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Solid phase synthesis has emerged as a versatile and powerful method in modern organic synthesis. 1 However, the application of solid-supported chiral auxiliaries is still relatively underdeveloped. Such solid-supported chiral auxiliaries offer some advantages as compared to their application in the solution phase, including a simple filtration procedure for the isolation of the desired compounds or the recovery of the expensive chiral auxiliaries, and their possible extension to a continuous flow system. 2 In addition, the microenvironment of the polymeric backbone could lead to an improvement in the stereoselectivity for a given transformation. 2a,4a Recently, we have investigated 2-phenylamino2-oxazolines as effective chiral auxiliaries for asymmetric alkylation, which provided some beneficial effects for the removal problem as well as stereoselectivity. 3 As a part of our interest in solid-supported chiral auxiliaries, 4 we herein wish to introduce 5,5-dimethyl-2-phenylamino-2-oxazoline chiral auxiliary in solid phase as a good leaving group in the final cleavage step. Asymmetric benzylation as a model alkylation reaction using this chiral auxiliary with different cleavage conditions for the parallel synthesis of several kinds of chiral products will be discussed. First, 5,5-dimethyl-2-phenylamino-2-oxazoline chiral auxiliary 5 was prepared from commercially available methyl ester hydrochloride 1 in 4 steps (Scheme 1). The 1,2-aminoalcohol 2 was synthesized according to the previous procedure by treatment with the methylmagnesium bromide. 3b The reaction of aminoalcohol 2 with phenyl isothiocyanate afforded the thiourea 3 in excellent yield, and the cyclization of the thiourea to the 2-phenylamino-2-oxazolines by a onepot reaction using p-toluenesulfonyl chloride and sodium hydroxide gave the chiral auxiliary 4 in 91% yield. 3 Finally, the desired chiral auxiliary 5 was formed after removing the O-protecting benzyl group of 4. With the free hydroxy group, chiral auxiliary 5 was conveniently linked to resin to carry out the asymmetric synthesis in the solid phase. Next, the solid-supported 5,5-dimethyl-2-phenylamino-2oxazoline chiral auxiliary 6 was formed by the reaction of compound 5 and Wang resin under Mitsunobu conditions using diisopropyl azodicarboxylate (DIAD) and triphenyl phosphine (Ph3P). Acylation in the solid phase was carried out by deprotonation of resin 6 with excess potassium tertbutoxide (10 equiv), followed by treatment with excess propionyl chloride (10 equiv) to afford resin 7 (Scheme 2). The monitoring of the reaction progress in the solid phase may be achievable by using the conventional TLC of compound 8 after the cleavage of the acylated resin 7 with trifluoroacetic acid (TFA). 4 However, we failed to monitor the acylated compound 8. The treatment of resin 7 with TFA for 5 min at room temperature provided the mixture of

Solid Phase Asymmetric Benzylation Using 5,5-Dimethyl-2-Phenylamino-2-Oxazoline Chiral Auxiliary