Cyclization to lactams

Pentenyl amides such as 15A cyclize to lactams 15B on reaction with phenyl selenenyl bromide. The 3-butenyl compound 15C, on the other hand, cyclizes to an imino ether 15D. What is the basis for the differing reactions ... 

Lactamization. In the presence of this reagent, w-amino acids cyclize to lactams. Yields are 75-93% for cyclization to 5- and 6-membered lactams. 

Laterally lithiated tertiary amides are more prone to self-condensation than the anions of secondary amides, so they are best lithiated at low temperature (—78 °C). N,N-Dimethyl, diethyl (495) and diisopropyl amides have all been laterally lithiated with aUcyllithiums or LDA, but, as discussed in Section I.B.l.a, these functional groups are resistant to manipulation other than by intramolecular attack" . Clark has used the addition of a laterally lithiated tertiary amide 496 to an imine to generate an amino-amide 497 product whose cyclization to lactams such as 498 is a useful (if rather low-yielding) way of building up isoquinoline portions of alkaloid structures (Scheme 194) ". The addition of laterally lithiated amines to imines needs careful control as it may be reversible at higher temperatures. ... 

Under certain conditions, the cyclization to lactam 499 occurs spontaneously, eliminating one equivalent of lithium diethylamide, which goes on to deprotonate the benzylic position a second time to yieid 500 and then 501 . 

Ketoester 208 derived from l-(2-nitrophenyl)-lH-pyrrole and ethyl oxalyl chloride can be selectively reduced at the keto group with zinc iodide and sodium cyanoborohydride. Further reduction of the nitro group and cyclization to lactam 209 has been accomplished by treatment with stannous chloride in refluxing ethanol (Scheme 43 (2003BMCL2195)). 

One application of lactone 140 as a chiral synthon may be found in the asymmetric synthesis of (+)-12b-epidevinylantirhine (143), a cleaved product of geissoschizol (Scheme 28) [62-63]. Treatment of 140 with tryptamine in hot toluene afforded 142, which cyclized to lactam 142 by mesylation and an Sn2 displacement. Hie Bischler-Napieralski reaction of 142, followed by reduction of the resulting iminium salt with NaBH4, produced stereoselectively, the indolo[2,3-a]quinolizine as a single isomer, which was further reduced with DIBAL to give (+)-12b-epidevinylantirhine (143). 

The reaction of secondary sulfonamides with carboxylic acids in the presence of DCC and4-pyrrolidinopyridine affords N-tosylamides. Also intramolecular cyclization to lactames is achieved using DCC. 

Several other transannular lactonizations and reductions have been reported to proceed in high overall yields. Also other acid derivatives, such as amides and esters, cyclize to form lactones. Alkynoic acids have been lactonized to y-alkylidene-y-lactones in good yield, e.g. the conversion of (31) to (32 equation 29). Unfortunately the vinyl selenide product can isomerize from ( ) to (Z) in a secondary process. Analogous lactam formation is also known. Unsaturated amides, when cyclized with benzenese-lenenyl halides, produce good yields of lactams or iminolactones depending upon the alkene utilized. The amide (33) cyclizes to the iminolactone (34), producing a mixture of stereoisomers (65 35 Scheme 5). The amide (35) is cyclized to lactam (36) in moderate yield. 

Substituted phenethyl isocyanates undergo cyclization to lactams when treated with BF3 Et20 [65]. Vinyl ether epoxides (Eq. 37) [66], vinyl aldehydes [67], and epoxyjS-keto esters [68] all undergo cyclization with BF3 Et20. 

Substituted phenethyl isocyanates undergo cyclization to lactams when treated with BF3-OEt2. Tnyl ether epoxides... 

Another route to this cyclohexyl derivative involves the preparation of 6.183 via an olefmation reaction with a substituted phenylalinal derivative followed by reduction of the phenyl ring. The alcohol moiety in 6.183 was converted to the N-phthal-oyl derivative (6.184) by a Mitsunobu inversion.m Conjugate addition with a higher order silyl cuprate gave 6.185. The silyl moiety was converted to an alcohol (6.186) by treatment with tetrafluoroboric acid and then KF/m-chloroperoxy-benzoic acid. Removal of the phthalimidoyl group with hydrazine led to an amino-ester, which cyclized to lactam 5.757.11 Hydrolysis gave 4-amino-5-cyclohexyl-3-hydroxypentanoic acid (6.188) in 60% yield. 

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