Grignard reagent chiral

Direct addition of Grignard reagents to Zincke-derived chiral pyridinium salts such as 99, meanwhile, allowed subsequent reduction to 1,2,3,6-tetrahydropyridines (e.g., 100, Scheme 8.4.32). This strategy provided entry to asymmetric syntheses of (-)-lupetidin and (+)-solenopsin. Tetrahydropyridines prepared by reduction of chiral... 

There has been recent interest in naphtho-fused dithiepines as chiral acyl anion equivalents, particularly since the starting dithiol 128 can be obtained in enan-tiomerically pure form (89TL2575). This is transformed using standard methods into the dithiepine 129, but showed only moderate diastereoselectivity in its addition to carbonyl compounds. On the other hand, as we have seen previously for other systems, formation of the 2-acyl compound 130 and reduction or addition of a Grignard reagent gave the products 131 with much better stereoselectivity (91JOC4467). 

By treatment of a racemic mixture of an aldehyde or ketone that contains a chiral center—e.g. 2-phenylpropanal 9—with an achiral Grignard reagent, four stereoisomeric products can be obtained the diastereomers 10 and 11 and the respective enantiomer of each. 

The high diastereoselectivity which is found in the nucleophilic addition of Grignard reagents to chiral 2-0x0 acetals can be explained by a chelation-controlled mechanism. Thus, coordination of the magnesium metal with the carbonyl oxygen and the acetal moiety leads to a rigid structure 3A in the transition state with preferred attack of the nucleophile occurring from the S/-side. 

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). 

Sturmer via the reaction of the chiral borate ester (45, 5S)-4,5-dicyclohexyl-2-isopropyloxy-1,3,2-dioxaborolane, and racemic Grignard reagent (l-methyl-2-butenyl)magnesium chloride16. A 97 3 mixture of (S)-4 and its tf-diastereomer was obtained in 89% yield. 

The reactions of 2-propenyltitanium reagents with chiral aldehydes (0) or ketones ( and ) usually exhibit enhanced induced diastereoselectivities compared to allyl Grignard reagents. This enhanced diastereoselection is mainly attributed to the greater bulk and lower reactivity of the reagent. Some examples are collected ( )52. 

The chiral auxiliary can be recovered without any racemization. A chelated transition state has been suggested in which the Grignard reagent is delivered to the 7t-face more distal from the sterically demanding toy-butyl group1 2. 

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