Preparation of phosphorothioate and boranophosphate oligomers

A method for synthesizing an oligomer having a boranophosphate linkage comprising the steps of:

• reacting a first synthon of Formula I:
• ##STR118## wherein:
• Q is independently O or S;
• R.sup.1 is a hydroxyl protecting group;
• R.sup.2 is a chiral auxiliary of formula
• --C(R.sup.8)R.sup.3 --C(R.sup.16)R.sup.5 --CHR.sup.6 --NHR.sup.7 ;
• R.sup.3 is hydrogen, alkyl, cyanomethyl, monohalomethyl, dihalomethyl, trihalomethyl,
• --CH.sub.2 R.sub.4,
• --CH.sub.2 Si(R.sup.4).sub.3, or --CH.sub.2 --SO.sub.k R.sup.4 where k is 0, 1 or 2;
• R.sup.4 is independently alkyl, aryl, aralkyl or alkaryl having up to 15 carbon atoms, --N(R.sub.70)--C(.dbd.O)--R.sub.71, --S--C(.dbd.O)--R.sub.70, or --O--C(.dbd.O)--O--N(R.sub.70)(R.sub.71);
• R.sub.70 and R.sub.71 are each independently alkyl, .alpha.-halo substituted alkyl, aralkyl, .alpha.-halo substituted aralkyl, or aryl substituted with up to three electronegative groups;
• R.sup.5 is H, --CN, --Si(R.sup.4).sub.3, SO.sub.k R.sup.4 or halogen;
• R.sup.8 is H or methyl;
• R.sup.16 is H, alkyl or aralkyl having up to 15 carbon atoms;
• or when R.sup.8 and R.sup.16 are each H, and R.sup.3 and R.sup.5, together, form one of the structures ##STR119## wherein:
• R.sup.10 and R.sup.11 are H, alkyl having from 1 to about 10 carbons, --CH.sub.2 C(.dbd.O)OR.sup.22, --CH.sub.2 CN, --CH.sub.2 Si(CH.sub.3).sub.3,
• or o- or p--C.sub.6 H.sub.4 --R.sup.21 ;
• R.sup.21 is hydrogen, --O--C(.dbd.O)CH.sub.3, alkoxy having from 1 to about 10 carbons, --NO.sub.2, or --N(R.sup.22).sub.2 ;
• R.sup.22 is independently H or alkyl having from one to about 10 carbon atoms;
• p is 1 or 2;
• Z.sup.1 and Z.sup.2 are independently halogen, CN, --Si(CH.sub.3).sub.3, and --C(.dbd.O)OR.sup.22 ;
• R.sup.30 is hydrogen, --O--C(.dbd.O)CH.sub.3, alkoxy having from 1 to about 10 carbons, or --O--Si(R.sub.4).sub.3 ;
• R.sup.6 is H, alkyl or aralkyl having up to 15 carbon atoms;
• or R.sup.5 and R.sup.6, together with the atoms to which they are attached, form a 5 or 6 membered ring;
• R.sup.7 is alkyl or aralkyl having up to 15 carbon atoms;
• or R.sup.6 and R.sup.7, together, form one of the structures ##STR120## wherein V, T, and Z are independently CH or N;
• R.sub.41, R.sub.42, R.sub.43, and R.sub.44 are each independently H or an electronegative group;
• B is a nucleobase;
• and
• n is an integer from 0 to 50;
• with a second synthon of Formula II:
• ##STR121## wherein:
• R.sup.9 is a hydroxyl protecting group or a linker connected to a solid support;
• and
• m is an integer from 0 to 50;
• in the presence of a catalyst, for a time and under reaction conditions effective to form a third synthon of Formula III:
• ##STR122## and contacting said third synthon with a boronating agent to form an oligomer of Formula IV:
• ##STR123## wherein D is a boranophosphate linkage having the formula:
• ##STR124## wherein G is a borano group.