Substituted alkenyl Grignard reagents

A transition metal catalyzes a similar carbomagnesation reaction, which has broaden the synthetic usefulness of this method for synthesis of alkenyl Grignard reagents. Among several transition metal salts that were reported to catalyze carbomagnesation of acetylenes [7,51,82 84], copper salts are most popular [7,13-15]. A variety of acetylenes, including acetylene itself [85], as well as substituted ones participated in this reaction. Some representative reactions are summarized in Table 11. 

Vinyl cyclopropanols have been prepared by the addition of alkenyl Grignard reagents to a variety of cyclopropanone equivalents. Upon treatment with acid, the vinyl cyclopropanols rearrange to a-substituted cyclobutanones. Alternatively, a variety of a-heteroatora-substituted cyclopropyllithiura reagents have been developed. These react with aldehydes and ketones to afford cyclopropylcarbinols which also rearrange to cyclobutanones under acid catalysis.Lastly, vinyl cyclopropanols and cyclopropylcarbinols have been prepared by the cyclopropanation of enol silyl... 

In the mid-1970s it was discovered that phosphine-Ni complexes (e.g., (Ph3P)2NiCl2) catalyzed the substitution of aryl halides with Grignard reagents at room temperature. The Ni catalysts were mostly phosphine complexes of NiCla. Alkyl (1°, 2°, or 3°), aryl, or alkenyl Grignard reagents could be used. 

In Summary Alkenyl halides are unreactive in nucleophilic substitutions. However, they can participate in carbon-carbon bond-forming reactions after conversion to alkenyllithium or alkenyl Grignard reagents, or in the presence of transition-metal catalysts such as Ni and Pd. 

Especially in the early steps of the synthesis of a complex molecule, there are plenty of examples in which epoxides are allowed to react with organometallic reagents. In particular, treatment of enantiomerically pure terminal epoxides with alkyl-, alkenyl-, or aryl-Grignard reagents in the presence of catalytic amounts of a copper salt, corresponding cuprates, or metal acetylides via alanate chemistry, provides a general route to optically active substituted alcohols useful as valuable building blocks in complex syntheses. 

In 2002, Figad re and coworkers reported the mono-reduction of 2-aryl (or heteroaryl)-1,1-dibromo-l-alkenes (Scheme 23). The reaction is achieved with one equivalent of isopropylmagnesium chloride in the presence of iron(III) acetylacetonate. Pure ( )-alkenyl bromides are obtained. With two equivalents of alkyl Grignard reagent, the mono-substituted product is obtained in moderate yield. 

Yamamoto and coworkers studied the substitution of ally lie phosphates by Grignard reagents in the presence of copper or iron salts. Only the Sn2 product is formed under copper catalysis whereas, in the presence of iron(III) acetylacetonate, the Sn2 product is generally obtained with an excellent selectivity (Scheme 49). It should be noted that aryl-, alkenyl-, aUcynyl- and aUcyhnagnesium halides can be used successfully. 

The addition of Grignard reagents or organolithiums (alkenyl, alkyl, alkynyl, allyl or aryl) to nitroenamines (281)213 was reported by Severin to afford P-substituted-a-nitroalkenes.214 b Similarly, ketone enolates (sodium or potassium), ester enolates (lithium) and lactone enolates (lithium) react to afford acr-nitroethylidene salts (294) which, on hydrolysis with either silica gel or dilute acid, afford 7-keto-a,(3-unsaturated esters or ketones (295)2l4c-d or acylidene lactones (296).214 Alternatively, the salts (294, X s CH2) can be converted to -y-ketoketones (297) with ascorbic acid and copper catalyst. 

Acetals as Chiral Auxiliaries. There have been many applications of acetals of 2,4-pentanediol as chiral auxiliaries to control the diastereoselectivity of reactions on another functional group. Examples include cyclopropanation of alkenyl dioxanes, lithium amide-mediated isomerization of epoxides to allylic alcohols, and addition of dioxane-substituted Grignard reagents or organolithiums to aldehydes. 

---