Wittig-cyclization sequence

Davis and coworkers carried out a Wittig-cyclization sequence with the partially protected 2-deoxyamino sugar 191 using an amino acid based phosphonate. Reaction of 191 with the cesium enolate 192 gave a 53% yield of epimers 193 and 194 (1 1 ratio) in which epimerization of the 2-amino group had taken place. The maimo isomer 194 was then epimerized to the more stable gluco 193 derivative by simple treatment with t-BuOLi in methanol (Scheme 38) [54]. 

Heating a-hydroxy amides 135 in xylene with the cumulated phosphoms ylide 134 gives the 2(3//)-oxazolones 140. The reaction proceeds via an addition-cyclization-intermolecular-Wittig olefination sequence, which imphes three different types of phosphorus ylides, 134,136, and 137, respectively, of increasing ylide activity (Fig. 5.33 Table 5.7, Figs. 5.34, 5.35). 

A phosphorus ylide serves as the carbanionic component in a synthesis of pyran-2-ones from 1,3-diketones (70ACS343). A Wittig reaction between the ylide and one of the carbonyl groups is envisaged as the first step in the sequence and the resulting keto ester spontaneously cyclizes. The reaction is conducted under pressure and yields are low. 

Phenyl isocyanate was used differently by Taylor and Patel (91JHC1857), who synthesized 2-anilinothieno[2,3-d]pyrimidine 76 by the sequence of reactions 48 — 74 — 75 — 76. This synthesis involves (i) adding the o-aminocarbonitrile 48 (R2 = R3 = H) to a mixture of triphenylphosphine and bromine at 0°C to give iminophosphorane 74, (ii) an aza-Wittig reaction on the iminophosphorane with phenyl isocyanate to yield carbodiimide 75, and (iii) cyclization of the latter with ammonia. 

Reduction of 202a to the lactol and a subsequent Wittig reaction led to 203 in 52% yield. Protecting-group exchange and tosylation of the resulting primary alcohol provided the cyclization precursor 204 (76%). Base treatment then afforded an 87% yield of cyclopentanes 205 epimeric at the nitrile (an epimerizable position). Hydrolysis and esterification of either isomer led to the trans geminally substituted cyclopentane 206 in 82% yield. Reduction of 206 and protection of the ester produced benzyl ether 207, which was converted to alkyne 208 via a bromination-dehydrobromination sequence in 78% yield. 

Treatment of azidoketones 8 with triphenylphosphine led to the formation of pyrrolidine 9 via a Staudiner-aza-Wittig reductive cyclization <05JOC4751>. The latter were converted into 2,3-disubstituted pyrroles 10 upon heating. Azidoketones 8 were prepared by the novel condensation of 1,3-bis-sUyl enol ethers 6 with azidoacetal 7. This sequence was exploited for the synthesis of a cyclododecyl-fused pyrrole. 

Therefore, despite lower stereoselectivity (3 1) in the epoxidation step the benzyl ether 118 (Scheme 20) was converted into 123 and then converted into tetrahydrofu-ran 124. After Swem oxidation a mixture of the aldehydes is generated the isomer with the correct stereochemistry at C-2 cyclizes to the hemiacetal 125 whereas the second C-2 epimer did not cyclize and was thus easily removed by chromatography. By Wittig reaction 125 was transformed into 126 which was smoothly debenzylated under Hanesssian s conditions (15) to give alcohol 127. Inversion of configuration at C-2 was achieved by an oxidation reduction sequence with complete stereocontrol. 

Construction of furan ring of 131 by acid-catalyzed cyclization of 134 cannot be achieved due to low reactivity of the a,a-difluorinated double bond toward protonation. Therefore, the following sequence was employed for the total synthesis of 131 (Scheme 12.20) fluorination of lactone 133, introduction of a double bond to 136 by Wittig olefination, and modification of R part of O ." " The use of manganese enolate of lactone 133 is useful for one-pot difluorination. The reaction of the lithium enolate of 133 with the conventional electrophilic fluorinating reagent such as N-fluorobenzenesulfonimide provides only monofluoride 135. 

Stork s strategy towards racemic morphine comprises a Diels-Alder cycloaddition reaction of a benzofuran to establish the B- and C-ring of morphine as the key step [53]. The reaction sequence started with the ketahzation of iodoisovaniUin 97 (Scheme 15). Subsequently, the phenol was reacted with methyl propiolate to afford 98 as precursor for the installation of the benzofuran moiety via a palladium-catalyzed Heck cyclization (99). Next, the key intermediate was prepared for the Diels-Alder reaction. Hydrolysis of the acetal under acidic conditions and Wittig homologation afforded aldehyde 100, which was converted to diene 101 via hydrozirconation of acetylene 105 employing the Schwartz reagent and subsequent reaction with aldehyde 100 followed by sUylation of the secondary alcohol. 

---