Homoallyl cleavage

It should be noted that the Grob fragmentation reaction and the reductive cyclization (homoallylation) discussed in this section involve the same oxanickellacyclopentane 66 as a common intermediate (Scheme 17). The reversibility of these C - C bond cleavage reaction and C - C bond formation reaction is also supported by the isolation and characterization (by X-ray analysis) of an oxanickellacyclopentane-like 66 (without a tether), which is prepared from a stoichiometric amount of Ni(cod)2, a diene, an aldehyde, and a monodentate phosphine ligand [41]. 

With the aid of BF3 OEt2, methoxyborolane (R,R)-114 reacts with (.E)- or (Z)-crotylpotassium to provide (is,R,R)-115 and (Z,R,R)-115, respectively. After adding the aldehyde to a solution of crotyl-borolane in THF at —78°C for 4 hours, 2-aminoethanol is added. The solution is warmed to room temperature, and oxidative cleavage at this point gives the homoallylic alcohols with high stereoselectivity. The borolane moiety can be recovered by precipitating it as an amino alcohol complex and can be reused without any loss of enantiomeric purity. As shown in Scheme 3-43, the (.E)- and (Z)-crotyl compounds lead to anti- and -products 116, respectively. The diastereoselectivity is about 20 1, and the ee for most cases is over 95% (Table 3-11). 

Intramolecular hydrosilylation.1 Hydrosilylation of internal double bonds requires drastic conditions and results in concomitant isomerization to the terminal position. However, an intramolecular hydrosilylation is possible with allylic or homoallylic alcohols under mild conditions by reaction with 1 at 25° to give a hydrosilyl ether (a), which then forms a cyclic ether (2) in the presence of H2PtCl6-6H20 at 60°. Oxidative cleavage of the C—Si bond results in a 1,3-diol (3). 

Homoallyl ethers or sulfides.1 gem-Methoxy(phenylthio)alkanes (2), prepared by reaction of 1 with alkyl halides, react with allyltributyltin compounds in the presence of a Lewis acid to form either homoallyl methyl ethers or homoallyl phenyl sulfides. Use of BF3 etherate results in selective cleavage of the phenylthio group to provide homoallyl ethers, whereas TiCl effects cleavage of the methoxy group with formation of homoallyl sulfides. 

P-Cleavage of homoallylic alcohols.1 Homoallylic tertiary potassium alkox-ides undergo cleavage in HMPT (or DMF) of the allylic C—C bond to give the enolate of a ketone (equation I). A rigid bicyclic system is not essential for the cleavage. 

Bis(homoallylic) alkoxides also undergo this 3-cleavage. The substrates (1) are available by reaction of a methyl carboxylate with 2 equiv. of allyl- or methallyl-magnesium chloride. The alcohols when heated at 80° in a slurry of KH in HMPT are converted into 3.7- and a,3-unsaturated ketones (2 and 3) in 75-85% yield. 

KH/HMPT is also useful for selective 3-cleavage of tris(homoallylic) alcohols, as shown by a new synthesis of a-damascone (4). In general, l,l-dimethyl-2-pro-penyl and benzyl groups are cleaved more readily than a l-methyl-2-propenyl group,... 

Resin 60 was successively treated at -78 °C with n-BuLi, ClTi(NEt2)3, and benz-aldehyde in THF to afford the polymer-bound homoallyl alcohol 61. The cleavage of the linker group of 61 was achieved through treatment with ClC02CH(Cl)Me in CH2CI2 at room temperature. Thereby a mixture of chlorohydrins syn-57 and anti-57 in a ratio of 2 1 was obtained. These chlorohydrins were treated with DBU, which gave oxiranes trans-SS and cis-58 in a ratio of 2 1 in an overall yield of 34% based on sulfoximine 12. 

Ring-cleavage reactions of cyclobutylmethyl compounds via bomoallylic carbanions have been reported.23,24 The reaction was denoted as a y-homoallylic rearrangement 25 and occurs with H-shift. 

The electrochemical allylation of carbonyl compounds by electroreductivc regeneration of a diallyltin reagent from allyl bromide and a Sn species leads to formation of homoallylic alcohols in yields of 70-90 % even in methanol or methanol/water (Table 7, No. 12) Bisaryl formation is possible also from aryl iodides or bromides in the presence of electro-generated Pd phosphane complexes (Table 7, No. 13) In the presence of styrenes, 1,3-butadienes, or phenyl acetylene the products of ArH addition are formed in this way (Table 7, No. 14) . The electroreductivc cleavage of allylic acetates is also possible by catalysis of an Pd°-complex (Table K No. 15)... 

Cleavage of homoallyl ethers 2,4-dienols.1 3,6-Dihydro-2H-pyrans are cleaved to (Z)-2,4-pentadienols by this combination of bases in 35-75% yield. Example ... 

The same cleavage is observed with acyclic homoallyl ethers. Example ... 

Fragmentation of homoallylic aikoxides.3 Thermolysis of homoallylic alcohols requires temperatures >200°. However, fragmentation of bicyclo[2.2.2]-5-octene-2-alkoxides (1) prepared as shown in equation (I), occurs at 90-120° and results mainly in unsaturated ketones (2) formed by cleavage of the allylic (C -C2) bond. Although the exo-alkoxide is cleaved noticeably faster than the endo-cpimer, both aikoxides give the same product. 

Selective cleavage of 2-methoxyethyl hemiacetats. 2-Methoxyethyl hemiacetals react with allyltrimethylsilane in the presence of TiCl4 (1 equiv.) to give a homoallyl ether with selective cleavage of the 2-methoxyethoxy group (cf, 7,370-371).8 Examples ... 

Interestingly, the use of optically active alcohol 51 in this protocol leads, after cleavage of the benzylic ether in the initial adduct 52, to the enantiomerically enriched homoallylic alcohol 26. This approach appears to be the first asymmetric preparation of homoallylic alcohols via open-chain acetal derivatives (Scheme 13.19). 

Since 1995, Tietze et al. [26-32] have studied the use of norpseudoephedrin derivative 61 as a chiral auxiliary in order to perform a diastereocontrolled SMS reaction. Further cleavage of the benzylic ether bond of 62 by Na/NH3 led to optically active homoallylic alcohol 26 with good yields and selectivity (Scheme 13.25). 

The following reactions proceed with the participation of the allylic boron system (i) allylboration and protolytic cleavage of organic compounds with multiple bonds, (ii) allylboron-alkyne condensation,598 599 (iii) reductive mono-and trans-a,a -diallylation of nitrogen aromatic compounds, (iv) disproportionation processes between tribut-2-enylborane and BX3 (X = C1, Br, OR, SR). Allylboration of carbonyl compounds, thioketones, imines, or nitriles leads to the homoallylic alcohols, thiols, or amines (Equations (136) and (137). It is most important that 1,2-addition to aldehydes and imines proceeds with high diastereoselectivity so that ( )-allylic boranes and boronates give the anti-products, while -products are formed preferentially from (Z)-isomers. 

Another synthetic application of Roush s crotylboration methodology using a (Z)-crotylboronate can be found in the formal synthesis of (+)-discodermolide (75)29 (Scheme 3.1z). The aldehyde (S)-67, which was prepared from the Roche ester, reacted with (Z)-crotylboronate (S,S)-43Z to give the syn-homoallylic alcohol 76. Silylation of alcohol and oxidative cleavage of the alkene 77 provided the aldehyde 78, from which the final product (75) can be synthesized according to a known procedure.30... 

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