HCl/EtOAc to remove the Boc protecting group (usually needs 12-24 h until the

disappearance of 3.9). [02JOC3109] [01JCS(P1)1767] We now find that 8 equiv of

CF3COOH in dry CH2C12 efficiently removes N-Boc in 2-5 h giving the a-amino-amides

3.10a-c in >88% yields. Treatment of 3.10a-c with 6 equiv of LiAlH4 in refluxing THF

for 2 days afforded chiral diamines 3.11a-c in >90% yields. Intermediates 3.9a-c,

3.10a-c and 3.11a-c were all used as crude products for the subsequent reactions.

 Ph
 Ph + RNH2 Ph O

 BocNH OH BocNH NHR H2N NHR
 3.7 3.8a-c 3.9a-c 3.10a-c

 iv

 N-R h Ph
 IN- N-R Bt, / \ / \
 N R BtN- N-R H2N NHR

 3.1a-c 3.12a-c 3.11a-c

 a, R = p-MeC6H4; b, R = c-C6H11; c, R = PhCH2

 i) CICOOBu-i, N-methylmorpholine; ii) CF3COOH; iii) aq. NaOH
 iv) LiAIH4; v) BtH, 2 HCHO (aq.); vi) AIC13

Scheme 3-2. Synthesis of 2-substituted hexahydroimidazo[1,5-b]isoquinolines

3.2.2 Syntheses of 1,2,3,5,10,10a-Hexahydroimidazo[ 1,5-b]isoquinolines 3.1a-c.

 Mannich condensation of chiral diamines 3.11a-c with 1 equiv of benzotriazole

and 2 equiv of formaldehyde (37% aqueous solution) in an aqueous solution at 25 C

gave benzotriazolyl intermediates 3.12a-c in 93%, 96% and 90% yields, respectively.

Compounds 3.12a,c were obtained solely as benzotriazol-1-yl isomers; 3.12b was

obtained as a mixture of Bt and Bt2 isomers in ca. 26:1 ratio.