The synthesis of 2,3,10,10a-tetrahydro-1H-cyclopropa[d]benzo[f]quinol-5-one (10, CBQ), containing a deep-seated structural variation in the CC-1065 and duocarmycin alkylation subunits with incorporation of a ring expanded fused six-versus five-membered ring, and its incorporation into analogs of the natural products are detailed. The approach was based on a key 6-exo-trig aryl radical-alkene cyclization of 22 to provide 23 in which an enol ether acceptor alkene served to reinforce the preferred 6-exo-trig versus 7-endo-trig cyclization and directly provided a suitably functionalized 1,2,3,4-tetrahydrobenzo[f]quinoline precursor. Conversion of 23 to 26 followed by Winstein Ar-3’ alkylation cleanly permitted the introduction of the activated cyclopropane and completed the synthesis of the CBQ nucleus. The evaluation of the CBQ-based agents revealed an exceptional solvolysis reactivity and mixed solvolysis regioselectivity. N-BOC-CBQ (9, t(1/2) = 2.1 h, k = 9.07 x 10(-5) s(-1), pH 3) proved to be 63 x more reactive than N-BOC-CBI (t(1/2) = 133 h, k = 1.45 x 10(-6) s(-1), pH 3) and its solvolysis was found to proceed with cleavage of both the external C9b-C10 and internal C9b-C10a cyclopropane bonds. The latter was shown to occur with exclusive inversion of stereochemistry illustrating for the first time that the solvolysis and alkylation reactions proceed by S(N)2 versus S(N)1 cyclopropane ring opening upon activation by C5 carbonyl protonation. A comparison of the X-ray crystal structures of the CPI alkylation subunit taken from (+)-CC-1065, the CBI alkylation subunit, and N-BOC-CBQ (9) provided the structural basis for this altered solvolysis reactivity and regioselectivity.