Remote asymmetric induction observed in the alkylation of propionate attached to a carbohydrate template

Chiral Linker 1. A Novel Chiral Auxiliary Derived from m-Hydrobenzoin as Enantiomerically Pure Linker for Solid Phase Organic Chemistry

“…As shown in Table 1, m-hydrobenzoin derived test system 5 induces chirality up to 31-36% de using LDA (entry 1) and 20% de using less basic LHMDS as deprotonating agent (entry 2), resp. While LiCl shows no effect on the resulting Thus, it could be shown that m-hydrobenzoin derived chiral linker systems in principal have the ability to induce chirality (entries 1, 2), which might be suggested as a consequence of chelation effects leading possibly to 7-membered cyclic enolate structures and consequently shielding one of the diastereofaces of the enolate more than the other, thereby controlling the approach of the electrophile [12]. Inversion of the resulting diastereoselectivity by using HMPA as an additive (entry 4) is, thus, a matter of different enolate geometry, as lined out in the literature [12,15,19,20] (Scheme 4).…”

“…Stereoselective α-benzylation of its propionate 6 was chosen as first test reaction, because this type of reaction [15] has been used for similar auxiliary structures derived from 1,2-diols only a few years ago [11,12]. In addition, there is still a need for alternative polymer bound auxiliaries for α-alkylation reactions, for the N-acyloxazolidinones of Evans [15] and the pseudoephedrine tertiary amides of Myers [15], which provide the gold standards in the field and have been applied on solid support both successfully [5,6], are still limited to some extent.…”

“…Hydrobenzoin derivatives are already known as chiral auxiliaries for ringopening reactions of oxiranes [8], oxidation reactions of sulfides [9], and the reduction of α-ketoesters [10] and similar structures derived from 1,2-diols have already been used in α-alkylation [11,12] and aldol addition reactions [11], resp. As all of these auxiliaries *Address correspondence to this author at the Institute of Applied Synthetic Chemistry, Vienna University of Technology, Getreidemarkt 9, A-1060 Vienna, Austria; E-mail: pgaertne@ioc.tuwein.ac.at possess structural subunits very similar to benzyl ethers like many commercially available linkers we suppose hydrobenzoins to serve as proper dual chiral auxiliaries and linkers for solid phase organic chemistry (Scheme 1).…”

Asymmetric processes

“…3 Alkylation of the two closely related glucose-derived propionate esters 3 and 4 containing pseudo-C 2 symmetry gives opposite diastereoisomers in у91% de, and requires the use of LiCl or HMPA as additives for 3 and 4 respectively, in order to obtain high selectivities. 4 The oxazolidinone 5 has been suggested as a more bulky version of the popular Evans' auxiliaries, and can be prepared from serine methyl ester. 5 It has been tested in alkylation, aldol and Diels-Alder reactions, and advantages claimed include crystalline aldol adducts and possible superiority in radical reactions.…”

Diacetone-glucose architecture as a chirality template. Part 9.1 Enantioselective synthesis of (R)-mevalonolactone and (R)-[2H9]mevalonolactone on carbohydrate template

“…Based on the elucidated transition-state of Overman's allyl imidate rearrangement, 10 together with other stereochemical outcomes of chiral induction on the diacetone--glucose template, 11, 12 it was envisaged that the diastereotopic face of an olefinic functionality of a spiro-ring implanted on the C-3 of the template could be effectively differentiated by either electrophilic or nucleophilic addition reactions, due to the high steric constraint of the isopropylidene glycol system attached to the C-4β position. Thus, expoxidation of the δ-lactone 3a under Structure of mevalonolactone 1a and [ 2 H 9 ]mevalonolactone 1b alkaline conditions was expected to afford preferentially the epoxide 5a with high stereoselection (see Scheme 1).…”