Chiral alkoxymethylation

Nucleophilic addition of furan to nitrone occurs upon treatment with trimethyl-silyl triflate (TMSOTf) (586, 587). Catalyzed TMSOTf stereoselective addition of 2-[(trimethylsilyl)oxy]furan to chiral nitrones was carried out in a short synthesis of [IS (la, 2[), 7f>, 8a, 8aa)]-l,2-di(t-butyldiphenylsilyloxy)-indolizidine-7,8-diol (588). Addition to N -gulosyl-C-alkoxymethyl nitrones led to the synthesis of the core intermediate of polyoxin C (218). 

Ponzo, V. L. Kaufman, T. S. Diastereoselective alkoxymethylation of aromatic aldehydes with chiral lithiomefhyl ethers. Synthesis of optically active monoprotected glycols. Can. J. Chem. 1998, 76,1338-1343. 

Having established the chiral synthesis of levoglucosenone 1 and its functionalized analogues in both enantiomeric forms, we next investigated the exploitation of 26, the functionalized isolevoglucosenone, for the enantiocontrolled construction of natural products on the basis of its inherent convex-face selectivity and functionality, in particular, the alkoxymethyl handle for the acetal cleavage. 

Without question, the most important developments in this field over the past 10 years have been in the area of enantioselective hydroborations. New chiral catalyst systems are typically tested in hydroborations of vinyl arenes, as reactions using HBcat and a cationic rhodium catalyst are well known to give selective formation of the unusual branched isomer. In related studies, enantiopure 2,2-disubstituted cyclopropyl boronates were easily prepared via the catalytic asymmetric hydroboration of 3,3-disubstituted cyclopropenes using a number of chiral neutral rhodium complexes (equation 13). Directing groups, such as esters and alkoxymethyl substituents, were necessary for achieving... 

When chiral thiocarbonyl S-oxides derived from (S)-proline, prepared from the appropriate l-(trimethylsilylalkylsulfonyl)-2-(alkoxymethyl)pyrrolidine, are subjected to Diels-Alder reaction with 2,3-dimcthyl-l,3-butadiene, the 2-substituted 2-[(2-alkoxymethyl-l-pyrrolidinyl)sul-fonyl]-3,6-dihydro-4.5-dimethyl-2/f-thiopyran 1-oxides 10A and 10B are formed as a mixture of diastereomers. Their ratio depends on the nature of the substituents R1 and R2 as well as on the reaction temperature. The diastereomeric excess values, determined by H NMR in the presence of Yb(tfc)3 or by HPLC, vary from 0 to 41 % 84. 

The asymmetric synthesis of a-hydroxymethyl carbonyl compounds is currently the subject of considerable interest because of their versatility as dual-function chiral synthons. There have been no reports of successful enantioselective hydroxymethylations of prochiral metal enolates with formaldehyde because of the instability and small steric size of gaseous formaldehyde. The author and Yamamoto et al. developed the enantioselective alkoxymethylation of silyl enol ethers by introducing suitable carbon-electrophiles in place of the activated-protons of LBA [142]. 

Alkoxymethyl Ethers The principal members of this set of protecting groups are methoxy-methyl ether (MOM) [188], methoxyethoxymethyl ether (MEM) [189], benzyloxymethyl ether (BOM) [190], /7-methoxybenzyloxymethyl ether (PMBM) [191], and trimethylsi-lylethoxymethyl ether (SEM) [192] (O Fig. 4). Since these protecting units are devoid of chirality, their use introduces no stereochemical complications. 

In addition to the alkoxymethyl derivatives, dihydroxosilicon(IV) phthalocyanines bearing alkoxy peripheral groups were prepared ((1) M = Si(OH)2, R = OC H2 +i, n = 2, 4, 6, 8, 10, 12, 14, 16, 18), and all displayed a Colh phase at low temperatures, with a decreasing mesophase stability due to the presence of axial hydroxyl groups.Similar silicon and silicon-free phthalocyanines substituted by chiral (S)-citronellol were shown to form a Colh and, at higher temperatures, a Col, with a helicoidal structure. 

Feder-Kubis, J., Kubicki, M. and Pernak, J., 3-Alkoxymethyl-l-(lR,2S,5R)-(-)-menthoxymethylimidazoliumsalts-based chiral ionic liquids, Tetrahedron-Asymmetry 21 (21-22), 2709-2718 (2010). 

Methyl-1 -(chloromethyl)-2-pyrro-lidinone. 5(i )-Methyl-l-(chloromethyl)-2-pyrrolidi-none (68.1) has been proposed as an auxiliary reagent for absolute configuration (and % ee) determinations of chiral secondary alcohols by the formation of the corresponding A/ (alkoxymethyl)-2-pyrro-lidinone derivative 68.2 (see Figure 68). 

---