Ketones organomagnesium compounds

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 . 

Ketone Organomagnesium compound Product isolated (yield, %) Ref. 

Organohthium and organomagnesium compounds find their chief use m the prepa ration of alcohols by reaction with aldehydes and ketones Before discussing these reac tions let us first examine the reactions of these organometallic compounds with proton donors... 

The organozinc compound 2 is less reactive than an organomagnesium compound the addition to an ester carbonyl group is much slower than the addition to an aldehyde or ketone. Nevertheless the addition of 2 to the carbonyl group of unreacted a-halo ester 1 is the most frequently observed side-reaction ... 

Organomagnesium compounds react with imines, prepared from 3-methoxy-2-naphth-aldehydes by a 1.4-addition mechanism. This reaction can be performed with high diastere-oselectivity. The method was applied for the synthesis of optically pure S-tetralones . Vinyhnagnesium bromide reacts as an acceptor with a ketone dimethyl hydrazone zincate 207, yielding a 1,1-bimetallic species, which can be reacted sequentially with two different electrophiles (equations 131 and 132) . The reaction proceeds via a metalla-aza-Claisen rearrangement, where the dimethylhydrazone anion behaves as an aza-allylic system . 

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). 

More reactive carbon nucleophiles than enolates can also be prepared on insoluble supports (see Chapter 4) and are used to convert aldehydes or ketones into alcohols. Organolithium compounds have been generated on cross-linked polystyrene by deprotonation of formamidines and by metallation of aryl iodides (Table 7.5). Similarly, support-bound organomagnesium compounds can be prepared by metallation of aryl and vinyl iodides with Grignard reagents. The resulting organometallic compounds react with aldehydes or ketones to yield the expected alcohols (Table 7.5). 

Although organomagnesium compounds are not sufficiently reactive to add to carboxylate anions, alkyllithium compounds add quite well. A useful synthesis of methyl ketones involves the addition of methyllithium to the lithium salt of a carboxylic acid ... 

A wealth of papers has been published on the kinetics and mechanism of the addition of organomagnesium compounds to ketones, nitriles, etc. It is not... 

Readily available THF solutions of LnCl3,2LiCl (Ln = La, Ce, Nd) have been found to be superior promoters for the addition of various organometallic reagents to ketones.85 They also catalyse efficiently the addition of organomagnesium compounds to imines. 

Acidic protons were a major problem in several syntheses of the anticancer compounds, daunorubicin and adriamycin, which start with a nucleophilic addition to a ketone with a pair of particularly acidic protons. Organolithium and organomagnesium compounds remove these pro-... 

Organomagnesium compounds add to unsubstituted arenes only under forcing or Barbier conditions [1], On the other hand, aromatic rings substituted by electron-withdrawing groups are surprisingly susceptible to attack by organomagnesium compounds. The early work on reactions of hindered aryl ketones [2] has been little further developed [3], despite some reports which should surely be followed up, e.g. [4],... 

Synthesis of ketones via addition of organomagnesium compounds to nitriles... 

The addition of organomagnesium compounds to the carbonyl group of aldehydes and ketones has a long history, and remains one of the most important reactions for carbon-carbon bond formation. While the overall reaction is simple, it is susceptible to a number of side-reactions, and its... 

As in the case of aldehydes, Barbier reactions of magnesium, organic halide and ketone can be an alternative to the reactions via preformed organomagnesium compounds [18, 53],... 

The stereochemistry of addition of organomagnesium compounds to ketones is governed by similar factors to those influencing their addition to aldehydes (see Section 6.1.1). For addition of achiral organomagnesium compounds to a-chiral ketones, steric approach control is commonly observed, but chelation control may also operate [63, 64], It is noteworthy that a pioneering asymmetric synthesis — one of the first which could be regarded as virtually stereospecific, was of this type [65] ... 

With 3- [66] and y-chiral ketones [67], examples are known where organomagnesium compounds add from the opposite face to organolithium compounds, as illustrated [66]. 

For reactions of chiral organomagnesium compounds with achiral ketones, references already cited in connection with aldehydes (e.g. Ref. [45]) are relevant. 

Until recently, attempts to achieve asymmetric syntheses by reactions of achiral carbonyl compounds with achiral organomagnesium compounds in the presence of chiral ligands had met with only limited success (see p. 119). Recently, however, very promising results have been reported involving additions to ketones [52, 68] TADDOLs (a,a,a, a -tetraaryl-2,2-dimethyl-l,3-dioxolane-4,5-dimethanols, where the aryl groups are phenyl or 2-naphthyl) are particularly effective, as in the following example [52] ... 

The stereochemistry of conjugate addition of organomagnesium compounds to a,[3-unsaturated ketones is governed by similar considerations to those governing addition to saturated ketones recent examples include diastereoselective additions to both acyclic (6) [77] and cyclic [78] (7) enones. 

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