Boronate esters 0-allylic

Type I (fast homodimerization) Terminal olefins, allylsilanes" Terminal olefins, allylsilanes," 1° allylic alcohols, ethers, and esters, " allyl boronate esters, allyl halides, alkyl-substituted allenes Terminal olefms, allyl boronate esters, 1° allylic alcohols, ethers, and esters,styrenes (no large ortho substit.), " " allyl allylsilanes, allyl sulfides, allyl phosphonates, " allyl phosphine oxides, protected allylamines ... 

Scheme 9.3 illustrates some examples of syntheses of allylic carbinols via allylic boranes and boronate esters. Entries 1 and 2 are among the early examples that... 

The directive effect of allylic hydroxy groups can be used in conjunction with chiral catalysts to achieve enantioselective cyclopropanation. The chiral ligand used is a boronate ester derived from the (VjA jA N -tetramethyl amide of tartaric acid.186 Similar results are obtained using the potassium alkoxide, again indicating the Lewis base character of the directive effect. 

The allyl boronate esters (R,R)- and (S,S)-1 are prepared by reaction of allylboronic acid, CH2=CHCH2B(OH)2 with l- and D-diisopropyl tartrate.1... 

As a conseqnence of their superior stability, many types of allylic boronates can be isolated and purified. It should be noted that most pinacol allylic boronic esters and other bnlky esters are stable to hydrolysis and can be conveniently pnrified by chromatography on silica gel. A potential pitfall of all allylic boron componnds is their stereochemical integrity, and snbstituted allylic boranes are known to nndergo reversible borotropic rearrangements at temperatures above —45° (see Eq. 12, M = Eor this reason, allylic boranes are nor-... 

The cyclic mechanism would predict that the addition reaction would be stereo-specific with respect to the geometry of the double bond in the allylic group. This has been demonstrated to be the case. The E- and Z-2-butenyl cyclic boronate esters 1 and 2 were synthesized and allowed to react with aldehydes. The /- -boronate gave the carbinol having anti stereochemistry whereas the Z-boronate gave the syn product.34... 

Addition reactions of allylic boron compounds have proven to be quite general and useful. Several methods for synthesis of allylic boranes and boronate esters have been developed.36 37 The reaction has found some application in the stereoselective synthesis of complex structures. 

The synthesis in Scheme 13.31 also relies on me.so-2,4-dimethylglutaric acid as the starting material. Both the resolved aldehyde employed in Scheme 13.30 and a resolved half-amide were successfully used as intermediates. The configuration at C-2 and C-3 was controlled by addition of a butenylborane to an aldehyde (see Section 9.1.2). The boronate ester was used in enantiomerically pure form so that stereoselectivity was enhanced by double stereodifferentiation. The allylic additions carried out by the butenylboronates do not appear to have been quite as highly stereoselective as the aldol condensations used in Scheme 13.30, because a minor diastereomer was formed in the boronate addition reactions. 

Syntheses of simple diols are described first, followed by a multistep synthesis of ribose. These syntheses illustrate the compatibility of alkoxy substituents on boronic esters with their reaction with (dihalomethyl)lithium. The limitations of this compatibility, as well as failure of a (chloro-allyl)boronic ester to undergo substitution by alkoxides, are also noted. Retention of configuration of the migrating group is a consistent and repeated feature of these syntheses. 

Allylic a-bromo boronic l,l,2,2-tctramethyl-l,2-ethanediyl esters are too labile to permit preparation in high stereochemical purity. Finacol l-bromo-2-propenylboronate with sodium methoxideyields 1-methoxy-2-propenyl boronic l,l,2,2-tetramethyl-l,2-ethanediyl ester54. Attempted conversion of the corresponding chloro boronic ester to alkoxy derivatives failed54. 

The cross-coupling of alkynylzinc halides or fluorinated alkenylzinc halides with fluori-nated alkenyl iodides allows the preparation of a range of fluorinated dienes or enynes - Functionalized allylic boronic esters can be prepared by the cross-coupling of (dialkylbo-ryl)methylzinc iodide 428 with functionalized alkenyl iodides. The intramolecular reaction provides cyclized products, such as 429 (Scheme 109) ° °. In some cases, reduction reactions or halogen-zinc exchange reactions are observed. 

SCHEME 109. In. situ generation of allylic boronic esters via cross-coupling reactions... 

Polystyrene-derived phenylboronic acids have been used for the attachment of diols (carbohydrates) as boronic esters [667]. Cleavage was effected by treatment with acetone/water or THF/water. This high lability towards water and alcohols severely limits the range of reactions that can be performed without premature cleavage of this linker. Arylboronic acids esterified with resin-bound diols can be oxidatively cleaved to yield phenols (Entry 8, Table 3.36). Alcohols have also been prepared by nucleophilic allylation of aldehydes with polystyrene-bound, enantiomerically enriched allyl-silanes [668], as well as by Pummerer reaction followed by reduction of resin-bound sulfoxides [669]. 

Micalizio and Schreiber [47] developed a key reaction, the transesterification of unsaturated boronic esters with allylic esters or propargylic alcohols. This reaction transiently provided mixed organoboronic esters that could be trapped by using... 

Diastereoselective allylation of optically pure sulfinyl dienal complexes using tributyl allyltin can be obtained (Scheme 138). 2,4-Hexadien-1,6-dial iron tricarbonyl complex (88) undergoes nucleophilic addition reactions with diaUcylzincs in the presence of a catalytic amount of an optically active amino alcohol (Scheme 139). Very high enantio-and diastereoselectivity is observed. Related reactions of (88) with chiral allyl boronic esters give allylated alcohols in very high enantiomeric excess. 

Allylic alcohols may be derived from alkenes by metallation to give the allylpotassium species, followed by treatment with fluorodimethoxyborane. Oxidation of the resultant boronic ester with hydrogen peroxide gives the allylic alcohol (Scheme 15). ° - ° Some allylic rearrangement may be observed for example, metallation of a-pinene with potassium r-butoxide in petroleum ether solution and subsequent boration and oxidation gave myrtenol (42%) and /rons-pinocarveol (1%) (equation 24), while treatment of the allylpotassium with oxirane gave the alkylated prc ucts in a ratio of ca. 2 1. ° ... 

A 2,5-disubstituted pyrrolidine was obtained by this method as a 1 1 mixture of cis- and tran.r-isomers. However, since diastereomeric or enantiomeric boronic esters can be easily prepared via asymmetric hydroboration, the control of the relative and absolute stereochemistry at C-2 and C-3 (ring numbering) should easily be achieved. Diisopinocampheylborane was employed in the first step, but exclusively with allyl bromide. 

The transfer of the allylic moieties from boron to the electrophilic carbonyl carbon proceeds via rearrangement to form intermediate boronic esters C and D (see below). The reaction is highly diastereoselective. The ( )-crotylboronate reacts to give the anfr-homoallylic alcohol and the (Z)-crotylboronate reacts to afford the syn-homoallylic alcohol.This behavior has been interpreted in terms of the Zimmerman-Traxler chair-type transition state model.Because of the double bond geometry, coordination of the (Ei-crotylboronic ester places the Me preferentially equatorial, whereas coordination of the (Z)-crotylboronic ester places the Me axial, as illustrated in the cyclohexane chair-form transition state conformations A and B, respectively. In both cases, the R moiety of the aldehyde must occupy a pseudo-equatorial position to avoid steric repulsion by one of the OR substituents on boron. 

Furthermore, this regio- and stereoselective bond formation between unsaturated carbon atoms was applied to the synthesis of functionalized dienes under extremely mild conditions. Thus, even vinylic boronic esters containing an allylic acetal moiety and alkenylboronate having a chiral protected allylic alcohol were successfully accomplished with vinylic iodides under aqueous conditions in 60-90% yield [30]. In addition, an exceptionally simple and efficient synthesis of a prostaglandin (PGEj) precursor was reported by Johnson, applying a DMF/THF/ water solvent mixture with a bis(diphenylphosphino)ferrocene palladium catalyst [31]. It is curious that the presence of water is an absolute necessity in order to succeed in this approach (Scheme 3). 

Allylic alcohols. Alkenes can be converted regio- and stereoselectively into 2-alkene-l-ols by hydrogen—metal exchange to give an alkenylpotassium followed by reaction with this borane. The allylic alcohol is obtained on oxidation of the boronic ester intermediate. 

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