Rearrangement 1,4-pinacol

Pinacols are vicinal carbinols with two OH groups on tert-C atoms. They are available by Mg-promoted reductive dimerization of ketones involving radical-type 

Recent technologies for the production of pinacols apply TiCl2 or TiCl3 as reducing agents in the presence of elementary Mn or Zn. This is a low-temperature reaction, usually performed at 0 °C in THF, and hydrolysis of the Ti complex is completed in an aqueous solution of potassium carbonate. 

Acid-catalyzed rearrangement leads to the migration of one alkyl group with contemporaneous elimination of water resulting in the formation of tert alkyl ketone. 

The next example demonstrates the important role of intermediary pinacol in the route to the target molecule. The second example reveals the difficulties in plaiming the synthesis of specific target molecules if the re/ro-pinacol consideration is 

Example 8.6 Dienestrol TM 8.6 exhibits estrogenic activity. Propose the ret-rosynthesis that in the key step conceives the formation of pinacol. 

Acid-catalyzed rearrangement of vicinyl diols (pinacols) to carbonyl compounds. 

The most electron-rich alkyl group (more substituted carbon) migrates first. The general migration order  

Name Reactions, 4th ed., DOI 10.1007/978-3-642-01053-8 202, Springer-Verlag Berlin Heidelberg 2009 

Pinacol rearrangement. In Name Reactions for Homologations-Part I Li, J. J., Corey, E. J., Eds., Wiley Sons Hoboken, NJ, 2009, pp 319-333. (Review). 

Name Reactions A Collection of Detailed Mechanisms and Synthetic Applications, DOI 10.1007/978-3-319-03979-4 216, Springer International Publishing Switzerland 2014 

Example 5, A Trivalent organophosphoms reagent induced pinacol rearrangement  

A change of a polarity from a polar to nonpolar state (reverse polarity change) can be accomplished by the pinacol-pinacolone rearrangement and has been exploited in chemically amplified lithographic imaging [151, 348-350]. The pinacol rearrangement involves conversion of vie-diols to ketones or aldehydes with an acid as a catalyst (Fig. 115). 

A polymeric pinacol,poly[3-methyl-2-(4-vinylphenyl)-2,3-butanediol],has been prepared by radical polymerization of the styrenic diol monomer and shown to be cleanly and quantitatively converted to a non-conjugated ketone in the solid state by reaction with a photochemically-generated acid [151,348, 350]. The rearrangement reaction can be readily monitored by IR spectroscopy as the disappearance of the hydroxyl OH absorption is accompanied by appearance of a new ketone carbonyl absorption (Fig. 116). Since a polar alcohol (isopropanol) dissolves the polar diol polymer in the unexposed regions but cannot dissolve the less polar ketone polymer produced in the exposed regions, the resist functions as a negative system with alcohol as a developer. The diol polymer is stable thermally to 225 °C in the absence of acid. 

An aqueous base developable negative resist for use in 193 nm lithography was developed by combining NBHFA and norbornene bearing a pendant vic-diol (Fig. 118) [352]. One problem in the design of 193 nm resists is that the benzylic stabilization effect cannot be utilized to drive the acidolysis reactions and two kinds of ketone can be formed in this case. 

The reverse polarity change mechanism to convert polar polymer to nonpolar polymer could be an excellent basis to design a resist that could provide positive-tone images upon development with supercritical C02. 

When a vicinal diol is treated with catalytic acid, an El-type dehydration and subsequent [l,2]-shift of an adjacent bond generates an aldehyde or ketone in a transformation known as a pinacol rearrangement. 

The first pinacol rearrangement was conducted by Fittig in 1860, though he did not know the precise constitutions of the starting material and product at the time of the experiment. On treatment of 2,3-dimethylbutane-2,3-diol (pinacol) with sulforic acid, 3,3-dimethylbutane-2-one (pinacolone) was formed.  

In 1873, Butlerov proposed the now-accepted mechanism for this reaction in which he suggested the involvement of a carbon skeleton 

The fundamental mechanism of the pinacol rearrangement is widely accepted and consists of protonation of an alcohol, departure of water to generate a carbocation, [1,2]-migration of an adjacent alkyl group, aryl group, or hydride, and deprotonation. 

Due to the symmetry of the carbocation intermediate, pinacol rearrangements of acyclic substrates are rarely stereoselective. However, conformational constraints in cyclic systems can lead to high stereoselectivities. The reactivity of the set of conformationally-locked stereoisomers 9-12 when treated with a Lewis acid is illustrative. Regardless of the stereochemistry at C-1, both C-2 (5) diastereomers (9 and 10) yield only the ketone a-(S) stereoisomer, indicating hydride migration proceeds stereoselectively from the bottom face of the ring system (pathway 

A vicinal diol 1, when treated with a catalytic amount of acid, can rearrange to give an aldehyde or ketone 3 by migration of an alkyl or aryl group. The prototype of this reaction is the rearrangement of pinacol (R = r2 = = r4 = CH3) to 

In the initial step one hydroxy group is protonated, and thus converted into a good leaving group—i.e. water. Subsequent loss of water from the molecule proceeds in such a way that the more stable carbenium ion species 2 is formed. The next step is a 1,2-shift of a group R to the tertiary carbenium center to give a hydroxycarbenium ion species 4  

The reaction is strictly intramolecular the migrating group R is never completely released from the substrate. The driving force is the formation of the more stable rearranged carbenium ion 4, that is stabilized by the hydroxy substituent. The 

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The disconnection is obvious, and gives us one way of making symmetrical 1,2-diols. What makes it more than trivial is that the products undergo the pinacol rearrangement ... 

Analysis This is a t-alk ketone so a pinacol rearrangement route will be possible ... 

Synthesis Ketone A is just pinacolone, the product of the pinacol rearrangement (frames 154-5). 

The pinacol rearrangement is frequently observed when geminal diols react with acid. The stmcture of the products from unsymmetrical diols can be predicted on the basis of ease of carbocation formation. For example, l,l-diphenyl-2-metltyl-l,2-propanediol rearranges to... 

Antithetic conversion of a TGT by molecular rearrangement into a symmetrical precursor with the possibility for disconnection into two identical molecules. This case can be illustrated by the application of the Wittig rearrangement transform which converts 139 to 140 or the pinacol rearrangement transform which changes spiro ketone 141 into diol 142. 

The lactone A was also used as starting material in the synthesis of the primary prostaglandins via an allylic substitution-semi-pinacolic rearrangement sequence (Ref. 2). 

Selective hydroxylation with osmium tetroxide (one equivalent in ether-pyridine at 0 ) converts (27) to a solid mixture of stereoisomeric diols (28a) which can be converted to the corresponding secondary monotoluene-sulfonate (28b) by treatment with /7-toluenesulfonyl chloride in methylene dichloride-pyridine and then by pinacol rearrangement in tetrahydrofuran-lithium perchlorate -calcium carbonate into the unconjugated cyclohepte-none (29) in 41-48 % over-all yield from (27). Mild acid-catalyzed hydrolysis of the ketal-ketone (29) removes the ketal more drastic conditions by heating at 100° in 2 hydrochloric acid for 24 hr gives the conjugated diketone (30). 

Base catalyzed pinacol rearrangement of vicinal m-glycol monotosylates is a simple and useful general method for preparing perhydroazulenes. Thus, treatment of cholestane-5a,6a-diol 6-tosylate (115a) with either one mole-equivalent of potassium t-butoxide in f-butanol at 25° or with calcium carbonate in dimethylformamide at 100° gives a quantitative yield of 10(5 6/5H)... 

A simple and direct approach to 10(5 4j H)<2Z)eo-5-lceto derivatives lacking functionality in ring A is the controlled pinacol rearrangement of vicinal cw-diols analogous to the process described in the previous section. An example is the reaction of cholestane-4a,5a-diol 4-tosylate (136) with 1 mole-equivalent of potassium t-butoxide or with dimethylforraamide-calcium carbonate at reflux which gives a quantitative yield of Q(5ApH)abeo-cholestan-5-one (137). ... 

A nonphotochemical method for the preparation of D-norsteroids involves the base-catalyzed pinacol rearrangement of a pregnane-16oc,17a-diol 16a-mesylate. ... 

The pinacol rearrangement is a dehydration reaction that converts a 1,2-diol into a ketone. The reaction involves two carbocation intermediates. 

The pinacol rearrangement reaction is of limited synthetic importance although it can be a useful alternative to the standard methods for synthesis of aldehydes and ketones." Especially in the synthesis of ketones with special substitution pattern—e.g. a spiro ketone like 5—the pinacol rearrangement demonstrates its synthetic potential ... 

DimethyI-2 3-butanediol has the common name piiuicol. On heating with aqueous acid, pinacol rearranges to pinacolone, 3,3-dimethyl-2-butanone. Suggest a mechanism for this reaction. 

Picric acid, synthesis of, 628 Pinacol rearrangement, 646 Pineapple, esters in, 808 Piperidine, molecular model of, 939 structure of. 918 P1TC, see Phenylisothiocyanate, 1031-1032... 

In a similar reaction, 2,3,6-trimethoxydibenz[6,/]oxepin gives 10,11-dihydro-2,3,6-trimeth-oxydibenz[/>,/]oxepin-cw-10,l 1-diol upon treatment with osmium(VIII) oxide in the presence of A-methylmorpholine A -oxide.262 When treated with acid the diol undergoes a pinacol rearrangement to the corresponding xanthene-9-carbaldehyde. 

The bishydroxylation of peripheral C —C double bonds of porphyrins, e.g. 6, with hydrogen peroxide under acidic conditions or with osmium(VlII) oxide yields the corresponding diols, e.g. 10, which on pinacol rearrangement are transformed into geminally dialkylated chlorins, e.g. 11.9,97... 

A major disadvantage of this procedure is the lack of regioselectivity of the bishydroxylation which can take place on each of the four pyrrole rings of the macrotetracycle so that, in addition to the monoadduct, two bisadducts and one trisadduct are formed. The subsequent pinacol rearrangement of the diols can also occur in two directions, leading to a complex mixture of additional constitutional isomers. 

The oxidation of octaethylporphyrin 418 with hydrogen peroxide in sulfuric acid leads under pinacol rearrangement to a mixture of hydroporphyrinones, among them the expected three constitutionally isomeric isobacteriochlorins. 

The above mechanism involves a-opening of the epoxysilane, followed by a 1,2-elimination of a /3-hydroxysilanc (Peterson olefination, Chapter 10). However, it has recently been shown that aj8-dihydroxysilanes, particularly t-butyldimethylsilyl species, undergo an acid-catalysed sila-pinacol rearrangement to produce /J-aldehydo- and /i-kctosilancs (5) ... 

In order to answer the question about inherent migratory aptitudes, the obvious type of substrate to use (in the pinacol rearrangement) is R RC—CRR since the... 

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