Transition state allyl alkyl ethers

Nitrile oxides react with the methyl enol ethers of (Rs)-l -fluoro-alkyl-2-(p-tolylsulfinyl)ethanones to produce (45,5/f,/fs)-4,5-dihydroisoxazoles with high regio-and diastereo-selectivity.87 In the 1,3-dipolar cycloaddition of benzonitrile oxide with adamantane-2-thiones and 2-methyleneadamantanes, the favoured approach is syn, as predicted by the Cieplak s transition-state hyperconjugation model.88 The 1,3-dipolar cycloaddition reaction of acetonitrile oxide with bicyclo[2.2.l]hepta-2,5-diene yields two 1 1 adducts and four of six possible 2 1 adducts.89 Moderate catalytic efficiency, ligand acceleration effect, and concentration effect have been observed in the magnesium ion-mediated 1,3-dipolar cycloadditions of stable mesitonitrile oxide to allylic alcohols.90 The cycloaddition reactions of acryloyl derivatives of the Rebek imide benzoxazole with nitrile oxides are very stereoselective but show reaction rates and regioselectivities comparable to simple achiral models.91. 

Zirconium imido complexes have been used to carry out S 2 reactions of allylic chloride, bromide, iodide, and alkyl, aryl, and trimethylsilyl ethers in high yields at room temperature.12 The syn stereochemistry, an inverse secondary (k /k Oy = 0.88 obtained using the ( )-l-(r-butyldimethylsilyloxy)-3-deuterioprop-2-ene and the rate expression led the authors to suggest the reactions occurred via the mechanism in Scheme 4 with transition state (9). 

Treatment of 1,3-dicarbonyl compounds with DBP in a methoxide/methanol system affords 2-alkyl-4-[(phenylsulfonyl)methyl]furans, where reaction proceeds by Initial addition-elimination on the vinyl sulfone moiety. In contrast, silyl enol ethers in the presence of silver tetrafluoroborate resulted in products derived from Sn2 displacement at the allylic site.11 Anions derived from 1,3-dicarbonyls substituted at the C-2 position are found to induce a complete reversal in the mode of ring closure.12 The major products obtained are 3-[(phenylsulfonyl)methyl]-substituted cyclopentenones. The internal displacement reaction leading to the furan ring apparently encounters an unfavorable Ai -interaction in the transition state when a substituent group is present at the 2-position ol the dicarbonyl compound. This steric Interaction is not present in the transition state leading to the cyclopentenone ring. 

These results are consistent with the chelated transition states depicted in Scheme 18. Steric interactions between the substituent and the carboxamide favor (AC) for ( )-allylic ethers. The R -substi-tuent of a (Z)-allylic ether, though less affected by this interaction, still experiences a certain degree of steric strain in the anti transition state (AB) thus diminishing anti selectivity. Enantioselectivity is controlled by the substituents R and R on the pyrrolidine ring. As pictured in Scheme 18, bonding occurs preferentially on the face of the enolate anti to R. For the diastereomeric secondary allylic ethers (Table 21, entries 8) transition state (AB) represents the matched arrangement for R = H and R = alkyl, whereas (AC) is matched for R = alkyl and R = H. The former arrangement would lead to an ( )-pro-duct and the latter to a (Z)-product. 

As mentioned in the discussion of the pathways to indoles (Scheme 27), a detailed indole synthesis with two points of diversity based on the Heck reaction has been reported [164]. The indole core structure was synthesized via a 5-exo-tng transition state, which provided the exocyclic double bond that subsequently underwent exo to endo double-bond migration. The anthranilate building block was prepared in solution and immobilized by a method previously described for the loading of 2-aminobenzophenones [Ij. After Fmoc cleavage, the resulting 4-bromo-3-amino-phenyl ether was treated with acid chlorides and pyridine in CH2CI2. As outlined in Scheme 29, alkylation of the anilide with substituted allyl bromides was achieved in the presence of lithium benzyloxazoHdinone in THF. The reaction mixture was treated with base for 1 h and then an aUylic halide was added and the mixture was vortexed for 6 h at room temperature. The alkylation reactions were... 

The inside alkoxy effect is useful for predicting the stereoselectivity of nitrile oxide cycloaddition reactions with chiral lylic ethers. The hypothesis states that allylic ethers adopt the inside position and alkyl substituents prefer the sterically less-crowded anti conformation in transition states for these electrophilic cycloadditions . The terms inside and outside are defined in (17) for a hypothetical nitrile oxide cycloaddition transition state. Both ab initio (Gaussian 80 with 3-2IG basis set) and molecular mechanics calculations agree, each predicting the lowest-energy transition state to be the one described, i.e. (18 H outside) just above it lies one where the alkyl group is anti, OR outside and H inside (19 ). As illustrated, the former leads to a product wherein OR and the nitrile oxide oxygen are anti, the latter to one with them syn (Scheme 19). 

Analogously, the polyisoprenoid plaunotol 164 was synthesized from allyl dimethylamine 159 tScheme 15.381. Alkylation with ethyl bromoacetate and deprotonation with KOt-Bu yielded ammonium ylide 161, which rearranged to a-aminoester 163. The exclusive formation of a single olefin isomer in 163 presumable occurs via transition state 162. Reductive removal of the dimethylamine group and benzyl ethers, along with conversion of the ester into the hydrocarbon side chain, yielded the natural product plaunotol 163. 

The Claisen rearrangement is a suprafacial, concerted, nonsynchronous pericyclic process that is considered occasionally as an intramolecular 8, 2 alkylation (Eq. 3.1.18) [2]. When the Claisen rearrangement can produce enantiotopic faces at both terminals of allyl vinyl ether, the rearrangement can proceed through two pairs of chiral transition states to prepare two racemic diastereomers bearing newly created stereocenters of the products 15 and 16 (Eq. 3.1.19). Achiral allyl vinyl ether 14 can provide two enantiomeric chair-like transition states chair 1 and 2, both of which lead to the racemic, diastereomeric aldehyde 15. Similarly, the enantiomeric boat-like transition states boat 1 and 2 provide racemic diastereomer 16. The two transition states are essentially different in energy and the ratio 15/16 reflects the transition state geometry. 

High regioselectivity has been observed for addition of silyl enol ethers to a,p-unsaturated aldehydes and ketones, promoted by lithium perchlorate in diethyl ether. Potassium enolates of acyclic y-alkoxy-a-methyl pentanoates can be alkylated with allylic and benzylic halides with high 2,3-syn selectivity. The results have been rationalized in terms of non-chelated (for potassium enolates) and chelated (for lithium enolates) transition states. 

A new approach to the preparation of a-branched-chain sugars by the Claisen rearrangement of hexenopyranoside allyl ethers has been reported (Scheme 24). Thus compound (68), on heating produces the axially substituted C-alkyl derivative (52) which can be epimerized to the equatorially substituted product with base. The rearrangement proceeds through a chair-like transition state as proved by the conversion of the E-crotyl ether derivative (69) to the tricyclic product (70). (See Scheme 11 for a different preparation of (52).)... 

---