Allene-esters, cyclization

With a nickel carbonyl catalyst, hydrochloric acid, and an alcohol die initially formed allenic ester cyclizes on distillation (198). 

Clavepictines A and B (210 and 211, respectively) were obtained from the allenic ester 227. The reduction of its ester group to aldehyde, followed of addition to the latter of hexylmagnesium bromide, OH protection, and N-deprotection gave compound 228. A silver(i)-mediated cyclization of this compound afforded quinolizidine 229 and its C-6 epimer in a 7 1 ratio (Scheme 44). The former compound was readily converted into the target alkaloids <1997JOC4550>. 

When the allenic esters bear a-substituents, the hydrogen shift occurred with intermediate 266. The resultant intermediate 267 undergoes a 6-endo cyclization followed by expulsion of PBu3 to generate tetrahydropyridine (Table 12.11) [193]. 

Besides simple enones and enals, less reactive Michael acceptors like /3,/3-disubstituted enones, as well as a,/3-unsaturated esters, thioesters, and nitriles, can also be transformed into the 1,4-addition products by this procedure.44,44a,46,46a The conjugate addition of a-aminoalkylcuprates to allenic or acetylenic Michael acceptors has been utilized extensively in the synthesis of heterocyclic products.46-49 For instance, addition of the cuprate, formed from cyclic carbamate 53 by deprotonation and transmetallation, to alkyl-substituted allenic esters proceeded with high stereoselectivity to afford the adducts 54 with good yield (Scheme 12).46,46a 47 Treatment with phenol and chlorotrimethylsilane effected a smooth Boc deprotection and lactam formation. In contrast, the corresponding reaction with acetylenic esters46,46a or ketones48 invariably produced an E Z-mixture of addition products 56. This poor stereoselectivity could be circumvented by the use of (E)- or (Z)-3-iodo-2-enoates instead of acetylenic esters,49 but turned out to be irrelevant for the subsequent deprotection/cyclization to the pyrroles 57 since this step took place with concomitant E/Z-isomerization. 

Allene carboxylic acids have been cyclized to butenolides with copper(II) chloride. Allene esters were converted to butenolides by treatment with acetic acid and LiBr. Cyclic carbonates can be prepared from allene alcohols using carbon dioxide and a palladium catalyst, and the reaction was accompanied by ary-lation when iodobenzene was added. Diene carboxylic acids have been cyclized using acetic acid and a palladium catalyst to form lactones that have an allylic acetate elsewhere in the molecule. With ketenes, carboxylic acids give anhydrides and acetic anhydride is prepared industrially in this manner [CH2=C=0 + MeC02H (MeC=0)20]. 

Reductive cyclization of a keto group linked to an ester-activated allene affords cyclization to the cyclopentenol, which is isolated as the lactone [Eq. (40)] [211]. Higher yields (64-96% as a mixture of diastereomers) are obtained when the keto group is replaced with an o, )6-unsaturated ester group. That cyclization, however, only takes place in an undivided cell (and with a consumption of 4.5-11.3 F) [211]. 

The allenic esters (169) yield the the cyclobuteneones (170) on irradiation. In these examples this is the major product and is accompanied by 1,1,4,4-tetraphenylbuta-l,3-diene. The cyclobutenones are photochemically unstable and C2in be completely destroyed by irradiation for 4-6 h. When the phenyl ester (171) was irradiated no cyclization occurred and the only compound obtained was the photo-Fries product (172). One interpretation of the cyclization process is that the ester undergoes Fission of the carbonyl-ester O bond yielding a radical pjur. Cyclization and recombination would afford the product. However, attempts to trap intermediates such as (173) were unsuccessful. ... 

Cross-conjugated trienes are also obtained in the cyclization of allene esters 130 in the presence of rhodium catalysts to give 131 . ... 

A ring opening reaction of (1-lactams promoted by methoxide generated nitrogen nucleophiles in situ that subsequently added to proximal allenes producing trisubstituted pyrroles <06CC2616>. In the event, treatment of (3-lactam 3 with MeONa led to pyrrole-2-acetic ester 4 after cleavage of the amide bond, 5-exo-dig cyclization, and loss of methanol. The sequence was notable as no metal catalyst was required. 

Chiral 2,5-dihydrofuran can be prepared through the HC1 gas promoted cyclization of the corresponding optically active allenic hydroxy-ester 83 with almost complete axis chirality (87% ee) to center chirality (85% ee) transfer <00TL9613>. 

Weinreb86 has reported the Alder-ene cyclization of enallenes under thermal conditions (Equation (85)). Varying the substitution pattern of alkene and allene groups had little effect on the yield of cyclized product. One exception was a,/ -unsaturated ester 130(Equation (86)) cycloisomerization under thermal conditions led to the formation of the Alder-ene product 131 and the unexpected hetero-Diels-Alder product 132 in a 3 1 ratio. 

N-Allenylazetidinone 181 rearranges to cephalosporin 182 in the presence of lithium chloride (Eq. 13.62) [70], This is a very unusual reaction that is presumed to be initiated by chloride ion-induced cleavage of the disulfide to give sulfenyl chloride 183. Thiolate attack at the allene sp carbon atom of 183 generates ester enolate 184, which cyclizes to 182. The reactivity of the allene function in 181 ensures the success of the reaction. 

An exceptionally interesting example of the electrohydrocyclization reaction involves the use of allenes which are tethered to a,/S-unsaturated esters (Table 3) [19]. The chemistry takes place in a manner wherein the new carbon-carbon bond forms between the central carbon of the allene and the /S-carbon of the unsaturated ester. Of particular value is the preservation of one of the double bonds of the original allene, thereby providing functionality for further elaboration. It is important to carry out these transformations in an undivided cell, as the use of a divided cell led to hydrogenation of the olefins instead of cyclization. 

Efforts have been made to find stereoselective routes which provide disubstituted azetidines. Palladium catalysed cyclization of an enantiomer of allene-substituted amines and amino acids gives the azetidine ester 2 and a tetrahydropyridine in variable yield and ratio, depending on the substituents and conditions <990L717>. The (TRIS)- and (253I )-isomeis of the substituted azetidine-2-carboxylic acids 3 (R = COjH) are obtained in several steps from the corresponding 3 (R = CHjOSiMejBu ) which, in turn, is produced in high yield by photochemical intramolecular cyclization <98HCA1803>. 

As a first approach to the synthesis of nagilactone 296, a norditer-penoid isolated from Podocarpaceae, which inhibit the expansion and mitosis of plant cells, an intramolecular Diels-Alder reaction of allene 1,3-dicarboxylic acid esters was used. The cyclization of 297 afforded the 8-lactone 298, rather than the y-lactone 299 [85JCS(P1)747]. 

Treatment of 1-bromoallenyl ethyl ester 869 with bromine leads to 3,4,5-tribromo-6,6-dimethyl-3,6-dihydropyran-2-one 871. The reaction proceeds through initial electrophilic addition of bromine to the central allene carbon atom and cyclization of the resulting carbenium bromide furnishing the intermediate 870. Further reaction with bromine followed by loss of FIBr affords the 3,6-dihydropyran-2-one 871 (Scheme 240) <1996LA171>. 

---