Organomagnesium chiral

Alkylation of chiral triflates with organomagnesium or organolithium reagents for construction of side chains of naturally occurring heterocycles, antibiotics, and enzyme inhibitors 99YGK334. 

Most successful approaches involving addition reactions in the presence of chiral additives utilize organolithium, organomagnesium and the recently introduced organotitanium reagents, which are known to coordinate with amines, ethers, metal amides and alkoxides. 

Without a means to easily control the chirality of benzylic stereocenter, Pettus group members decided to focus on the development of procedures for the construction of adducts without chiral centers. These researchers found that organomagnesium reagents can be used to both generate and consume the o-QM from the corresponding... 

Sulfonylhydroxylamines and hydroxylamine O-sulfonic acid have found wide apph-cation in synthesis of amines from achiral or chiral organoboranes and boronate esters and the hydroboration-amination methodology is successfully used for direct amination of alkenes. 0-Sulfonyloximes were also found to be good reagents for synthesis of amines from organomagnesium, -copper and -zinc reagents. 

Chiral organomagnesium amides form an efficient method to realize enantioselective conjugate addition. Sibi and Asano have reported the Michael addition of cr-bound magnesium reagents derived from bisoxazolines to enamidomalonates (equation 41). The enantioselectivity of the addition is discussed in Section El. This method allows the preparation of chiral -amino acid derivatives. ... 

The enantioselective addition of organomagnesium compounds to ketones can be most conveniently performed by using a chiral auxiliary in the substrate molecule. Primary aUsyhnagnesium reagents react with aryl and heteroaryl ketones in the presence of magnesium TADDOLate at — 100°C, yielding products with up to 98% ee (equation 143). Chiral a-ketoacetals 214, prepared in two steps from a-substituted cinnamic aldehydes, add organomagnesium species with up to 98% diastereoselectivity (equation 144). 

Chiral sulfinimines 236 are very useful intermediates for the preparation of enantiomer-ically pure primary amines 237 (equation 158) . This reaction has been applied to the synthesis of a-amino acids . For sulfinimines obtained from simple ketones, lithium reagents are preferable for the addition , while for cyclic ketones organomagnesium compounds gave the best results. Addition of alkyl and aryl Grignard compounds to sulfinimines, derived from 3- and 4-substituted cyclohexanones, proceeds with excellent diastereoselectivity, depending on the stereochemistry of the ring substituents rather than the sulfinyl group . 

In 2003, FUrstner and Mdndez reported an elegant reaction between optically active propargyhc epoxides and organomagnesium compounds in the presence of iron(III) acetylacetonate (Scheme 50). Interestingly, the chirality of the starting product is transferred to the final 2,3-allenols which are obtained with a good enantiomeric purity. 

The first successful approaches were based on the, often Cu-mediated, conjugate addition of organolithium and organomagnesium (Grignard) reagents to o ,/ -unsaturated systems covalently modified with chiral auxiliaries (Scheme 1 ). ... 

The asymmetric addition of organomagnesium and organolithium reagents to a,P-unsaturated carbonyl compounds and especially imines can be achieved in situations where rigid chelation controls the geometry of the transition state. Stereospecific alkyl addition occurs in the case of a chiral leucine-derived imine to provide overall asymmetric alkyl addition to an a,P-unsaturated aldehyde (Scheme 107).380 381... 

Chiral aminals 1,4-dihydropyridine-3-carboxaldehydes.1 The chiral aminal 2 prepared from pyridine-3-carboxylaldehyde and (S,S)-12 reacts with organocopper reagents in the presence of methyl chloroformate to give almost exclusively products of 1,4-addition, as expected from reactions of the free aldehyde.3 No products of 1,2-addition are formed, but 1,6-adducts are minor products in some cases. The 1,4-adducts are formed in 82-93% de (R-configuration). Addition of butyl and ethyl groups is best effected with lithium cuprates, but addition of methyl, vinyl, or aryl groups is best effected with organomagnesium cuprates. Under these conditions,... 

Imines derived from 3-methoxy-2-naphthaldehydes react with organomagnesium compounds by a 1,4-addition mechanism. This reaction can be performed with high diastereoselectivity by using an apropriate chiral auxiliary. The method was applied for the synthesis of optically pure /3-tetralones.243... 

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