Sparteine reagents

Since the (—)-sparteine reagent does not support the deprotonation of the neopentyl carbamate 29a (1.5 equivalents of s-BuLi, diethyl ether, 5 h at —78 °C) it becomes evident that fraw5-l,2-bis(dimethylamino)cyclohexane, which is available in both enantiomers , is the chiral additive of choice for bulky alkyl carbamates. (—)-a-Isosparteine (14), which holds two fraw5-fused piperidine rings, does not support the deprotonation of alkyl carbamates at alP . 

The first reports on enantioselective addition reactions of achiral organometallic reagents, modified by aprotic chiral additives, described the addition of Grignard reagents to prostereogenic carbonyl compounds in the presence of ( + )-(/ ,/J)-2,3-dimethoxybutane (l)4 5, (-)-tetrahydro-2-methylfuran (2)6, (-)-l-[(tetrahydro-2-furanyl)methyl]pyrrolidine (3)7 or (-)-sparteine (4)8. The enantioselectivity, however, was poor (0-22% ee). 

In the course of structure elucidation of dehydrosparteines the reaction of dehydrosparteinium perchlorate 1 prepared from t.-sparteine with several Grignard reagents was investigated. Structure 2 can be assigned to the products on the basis of stereochemical considerations30. 

When chiral additives such as ( —)-sparteine has added to the initial reaction with the organolithium reagent, quenching with CO2 produces carboxylic acids with good asymmetric induction. 

Scheme 12 (-)-Sparteine-mediated addition of a-amino organometallic reagents to imines...

Organolithium Reagents/Sparteine Combinations as Chiral Nucleophiles for Enantioselective Additions... 

Isoquinoline 53 was also used as a substrate for the addition of organo-lithium reagents by Alexakis and Amiot (Scheme 13) [13]. While remaining quite modest, the best enantioselectivities (48%) were still reached with sparteine after quenching with methyl chloroformate. However, a mixture of mono- and bisacylated products 54 and 55 were obtained in all cases and the use of a catalytic amount of sparteine lowered the selectivity of the adducts. 

As Stated earlier, the combination of an organolithium reagent with sparteine has been widely used to generate chiral carbanions. We will focus here on recent examples where the efficiency of sparteine was compared with other chiral chelating ligands. 

Crimmins and co-workers have developed (V-acyloxazolidinethiones as chiral auxiliaries. These reagents show excellent 2,3-syn diastereoselectivity and enantio-selectivity in additions to aldehydes. The titanium enolates are prepared using TiCl4, with (-)-sparteine being a particularly effective base.141... 

The enantioselectivity is due to the retention of the chiral sparteine in the lithiated reagent. The adducts have been used to synthesize a number of pyrrolidine and piperidine derivatives. 

Sparteine has been widely studied as a catalyst for asymmetric synthesis. Because only (—)-sparteine 10 is commercially available, there has been much interest in the development of (-l-)-sparteine mimics, among which the most important is diamine 467, which has been employed as a chiral reagent or catalyst in a large number of asymmetric synthesis procedures <2006S2233>. 

A catalyzed asymmetric alkylation of glutaric anhydrides has yet to appear. However, Fu has reported that stoichiometric amounts of sparteine efficiently mediate the addition of aryl Grignard reagents to 4-substituted glutaric anhydrides, providing the 5-ketoacids in good yields and excellent enantioselectivities ... 

The C2 symmetric chiral diether 28" and the naturally occurring chiral diamine, (—)-sparteine (29), have been the most successful external chiral ligands for asymmetric conjugate addition of organolithium reagents. The rest of this review highlights organolithium addition, which is mediated or sometimes catalyzed by 28 or 29. 

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