Hydroxy acidic activation with additional reagents

In addition to the conversion into phosphonochloridates as described in Section 10.10.2.1.2, phosphonate monoacids can also be activated for coupling via some of the popular reagents from standard peptide chemistry, such as BroP, 77 BOP/ and PyBOP. 79 One-pot activation and coupling of hydrogen phosphinates with a-hydroxy acids is also possible via the method outlined in Section 10.10.2.1.3. 76 The procedure outlined in Scheme 19 illustrates an optimized procedure for coupling a hindered phosphonate 57 and an a-hydroxy acid derivative via the phosphonochloridate 72 ... 

Several other attempts to activate 1-hydroxy sugars with cationic activators or Lewis acid catalysts have appeared in literature, in which a second active species is generated in situ by additional reagents. 

Cydization of P-hydroxy-a-amino esters under Mitsunobu reaction conditions is an alternative approach to aziridine-2-carboxylic esters [6b, 13-16], In this case the P-hydroxy group is activated by a phosphorus reagent. Treatment of Boc-a-Me-D-Ser-OMe 13 (Scheme 3.5) with triphenylphosphine and diethyl azodicarboxylate (DEAD), for example, gave a-methyl aziridinecarboxylic acid methyl ester 14 in 85% yield [15]. In addition to PPh3/DEAD [13b, 15], several other reagent combi-... 

In Eq. (14), Yoda et al. [50] studied the preparation of optically active lactones, with three contiguous stereogenic centers, from imides with two stereogenic centers. The precursor chiral imide was easily prepared from tartaric acid. Silylation of the 2,3-diol and addition of lipophilic Grignard reagents to the imide gave the ( -hydroxy amide. The authors are investigating the stereochemical consequences of their work. 

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