ALCOHOL SYNTHESIS USING GRIGNARD REAGENTS

Reduction of7,7-dimethylbicyclo[2.2.1]heptan-2-one with sodium borohydride yields two isomeric alcohols in a 6 1 ratio. Considering the effect of the methyl groups, write the structures of the products. 

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A-7. Synthesis of the following alcohol is possible by three schemes using Grignard reagents. Give the reagents necessary to carry out each of them. 

Although the majority of sulfides used as precursors to organolithiums have been thioacetals or sulfides bearing other a-substituents, the usefulness even of simple phenylsulfides related to 56 was demonstrated in the synthesis of dihydroerythronolide A by Stork,74 which used a sulfide intermediate 59 in the conversion of an alcohol to a Grignard reagent. 

Equation 2 shows that ketones form tertiary alcohols with the Grignard reagent. The objective of the present experiment is to provide an illustration of the use of the Grignard reagent for the synthesis of alcx)hols. 

Show how you would use Grignard reagents in the synthesis of each of the following alcohols ... 

An ability to form carbon-carbon bonds is fundamental to organic synthesis The addition of Grignard reagents to aldehydes and ketones is one of the most frequently used reactions m synthetic organic chemistry Not only does it permit the extension of carbon chains but because the product is an alcohol a wide variety of subsequent func tional group transformations is possible... 

Tertiary alcohols can be prepared by a variation of the Grignard synthesis that uses esters as the source of the carbonyl group Methyl and ethyl esters are readily available and are the types most often used Two moles of a Grignard reagent are required per mole of ester the first mole reacts with the ester converting it to a ketone... 

Alcohol synthesis via the reaction of Grignard reagents with carbonyl com pounds (Section 14 6) This is one of the most useful reactions in synthetic organ ic chemistry Grignard reagents react with formaldehyde to yield primary alco hols with aldehydes to give secondary alcohols and with ketones to form terti ary alcohols... 

Synthesis of alcohols using organolithi um reagents (Section 14 7) Organolithi um reagents react with aldehydes and ketones in a manner similar to that of Grignard reagents to produce alcohols... 

Miscellaneous Reactions. Sodium bisulfite adds to acetaldehyde to form a white crystalline addition compound, insoluble in ethyl alcohol and ether. This bisulfite addition compound is frequendy used to isolate and purify acetaldehyde, which may be regenerated with dilute acid. Hydrocyanic acid adds to acetaldehyde in the presence of an alkaU catalyst to form cyanohydrin the cyanohydrin may also be prepared from sodium cyanide and the bisulfite addition compound. Acrylonittile [107-13-1] (qv) can be made from acetaldehyde and hydrocyanic acid by heating the cyanohydrin that is formed to 600—700°C (77). Alanine [302-72-7] can be prepared by the reaction of an ammonium salt and an alkaU metal cyanide with acetaldehyde this is a general method for the preparation of a-amino acids called the Strecker amino acids synthesis. Grignard reagents add readily to acetaldehyde, the final product being a secondary alcohol. Thioacetaldehyde [2765-04-0] is formed by reaction of acetaldehyde with hydrogen sulfide thioacetaldehyde polymerizes readily to the trimer. 

All that has been said in this section applies with equal force to the use of organo-lithium reagents in the synthesis of alcohols. Grignard reagents are one source of nucleophilic carbon organolithium reagents are another. Both have substantial carbanionic char acter in their- car bon-metal bonds and undergo the same kind of reaction with aldehydes and ketones. 

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. 

Wang used method D to fashion a key intermediate for the synthesis of rishirilide B (Fig. 4.20).21 The 2,4-bis-OBoc-3-methyl-benzyl alcohol (31) undergoes the addition of two equivalents of corresponding Grignard reagent to afford phenol 32 in 75% yield (Fig. 4.20). This material was subsequently elaborated by Mejorado in three steps (61% yield) to the corresponding 2,5-chiral cyclohexadienone 33, which was ultimately transformed into ( + )-rishirilide B (34).22... 

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