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A general method for the generation of isobenzofuran intermediates is described. Lithiated aromatic acetals are converted to hydroxyacetals (A) which may be cyclized to isobenzofurans by mild acid treatment through the 1-hydroxyphthalans (B). The isobenzofurans generated insitu are trapped by a variety of dienophiles to provide the expected oxo-bicyclo adducts (C). The mass and 1Hmr spectra of B and C are discussed.

. 1093 (1984).Two general 5-endo-trig reversals of 7-oxabicyclo[2.2, llheptanes and heptenes are described and discussed. The reverseMichael reaction occurs with the aldehyde, ketone, ester, and nitrile derivatives while the reverse aldol reaction catalysed by acid is confined to the aldehydes and ketones. These properties of the title compounds are rationalized in terms of the geometric alignments of the bonding and antibonding orbitals of the bridging oxygen atom and its neighboring carbons. New isobenzofuran and cyclohexadiene syntheses form a part of the report. Early in our studies of the Diels-Alder reactions of isobenzofurans (1) we made the useful and intriguing discovery that adduct l a was smoothly converted to the dihydronaphthalene 2 a with methanolic sodium methoxide. The same reaction applied to the closely related adduct 3 was a key transformation in our recent synthesis (2) of ( 2 ) daunomycinone. An examination of the process with a variety of oxabicyclo adducts' was conducted and the results (Table 1, Entries 1, 3, 6, 8, 1 1,13,16,18) confirmed the generality of the reaction. A reverse-Michael rationalization shown in Scheme 1 requires the development of some double bond character at a bridgehead and is also a 5-endo-trig reversal in violation of rules (3) formulated earlier and illustrated (4) with the furan 9. No evidence could be obtained, however, to support any alternative mechanism; for example, no products of C(4)-0 cleavage were ever observed, thus excluding the possibility of a simple nucleophilic displacement at C ( l ) and(or) C(4). Deuteration at C(2) took place with esters and nitriles (entries 5, 7 , 10, 12, 15, and 17) and the deuterated products were endo-exo mixtures even when pure endo substrates ( l c and I d , entries 5 and 7) were used. Oxabicyclo ketones and aldehydes could not be deuterated cleanly with methanolic methoxide because of the rapid formation of products under the conditions. After 1 h at 20°C with this reagent, l a and l b , for example, were converted to a 1 : 1 mixture of products (2a and 2 b respectively) and deuterated starting materials. The lower acidity of the esters and nitriles must be responsible for rapid reprotonation of their enolates in methanolic methoxide, permitting clean deuteration in these cases and revealing the existence of a kinetic barrier to the reverse-Michael fission of the C(1)-0 bond. This behaviour is similar to the previously observed (4) deuteration of furan 9 and is interpreted similarly. Unlike the simple furan 9, however, which was inert to all bases, these compounds do suffer a forbidden 5-endo-trig cleavage with the strong base LDA under aprotic conditions (entries 6, 8, 1 1, 13, 16, and 18). Base-catalysed aromatizations observed in entries I Author to whom correspondence may be addressed. 'prepared by Diels-Alder reaction of furans and isobenzofurans with the appropriate dienophiles and used as endo-exo mixtures.2, 4, and 9 and previously with sodium acetate in refluxing methanol (5) must also occur through an initial ...

, 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.