Menthone and p-menthyl-3-carboxaldehyde as chiral auxiliaries

Abstract

Two chiral auxiliaries and the role they play in the preparation of chiral carbonyl compounds and heterocyclic compounds are presented. Key reactions include S(N)2' displacements, Mitsunobu with hydrazoic acid, and 3,3-sigmatropic rearrangements. One of the auxiliaries serves many functions and is removed either by oxidative cleavage or RCM reaction.

Constraining the Side Chain of C-Terminal Amino Acids in Apelin-13 Greatly Increases Affinity, Modulates Signaling, and Improves the Pharmacokinetic Profile

“…The l -α-MeTyr­(OBn) residue was prepared from commercially available l -α-MeTyr, whereas the d -α-MeTyr­(OBn) analogue was synthesized from 4-(benzyloxy)­benzyl chloride 16 using p -menthyl-3-carboxaldehyde as a chiral auxiliary (Scheme B) . Critical steps in this synthesis are the Zr-catalyzed carboalumination of the triple bond of intermediate 17b , followed by trapping of the vinylalane intermediate with p -menthyl-3-carboxaldehyde to produce chiral allylic alcohol 18 as a single detected diastereomer.…”

“…The L-α-MeTyr(OBn) residue was prepared from commercially available L-α-MeTyr, whereas the D-α-MeTyr(OBn) analogue was synthesized from 4-(benzyloxy)benzyl chloride 16 using p-menthyl-3-carboxaldehyde as a chiral auxiliary (Scheme 3B). 67 Critical steps in this synthesis are the Zrcatalyzed carboalumination of the triple bond of intermediate 17b, followed by trapping of the vinylalane intermediate with p-menthyl-3-carboxaldehyde to produce chiral allylic alcohol 18 as a single detected diastereomer. The α-nitrogen was introduced using trichloroacetyl isocyanate, first forming carbamate 19, followed by [3,3]-sigmatropic rearrangement to construct the asymmetric center of the α-amino acid precursor in the form of isocyanate 20.…”

The Allyl Cyanate/Isocyanate Rearrangement: An Efficient Tool for the Stereocontrolled Formation of Allylic C–N Bonds

“…Given that this kind of rearrangement occurs with complete transfer of configuration, several reports have described this strategy, with different routes to access the chiral allyl carbamates as key intermediates. A diastereoselective approach was proposed by Spino et al, who used p ‐menthane‐3‐carbaldehyde ( 93 ) as a chiral auxiliary (Scheme ) . The addition of vinyllithium compounds to the α‐chiral aldehyde in the presence of trimethylaluminum afforded the corresponding allylic alcohols 94 in good yields and excellent diastereomeric ratios .…”

Menthane‐Based Chloride‐Bridged η3‐Bis‐π‐Allylpalladium Chloride Dimers: Catalytic Asymmetric Allylation of Imines

“…Considering the limited chiral frameworks examined by Yamamoto and co‐workers and low overall yield in catalyst preparation,, , in 2012 we reported the improved synthesis of π‐allylpalladium chloride complexes based on pinene skeleton and also achieved higher enantioselectivity up to 99:1 er. [12a] In the same year, we also developed the first menthane‐based chiral π‐allylpalladium catalysts;[12b] since before the menthane moiety had been used extensively as a chiral auxiliary . The menthane‐based chiral catalyst effected asymmetric allylation of imines up to 89:11 er.…”