Titanat‐katalysierte enantioselektive Addition von in situ aus Grignard‐Reagentien in Ether erzeugten Alkylzinkverbindungen an Aldehyde

Abstract

Da die Handhabung von Alkylzinkverbindungen nicht ungefährlich ist, ist es äußerst vorteilhaft, diese aus Grignard‐Reagentien in situ herstellen zu können und danach in einem Eintopfverfahren an Aldehyde enantioselektiv zu addieren. Dabei entstehen sekundäre Alkohole, z. B. vom Typ 1 (R vom Grignard‐Reagens), mit hohem Enantiomerenüberschuß (90‐98% ee).

TADDOLs, Their Derivatives, and TADDOL Analogues: Versatile Chiral Auxiliaries

“…We also developed a simple procedure for in situ preparation of other organozinc compounds, starting from lithium or XMg precursors. [230,248] The organometallic titanates RTi(OiPr) 3 , which are accessible by the same route, also add to aldehydes with high enantioselectivity in the presence of titanium TADDOLate (and with better stoichiometric utilization, relative to R 2 Zn, of the group R that is to be introduced!). [249] This observation is especially noteworthy because such organotitanates react with aldehydes at temperatures as low as À 60 8C, albeit not enantioselectively.…”

Catalytic Enantioselective Addition of Alkyl Grignard Reagents to Aliphatic Aldehydes

“…[8] In particular, early reports from Seebachs group focused on the transmetalation of alkyl Grignard reagents into the corresponding organotitanium derivatives, that add successfully to aliphatic aldehydes prior to removal of the generated magnesium salts. [9] More recently, and avoiding the tedious salt exclusion process, Haradas methodology [10] achieves the ethylation of 3-phenylpropanal in 36% yield (92% ee) and Das [11] approach describes the addition of butylmagnesium bromide and phenethylmagnesium bromide to a limited group of substrates with yields in the range 23-46% (88-98% ee). We have recently developed a catalytic system for the addition of Grignard, [12] organoaluminum [13] and organolithium [14] reagents to aldehydes, based on the readily available chiral ligand L1 (introduced by Kiyooka, Lai, and Xu) [15] and an excess of titanium(IV) isopropoxide (Scheme 1).…”

Catalytic Asymmetric Synthesis of Allylic Alcohols and Derivatives and their Applications in Organic Synthesis

“…Pioneering work in this field was conducted by the research groups of Mukaiyama, [99] Tomioka, [100] and Seebach, [101][102][103][104] who used 71, 72, and 73 to promote the asymmetric additions to aldehydes [99][100][101][102][103] and ketones. [104] These methods usually require a stoichiometric amount of chiral modifier [99][100][101][102]104] and/or strict exclusion of the magnesium salts generated by the transmetalation of the Grignard reagents (RMgX) with ZnCl 2 [101,102] or ClTi(OiPr) 3 to achieve high enantiomeric excess. [103] In these cases, R 2 Zn and RTi-(OiPr) 3 are the nucleophilic species.…”