Grignard reagent, carbinol synthesis

An acceptable method is to oxidize methyl benzyl carbinol (l-phenyl-2-propanol) to phenylacetone (methyl benzyl ketone) with chrome oxide (CrO3) in pyridine solvent. The problem with this is that methyl benzyl carbinol is not commercially available, and so must be made from benzyl chloride grignard reagent and acetaldehyde. This grignard works well, although there can be a problem getting unreacted benzyl chloride out of the product. Their boiling points are very close, so distillation does not separate them completely. But the real question is Why make the synthesis of phenylacetone a two-step process when it can be done with one reaction ... 

In the second class of synthesis two thiophene rings become joined through a carbon atom that is already a substituent of one of them by this means symmetrically and unsymmetrically substituted products in the 2,2, 2,3, and 3,3 series are available. Three main reaction types have been employed in this approach. In one of these a thiophene is alkylated with a thenyl halide (Eq. 3). Friedel-Crafts acylation of a thiophene by a thenoyl chloride or thenoic acid followed by reduction of the resulting dithienyl ketone provides a second route in this category. The last and most versatile synthesis in this class involves reaction of a thienyllithium (or Grignard reagent) with a thienylaldehyde or thienyl ketone reduction of the carbinol (see Eq. 2) then gives the dithienylalkane. 

The usual synthesis of the carbinols 92 is carried out by reaction of an ester with a thienyllithium or Grignard reagent an alternative approach118 (from a dithienyl ketone and organometallic compound) has been used recently, however. Dehydration to the thiambutene is most often achieved by treatment with hydrogen chloride in a solvent (normally ethanol or acetic acid), but it has been found that trifluoroacetic acid gives the same result under very mild conditions.119... 

Regiocontrolled synthesis of alkoxynaphthalenes has been achieved by aromatic annelation of the carbinol dithioacetates formed by regioselective 1,2-addition of alkoxybenzyl Grignard reagents to a-oxoketene dithioacetals. ... 

Cyclopentane-l,2-dione can be transformed in good yield into its isobutyl mono-enol ether in the same way as the 1,3 dione reaction of the free ketone group with Grignard reagents followed by dehydration of the intermediate carbinol constitutes a general synthesis of 2-alkyl-cyclopentenones... 

MAD and MAT have played a crucial role in the stereoselective synthesis of hitherto inaccessible equatorial carbinols from cyclohexanones and primary allyl Grignard reagents or methyllithium [44). In the reaction of cyclohexanone derivatives with tert-butylmagnesium chloride, reduction takes precedence over alkylation in the presence of MAD (Scheme 6.37) [45). 

Another example is tamoxifen (89). Its synthesis begins with Grignard addition of reagent to aryl ketone giving carbinol Dehydration leads to the readily separable and... 

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