Shikimic acids from furan; methods of stereocontrolled access to 3,4,5-trioxygenated cyclohexenes

Abstract

, 826 (1984). Oxabicycloheptenes 1 and 2 are converted to 3,4,5-oxygenated cyclohexenes by stereocontrolled hydroxylations and epoxidations coupled with reverse-Michael cleavage of the oxabicyclo system. Three epimers of shikimic acid are synthesized by these methods. In a current paper ( I ) we report the general occurrence of some 5-endo-trig reversals of 7-oxabicyclo[2.2. llheptenes and provide a stereoelectronic rationale for the violations of Baldwin's Rules (2) observed in these cases. The reverse-Michael reactions (1, 3) of such compounds, coupled with standard epoxidations and hydroxylations, offer significant opportunities for the generation of multi-oxygenated cyclohexenes with virtually complete control of stereochemistry. We illustrate herein the application of these procedures to the efficient synthesis of some shikimic acids (4).* Oxabicycloheptenes 1 and 2, easily obtained from furan (5), were employed as starting materials. Conversion (1) of cyanide 2 to cyclohexadiene 3 followed by osmylation (osmium tetroxide/pyridine) produced diol 4 with complete regio and stereoselectivity. There is little doubt that the bulky TBDMS group is responsible for directing hydroxylation from the lower face of the 3,4 double bond. The synthesis of (+) shikimic acid 5 was then completed by the standard procedures of desilylation (tetrabutylammonium fluoride/THF) and alkaline hydrolysis in 3 1% overall yield from 2.If the osmylation is conducted before the reverse-MichaeI fission, the stereochemistry of the cis-diol function thereby introduced is reversed and 5-epishikimic acid should result. Accordingly, bicyclo ester 1 was osmylated as before and the resulting exo-diols 6 converted to the acetonides 7. ReverseMichael cleavage of the latter (LDA, THF, 0°C) provided the expected cyclohexenol 8 (86%). Hydrolysis of the acetonide (aqueous acetic acid, 16 h, 20°C) and saponification produced (+) 5-epishikimic acid 9 in 39% overall yield from 1. This epimer of shikimic acid has not been previously synthesized but its methyl ester (6) and a related triacetate 10 are known (7). Hydrolysis of the acetonide 8, as before, and acetylation confirmed the identity ('Hmr) and stereochemistry of our product.Expoxidations of the double bond similarly timed can produce the other two isomers to shikimic acid. Thus exo-epoxides 11 obtained by MCPBA treatment of 1 reacted with LDA at -78°C to afford a 1 : 1 mixture of two products (86%). These were separated by distillation and identified as epoxycyclohexenol 12 (bp 1 10°C/0.05 Torr) and cyclopropane 13 (bp 92-100°C/0.05 Torr). The former has recently been con-H 0 , , , , , 3 q R 1 :ZmCO2Me' Author to whom correspondence may be addressed.

Using ring-opening reactions of oxabicyclic compounds as a strategy in organic synthesis

“…derivatives have utilized this approach [17b, [153][154][155][156][157][158], as did the earlier work on 11-ketotestosterone [ 152], and gibberellic acid [ 159]. …”

Production and Synthetic Modifications of Shikimic Acid

“…Rodrigo and co-workers reported the synthesis of (±)-shikimic acid from cycloadduct 114 . A strategy similar to that discussed previously was adopted, wherein early stage base-promoted ring opening of 114 followed by diastereoselective dihydroxylation of 115 , controlled by the presence of bulky protecting group, furnished (±)-shikimic acid in 31% overall yield from 113 (Scheme ).…”

Chemistry of Epoxyquinols A, B, and C and Epoxytwinol A

“…[29] As a result, it was necessary to find an alternative route that would provide the endo epoxide isomer. After some experimentation, selective formation of the endo epoxide was accomplished via iodolactone (-)-26.…”