Iodomethyl Group as a Hydroxymethyl Synthetic Equivalent:  Application to the Syntheses of d-manno-Hept-2-ulose and l-Fructose Derivatives

Abstract

The one-carbon elongation of aldoses to ketoses using iodomethyllithium as the key reagent in the homologation step is exemplified by the preparation of two carbohydrates of chemical and biological interests: d-manno-hept-2-ulose from d-mannose and l-fructose from l-arabinose.

Cascade N-Alkylation/Hemiacetalization for Facile Construction of the Spiroketal Skeleton of Acortatarin Alkaloids with Therapeutic Potentiality in Diabetic Nephropathy

“…Based upon the proposed biogenesis of acortatarins [ 2 ], we envisaged the chemoselective Amadori rearrangement to get the furanoid amino sugars, but our attempts did not give acceptable preparative yields (see supporting information). The work of Morin [ 9 ] and Wadouachi [ 10 ] made us recognize that the iodomethyl group acts as an interchanging hydroxymethyl or aminomethyl synthetic equivalent (Scheme 1 ). At the meanwhile, we noticed that the regioselective protection of fructofuranosyl acceptors directly from d -fructose needs time-consuming long process [ 11 ].…”

“…With the goal of devising a concise synthesis of this uncommon core, the exploration was initiated with the preparation of lactones 7a and 7b by the oxidation of 4a and 4b buffered in an aqueous K 2 CO 3 solution (Scheme 3 ) [ 14 ], then subjected to one-pot protection without further purification to get TBDMS ethers 8a and 8b in approximately 75 % overall yield for both (Scheme 3 ) [ 15 ]. Previously employed iodomethylation [ 9 ] for the conversion of 8a to 9 was proved to be unfavorable in this case, because it was very difficult to separate the iodide 9 from starting material recovered by chromatography along with liable decomposition in chloroform (or CDCl 3 ). The focus shifted to the more stable bromomethylating compounds prepared by BrCH 2 Li (in situ generation from CH 2 Br 2 and n -BuLi in the presence of LiBr) [ 16 ].…”

“…The detailed functional compatibility resulted in the improvement for preparation of benzyl ethers (Scheme 3 ). Some problems were associated with the conventional O -benzylation methods in our hands, such as low yield for normal or mildly basic Williamson conditions (NaH/BnBr [ 4 ] or Ag 2 O/BnBr [ 9 ] ), tedious purification steps for benzyl 2,2,2-trichloroacetimidate (BTCAI) methodology [ 12 , 20 ]. Better result was achieved finally to get benzyl ether 8c through 2,4,6-tris(benzyloxy)-1,3,5-triazine (TriBOT) [ 21 ] catalyzed by TfOH in one-pot (65 % total yield without further optimization) (Scheme 3 ).…”

“…The iodomethylation of 8d with CH 2 I 2 and n -BuLi (even 1.2/1 equivalents) was very complicated in THF. Changing the solvent to toluene [ 9 ] gave very slow conversion to 14b even after 3 h, as shown by the crude NMR of the reaction mixture (see supporting information). However, we noticed that the β-elimination becomes negligible at low temperature (−82 °C).…”

Lithium Halomethylcarbenoids: Preparation and Use in the Homologation of Carbon Electrophiles

“…Although a more recent report deals with the formation of chloromethyllithium at slightly higher temperatures (−65 °C),26 it is remarkable that the preparation of iodomethyllithium for the epoxidation of carbonyl compounds 6 proceeded at 0 °C, as noticed by Concellón in 2001 (Scheme ) 27. Unfortunately, there is no literature agreement with this finding, as for example stressed by Morin, who found the employment of a temperature of −70 °C mandatory in order to accomplish chemistry involving this species 28. In the course of investigations aimed at iodomethylate lactones 11 , this author observed a prominent role played by toluene as the reaction medium.…”