N-Tritylprolinal:  An Efficient Building Block for the Stereoselective Synthesis of Proline-Derived Amino Alcohols

Abstract

N-Tritylprolinal (prepared in four steps from l-proline) shows a very high Felkin diastereoselectivity in its reaction with various nucleophiles, leading to a straightforward and highly stereoselective access to syn-proline-derived amino alcohols.

A new strategy for the synthesis of hydroxylated pyrrolizidinic alkaloids by highly stereoselective indium-mediated allylation of pyrrolidinic aldehydes

“…Although a synthesis of 4 and 5 has been previously published, 5 data on their optical spectroscopic properties that would allow the determination of the configuration of our compounds, were not included in that report. Thus, upon treatment of 4 with aq KOH, bicyclic carbamate 6 was isolated showing identical spectroscopic data to that previously reported 5,6 for…”

“…GLC analysis then revealed the absence of 4 and the appearance of a new product (t R = 2.98 min). The reaction mixture was concentrated and the residue dissolved in Cl 2 CH 2 , washed with brine, supported on silica gel and then chromatographed (Et 2 O-hexane 2:1) to yield 6 (20 mg, 20%) with spectroscopic data in accordance with those previously reported 6 To a stirred solution of 4 (1.13 g, 4.1 mmol) in anhydrous CH 2 Cl 2 (5 ml) was added a solution of MCPBA (2.12 g, 6.15 mmol) in the same solvent (25 ml). After 24 h TLC (Et 2 O) revealed the absence of 4 and the presence of a slower-running product.…”

Ring Expansion Induced by DAST: Synthesis of Substituted 3‐Fluoropiperidines from Prolinols and 3‐Fluoroazepanes from 2‐Hydroxymethylpiperidines

“…In the case of a N-methyldiphenyl substituent, prolinol 11b was transformed into a mixture of 12b and 13b in a ratio of 76:24 in favour of the ring-expanded product 12b in 71 % yield (Table 3, Entry 2). As an increase in the steric hindrance on the nitrogen atom seems to improve the selectivity of the reaction, N-tritylprolinol 11c [22] was treated with DAST and N-trityl-3-fluoropiperidine 12c was obtained as the only observed product, which was isolated in 64 % yield (Table 3, Entry 3). When N-alkyl-2-alkylprolinols 14a-e were treated with DAST, the ring expansion was very selective as only Nalkyl-3-fluoro-3-alkylpiperidines were observed.…”

Evidence that Additions of Grignard Reagents to Aliphatic Aldehydes Do Not Involve Single-Electron-Transfer Processes

“…It is more likely that a two-electron process gives rise to the addition products. In the case of allylmagnesium reagents, those processes could involve six-center (10,11) or four-center (12) transition states ( Figure 1); 16,55−57 the radical clock experiments cannot differentiate between these possibilities. We cannot discount a stepwise single-electron mechanism completely, however.…”