Homoallylic aldehydes

When a y-hydrogen is present, the ring contraction product undergoes in turn ringopening into homoallylic aldehyde, by a thermal homo[1.5]hydrogen shift (cf equation 25) . ... 

Chiral aldehydes react with the allylborane reagent, affording homoallylic aldehydes in high stereoselectivity, via a putative chair-like transition structure. Substituted allyl groups, including 2-haloallyl groups, can also be used to produce a wide array of products. 

The 4-hydroxy-1-alkene (homoallylic alcohol) 81 is oxidized to the hetni-acetal 82 of the aldehyde by the participation of the OH group when there is a substituent at C3. In the absence of the substituent, a ketone is obtained. The hemiacetal is converted into butyrolactone 83[117], When Pd nitro complex is used as a catalyst in /-BuOH under oxygen, acetals are obtained from homoallylic alcohols even in the absence of a substituent at C-3[l 18], /-Allylamine is oxidized to the acetal 84 of the aldehyde selectively by participation of the amino group[l 19],... 

HOFFMAN - YAMAMOTO Stereoselective adylations Synthesis of syn or anti homoallylic alcohols from Z or E crotylboronate and aldehydes (Hoffman) or of syn homoallylic alcohols from crotylstannanes, BF3 and aldehydes (Yamamoto)... 

The regiochemical control of Pd-catalyzed hydnde transfer reacdon is much more effeedve than that of the radical denitradon, as Shown in Eq 7 98 The base-catalyzed reacdon of nitroolefins with aldehydes followed by denitradon provides a new syntbedc method of homoallyl aicohols fEq 7 99 Exomethylene compounds are obtined by denitradon of cyclic allylic nino compounds with PdfO, HGO-,H and Et- N fEq 7 100 ... 

Allylboron compounds have proven to be an exceedingly useful class of allylmetal reagents for the stereoselective synthesis of homoallylic alcohols via reactions with carbonyl compounds, especially aldehydes1. The reactions of allylboron compounds and aldehydes proceed by way of cyclic transition states with predictable transmission of olefinic stereochemistry to anti (from L-alkene precursors) or syn (from Z-alkene precursors) relationships about the newly formed carbon-carbon bond. This stereochemical feature, classified as simple diastereoselection, is general for Type I allylorganometallicslb. 

The surprising selectivity in the formation of 4 and 5 is apparently due to thermodynamic control (rapid equilibration via the 1,3-boratropic shift). Structures 4 and 5 are also the most reactive of those that are present at equilibrium, and consequently reactions with aldehydes are very selective. The homoallylic alcohol products are useful intermediates in stereoselective syntheses of trisubstituted butadienes via acid- or base-catalyzed Peterson eliminations. 

Isopinocampheyl(l-isopinocampheyl-2-octenyl)borinic acid (1), available with a diastereomer-ic purity of approximately 80 85% de, reacts smoothly with aldehydes at —15 °C in tetrahy-drofuran to provide a homoallylic alcohol with 79-85% ee after oxidative workup (30% hydrogen peroxide, 40 °C)6. 

Ally 1(trialky 1)- and allyl(triaryl)stannanes react with aldehydes and electron-deficient ketones on heating to give homoallylic alcohols48, although rather high temperatures are required. 2-Methylene-l,3-bis(tributylstannyl)propane is somewhat more reactive49-50, as are allyltin halides, which can be used in the presence of water51. 

A )-1-Methyl-2-butenylstannanes similarly give ann-homoallylic alcohols on healing with aldehydes, only traces of the sjn-isomers being detected. Moreover, these reactions are highly stereoselective for formation of (Z) double bonds in the products. It would appear that small amounts (ca. 10%) of the (Z)-isomers in the (A)-l-methyl-2-butenylstannanes (see Section 1.3.3.3.6.1.1.2.) do not interfere because they are significantly less reactive17. 

One limitation of these noncatalyzed allyl(trialkyl)- and allyl(triaryl)stannane-aldehyde reactions is the high temperature required unless the aldehyde is activated towards nucleophilic attack. Allyltin halides are much more reactive because of their enhanced Lewis acid character however 2-butenyltin halides show reduced syn I anti selectivity45, and give other products including linear homoallylic alcohols and tetrahydropyrans47. 

Transmetalation to give l-methyl-2-propenylaluminum followed by isomerization to 2-butenyl isomers may be involved in reactions between aldehydes and 2-butenyl(tributyl)-stannane induced by aluminum(III) chloride in the presence of one mole equivalent of 2-propanol. Benzaldehyde and reactive, unhindered, aliphatic aldehydes give rise to the formation of linear homoallyl alcohols, whereas branched products are obtained with less reactive, more hindered, aldehydes66,79. 

Treatment of allyl bromides with the complex obtained from tin(II) chloride and the disodium salt of diethyl 2,3-dihydroxybutanedioate gives an intermediate which reacts with aldehydes to provide homoallylic alcohols with 50-65% ee. Lower enantiomeric excesses were obtained with bulky aldehydes and for allylstannanes with y-substituents. Pentacoordinated allyltin complexes may be involved97. 

The complex 8, formed by the addition of 2-propenylmagnesium chloride to 7, adds to aromatic aldehydes, 1-alkanals, a-branched and unbranched alkanals uniformly from the 7 c-face leading to hoinoallylic alcohols with 88-94% ee35 (Method A). After hydrolytic workup, both components can be recycled. Allyl complexes 10, generated from 9, prefer 67-attack and lead to the ent-homoallylic alcohols with excellent enantioselectivity36 (Method B) (Table 8). 

Coupling to both termini of the 2-methyl-2-propcnyl residue occurs when the complex 5, formed from the iodo compound 4 and stiver tetratluoroborate, is allowed to react with an excess of aldehyde, giving rise to diastcreomerically pure 4-fluoro-2,4,6-trisubstituted tetrahy-dropyrans 617. The details of the reaction and, as well, the origin of stereoselectivity is unclear at present. It would not be surprising if the reaction is restricted to those aldehydes leading in the first step to homoallylic alcohols capable of forming mesomerically highly stabilized carb-enium ions on solvolysis. 

Alternatively, chiral hydrazones can be prepared from chiral aldehydes, e.g., 161, which underwent addition of allyltrichlorosilane in DMF to give the homoallylic hydrazine 162 with high yield and excellent diastereoselectiv-ity [76] (Scheme 25). 

Additions of silylated ketene acetals to lactones such as valerolactone in the presence of triphenylmethyl perchlorate in combination with either allyltrimethylsilane 82, trimethylsilyl cyanide 18, or triethylsilane 84b, to afford substituted cyclic ethers in high yields have already been discussed in Section 4.8. Aldehydes or ketones such as cyclohexanone condense in a modified Sakurai-cyclization with the silylated homoallylic alcohol 640 in the presence of TMSOTf 20, via 641, to give unsaturated cyclic spiro ethers 642 and HMDSO 7, whereas the 0,0-diethyllactone acetal 643 gives, with 640, the spiroacetal 644 and ethoxytrimethylsilane 13b [176-181]... 

A further improvement on the tetrahydropyranol formation was made by using the Amberlite IR-120 Plus resin—an acidic resin with a sulfonic acid moiety, in which a mixture of an aldehyde and homoallyl alcohol in water, in the presence of the resin and under sonication, yielded the desired tetrahydropyranol derivatives.111... 

Indium-mediated allylation of an unreactive halide with an aldehyde132 was used to synthesize an advanced intermediate in the synthesis of antillatoxin,133 a marine cyanobacteria (Lyngbya majus-cula) that is one of the most ichthyotoxic compounds isolated from a marine plant to date. In the presence of a lanthanide triflate, the indium-mediated allylation of Z-2-bromocrotyl chloride and aldehyde in saturated NH4C1 under sonication yielded the desired advanced intermediate as a 1 1 mixture of diastereomers in 70% yield. Loh et al.134 then changed the halide compound to methyl (Z)-2-(bromomethyl)-2-butenoate and coupled it with aldehyde under the same conditions to yield the desired homoallylic alcohol in 80% yield with a high 93 7 syn anti selectivity (Eq. 8.55). 

B. Potassium allyl- and crotyltrifluoroborates undergo addition to aldehydes in biphasic media as well as water to provide homoallylic alcohol in high yields (>94%) and excellent diastereoselectivity (dr >98 2). The presence of a phase-transfer catalyst (e.g., B114NI) significantly accelerates the rate of reaction, whereas adding fluoride ion retards the reaction (Eq. 8.70).165 The method was applied to the asymmetric total synthesis of the antiobesity agent tetrahydrolipstatin (orlistat).166... 

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