Norbomenone

Mehta et al. also studied the facial selectivities of exo-substituted 7-norbomenones 15a and 15b, which exhibit steric bias with respect to the anti side of the n face (with respect to the exo substituent) [76, 77]. In the reduction with sodium borohy-dride, high anti preference (more than 85%) was observed in the parent derivative 15a. Weak electron-withdrawing substituents (CH OCH, CH OAc, COONa) also showed anti preference, the magnitude being comparable to that in the case of the parent compound (15a) this is indicative of the steric bias of 15a. In the case of a strong electron-withdrawing substituent (di- or mono-CO CH, CN), the syn preference of addition was increased, becoming predominant in some cases (di-CO CHj (15b) syn. anti = 55 45 mono-CO CH synianti = 32 68 mono-CN syn anti =... 

Keywords 7-norbomenone, NaBH4, 71-face selectivity, alcohol... 

Because the Corey synthesis has been extensively used in prostaglandin research, improvements on the various steps in the procedure have been made. These variations include improved procedures for the preparation of norbomenone (24), alternative methods for the resolution of acid (26), stereoselective preparations of (26), improved procedures for the deiodination of iodolactone (27), alternative methods for the synthesis of Corey aldehyde (29) or its equivalent, and improved procedures for the stereoselective reduction of enone (30) (108—168). For example, a catalytic enantioselective Diels-Alder reaction has been used in a highly efficient synthesis of key intermediate (24) in 92% ee (169). 

Curran s synthesis of ( )-A9(l2)-capnellene [( )-2] is detailed in Schemes 30 and 31. This synthesis commences with the preparation of racemic bicyclic vinyl lactone 147 from ( )-norbomenone [( )-145] by a well-known route.61 Thus, Baeyer-Villiger oxidation of (+)-145 provides unsaturated bicyclic lactone 146, a compound that can be converted to the isomeric fused bicyclic lactone 147 by acid-catalyzed rearrangement. Reaction of 147 with methylmagne-sium bromide/CuBr SMe2 in THF at -20 °C takes the desired course and affords unsaturated carboxylic acid 148 in nearly quantitative yield. Iodolactonization of 148 to 149, followed by base-induced elimination, then provides the methyl-substituted bicyclic vinyl lactone 150 as a single regioisomer in 66% overall yield from 147. 

Norbomenone 26 undergoes reduction by sodium borohydride under kinetic conditions to produce 5% exo- (i.e., endo attack) and 95% endo- (i.e., exo attack) 2-norbomeol. This leads to the partial rate constants of 11.4 for exo and 0.6 for endo attack (relative rate with respect to the rate of LiAlH reduction of cyclopen-tanone (1.00)) [80]. In the saturated 2-norbomanone 25, the values are 4.55 for exo and 0.74 for endo attack. Thus, the introduction of the double bond enhances the... 

Thus, a-methylthio methyl acrylate (1) was shown to react with cyclopentadiene at room temperature. The adduct (2) was isolated in a 94% yield (exo-endo isomeric mixture). Further transformation of (2), according to Trost s method [250], (see also Section 3.6), afforded norbomenone (3) (60% yield), establishing (1) as a useful ketene synthetic equivalent [526]. 

C2-symmetric cyclic alkenyl sulfoxide (187), with cyclopentadiene, proceeded under mild conditions to give a single diastereomeric adduct (188) in excellent yield (Scheme 48). Other acyclic dienes also gave single diastereomeric adducts often without the necessity of using Lewis acids. The Ws-sulfoxide moiety can be readily deprotected using a two-step sequence of sulfoxide reduction followed by hydrolysis of the dithiolane to give the enantiomerically pure norbomenone (189). 

These two / f( -reactions have been used for a stercospecific synthesis of dihydrone-petalactone (7) from norbomenone (3).- Addition of propynylmagnesium bromide, followed by Lindlar reduction of the triple bond, acetylation, and reaction with 2. provides the allylsilane 4. Epoxidation of 4 and dcsilylation results in 5. Oxy-Cope rearrangement of 5 results in a single ketone (6) with the desired four chiral centers. The remaining steps to 7 involve conventibnal reactions. 

R)- and (S)-f-Butyl-5-methylene-l,3-dioxolan-4-one, a Chiral a-Alkoxy Acrylate. It is also possible to introduce an ex-ocyclic double bond onto the dioxolanone ring, as in compounds (9)-(ll), derived from lactic and malic - acids. These a,3-unsaturated carbonyl derivatives are acceptors for radical additions and undergo cycloadditions with dienes and heterodienes. The Diels-Alder adduct (12) of ent-(9) with cyclopentadiene is formed with exo selectivity (96 4) and serves as aprecursor to norbomenone (13). Cycloadduct (14), obtained from methylenedioxolanone (9) and an open-chain triene, is also the result of an exo addition and is used in tetronolide synthesis. ... 

A useful observation on the cycloaddition of cyclopentadiene and methyl acrylate catalyzed by an aluminum complex of VAPOL 63 is the autoinduction of asymmetry in the presence of an aldehyde or ester (including malonates). With a complex derived from a bisoxazoline ligand and CuBtj-AgSbF the cycloaddition between cyclopentadiene and 2-phenylthioacrylic esters is highly stereoselective, providing chiral precursors of (15,4S)-norbomenone in good yields. 

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