Cyclization of epoxides

The electron-rich thiophene ring system can be elaborated into complex, fused thiophenes by acid-mediated intramolecular annelation reactions. For example, treatment of alcohol 96 with trimethylsilyl triflate promoted a Friedel-Crafts acylation and subsequent dehydration giving benzo[b]thiophene 97, a potential analgesic <00JMC765>. Treatment of ketone 98 with p-toluenesulfonic acid resulted in the formation of fused benzo[b]thiophene 99 <00T8153>. Another variant involved the cyclization of epoxide 100 to fused benzo[f>]thiophene 101 mediated by boron trifluoride-etherate . 

Cross-Cyclization of Epoxides with Homoallylic Alcohols. 232... 

Cross-cyclization of epoxides with homoallylic amines is an easy way to access tetrahydropyran moieties, which form the core structure of many biologically important natural products such as avermectins, aplysiatoxin, oscillatoxins, latrunculins, talaromycins, acutiphycins, and apicularens. Even though many methods are available for the synthesis of this moiety [14—24], its importance and wide applicability demands further methods. 

Table 1 Cross-cyclization of epoxides with homoallylic alcohols...

Fig. 3 Aza-Prins cyclization of epoxides with N-protected homoallylic amines...

Competition of the biomimetic cyclization of epoxides, either with an aromatic ring or with a double bond, has been studied. Evidence for an early transition state has been provided and the biosynthetic implications discussed403. 

According to the Baldwin rule, the exo cyclization mode is favored in intramolecular reactions of alkynyloxiranes with alcohols to afford cyclic ethers. However, the unfavorable endo cyclization mode is observed by the complexation. Thus exclusive endo cyclization of epoxide complex 146 takes place regioselectively to give 147, without forming the five-membered ether 148 by exo mode reaction [37]. 

Ketone 1 is highly general and enantioselective for the epoxidation of fran.v-substituted and trisub-stituted olefins. Its ready availability and predictability potentially make this ketone useful. Its utilization in synthesis has been reported by other researchers.79 100 For example, Corey and coworkers have reported that pentaoxacyclic compound 24 can be obtained in 31% overall yield by enantioselective epoxidation of (f )-2,3-dihydroxy-2,3-dihydrosqualene (22) and subsequent cyclization of pentaepoxide 23 (Scheme 10.7).82 Eli Lilly has also used the epoxidation to introduce the epoxide on the sidechain of Cryptophycin 52 (Scheme 10.8).90 The epoxidation has been carried out at multi-kilogram scale at DSM-Catalytica. Around 100 kg of lactone 29 was prepared by the epoxidation of olefin 27 and subsequent in situ cyclization of epoxide 28 (Scheme 10.9).101... 

Rearrangements of epoxyalcohols and related compounds 90OPP547. Regio- and stereoselective intramolecular cyclizations of epoxides 92 YGK638. 

Indolines and indoles were prepared by a direct electrochemical reduction of arenediazonium salts. As a result, radical intermediates were generated from which 3,4-disubstituted tetrahydrofuran skeleta were constructed <02OL2735>. A short and stereoselective total synthesis of furano lignans was realized by radical cyclization of epoxides using a transition-metal radical source <02JOC3242>. Other preparations of tetrahydrofurans using radical cyclization include the synthesis of novel amino acids L-bis-... 

The reductive cyclization of epoxides with alkenes and alkynes provides a very useful method for the synthesis of complex carbocyclic ring systems. Several interesting applications of this methodology have been reported in the past year. Two examples report the cyclization of an epoxide with an acrylate as the terminating group <07T 11341 ... 

Most of the reductive cyclizations of epoxides use Ti(III) species to reduce the epoxide and generate the reactive radical species. Nickel can also be used to effect this type of reductive cyclization <07JOC7451>. The reaction of epoxide 35 with Ni(cod)2 provides pumiliotoxin 209F in good yield. 

A biomimetic synthesis of ( )-pallescensin A (107 R = H) has been achieved through the concerted Bp3 Et20-induced cyclization of epoxide (106) to yield crystalline (107 R = OH) (25%), followed by subsequent deoxygenation. The cyclization of the parent diene with BF3-Et20 gave (107 R == H) directly (84%) as an almost pure oil. 

Scheme 4.24 Polymer-supported base-catalyzed domino ring opening/cyclization of epoxide 120.

Example 5.9 Consider the retrosynthetic analysis of TM 4.9, a key intermediate in the synthesis of the anti-asthmatic drug salbutamol, and then propose the synthesis. Use the dimsyl anion (MeSOCH2US[a as the source of carbene for cyclization of epoxide. 

One early example was reported by Chatteijee in 1979 for stereospecific synthesis of the sesquiterpene isocomene by transannular cationic cyclization. The acid-catalyzed cyclization of epoxide 152 through transannular participation of the remote double bond led to the formation of 153 (Scheme 20.37), which was further transformed to isocomene. The reaction was stereoselective since formation of any other diastereomers will lead to the formation of much strained polycyclic systems with trans-fased cyclopentanes. 

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