A theoretical study specifically addresses the question of whether nucleophilic addition to the carbonyl groups of acid chlorides, esters, and anhydrides involves an addition-elimination pathway or proceeds by a concerted S(N)2-like mechanism in the absence of the generally assumed tetrahedral intermediate. Density functional calculations [B3LYP/6-31+G(d,p)] establish that chloride ion exchange reactions with both formyl and acetyl chloride proceed by a pi attack on the C=O bond. No discernible tetrahedral intermediate typical of an addition-elimination pathway was found in either case. While a tetrahedral intermediate does exist for the addition of fluoride ion to (Cl)(2)C=O, halide exchange of LiCl with both ClFC=O and (Cl)(2)C=O also proceeds by a concerted S(N)2-like pathway. The formation of a tetrahedral intermediate from the addition of methanol to acetyl chloride is slightly exothermic (4.4 kcal/mol). The ion-dipole complex of methanol weakly bonded to the carbonyl carbon of protonated acetyl chloride is stabilized by 13.8 kcal/mol but does not collapse to a tetrahedral intermediate. When four CH(3)OH molecules are H-bonded to protonated acetyl chloride, a tetrahedral intermediate is not completely formed and this solvated complex more closely resembles the precursor to an S(N)1-type ionization of Cl(-). With six H-bonding methanol molecules, a methanol adds to the carbonyl carbon and a proton relay occurs with formation of a tetrahedral-like structure that immediately loses chloride ion in an S(N)1-like solvolysis. These results corroborate earlier suggestions (Bentley et al. J. Org. Chem. 1996, 61, 7927) that the methanolysis of acetyl chloride does not proceed through the generally assumed addition-elimination pathway with a discrete tetrahedral intermediate but is consistent with ionization of Cl(-). The reaction of methoxide ion with methyl acetate proceeds via a multiple-well energy surface and involves the intermediacy of an asymmetrical species with differing C-OMe bond lengths. Models of synthetic applications of acyl transfer reactions involving anhydrides that form N-acyloxazolidinones also proceed by a concerted S(N)2-type pathway even with the carboxylate leaving group. Concerted transition states were observed for the reactions of each enantiomer of a 1,3-diphenylcycloprop-2-ene carboxylic anhydride by S-3-lithio-4-phenyloxazolidinone. Despite close structural similarities between the diastereomeric transition states, the relative energies correlated closely with the experimental results.

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[reaction: see text] In this Letter, we describe a general method for preparing the dianions of cyclopropene carboxylic acids, and we show that their subsequent reactions with electrophiles provide a general means for selectively introducing diverse types of functional groups. This provides a general method for the synthesis of chiral 1,2-disubstituted cyclopropenes, and opens new avenues for the enantioselective preparation of cyclopropenes.

A Cu-catalyzed method for the addition of Grignard reagents to 1-alkyl-3-hydroxymethylcyclopropenes and their MOM ethers is described. The face of addition is syn relative to the hydroxymethyl and alkoxymethyl groups. Excellent diastereoselectivity is observed for a range of alkyl, alkenyl, and alkynylmagnesium halides. The addition reactions create chiral all-carbon quaternary centers, and the cyclopropylmetals that are generated can be reacted with electrophiles to produce highly functionalized cyclopropanes.

A new type of parallel kinetic resolution (PKR) is reported in which quasienantiomers with very similar reactivities give products whose chromatographic properties diverge upon the addition of fluoride. This concept of a reactivity/affinity switch is applied to the PKR of cyclopropene carboxylic acids with all-carbon quaternary centers. This is the first application of alpha-amino acid quasienantiomers in PKR, and it is a complementary approach for acyltransfer systems where the asymmetry is induced by the nucleophile rather than the leaving group. Excellent diastereoselectivities (ranging from 90:10 to 99.5:5) and good yields were obtained for both quasienantiomeric products, and the reactions can be run on significant scale because the separation is trivial. High-level DFT calculations (B3LYP functional with the 6-31+G(d,p) basis set) provided transition-state structures with relative energies that are in accord with the experimental observations.

Page 4937. In a previous report, we described the preparations and reactions of dianions of cycloprop-2-ene carboxylic acids. Dianions were prepared using MeLi in Et 2 O or THF and subsequently reacted with electrophiles at the vinylic position. Upon further study, we have found that the reactions employing Et 2 O as solvent could not be consistently repeated (see Table 1, all three entries in row 1 and the first entry in row 2). The dianions can indeed be generated in Et 2 O as previously described. However, the rate of dianion decomposition in Et 2 O is competitive with the rate of alkylation by MeI, MeOTs, or EtI. These reactions do work in high yield when THF or THF/NMO is used as the solvent. Additionally, an experimental procedure in the Supporting Information describes the dianion 12 (Scheme 6) being warmed to 0-5°C, but we have observed that this dianion decomposes at temperatures above -40°C. Addition of electrophiles to this dianion should be carried out at low temperature.Working under the assumption that an impurity may have promoted the earlier reactions, we have investigated the effect of solvents and various additives on the stability and reactivity of dianions. While it is not possible to prove that an impurity was present in the earlier study, we have found that certain additives can have a substantial effect both on the reactivity and on the stability of dianions. In particular, amine-N-oxides both enhance dianion stability and increase their rate of reactivity toward alkyl halides. With the modifications to the procedure, the scope of the reaction is now broader than that described previously. The results of a full study will be submitted for publication.

Cyclopropane derivatives Q 0021Dianion Approach to Chiral Cyclopropene Carboxylic Acids. -The dianions of cyclopropene carboxylic acids are shown to be stable and do not rearrange in contrast to the corresponding monoanions of their esters. Subsequent capture by electrophiles provides a general synthesis of 1,2-disubstituted derivatives cyclopropenes. The deprotonation/ alkylation occurs with excellent transfer of absolute stereochemistry as is shown by example (R)-(Ib). -(LIAO, L.-A.; YAN, N.; FOX*, J. M.; Org. Lett. 6 (2004) 26, 4937-4939; Dep. Chem. Biochem., Univ. Del., Newark, DE 19716, USA; Eng.) -Steudel 17-075

Stereochemistry Stereochemistry O 0030An Efficient and General Method for Resolving Cyclopropene Carboxylic Acids.-The chemical resolution of cyclopropenecarboxylic acids is smoothly achieved via their N-acyloxazolidinones which can be separated by simple flash chromatography.Best results are obtained with the oxazolidinones of (S)-phenylglycine, (S)-phenylalaninol and (1S,2R)-cis-1-amino-2-indanol. Removal of the oxazolidinone moiety is then achieved by LiBH 4 reduction. A wide range of substituted cyclopropenecarboxylic acids can be applied in this resolution method. -(LIAO, L.-A.; ZHANG, F.; YAN, N.; GOLEN, J. A.; FOX*, J. M.; Tetrahedron 60 (2004) 8, 1803-1816; Dep. Chem. Biochem., Univ. Del., Newark, DE 19716, USA; Eng.) -Mischke 21-022