Anti-Markovnikov addition alcohol synthesis

Catalytic transformations of alkynes have recently led to tremendous developments of synthetic methods with useful applications in the synthesis of natural products and molecular materials. Among them, the selective activations of terminal alkynes and propargylic alcohols via vinylidene- and allenylidene-metal intermediates play an important role, and have opened new catalytic routes toward anti-Markovnikov additions to terminal alkynes, carbocyclizations or propargylations, in parallel to the production of new types of molecular catalysts. 

As mentioned, the synthesis ends easily enough changing the OH of 4-heptanol to Cl with SOC12. To form bonds a and b , you must make CH3CH2CH2MgBr. That will require an anti-Markovnikov addition to propene. Working backward, bond a is addition of this Grignard to an aldehyde. Where does the aldehyde come from It must be from oxidation of a primary alcohol with PCC. The alcohol then comes from formation of bond b from addition of the same Grignard to formaldehyde. So you have... 

Our previous method for alcohol synthesis, hydration of aikenes, necessarily produced the more substituted alcohol. So now we have complementary synthetic methods for producing hoth possible alcohols from a given alkene (Fig. 9.69). Direct hydration gives the more substituted product (Markovnikov addition) and the indirect hydroboration/oxidation method gives the less substituted alcohol (anti-Markovnikov addition). Be sure to add these reactions to your file-card collection of synthetically useful reactions. 

This synthesis requires the conversion of an alcohol to an alkyl bromide with the bromine atom at the neighboring carbon atom. This is the anti-Markovnikov product, which could be formed by the radical-catalyzed addition of HBr to 1-methylcyclohexene. 

Preparation. - By Addition to Alkenes. Triethylborane and phenyl-borinic acid have been found to catalyse hydroalumination of alkenes, and reaction of the intermediate alane with atmospheric oxygen efficiently furnished alcohols resulting from anti-Markovnikov hydration.1 Procedures for the preparation of methylborane and dimethylborane and their use in the synthesis of... 

Because the oxidation step in the hydroboration-oxidation synthesis of alcohols takes place with retention of configuration, the hydroxyl group replaces the boron atom where it stands in the alkylboron compound. The net result of the two steps (hydroboration and oxidation) is the syn addition of —H and —OH. We can review the anti-Markovnikov and syn aspects of hydroboration-oxidation by considering the hydration of 1-methylcyclopentene, as shown in Fig. 8.3. 

In this chapter, we see the synthesis of alkyl halides and alcohols from alkenes through addition reactions. Hydroboration allows us to do addition reactions in the anti-Markovnikov sense. The 8 2 and 8 1 reactions from earlier chapters allow us to do further transformations of the alcohols and halides. The new synthetic methods are summarized below. 

Because borane additions to double bonds and subsequent oxidation are so selective, this sequence allows the stereospeeific and regioselective synthesis of alcohols from alkenes. The anti-Markovnikov legioselectivity of the hydroboration-oxidation sequence complements that of acid-catalyzed hydration and oxymercuration-demercuration. In addition, hydroboration, like oxymercuration, occurs without the participation of carbocations therefore, rearrangements are not observed. 

A-Alkylation of amides and amines and dehydrative -alkylation of secondary alcohols and a-alkylation of methyl ketones " have been carried out by an activation of alcohols by aerobic oxidation to aldehydes, with copper(II) acetate as the only catalyst. A relay race process rather than the conventional borrowing hydrogen-type mechanisms has been proposed for the aerobic C-alkylation reactions, based on results of mechanistic studies. A Winterfeldt oxidation of substituted 1,2,3,4-tetrahydro-y-carboline derivatives provides a convenient and efiflcient method for the synthesis of the corresponding dihydropyrrolo[3,2-fc]quinolone derivatives in moderate to excellent yields. The generality and substrate scope of this aerobic oxidation have been explored and a possible reaction mechanism has been proposed. Direct oxidative synthesis of amides from acetylenes and secondary amines by using oxygen as an oxidant has been developed in which l,8-diazabicyclo[5.4.0]undec-7-ene was used as the key additive and copper(I) bromide as the catalyst. It has been postulated that initially formed copper(I) acetylide plays an important role in the oxidative process. Furthermore, it has been postulated that an ct-aminovinylcopper(I) complex, the anti-Markovnikov hydroamination product of copper acetylide, is involved in the reported reaction system. Copper(I) bromide... 

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