Intermediates for the preparation of analogs of halichondrin B

A method of synthesizing a compound of formula F-2, the method comprising reacting a compound of formula F-2d:

• wherein:
• R′ is —CH═CH2 or —C(O)H;
• Alk is a C1-4 straight or branched aliphatic group;
• and
• PG5 is a suitable hydroxyl protecting group
• with a compound of formula F-2e:
• wherein:
• R″ is OH, OPG3, or LG4;
• LG4 is a suitable leaving group;
• and
• each PG3 is independently a suitable hydroxyl protecting group
• to produce a compound of formula F-2f:
• and
• converting the compound of formula F-2f into the compound of formula F-2:
• wherein:
• each is independently a single or double bond, provided that both groups are not simultaneously a double bond;
• LG1 is a suitable leaving group;
• X is halogen or —OSO2(Ry);
• Ry is C1-6 aliphatic or a 5-7 membered saturated, partially unsaturated, or fully unsaturated ring, wherein Ry is optionally substituted with up to 3 groups selected from halogen, R, NO2, CN, OR, SR, or N(R)2;
• and
• each R is independently hydrogen, C1-4 haloaliphatic, or C1-4 aliphatic.

A method for preparing a compound of formula:

• or a pharmaceutically acceptable salt thereof;
• the method comprising producing the compound of formula B-1939 or a pharmaceutically acceptable salt thereof from a compound of formula F-2d:
• wherein:
• R′ is —CH═CH2 or —C(O)H;
• Alk is methyl;
• and
• PG5 is a suitable hydroxyl protecting group.