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Transition state control in BINOL-Ti-catalyzed asymmetric carbonyl-ene cyclization by tuning the 6-Br-BINOL ligand completes the synthesis of the A ring of the 2-methyl-19-nor-22-oxa D 3 analogue (2), which shows the significant activity in differentiation of HL-60 cell.Basic research on the synthesis of analogues of the biologically active form of vitamin D 3 , 1a,25-dihydroxyvitamin D 3 [1a,25(OH) 2 D 3 ], has brought about the development of an important new field in medicinal chemistry. 2 A number of analogues have been synthesized and used to clarify the mode of action of vitamin D hormones and find new therapeutically useful compounds. These analogues are useful not only for calcium metabolism disorder and bone diseases, but also for differentiation of myelocytic leukemias and the treatment of psoriasis. 3 10-Oxo-19-nor-25(OH) 2 D 3 has been reported to exhibit a selective activity for differentiation of myelocytic leukemias. 4 19-Nor1a,25(OH) 2 D 3 also shows a selective activity profile, i.e., high potency in differentiation of malignant cells, but low calcitropic liability. 5 22-Oxa-1a,25(OH) 2 D 3 (OCT) shows a significant activity in the inhibition of cancer cell growth. 6 We have thus reported the hybridization analogue, 7 19-nor-22-oxa-1a,25(OH) 2 D 3 (1) on the basis of asymmetric carbonyl-ene cyclization 8b catalyzed by a binaphthol-derived titanium (BINOL-Ti) complex. 9 Recent papers 10 prompt us to report the synthesis of 2-methyl-19-nor-22-oxa vitamin D 3 analogue (2) 1,11 by tuning the chiral ligands for the ene cyclization 12 (Scheme 1) and the significant activity in differentiation of myelocytic leukemia, HL-60 cell.The preparation of the 2-methyl ene-cyclization substrate ((R,R)-3) is worth mentioning (Scheme 2). The allylic alcohol (7) was obtained through highly regioselective propiolate-ene reaction using triisopropylsilyl ethers (5) 13 (regioisomer ratio = 94:6) 14 with methyl propiolate (6) using EtAlCl 2 as the promoter. The ene substrate 3 was prepared in 96% ee via catalytic enantioselective epoxidation of allylic alcohol 15 (7) with (S,S)-diethyl tartrate (DET), O OBn OMPM OBn OMPM HO HO O OH OH HO O OH OH (R,R)-3 (R)-6-Br-BINOL-Ti

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