Allylic hydride addition

Each subunit was constructed by a phosphate-mediated desymmetrization of 24, followed by the aforementioned CM and allylic phosphate displacements. The C1-C14 subunit was envisioned to have the C1-C6 side chain appended via CM to yield advanced intermediate 40 from R,R,Ps)-26. Subsequent regioselective hydrogenation of the C5 - C6 olefin and regioselective Pd(0) -mediated allylic hydride addition (to CIO) would afford a terminal olefin armed for oxidation and subsequent installation of the Cll carbinol center (Scheme 4.15) [7a]. The C15-C30 subunit largely depended on the CM/cuprate approach (Scheme 4.13) and the advanced intermediate 41 would be synthesized from (S,S,Pr)-26 [7bj. 

Introducing Pd(0) to phosphate 44 gave rise to jr-allyl complex 44a (Scheme 4.17). The Pd(0)-mediated allylic hydride addition [26] to phosphate 44 gave the desired regioselectivity of hydride addition at the internal position (CIO) of 44a (regiose-lectivity C10/C12 = 37 1), similar to the previous cuprate additions to 26. Both examples are illustrative of the preference in regioselectivity of allyhc phosphate displacements with the endocyclic n bond. 

Double-bond isomerization can also take place in other ways. Nucleophilic allylic rearrangements were discussed in Chapter 10 (p. 421). Electrocyclic and sigmatropic rearrangements are treated at 18-27-18-35. Double-bond migrations have also been accomplished photochemically, and by means of metallic ion (most often complex ions containing Pt, Rh, or Ru) or metal carbonyl catalysts. In the latter case there are at least two possible mechanisms. One of these, which requires external hydrogen, is called the nwtal hydride addition-elimination mechanism ... 

The proposed mechanism for Fe-catalyzed 1,4-hydroboration is shown in Scheme 28. The FeCl2 is initially reduced by magnesium and then the 1,3-diene coordinates to the iron center (I II). The oxidative addition of the B-D bond of pinacolborane-tfi to II yields the iron hydride complex III. This species III undergoes a migratory insertion of the coordinated 1,3-diene into either the Fe-B bond to produce 7i-allyl hydride complex IV or the Fe-D bond to produce 7i-allyl boryl complex V. The ti-c rearrangement takes place (IV VI, V VII). Subsequently, reductive elimination to give the C-D bond from VI or to give the C-B bond from VII yields the deuterated hydroboration product and reinstalls an intermediate II to complete the catalytic cycle. However, up to date it has not been possible to confirm which pathway is correct. 

In addition, a 532 (visible) or 355 (UV region) nm laser-induced photoisomerization of allylic alcohols to aldehydes catalyzed by [Fe3(CO)i2] or [Fe(CO)4PPh3] was developed by Fan [176]. In this reaction, key intermediates such as the 7i-allyl hydride species [FeH(CO)3(q -C3H3ROH)] (R = H, Me) were detected by pulsed laser FTIR absorption spectroscopy. These results strongly support the 7i-allyl mechanism of photoisomerization of allyl alcohols. 

The most representative results of these additive systems are (1) allyl alcohol seems to inhibit the Si-face attack of the hydride, and (2) allyl bromide inhibits the. Re-face attack. In this system, if it is assumed that CF3 is sterically less demanding than the CH2COCH3 substituent, Prelog s rule holds for the yeast-allyl bromide additive reduction system, whereas it is not followed when the additive is allyl alcohol [26]. 

The two mechanisms may result in substantial and characteristic differences in deuterium distribution. The metal hydride addition-elimination mechanism usually leads to a complex mixture of labeled isomers.195 198 208-210 Hydride exchange between the catalyst and the solvent may further complicate deuterium distribution. Simple repeated intramolecular 1,3 shifts, in contrast, result in deuterium scram-bling in allylic positions when the ir-allyl mechanism is operative. ... 

Reduction with LiAlH(OBu )3293 or LAH292 also gives selective hydride addition to the less substituted allyl end (equations 317 and 318). In contrast, formate reductions selectively deliver hydride to the more substituted allyl terminus (equations 319 and 320).302-303 Si—H-mediated reduction, conveniently performed with polymethylhydrosiloxane (PMHS), demonstrates no clear pattern of regioselectivity (equation 321).320 LiHBEt3 delivers hydride regioselectivity to the less substituted allyl terminus (equation 322)289-291... 

The propargylic alcohol group may be exploited as an allylic alcohol precursor (Eq. 6A.2) and may be generated by nucleophilic addition to an electrophile [25] or by addition of a formaldehyde equivalent to a preexisting terminal acetylene group [26], Once in place, reduction of the propargylic alcohol with lithium aluminum hydride or, preferably, with sodium bis(2-methoxyethoxy)aluminum hydride (Red-Al) [27] will produce the trans allylic alcohol. Alternately, catalytic reduction over Lindlar catalyst can be used to obtain the cis allylic alcohol [28]. The addition of other lithium acetylides to ketones produces chiral secondary alcohols, which also can be reduced by the preceding methods to the cis or trans allylic alcohols. Additional synthetic approaches to allylic alcohols may be found in the various references cited in this chapter. 

The mechanism of the catalytic cycle is outlined in Scheme 1.37 [11]. It involves the formation of a reactive 16-electron tricarbonyliron species by coordination of allyl alcohol to pentacarbonyliron and sequential loss of two carbon monoxide ligands. Oxidative addition to a Jt-allyl hydride complex with iron in the oxidation state +2, followed by reductive elimination, affords an alkene-tricarbonyliron complex. As a result of the [1, 3]-hydride shift the allyl alcohol has been converted to an enol, which is released and the catalytically active tricarbonyliron species is regenerated. This example demonstrates that oxidation and reduction steps can be merged to a one-pot procedure by transferring them into oxidative addition and reductive elimination using the transition metal as a reversible switch. Recently, this reaction has been integrated into a tandem isomerization-aldolization reaction which was applied to the synthesis of indanones and indenones [81] and for the transformation of vinylic furanoses into cydopentenones [82]. 

Isomerization of allylic alcohol to ketone has been extensively studied [13], and two different pathways have been established, including tt-allyl metal hydride and the metal hydride addition-elimination mechanisms [5,14]. McGrath and Grubbs [ 15] investigated the ruthenium-catalyzed isomerization of allyl alcohol in water and proposed a modified metal hydride addition-elimination mechanism through an oxygen-functionality-directed Markovnikov addition to the double bond. 

Related chemistry of a cationic rf-a- yrm Mo(ll) complex is shown in Scheme 28. Hydride addition to the cationic reactant complex gives a neutral allyl-Mo that is oxidized by pyridinum dichromate (PDC) to a cation. Nucleophilic addition of water and oxidative decomplexation of the Mo fragment gives an enone. Substituted a-pyran hgands follow one of two paths depending on the electronic and steric effects of the substituent, as shown. 

Isoxazolines 54, prepared by stereoselective 1,3-DC of nitrile oxides and enantiopure allylic alcohols, were converted into p-amino acids 56 eind 58 by nucleophilic addition to the C=N bond followed by reductive cleavage of the N-0 bond and oxidative cleavage of the diol moiety. The facial selectivity in the nucleophilic addition was dictated by the C-5 substituent in either a directed (hydride addition) or a sterically (Grignard reagents addition) controlled manner <03JA6846>. 

The two established pathways for transition metal-catalyzed alkene isomerization are the jr-allyl metal hydride and the metal hydride addition-elimination mechanisms. The metal hydride addition-elimination mechanism is the more common pathway for transition metal-catalyzed isomerization. In this mechanism, free alkene coordinates to a metal hydride species. Subsequent insertion into the metal-hydride bond yields a metal alkyl. Formation of a secondary metal alkyl followed by y3-elimination yields isomerized alkene and regenerates the metal hydride. The jr-allylhydride mechanism is the less commonly found pathway for alkene isomerization. Oxidative addition of an activated allylic C-H bond to the metal yields a jr-allyl metal hydride. Transfer of the coordinated hydride to the opposite end of the allyl group yields isomerized alkene. 

The fundamental differences between these two mechanisms are that 1) the jr-allyl metal hydride mechanism involves a 1,3-hydrogen shift while the metal hydride addition-elimination mechanism involves a 1,2-hydrogen shift and 2) the hydrogen shift in the Jt-allylhydride mechanism proceeds in an intramolecular fashion while that in the metalhydride addition-elimination mechanism proceeds in an intermolecular fashion. 

Correct reagent selection allowed reduction of steroidal enone (74) to either diastereoisomeric allylic alcohol, uncontaminated by its isomer. Sodium borohydride/cerium chloride in methanol-THF gave the equatorial alcohol (73), while L-selectride produced the axial isomer (75) via equatorial attack (Scheme 12). Unexpected axial attack on diketone (76) to give equatorial alcohol (77 equation 19) led to the proposition that for hydride additions to decalones two 1,3-diaxial interactions override one peri interaction which in turn takes precedence over a single 1,3-diaxial interaction. ... 

This reaction constitutes a special type of process in which a hydrogen atom and a nucleophile are added across the diene with fonnation of a carbon-hydrogen bond in the 1-position and a carbon-Nu bond in the 4-position. Some examples of such reactions are hydrosilylation [12-18], hydrostannation [19,20] amination [21,22], and addition of active methylene compounds [21 a,23,24], These reactions are initiated by an oxidative addition of H-Nu to the palladium(0) catalyst, which produces a palladium hydride species 1 where the nucleophile is coordinated to the metal (Scheme 8-1). The mechanism commonly accepted for these reactions involves insertion of the double bond into the palladium-hydride bond (hydride addition to the diene), which gives a (jr-allyl)palladium intermediate. Now depending on the nature of the nucleophile (Nu) the attack on the jr-allyl complex may occur either by external trans-aVtBck (path A) or via a cw-migration from palladium to carbon (path B). 

Analogous dienyl zirconium compounds can be prepared by addition of unconjugated dienes that contain enol ethers to 105 (Scheme 19).56-58 These reactions are believed to proceed by initial coordination of the terminal olefin followed by isomerization via zirconocene allyl hydride intermediates to eventually yield zirconacyclopentanes that... 

The square planar complex 73 undergoes P-elimination via liberation of L to form a transient equilibrium of the iminium-rhodium hydride o-complex 74a and the Jt-complex 74b, Eq. 16. These complexes 74a and 74b represent a unique nitrogen-triggered mechanism that is different from either the hydride addition-elimination pathway or the 7i-allyl mechanism resulting in the intramolecular 1,3-hydrogen shift. 

Catalytic reduction of pyridinium salts to piperidines is particularly easy in ethanol at room temperature and pressure they are also susceptible to hydride addition by complex metal hydrides or formate, and lithium/ammonia reduction. In the reduction with sodium borohydride in protic media, the main product is a tetrahydro derivative with the double bond at the allylic, 3,4-position, formed by initial hydride addi-... 

The stereoselectivity seen in the reduction of the seven-membered ketone above has proved to be general. This particular result, rationalized by the propensity for pseudoaxial hydride addition under Luche conditions, proved useful in the convergent total synthesis of Gymnocin-A, a polycyclic ether toxin isolated from the red tide dinoflagellate—Karenia mikimotoi.u The Luche reduction was used for the production of allylic alcohol 9 from ketone 8 in 84% yield. Luche conditions were similarly applied to the synthesis of the related polycyclic ether toxin gambierol.12... 

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