Aryl Grignard reagents addition

Subsequent addition of aryl Grignard reagents then provides the secondary alcohols 161, which easily undergo elimination under the conditions shown in the scheme to provide the 1,3-disubstituted allenes 162 in excellent yields (-90%). 

Grignard reaction, addition of methyl-magnesium bromide to thiophos-phoryl chloride, 46,102 addition of aryl Grignard reagents to diphenylchlorophosphine, 49, 66 Grignard reagents, synthesis and utility of unsolvated, 47, 116 titration of, 48, 48... 

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 behavior of BnMgBr (5d) is similar to that observed for compounds with higher alkyl groups, i.e. only the coupling product was detected and the earlier report on the additional formation of benzyl alcohol was not confirmed. On the other hand, reactions of Ar" radicals formed in the anodic oxidation of aryl Grignard reagents are different from those established for Aik, as is evident from the percent distribution of parent radicals in major products given in Table 7. 

Many years later, Fukuhara and Urabe showed that aryl Grignard reagents react with ethyl 2,4-dienoates or 2,4-dienamides, in the presence of iron salts, to give the 1,6-addition products (Scheme 60). This reaction is stereoselective and leads to the (Z)-trisubstituted olefins. 

When the phenyl-substituted alkynyl sulfone 42 is used as a substrate for the Cu-catalyzed carbomagnesiation, interesting nucleophile-dependent stereoselectivity is observed. While the use of allyl Grignard reagent results in a syn addition, the use of aryl Grignard reagent results in an awh -carbomagnesiation (Scheme 25). ... 

Other carbon nucleophiles may also be employed in such a coupling reaction that provides (3-amino ketones and polyol intermediates. As shown in Scheme 32, aryl-Grignard reagents react at low temperature with the Ai-Boc p-lactam 96 to afford p-aminoketones 97 in 90-96% yields as the exclusive products. In no case over-addition is observed, even when an excess of the Grignard reagent is present in the reaction medium. On the other hand, when the reaction is performed at room temperature, only tertiary carbinols 98 are produced. 

A new role of iron catalyst in the Grignard conjugate addition has been disclosed.97 It catalysed 1,6-addition of aryl Grignard reagents to 2,4-dienoates or -dienamines in a highly regio- and stereo-selective manner. 

Diphenylprolinol (4) itself is now commercially available at scale, or it can be prepared several ways (Scheme 16.2) Direct addition of an aryl Grignard reagent to a proline ester leads to the diarylprolinol with a low yield in the range of 20-25%.33 A more efficient route is based on an... 

An approach that has allowed for considerable structural variety and was used most frequently at Burroughs Wellcome to construct the appropriate benzhydrols is the addition of an aryllithium or an aryl Grignard reagent to an appropriate benzaldehyde. This can be an extremely effective approach, as demonstrated by the construction of the complete benzhydrol needed for SNC80 in 91% yield (Scheme 4) [27,29],... 

One approach utilizes Katritzky s route to tertiary amines to construct the benzhydrylpiperazine (Scheme 7) [42]. This method involves addition of an aryl Grignard reagent to a masked iminium, an adduct formed from the piperazine, an appropriate benzaldehyde, and benzotriazole. In solution, this adduct is in equilibrium with an iminium ion formed by elimination of the benzotriazole, and it is likely that the Grignard reagent adds to this species. Assuming that the iminium ion is the reactive entity, the stereoselectivity appears to rely on two separate events 1) preferential formation of one of the... 

CP-96,345 (2) was synthesized by a route with literature precedent based on the 1,4-addition of aryl Grignard reagents to benzylidene quinuclidone derivatives such as 6.3 The hindered borane reagent 9-BBN afforded compound 7 with the desired cis-stereochemistry. Subsequent deblocking and reintroduction of the benzyl side chain furnished analogs depicted by 8 for exploring benzylamine side chain SAR. 

Fig. 13.7. Presumed elementary steps of a Ni-catalyzed C,C coupling between an aryl Grignard reagent and an alkyl halide—using the example of the reaction in Figure 13.6. The elementary steps, discussed in the text, are (1) complexation, (2) oxidative addition, (3) transmetallation, (4) reductive elimination, and (5) dissociation.

---