Silyl ether cycloaddition

Diene 265, substituted by a bulky silyl ether to prevent cycloaddition before the metathesis process, produced in the presence of catalyst C the undesired furanophane 266 with a (Z) double bond as the sole reaction product in high yield. The same compound was obtained with Schrock s molybdenum catalyst B, while first-generation catalyst A led even under very high dilution only to an isomeric mixture of dimerized products. The (Z)-configured furanophane 266 after desilylation did not, in accordance with earlier observations, produce any TADA product. On the other hand, dienone 267 furnished the desired macrocycle (E)-268, though as minor component in a 2 1 isomeric mixture with (Z)-268. Alcohol 269 derived from E-268 then underwent the projected TADA reaction selectively to produce cycloadduct 270 (70% conversion) in a reversible process after 3 days. The final Lewis acid-mediated conversion to 272 however did not occur, delivering anhydrochatancin 271 instead. 

Kibayashi and coworkers have used enantiometrically pure allylic silyl ethers obtained from amino acids in cycloaddition with nitrones (Eq. 8.49).71 Cyclic nitrone reacts with a chiral allyl ether to give selectively the exo and erythro isomer (de 90%). Optically active alkaloids containing a piperidine ring such as (+)-monomorine,71c (+)-coniine,71a and (-)-oncinotine71b have been prepared from the addition product. 

The sesquiterpene skeleton has also been assembled by the intramolecular nitrile oxide cycloaddition sequence. Oxime 238 (obtained from epoxy silyl ether 237), on treatment with sodium hypochlorite gave isoxazoline 239, which was sequentially hydrolyzed and then subjected to the reductive hydrolysis conditions-cyclization sequence to give the furan derivative 240 (330) (Scheme 6.93). In three additional steps, compound 240 was converted to 241. This structure contains the C11-C21 segment of the furanoterpene ent-242, that could be obtained after several more steps (330). 

Triazines are generally more reactive in [2 + 4] cycloaddition in comparison with 1,2,3-tria-zines. The wide variety of dienophiles can be employed enamines, enaminones, vinyl silyl ethers, vinyl thioethers, cyclic ketene jV,O-acetals, /V-phenylmaleimide, 6-dimethylaminopentafulvene, 2-alkylidene-imidazolidines (cychc ketene aminals), cyclic vinyl ethers, arynes, benzocyclopropene, acetylenes, and alkenes like ethylene, (Z)-but-2-ene, cyclopentene, cyclooctene and bicyclo[2.2.1]hept-2-ene, hexa-1,5-diene, cycloocta-1,5-diene, diallyl ether, cyclododeca-l,5,9-triene,... 

An enantioselective synthesis of (+)-estradiol has been accomplished from 1,3-dihy-drobenzo[c]thiophene 2,2-dioxide (306) by successive thermal S02-extrusion and cycloaddition (80HCA1703). Treatment of the optically active iodide (307) with two mole equivalents of the masked quinodimethane (306) in the presence of two mole equivalents of sodium hydride gave (308) as a 1 1 mixture of diastereoisomers. Thermolysis of this alkenic sulfone in 1,2,4-trichlorobenzene furnished the trans-anti-trans steroid (309) in 80% yield. Treatment of (309) with methyllithium gave the methyl ketone, which was subjected to a Baeyer-Villiger oxidation and then silyl ether-acetate cleavage to afford (-l-)-estradiol (310 Scheme 66). 

Diels-Alder reactions.1 The diene undergoes uncatalyzed [4+2]cycloaddition with very reactive dienophiles, but generally a Lewis acid catalyst (ZnCl, or C2H5A1C12) is required. Thus, the catalyzed reaction of 1 with methyl acrylate proceeds at 0° to afford, after silyl ether cleavage, the cycloadducts 2 and 3. 

Dehydrobromination.3 One approach to trialkylsiloxyalkynes involves de-hydrobromination of 1, prepared from tribromoethanol, with BuLi (2 equiv.) to form (Z)-2-bromovinyl silyl ethers 2, which can be converted by LDA followed by alkylation into siloxyalkynes (4). These products undergo cycloaddition with vinyl... 

Ethyl aluminum dichloride mediates a formal [5 + 2] cycloaddition of complex (164) and (166) with enol silyl ethers to produce the highly strained seven-membered rings (165) and (167) respectively (Schemes 239 -240). Excellent stereoselectivity is observed in both cases. A related double alkylation affords complexed seven-membered rings via a formal [4 - - 3] cycloaddition. Incorporation of fluorine is observed using boron trifluoride etherate (Scheme 241). 

By the cycloaddition of dibenzyl diazenedicarboxylate and furanoid and pyranoid glycals it is possible to diastereoselectively introduce an amino function at the C-2 position of a carbohydrate29-34. A single diastereomer is produced from furanoid glycals, where the cycloaddition takes place trans to the C-3 hydroxy substituent protected as the silyl ether, e.g., formation of 14-1630. The more reactive bis(2,2,2-trichloroethyl) diazenedicarboxylate can be employed even with less reactive 3-acetyl glycals31. 

Boeckman, R. K., Jr., Liu, Y. Toward the Development of a General Chiral Auxiliary. 5. High Diastereofacial Selectivity in Cycloadditions with Trienol Silyl Ethers An Application to an Enantioselective Synthesis of (-)-Cassioside. J. Org. Chem. 1996, 61, 7984-7985. 

Construction of the triene required for the Diels-Alder cycloaddition began with the chain extension of glycidaldehyde (8) to the a,p-unsaturated ester and hydrolysis to the diol 9 in 66% overall yield. Selective protection of the primary alcohol as the silyl ether and oxidation of the free secondary hydroxyl group gave the unsaturated keto ester 10 (78%). Ester 10 was condensed with ethylidene triphenyphosphorane and reduced to afford a 66% yield of a mixture of dienes 11. Upon NMR analysis, this material was established to be a mixture of the desired and (Z,Z)-isomers (5.7 1). Chromatographic separation led to... 

The required chain extension of 12 was accomplished via deprotonation with NaH and condensation with aldehyde 7 to afford the Diels-Alder precursor 13 in 50% yield. Thermolysis of triene 13 and lactam 3 in xylene at 170 C for four days resulted in the desired cycloaddition to 14. Chromatographic purification permitted isolation of pure 14 in addition to a small amount of an exo isomer (>4 1 ratio). Acid treatment induced cleavage of both the silyl ether and acetonide. Reprotection of the diol and selective epoxidation of the A olefin produced 15 in 64% yield from 12. Epoxide 12 was then transformed to the isomeric allylic alcohol 16 by conversion of the alcohol to the bromide followed by reductive elimination. Protecting-group manipulation and subsequent oxidation the gave aldehyde 17, which was homologated and hydrolyzed to give seco acid 18 in 32% overall yield from 16. 

Aldol reaction and alkylation of ketones at the a-position via enol silyl ethers (11) under neutral conditions are good examples [8]. Ortho-quinodimethane (15) is afforded at room temperature and undergoes [4 + 2] cycloaddition [10]. In contrast, the thermal ring opening of benzocyclobutane requires a much higher temperature (180-190°C) [11]. The fluorine-mediated Si—C activation protocol was the preferred method for the formation of tetrafluoro-para-quinodimethane (19), which then dimerizes to octafluoro-para-cyclophane (20) [12]. Azomethine ylide (22) can be generated from 21 byAgF catalysis and is used for heterocycles syntheses [13]. 

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