Amino acids, enantioselective synthesis rearrangement

The Rh2(DOSP)4 catalysts (6b) of Davies have proven to be remarkably effective for highly enantioselective cydopropanation reactions of aryl- and vinyl-diazoacetates [2]. The discovery that enantiocontrol could be enhanced when reactions were performed in pentane [35] added advantages that could be attributed to the solvent-directed orientation of chiral attachments of the ligand carboxylates [59]. In addition to the synthesis of (+)-sertraline (1) [6], the uses of this methodology have been extended to the construction of cyclopropane amino acids (Eq. 3) [35], the synthesis of tricyclic systems such as 22 (Eq. 4) [60], and, as an example of tandem cyclopropanation-Cope rearrangement, an efficient asymmetric synthesis of epi-tremulane 23 (Eq. 5) [61]. 

The synthesis of chiral, non-racemic a-amino acids remains an interesting field of investigation and the synthesis of fully protected a,a-disubstituted a-amino acids 331 via the Beckmann rearrangement of tosylated oximes was achieved (equation 123). As expected, the migrating group was able to retain the original stereochemistry and good yields and excellent enantioselectivities were observed ... 

Liu, G., Sieburth, S. M. Enantioselective a-Silyl Amino Acid Synthesis by Reverse-Aza-Brook Rearrangement. Org. Lett. 2003, 5,4677-4679. 

In 1998, Kawahara and Nagumo reported the first total synthesis of a member of the TAN1251 series [63] and five years later both authors revisited the TAN1251A alkaloid by means of a new enantioselective synthesis (see Section 5.6). The retro synthetic analysis of TAN 1251A is outlined in Scheme 37. The target compound could be obtained by aldol reaction of tricyclic lactam 119, whose disconnection at the amide bond led to the bicyclic amino acid 120, which could be prepared from azaspirocyclic compound 121 by means of alkylation of the secondary amine and Mitsunobu-type chemistry. Azabicycle 121 may be prepared by an intramolecular alkylation of 122, which in turn could be available from allyl derivative 123. The latter can be prepared from carboxylic acid 124 by alkylation and subsequent Curtius rearrangement. 

Amino-Inositols. - An enantioselective synthesis of (-)-fortamine in a multistep procedure from a chiral half-ester of cyclohex-4-ene-cis-1,2-dicarboxylic acid has been described,as has a conversion of D-glucose to valienamine, using the Perrier rearrangement to form... 

During the total synthesis of Dragmacidin F (537) from quinic acid, Stoltz and col-leagues applied a high-yield late-stage Neber rearrangement to introduce in a completely enantioselective manner an amino group into a complex framework (equation 238). 

The same catalyst has been used by this research group in synthesis of j -amino-aldehydes (146) by combining two catalytic reactions, i.e. a Ni(II) complex-catalyzed isomerization of a double bond and a chiral phosphoric acid (127)-catalyzed aza-Petasis-Ferrier rearrangement in a highly dia-stereo- and enantioselective manner (Scheme 39). ... 

A Br0nsted-acid-catalysed enantioselective indole aza-Claisen rearrangement has been applied for the synthesis of chiral 3-amino-2-substituted indoles where an arene CH-O interaction is the source of activation and stereoinduction (Scheme 24) ... 

Subsequently, the same group demonstrated an asymmetric synthesis of 3-amino aldehydes via catalytic double-bond isomerization/enantioselective aza-Petasis-Ferrier rearrangement reaction (Scheme 2.93) [128]. Similarly, the hemiaminal allyl ether substrates 346 were first isomerized by Ni(II) complexes to stereoselectively form Z-configured vinyl ethers 347, which then underwent a phosphoric acid-catalyzed... 

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