Aldehydes organomagnesium compounds

Aldehyde 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). 

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... 

The addition of an organomagnesium compound to an aldehyde is an excellent general method for preparing secondary alcohols, and the side-reactions referred to above are a problem only in particularly unfavourable cases. Large numbers of examples have been tabulated [A] and examples from Organic Synthesis are listed in Table 6.1. a,[3-Unsaturated aldehydes normally undergo mainly or exclusively 1,2-addition, as in the examples in Table 6.1. The following experimental procedure is typical. 

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] ... 

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

Similar considerations apply to reactions of organomagnesium compounds with formate esters (leading to aldehydes), chloroformates or carbonates (leading to esters) or carbamoyl chlorides (leading to amides) ... 

For an alternative and often superior synthesis of aldehydes from organomagnesium compounds, by reaction with orthoformates, see Section 8.2.1. 

Synthesis of aldehydes and ketones by reactions of organomagnesium compounds... 

Organoberyllium compounds react with aldehydes and ketones in a fashion similar to organomagnesium compounds. Reduction competes with addition, and (32) is quite effective for asymmetric reductions. ... 

Amides and Lactams. The amide carbonyl group is less reactive than that of aldehydes or ketones, but the intermediate formed on addition of one equivalent of organomagnesium compound is relatively stable to elimination of a magnesium dialkylamide, and so protects... 

Many straight-chain and branched secondary alcohols have been made by the action of organomagnesium compounds on higher aldehydes. The method is popular for the preparation of arylalkylcarbinols from either the aromatic aldehyde or the aromatic Grignard reagent. ... 

Less acidic than Ti and Zi chloroderivatives, MeTi(OPr )3 perfoims chelation-controlled addition to chiral alkoxy ketones as well as or better than organomagnesium compounds, but fails to chelate to aldehydes or hindered ketones. Should the formation of a cyclic chelation intermediate be forbidden, the reaction is subject to nonchelation control, according to Ae Felkin-Anh (or Comforth) model. Under these circumstances, the ratio of the diastereomeric products is inverted in favor of the anti-Cram product(s). In the case of benzil (83 Scheme 7) this can be accounted for by the unlikely formation of a cyclic intermediate such as (85), and thus the preferential intermediacy of the open chain intermediate (86) that leads to the threo compound (88). This view is substantiated by the fact that replacement of titanium with zirconium, which is characterized by longer M—O bonds, restores the possibility of having a cyclic intermediate and, as a consequence, leads to the erythro meso) compound (87) thus paralleling the action of Mg and Li complexes. 

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