Esters cycloisomerization

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. 

Ester-tethered enyne systems cycloisomerized to give lactone products (Eq. 11) [24]. Eor example, enyne 6 reacted under the Alder-ene conditions of [Rh(COD)Cl]2/BlNAP/ AgSbEg to give the corresponding lactone (Eq. 11). Once again free hydroxyl groups on the allylic terminus were incorporated into the cyclization precursors and subjected to the Alder-ene conditions, which led to the exclusive formation of the tautomerized products in good yields and enantioselectivities (Eq. 12). 

Saa and coworkers reported a remarkable cycloisomerization of alkynal to cycloalk-ene derivatives with loss of a CO molecule [30] some examples are shown in Table 6.3. Heating 5-alkynal 94a in AcOH (90 °C, 24h) with [Ru(Cp)(CH3CN)3]PF6 (5 mol%) afforded the cyclopentene derivative 9Sa in 90% yield. Ketone 94e afforded the cyclopentene 9Se in moderate yield, whereas the ester 94f gave the noncyclized product 96 with loss of one carbon unit (Table 6.3) (Scheme 6.32). 

Although a number of competing pathways have been shown to be involved301 in the thermal cycloisomerization of hexa-l,3-dien-5-ynes (255), isobenzenes (256) have been established302 as intermediates in their thermal rearrangement to arenes. On solvolysis, the diethylphosphate ester of l-(2-ethynylphenyl)-4-trimethylsilyl-4-(trimethylsilyl-oxy)pent-2-yn-l-ol has been found303 to afford 5-(2-ethynylphenyl)-3-trimethylsilyl-... 

C-H activation pathway cannot be ruled out for this transformation, however. They subsequently observed C-H insertion of a cis substituent by means of isotope studies [32], The cycloheptene product was observed as the major product when cis- or tri-substituted enyne and acetylenic ester termini were present. Ruthenium hydride catalysts reported by Mori and Dixneuf can also initiate the cycloisomerization of 1,5- and 1,6-enynes and dienes [33, 34], The vinylruthenium hydride can be obtained from RuClH(CO)(PPh3)3 or in the presence of acetic acid or ethanol. 

Rh-catalyzed cycloisomerization and a kinetic resolution process to conduct a formal synthesis (Scheme 11). Starting from the easy accessed enyne ester 28, a kinetic resolution process gives a highly functionalized y-lactone 29 with excellent enantioselectivity. Considering the ideal yield can only be as high as 50%, this transformation is very efficient. Further reduction of the exo-methylene proved highly selective and the three adjacent chiral center unit 30 could be obtained in high yield [71]. 

The synthesis of dihydrofurans from propargyl esters is another reaction in which both gold and silver have been employed. In early work, Shigemasa et al.37 reported the efficient chirality transfer in the cycloisomerization of monoesters of butynediols. They used 8-15 mol% of AgBF4 as catalyst in benzene at 80°C in the dark. 

An intramolecular rhodium-catalyzed [2+2+2] cycloaddition of diynenitriles <07OL1295> diyne esters <07T12853> and alkynevinyl oximes <07TL6852> also afforded pyridine versions of dihydrobenzo[c]furans. Trost prepared these pyridine derivatives employing a similar ruthenium-catalyzed cycloisomerization-6 cyclization route as depicted in the following scheme <07OL1473>. 

The metal-catalyzed conversion of 2,3-allenoates to A -butenolides has proven to be superior to the acid-catalyzed cyclization of the corresponding carboxylic acids. The reaction of the esters can be effected by Au(m) catalysts in improved yields <2005TL7431>, and furan-2(5//)-ones functionalized in the 4-position can be prepared by iodo- or seleno-lactonization in moderate to good yields (Scheme 33) <2006T4444, 2005EJO3942>. The cycloisomerization of optically active 2,3-allE itoic acids, on the other hand, can proceed with complete conservation of stereochemical information when copper(i) chloride is used as a catalyst <2006S3711>. 

When the benzyl ether derivative (Z)-16 of (Z)-13 is employed in an analogous reaction, cycloisomerization occurs to yield a diastereomeric mixture of methyl 6-benzyloxy-3a-methyl-3-methyleneoctahydropentalene-l-carboxylates (17A, B) in a combined yield of 43%. The products could be separated after reduction of the ester groups with diisobutylaluminum hydride which yielded a 5 1 mixture of the corresponding hydroxymethyl derivatives (36% combined overall yield). 

A multi-step asymmetric synthesis of a hydrindane framework was achieved in water via asymmetric allylic alkylation, propargylation and aquacatalytic cycloisomerization of a 1,6-enyne, where all three steps were performed in water with the recyclable polymeric catalysts. The racemic cyclohexenyl ester 27 reacted with diethyl malonate under the conditions mentioned in Table 6.1 to give 90-92% ee of 34b. The polymeric chiral palladium complex 23-Pd was reused four times... 

CycloeUmination. On exposure to AuCl, esters of l,4,5-alkatrien-3-ols are subject to cycloisomerization and ehmination to provide benzene derivatives. ... 

For cycloisomerization of a-alk3myl-p-keto esters the use of Tf2NAu in conjunction with very bulky tris[(triarylsilyl)ethynyl]phosphine hgands, remarkable rate enhancements are observed. The effect is attributable to the cavity environment created by the ligand to keep the nucleophilic center and the Au-activated triple bond of the substrate close. 

Indolizines. Cycloisomerization of 7-(2-pyridyl)propargylic esters catalyzed by Ptl2-Ph3P is found to be affected by substituents at the a-position and the acyl group. Perhaps formation of two different types of products is determined by the degree of loosening of the propargyloxy bond. ... 

During work on the chemistry of penicillin a variety of methods were developed for the synthesis of 5-aminooxazoles. It has been found that cycloisomerization of acylaminocyanoacetic esters (135) by treatment with hydrogen chloride (in alcohol, ether or acetone), phosphorus pent-oxide, or pentachloride leads to 5-aminooxazole-4-carboxylic esters (136),2 61 which have also been obtained by dehydration of acylamino-malonamic esters (137) with phosphorus oxychloride.2... 

Cycloisomerization. The photoinduced formation of methylenecyclopentane derivatives from a-(4-pentynyl)acetoacetic esters represents a new way to prepare these substances. 

Equation 26 illustrates the rare enyne cycloisomerization process which is feasible under relatively mild conditions (in acetic acid at 80 °C for 6 h) in the presence of a palladium (0) catalyst. In the presence of EtAlCl2, alkenes undergo ene reactions with 2-(dialkoxyphosphinoyl)propenoic esters (equation 27 " ) the same catalyst, and other Lewis acids, catalysed the intramolecular reactions of 385 and 386 ( = 0 or 1), which are exemplified by reaction 28 . 

A two-step one-pot synthesis of 2,3,5-trisubstituted furans from epoxyalkynyl esters was reported, in which a facile Sml -mediated reduction was used for the generation of the 2,3,4-trien-l-ols, and the reduction was followed by a Pd(ll)-catalyzed cycloisomerization <01JOC564>. An attractive variant of this reaction was extended to the preparation of tetrasubstituted furans. Thus, when electrophilic Pd(ll) complexes were generated in situ by an oxidative addition of aryl halides or triflates to Pd(0), the oxypalladation process was followed by a reductive elimination and tetrasubstituted furans were formed <01TL3839>. 

Bisdiene 35 bears a complementary substitution pattern to that of 32b that is, the benzyl substituent resides adjacent to the methyl-bearing 1,3-diene moiety. Bisdiene 35 also cyclizes smoothly under the conditions employed for 32b and affords compound 36 in high yield (95%), and with good diastereoselectivity (>90% diastereomeric purity). Thus, bisdienes bearing an ester substituent undergo facile Pd-catalyzed cycloisomerization via a pathway that complements that found for substrates without the ester substituent. This defines a new bond construction that is inaccessible by classical... 

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