could be achieved with (82). ... 

Amides can be easily prepared under mild conditions from acid chlorides with ammonium acetate and from oximes by a mild modification of the Beckmann rearrangement Lactams can be prepared by this method from cyclic oximes. and 7-Lactams have been synthesized in a simple manner from aminomalonates a-Aminoacids can be converted into a-ketoacids and related compounds through 2-trifluoromethyl-5-oxazolones... 

Regioselective Beckmann rearrangements were used as key steps in the synthesis of phosphonoalkyl azepinones (Scheme 36) [43b] and in a formal total synthesis of the protein kinase C inhibitor balanol (Scheme 37) the optically active azide 197 derived from cyclohexadiene mono-oxide was converted into ketone 198 in several steps. After preparation of the oxime tosylates 199 (2.3 1 mixture), a Lewis acid mediated regioselective Beckmann rearrangement gave the lactams 200 and 201 in 66% and 9% yield, respectively. Lactam 201 underwent a 3-e im-ination to give additional 200, which served as a key intermediate in a balanol precursor synthesis (Scheme 37) [43 cj. 

New azacyclic diterpenoid compounds were also prepared in good yields by ring expansion and only one isomer of the lactam 363 product was obtained (equation 142). However, when the oxime was tosylated, a nitrile compound resulting from ring opening was obtained in good yield (72%) as a result of the Beckmann degradation reaction. 

Scanlan, E.M., Slawin, A.M.Z., and Walton, J.C. (2004) Preparation of [5- and y-lactams from cabamoyl radicals derived form oxime oxalate amides. Organic e[ Biomolecular Chemistry, 2, 716-724. 

Dehydration. This reagent is useful for synthesis of acyl azides from carboxylic acids, NaCN, and pyridine, with tetrabutylammomum bromide as catalyst (75-95% yield). In combination with pyridine, it effects dehydration of oximes to nitriles in 80-90% yield, P-Lactams can be prepared directly in 40-75 )t yield from carboxylic acids and imines with the reagent (1 equiv,) and triethylamine (excess). In general, a mixture of cis- and rra/j5-azetidinones is formed. 

An in situ method for the preparation of N-methyleneamines has been devised by Overman and Osawa for use in condensation reactions with enolates and organometallic reagents. These species, with the exception of very hindered N-methyleneamines, cannot be isolated in the condensed phase because they rapidly trimerize to hexahydro-l,3,5-triazines. In this in situ method, A -methyleneamines (230) are generated from N-(cyanomethyl)amines (228) by deprotonation with an equivalent of enolate to give an intermediate amide (229) which loses LiCN (equation 22). When two equivalents of enolate are present, addition to the N-methyleneamine occurs and 3-lactams (233) are obtained in 60-70% yield upon warming the reaction mixture to 25 C (Scheme 48 Table 26). Uncyclized 3-amino esters can be isolated if the reaction is quenched at lower temperature a possible cycloaddition mechanism is thus ruled out. It is not clear to what extent, if any, the reaction is limited to a,a-disubstituted enolates. N-Methyleneamines, like oxime ethers, are useful for the synthesis of 4-unsubstituted 3-lactams and should also have important applications in the synthesis of monobactam antibiotics. 

Alternative syntheses of a-lycorane (23) and y-lycorane (25) depend on the preparation of unsaturated lactams (20) and (21) whereby ring c is derived from an aryl-cyclohexanone (17) (Scheme 2). Reduction of the oxime of the 2-... 

Oximes, Amides, Amidoximes, Lactams, Hydroxamic Chlorides, Imide Chlorides, and Dichloroketcmes. The preparation of 1,5-penta-methylenetetrazole from cyclohexanoneoxime and sodium azide in the... 

The ketal-lactam (4) has been prepared by Beckmann rearrangement of the oxime of the mono-ketal (3) from cyclohexane-1, 4-dione and catechol [34]. 

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