C2-symmetric bicyclic guanidines

Several years later, Corey disclosed the C2 symmetric bicyclic guanidine 19 as an effective bifunctional catalyst for the Strecker reaction (Scheme 5.40) [74]. According to the catalytic cycle, HCN should hydrogen bond to the catalyst to form guanidinium-cyanide complex A. A subsequent increase in acidity of the catalyst N—H proton allows donation of a hydrogen bond to the aldimine to form TS assembly B. Enantiofacial attack of CN to the bound aldimine gives the Strecker product. 

In the kinetic resolution of 1-indanol with diphenylphosphoryl azide in dichloromethane (DCM) using modified guanidine [68], (7 )-excess azide compound was produced in 58% yield with 30% ee after six hours when a C2-symmetrical bicyclic guanidine 13 [37] was used as a chiral auxiliary (Scheme 4.26). 

C2-symmetric bicyclic guanidine (22) turned out to be efFective for the trimethylsi-lylcyanation of aldehydes (Scheme 2.63) [123]. 

In 2002, a C2-symmetrical bicyclic guanidine 12 (Scheme 30.2) was successfully used to for the cyanation of aliphatic aldehydes 11 to give (R)-cyanohydrins 13 in quantitative yields and reasonable enantioselectivities (60-70% ee) [10]. The use of ketones resulted in lower enantioselectivities. 

Scheme 30.2 Application of a C2-symmetrical bicyclic guanidine as catalyst.

The Michael additions of 3-benzyl-substituted oxindoles to M-substituted maleimides has been reported to proceed with <99% ee in the presence of the C2-symmetric bicyclic guanidine (302) as a basic organocatalyst in toluene at -50 C over 48 h. A plausible transition state has been proposed4 ... 

In 2006, Tan and co-workers reported the first asymmetric guanidine catalyzed Diels-Alder addition of anthrone to maleimides (Scheme 75) [130], The authors observed very high yields and enantioselectivities using a derivative of Corey s C2-symmetric bicyclic gnanidine catalyst. The addition of anthrones to maleimide also worked well for snbstitnted anthrones. Interestingly, the anthors observed the oxidized prodnct when the anthrone was substituted at the meto-positions (Scheme 76). 

C2-Symmetrical (or pseudo-symmetrical) chiral bicyclic guanidines are synthesized from amino acid derivatives [21b,22]. The typical synthetic route for a 2,7-disubstimted bicyclic system, (5, 5)-2,7-di(hyroxymethyl)-l,5,7-triazabicyclo[4.4.0]dec-l-ene 9, from asparagine is shown in Scheme 4.6 [22a]. 

---