Dienolates solvent effects

As shown in Scheme 34, a rather profound solvent effect on dienolate alkylation diastereoselectivity has been noted for the steroidal enone (71). Such large solvent effects have not been documented for other systems. Possible explanations based upon the position of the transition state along the reaction coordinate and/or specific solvation of the dienolate have been advanced to account for preferential axial alkylation in benzene and equatorial alkylation in t-butyl alcohol.However, in view of the fact that the degree of aggregation of the dienolate as well as the structure of the aggregates may be modified considerably in going from one solvent to the other, rationalization of the results is difficult. 

When lactate is used as a chiral auxiliary, the proximity of the enolic hydroxyl group and the carboxyl of the lactate induces an interaction between the functional groups in the photodienol. Therefore, a surprising solvent effect, and even a reversal of the diastereoselectivity with the content of 2-propanol in water, was reported [53]. Except for lactate 8f in methanol and 2-propanol/water mixtures, it was possible to correlate the chirality of the new asymmetric center with the configuration of the lactyl chiral auxiliary. When (S)-lactyl derivatives were examined, models indicated that the S-configuration of the new chiral center can be deduced from a sterically easier approach of the carboxylate group at the re face of the a-carbon of the dienol. 

Mattay et al. employed asymmetric copper(I)-catalyzed intramolecular [2 + 2]-photocycloaddition reactions in a synthetic approach to (+)- and (— )-grandisol [56]. Racemic dienol 33 was irradiated in the presence of CuOTf and a chiral ligand to yield mainly cyclobutanes 34 and ent-34 as a mixture of enantiomers. Other 1,6-dienes were also employed. A number of chiral nitrogen-containing bidentate ligands were tested, the most effective of which, (4S,4 S)-4,4 -diisopropyl-2,2 -bisoxazoline (35) and (4R,47 )-4,4 -diethyl-2,2 -bisoxazoline (36), ensured a minor enantiomeric excess of <5% ee (Scheme 12). The coordination of the diene to the chiral Cu(I) complex under formation of a complex of type 37 was proved by CD analysis. The authors suggest a lower reactivity of the chiral complex compared to the copper ion coordinated to solvent molecules as the reason for the low enantioselectivities observed. 

More modern studies have made use of copper(I) triflate (CuOTf) as the reagent. This compound is well known to form complexes with dienes and it provides a template on which cycloadditions can be effected. Several examples of this type of cyclization have been reported and cycloadditions based on this approach provide a useful route to cyclobutane derivatives. Thus, a new stereochemical synthesis of grandisol has been developed using the copper(I)-catalysed cycloaddition of the dienol 95 to afford the isomeric bicyclo-heptenols 96 exo endo ratio in this cyclization is solvent-dependent. The racemic... 

Alkylation of the dienolate ion derived from 4-methyl-19-nortestosterone (313) with CD3I in benzene solution gave the 4,4-dimethyl compound (314), with 70% of the labelled methyl groups in the 4j5-orientation. With t-butyl alcohol as solvent the product showed predominant (90%) introduction of 4a-CD3 (iWs latter conclusion, which reverses that reached in an earlier study, depended upon application of the nuclear Overhauser effect for the assignment of n.m.r. signals of the C-4 methyl groups). Solvent-dependence of the stereochemistry of alkylation has not been suspected before. ... 

The conversion of an aj3-unsaturated ketone to its dienol ether is usually effected by treatment with an orthoformic ester [112, 113, 114] or with 2,2-dimethoxy-propane [115] in the presence of an acid catalyst and in the corresponding alcohol or in dioxan as solvent. For the formation of a dienethiol ether treatment with the more reactive corresponding thiol is sufficient benzyl thiol has been used most frequently [116, 117]. Under the conditions generally used (at room temperature) saturated ketone groups react much more slowly and it is usually possible to differentiate completely between the two types of ketone group [112, 117]. With unhindered a,/5-unsaturated ketones and under more basic conditions alternative 1,4-addition of a thiol to the conjugated system may occur [117]. 

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