Efficient Desymmetrization ofmeso-cis-1,2-Cyclohexanedimethanol with Differentiation between Diastereotopic and Enantiotopic C−H Bonds by (−)-Sparteine-Mediated Deprotonation

Abstract

The deprotonation of a dicarbamate prepared from cis-1,2-cyclohexanedimethanol by sec-butyllithium/(À)-sparteine proceeds with efficient selection between the enantiotopic branches and their diastereotopic protons with high preference for the pro-S proton at the R branch to afford the intermediate, configurationally stable lithium compound as a single diastereomer. Trapping of this intermediate by electrophiles (DOMe, CO 2 , CH 3 I, Me 3 SiCl, or R 3 SnCl) takes place with retention of the configuration to yield highly enantiomerically and diastereomerically enriched substitution products, which are easily converted to diols, to anellated tetrahydrofurans, or to g-lactones. The chiral base is also capable of efficient kinetic resolution of the racemic adeuterated starting material, by the utilization of an extraordinarily high kinetic H/D isotope effect within the deprotonation step. The, presumably, first example of the kinetic resolution of a racemic stannane by lithiodestannylation, utilizing methyllithium/(À)-sparteine, is reported.

Diastereoselective Lithiation and Substitution of (S)-N-Benzylprolinol and rac-N-Benzylpiperidine-2-methanol via the Carbamate Esters: Kinetic Resolution by Means of (-)-Sparteine-Mediated Deprotonation

“…The reaction of (S)-8 via 10 with methyl iodide, chlorotrimethylsilane, chlorotributyltin, and acetone also yielded the expected compounds 14 with high diastereoselectivity (for spectroscopic data, see Table 3). As we had already observed in related cases, 12 no stereospecifity with respect to the former carbanionic center was achieved in the reaction with allyl bromide (Table 1, Entry 11). In all other cases, deprotonation and substitution -as found for all sp 3carbamoyloxy-substituted carbanions -proceeded with complete stereoretention.…”

The Preparation of Nonracemic Secondary α-(Carbamoyloxy)alkylzinc and Copper Reagents. A Versatile Approach to Enantioenriched Alcohols

“…A spectacular development in this field was achieved by Hoppe et al, who demonstrated that the complex s BuLi/ (−)-sparteine could induce the enantioselective deprotonation of achiral alkyl carbamates. , The chiral lithium species thus formed can be alkylated with retention of configuration to give the protected secondary alcohols in high ee’s. The use of these lithium species has so far been limited as a result of their configurational lability above −70 °C, although Hoppe and others have reported various applications of this methodology.…”

Non-Deprotonating Methodologies for Organolithium Reagents Starting from Non-Halogenated Materials. Part 2: Transmetallation and Addition to Multiple Bonds

“…Thus, the whole transmetallation/alkylation process occurred with retention of the configuration [20]. The treatment of the trimethyl-or tributylstannanes 25 with nbutyllithium at low temperature generated the corresponding organolithium intermediates with high yields and purities, as estimated from the trapping experiments with some electrophiles, obtaining the corresponding products 26 with diastereomeric ratios of 99:1 and >95% of enantiomeric excess (Scheme 5) [21].…”