Acyclic systems selectivity

For acyclic systems, the anti diastereoselectivity of the (i )-enolates is lower than the syn diastereoselectivity of comparable (Z)-enolates. For example, carboxylic acid esters, which form predominantly ( )-enolates, react with aldehydes with high anti selectivity only in those cases where bulky aromatic substituents are in the alcoholic part of the ester22 25. 

Direct alkylation of allylic alcohols via the (allyloxy)phosphonium ion intermediate normally proceeds with anti-y selectivity for the Cyclic system, and sy/i-y selectivity for the acyclic system (see Table l)35 36. 

This procedure illustrates a highly selective and facile method for introducing a phenylsulfonyl group into the Z-position of 1,3-diene systems by using commercially available starting materials. The method can be applied to cyclic as well as acyclic systems giving 2-(pheny1sulfonyl)-l,3-dienes. In an alternative synthesis via condensation of allyl sulfone with aldehyde and subsequent acylation-elimination, the 2-(phenylsulfonyl)-l,3-dienes obtained are limited to acyclic systems. 

The potential of using free radical reactions as synthetic methods will be increased when the origin of selectivity, especially in acyclic systems, is better imderstood [100,101]. 

A comparison of calculated and experimentally measured conformational energy differences for a small selection of singlerotor acyclic systems is provided in Table 8-1. The experimental data for some systems are subject to large uncertainties, and too much weight should not be placed on quantitative comparisons. 

Cleavage of ethers. A few reports have mentioned that acyl iodides can cleave ethers in the absence of a Lewis acid. Since acyl iodides are not readily available, Oku et al. have used Nal and an acyl chloride as a possible equivalent. In any case, the system does cleave both cyclic and acyclic ethers selectively at the less substituted a-C—O bond. Although any acyl chloride can be used, use of pivaloyl chloride is particularly attractive because the resulting pivaloyl esters are readily hydrolyzed. Indeed this system is particularly useful for deprotection of methyl ethers. 

Hoffmann has shown that diastereoselective bromine-lithium exchange may be achieved even in acyclic systems.118 Treatment of 138 with BuLi in the Trapp solvent mixture at -120 °C in the presence of acetone generates the epoxides 139 and 140 in a 94 6 ratio of diastereoisomers.119 120 The selectivity was found to depend on the organolithium used for the bromine-lithium exchange, and it must therefore be under kinetic control. 

Cleavage of allylic alcohols. The system selectively cleaves the double bond and the adjacent bond bearing the hydroxyl group of acyclic and aromatic allylic alcohols. Cyclic allylic alcohols are oxidized in low yield to dicarboxylic acids. 

The rules that apply to acyclic systems are also applicable to cyclic compounds with an exo-double bond. Thus 3-arylideneflavanones 1 were stereo selectively epoxidized with alkaline hydrogen peroxide and stereospecifically with 3-chloroperoxybenzoic acid20 and potassium hypochlorite21 and, similarly, 6-methoxyaurones 6 were stereoselectively epoxidized with alkaline hydrogen peroxide and stereospecifically with 2-chloroperoxybenzoic acid22. 

Monosubstitution or different substituents at C-l of the allylic moiety open up the possibility for formation of (E)- or (Z)-allylic alcohols in acyclic systems. The transition state with one substituent R at C-l in an equatorial position ( transoid transition state) seems to be about 1.5 keal/mol more stable than the cisoid transition state7. The sigmatropic rearrangement via the energetically preferred transition state yields (T)-alkenes, usually with a selectivity of greater than 95 %86,87. 

In acyclic systems, Claisen rearrangements show a well-established prefoence for chair-like transition states. With crotyl propenyl ether, the chair selectivity amounts to 97-98% at 142 C, which corresponds to an approx. 3 kcal mol difference between the fiee energy of activation (AAG ) of chair and boat TS (equation 26). The preference for a chair-like geometry in the TS is even more pronounced in the Cope reaiT ement 99.7% of the 3,4-dimethylhexa-1,5-diene rearranges at 225 C via a chair-like TS, corresponding to a AAG chair-boat of -5.7 kcal mol" . - The latter result closely parallels the difference in energy of the chair and boat conformations of cyclohexane (5-6 kcal mol" ). ... 

The issue of stereoselectivity in acyclic systems has not been studied systematically, but a high degree of control is not expected. There is one report of the formation of an ethylideneazacyclohexane with excellent control of stereoselectivity (Scheme 59). No explanation for this dramatic selectivity was offered, nor is one readily apparent. Note also the strong preference for the formation of the more highly substituted regioisomer. 

Diastereofacial selection in nucleophilic additions to acyclic aldehydes and ketones is of major importance in synthetic organic chemistry." The greater conformational freedom of acyclic systems makes predictions as to the stereochemical outcome of such reactions more difficult than when the carbonyl group is contained within a cyclic framework. 

In acyclic systems like (290) the facial selectivity of the double bond addition may be directed by a free OH function (Scheme 9). It can also be shown that the regiocontrol depends on the reagent. Mer-curilactonizations (equation 103) are related to halolactonizations. The C—Hg bond may be cleaved leductively by a radical process. 

Because of the number of conformations that need to be considered for acyclic systems, cyclohexanones are somewhat simpler for analysis. However, even for these systems the situation is not easily amenable to isolating specific components of selectivity. Several explanations have been proposed over the years to account for the preference of axial attack of cyclohexanones by sterically unhindered nucleophiles (L1A1H4, NaBH4, AIH3) [9]. Equatorial attack is favoured for sterically hindered cyclohexanones or reducing agents (Fig. 6-7). 

In acyclic systems, reductions of the ketone group of 1.155 (Y = COR) give poor selectivities. Reactions of o-substituted aldehydes 1.155 (Y = CHO) with organomagnesium reagents, perfluoroalkyllithiums or nitromethane [540] or chloracetophenone [540, 544] anions are very selective. Such is also the case for their reactions with functionalized isonitriles [540], silyl enolethers or thioketene acetals in the presence of Lewis acids [545, 546], or in B aylis-Hillmann reactions [547],... 

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