Acid catalyzed, addition rearrangement

MacMillan has developed a Lewis acid-catalyzed addition-rearrangement sequence which facilitates the conjugate addition of allylamine 408 to allenoate ester 409 to generate the zwitterionic intermediate for the Claisen rearrangement. The minimization of steric interactions between the ammonium species and the y-allenyl substituent led... 

The preparation of neopentyl alcohol from diisobutylene herein described represents an example of acid-catalyzed addition of hydrogen peroxide to a branched olefin, followed by an acid-catalyzed rearrangement of the tertiary hydroperoxide formed. In addition to neopentyl alcohol, there are formed acetone and also small amounts of methanol and methyl neopentyl ketone by an alternative rearrangement of the hydroperoxide. 

Carbon monoxide rapidly inserts into the carbon—zirconium bond of alkyl- and alkenyl-zirconocene chlorides at low temperature with retention of configuration at carbon to give acylzirconocene chlorides 17 (Scheme 3.5). Acylzirconocene chlorides have found utility in synthesis, as described elsewhere in this volume [17]. Lewis acid catalyzed additions to enones, aldehydes, and imines, yielding a-keto allylic alcohols, a-hydroxy ketones, and a-amino ketones, respectively [18], and palladium-catalyzed addition to alkyl/aryl halides and a,[5-ynones [19] are examples. The acyl complex 18 formed by the insertion of carbon monoxide into dialkyl, alkylaryl, or diaryl zirconocenes may rearrange to a r 2-ketone complex 19 either thermally (particularly when R1 = R2 = Ph) or on addition of a Lewis acid [5,20,21]. The rearrangement proceeds through the less stable... 

Treatment of 4,4-dimethyl-2-phenyl-l,3-thiazole-5(4//)-thione with ethyl diazoacetate gives, among other products, ethyl 1,3-thiazine carboxylate (179) (99). The formation of 179 has been rationalized by an acid-catalyzed addition of ethyl diazoacetate to the thiocarbonyl ylide 177 to first give intermediate 178, which undergoes a subsequent ring enlargement reaction via a Tiffeneau-Demjanov rearrangement. 

Hoffmann and Pete [106] have irradiated D-alk- 3 -e n y I salicylates and obtained products which result from rearrangement reactions of primary ortho adducts (Scheme 31). The authors realized that the linear tricyclic dienes, formed by ring closure of the cyclooctatriene derivatives, are enol ethers which can be converted into acetals by acid-catalyzed addition of an alcohol. This shifts the... 

Although this reaction involves two steps, they can be run sequentially in the same flask. This procedure is usually the preferred method for the hydration of an alkene because the yields are higher than the acid-catalyzed addition described in Section 11.3, and rearrangements do not occur. 

Some additional examples are provided by the following equations. Note the excellent yields in all of the examples. Also note that the last example proceeds without rearrangement because the intermediate is a mercurinium ion rather than a carbocation. Attempts to prepare this alcohol by acid-catalyzed addition of water result in completely rearranged product. 

The rearrangement processes, which can easily be studied in Lewis acid-catalyzed additions of alkyl halides to alkenes (Section III.B.2), give information about possible rearrangements in a growing chain produced from the corresponding monomer. 

Titanium trichloride fimctions as an excellent reductive Nef alternative reagent. This aqueous reagent is very acidic, so that acid sensitive groups such as ketals and esters do not survive unless an acetate buffer is used. Systems prcme to acid-catalyzed rearrangements may then successfully undeigo the reaction (equation 10).Some veiy sensitive multifunctional compounds have been obtained using this modified Nef procedure (equation 11). A related process is the formation of 1,4-diketones via in situ generation of a nitronatc anion by the Lewis acid catalyzed addition of an enol silyl ether to a nitroalkene (equation 12). ... 

Although the addition of H2O to an alkyne resembles the acid-catalyzed addition of H2O to an alkene in some ways, an important difference exists. In the presence of strong acid or Hg " catalyst, the elements of H2O add to the triple bond, but the initial addition product, an enol, is unstable and rearranges to a product containing a carbonyl group—that is, a C=0. A carbonyl compound having two alkyl groups bonded to the C=0 carbon is called a ketone. 

Double bonds are converted to monohydroxy derivatives by acid catalyzed addition of carboxylic acids, followed by hydrolysis. The carbocation intermediate is prone to rearrangement, leading to a mixture of positional isomers. Hydroboration with borane l,4-oxathiane followed by aUcahne hydrolysis a regioselective reaction (62) has been used to prepare hydroxy fatty acids as GC-MS standards in high yield (63). 

In a mechanistic study on the Lewis acid catalyzed addition of ethyl diazoacetate to ketones a similar profile of rearrangement to the 3-keto esters was observed (Scheme 9). In the same reaction with acetophenones, substitution on the benzene ring was found to only slightly affect the otherwise 90 10 preference for migration of aryl versus methyl. ... 

Hydroperoxides as intermediates or products. Neopentyl alcohol (3) can be prepared by acid-catalyzed addition of hydrogen peroxide to diisobutylene (1, Texaco) to form the hydroperoxide (2), which in a more strongly acidic medium rearranges to neopentyl alcohol and acetone. Thus 800 g. of 30% hydrogen peroxide ipH,... 

In Section 4.5, you learned that water adds to an alkene if an acid catalyst is present. This is the way aUcenes are converted into alcohols industrially. However, under normal laboratory conditions, water is added to an alkene by a procedure known as oxymercuration-reduction. The addition of water by oxymercuration-reduction has two advantages over acid-catalyzed addition It does not require acidic conditions that are harmful to many organic molecules, and because carbocation intermediates are not formed, carbocation rearrangements do not occur. 

The addition of hydrogen halides and the acid-catalyzed addition of water and alcohols form carbocation intermediates. Hyperconjugation causes tertiary carbocations to be more stable than secondary carbocations, which are more stable than primary carbocations. A carbocation will rearrange if it becomes more stable as a result of the rearrangement. Carbocation rearrangements occur by... 

When an alkyne undergoes the acid-catalyzed addition of water, the product of the reaction is an enol. The enol immediately rearranges to a ketone. A ketone is a compound that has two alkyl groups bonded to a carbonyl (C=0) group. An aldehyde is a compound that has at least one hydrogen bonded to a carbonyl group. The ketone and enol are called keto-enol tautomers they differ in the location of a double bond and a hydrogen. Interconversion of the tautomers is called tautomerization. The keto tautomer predominates at equilibrium. Terminal alkynes add water if mercuric ion is added to the acidic mixture. In hydroboration-oxidation, H is not the electrophile, H is the nucleophile. Consequently, mercuric-ion-catalyzed addition of water to a terminal alkyne produces a ketone, whereas hydroboration-oxidation of a terminal alkyne produces an aldehyde. 

An additional ethinylation (C2) of 6-methyl-5-hepten-2-one (Cg) leads to dehydro-linalool (Cio) as a monoterpene which is partially hydrogenated to linalool. The acid-catalyzed allyl rearrangement of linalool affords geraniol. 

Sol 12. In the first step, expected Claisen rearrangement of allyl ether I takes place to give III. However, III being an alkene can undergo acid-catalyzed addition of phenol to give II. So this unwanted reaction can be suppressed by the addition of a weak base such as PhNMe2 (typical alkenes do not undergo nucleophilic addition reactions). 

Since the ionic addition of hydrogen bromide and the acid-catalyzed addition of water to an alkene proceed via planar carbocations, the formation of products derived from rearranged carbocations is relatively common. In contrast, the bromi-nation of alkenes, which is illustrated by the addition of bromine to cyclopentene (Eq. 10.18), occurs via a cyclic bromonium ion 38 related to 33, so skeletal rearrangements of such cations are not generally observed. Moreover, the intervention of this cyclic ion dictates that the stereochemistry of the addition is completely in the anti sense, as shown. The reddish color of bromine is discharged upon addition to an alkene, making this reaction a useful qualitative test for unsaturation (Sec. 25.8A). 

The Lewis acid-catalyzed Fries rearrangement is performed under strong acidic conditions and therefore reqnires protection of sensitive functional groups. Conversely, the PFR can be achieved nnder milder conditions (organic solvents, nentral media, room temperature, etc.) and is therefore free from this type of problems. Moreover, polyacylation of aromatics is usually difficult to achieve. In the PFR, this problem can be solved by using acetals [144—146] or enol esters [147] as carbonyl protecting groups. Addition of anhydrous K CO is convenient to avoid deprotection [148]. 

---