Chloromethylation, diastereoselective

These reagents are also useful for the preparation of 1,2-diols. Upon exposure to Lewis acids such as boron trifluoride etherate (BFa-OEta), the a-alkoxy and oc-siloxyallyl stannanes undergo a stereospecific, intermolecular 1,3-isomerization to give y-alkoxy- and y-siloxy allylic stannanes.3. .7 When tert-butyldimethylsilyl trifluoromethanesulfonate is substituted for chloromethyl methyl ether in the above procedure, the isomeric -y-siloxy allylic stannane can be obtained directly with no loss of enantioselectivity.6 These stannanes can then be added to various aldehydes to give monoprotected 1,2-diols with high diastereoselectivity.8... 

Recently, Steckhan and coworkers [485,486] have reported that anodic methoxyla-tion of chiral 5-methyl- and 5-chloromethyl-2-oxazolidinones followed by Lewis acid-catalyzed allylation provides 4-allyl products highly diastereoselectively. Similarly, anodic methoxylation of cyclic dipeptides and dipeptolides derived from chiral a-amino acid [487] or a-hydroxy acid [488] provides useful chiral synthetic building blocks, as in Eq. (64). a-Alkoxylation of lactic amide derivatives was also reported [489]. However, the diasteros-electivity was low. 

The carbenoid generated from chloromethyl phenyl ether with butyllithium reacts with (E)- or (Z)-2-butene in a stereospecific manner3. The simple diastereoselectivity of this and related carbenoids is generally moderate to good, favoring the formation of exo- or trans-cydoaddnets (see Vol. E 19b, p 1633)3 4. 

From hydroxyalkenes derived from (/ )-(-)- or (5)-(+)-phenethyIamme and/or (5 )-(+)-lactic acid or (li , 25)-(-)-ephedrine, optically active tetrahydro-l,4-oxazines have been synthesized by using either MeOH or H2O as the nucleophile (Scheme The diastereoselectivities observed are high. In this case, the use of excess amounts of copper salts makes the reaction catalytic even in the absence of Oj. Interception of the Pd—C bond in oxypalladation adduct by chloride ion yields 2-chloromethyl-l,4-oxazines as shown in Scheme 30. ... 

The iron-catalyzed redox radical cyclization of 1,6-dienes furnishes pyrrolidine and tetrahydrofuran derivatives. Using catalytic amounts of iron phthalocyanine [Fe(Pc)] in the presence of sodium borohydride in an oxygen atmosphere, the corresponding hydroxymethyl-substituted pyrrolidines, tetrahydroflirans, or acceptor-substituted cyclopentanes are obtained (Scheme 4-357). Employing stoichiometric amounts of iron(lll) chloride in air, the corresponding chloromethyl-substituted five-membered rings are obtained. The diastereoselectivity is only moderate in both cases. 

Keck, G.E., Yu, T., and McLaws, M.D. (2005) Enantio- and diastereoselective additions to aldehydes using the biftmctional reagent 2-(chloromethyl)-3-(tributylstannyl)propene Application to a synthesis of the C16-C27 segment of bryostatin 1. J. Org. Chem., 70, 2543-2550. 

Ethyl lactate can be protected as a BOM ether for subsequent nucleophilic additions to the corresponding aldehyde with high diastereoselectivity. A synthesis of zoapatanol used selective protection of a diol (eq 3). Primary alcohols can be protected selectively in the presence of secondary hydroxy groups, and secondary hydronyls react more quickly than tertiary ones with benzyl chloromethyl ether and base. Removal of this protecting group can be carried out by hydrogenolysis over Pd. 

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