Stereoselective Synthesis of 3‐Hydroxyproline Benzyl Esters from N‐Protected β‐Aminoaldehydes and Benzyl Diazoacetate.

Abstract

Stereoselective Synthesis of 3-Hydroxyproline Benzyl Esters from N-Protectedβ-Aminoaldehydes and Benzyl Diazoacetate. -Lewis acid mediated treatment of N-protected β-aminoaldehydes with the diazoacetate (VII) offers a new, efficient, and stereoselective approach to 3-hydroxyprolines. In this connection, a new synthetic route is presented for the unstable substrate (VI) which is directly used for the preparation of target compound (VIII).The nature of the N-protecting group and the α-substituents play an important role in the title process. In some cases, a second product is formed [cf. β-ketoesters (XIII)]. -(ANGLE*, S. R.; BELANGER, D. S.; J. Org.

Cutting-Edge and Time-Honored Strategies for Stereoselective Construction of C–N Bonds in Total Synthesis

“…786,787 Angle and co-workers reported the total synthesis of indolizidine and pyrrolizidine alkaloids based on the method for the diastereoselective preparation of 3-hydroxyproline benzyl esters reported by the same group previously. 788 The key proline intermediate was prepared 789 15.3. Formation of Aminals and Hemiaminals (Figure 43) Stereogenic C−N bonds at a more oxidized carbon atom as a part of hemiamimal or aminal groups have been found in many complex natural products.…”

Novel Acetylcholine and Carbamoylcholine Analogues: Development of a Functionally Selective α4β2 Nicotinic Acetylcholine Receptor Agonist

“…83 3-Amino-2-methylpropan-1-ol (9). 84 9 was prepared as described for 8 from 3-amino-2-methylpropanoic acid (10.0 g, 97.0 mmol), affording 9 as a colorless oil (9.0 g, 105%), which was used without further purification. The NMR data of 9 were in concordance with the NMR data found in the literature.…”

“…The NMR data of 9 were in concordance with the NMR data found in the literature. 84 2-Methyl-3-(4-methylphenylsulfonamido)propyl 4-Methylbenzenesulfonate (10). 3-Amino-2-methylpropan-1-ol (9) (5.00 g, 56.1 mmol) was dissolved in pyridine (80 mL) and cooled to 0 °C.…”