1.4-Adducts, lithium reactions give

A study of 1,2-versus 1,4-addition to a series of cyclopenten-l-ones bearing a-donor substituents (X = H, Cl, Br, OMe, pyrrolidin-l-yl, SPh, and SePh) at position 2 has established that MeLi gives 1,2-adducts in 28-75% yield and no 1,4-adduct, lithium dimethylcuprate gives only 1,4-addition (51-76%), and cyanomethyl lithium gives mainly 1,2-adducts (43-60%). Theoretical calculations reveal that the predominance of 1,2-attack in the reactions involving MeLi and cyanomethyllithium cannot be explained by the relative thermodynamic stabilities of the products. 

The stereochemical outcome of the Wittig reaction can depend on the presence or absence of lithium salts. This may be due to a betaine intermediate stabilized by lithium cation. A stable adduct of this type has now been observed during a Wittig reaction. When Ph3P=CH2 is treated with 2,2 -dipyridyl ketone, P NMR shows the formation of an oxaphosphetane (72) and addition of lithium bromide gives the chelation-stabilized betaine lithium adduct (73). 

Stereoselective reaction with ketones. The reaction of ketone 1 with methyl-lithium, trimethylaluminum, and lithium letramethylaluminate shows no stcrco-specificity. The reaction with mcthylmagncsium bromide gives the two possible adducts in the ratio 2.4 1. The best stereospccificity is observed with dimethylsulf-oxonium methylide, which converts 1 into 2 and 3 in a ratio about 5 1. Reduction of the epoxides with lithium triethylborohydride gives the desired tertiary alcohols. This reaction was used in a synthesis of ( ) stemodin (4).2... 

Lithium halocarbenoids are no more subject of mechanistic interest only. Improvement of preparative techniques in the last ten years made them to valuable synthetic intermediates which are stable in the temperature range between —130 and —70 °C. They are generated from readily available starting materials and give high yields of adducts on reaction with electrophiles. 

This more dramatic reaction starts with the simple conjugate addition of the Davies chiral version of LDA 89 to unsaturated esters first given in chapter 24. The lithium amide gives the Z-enolate of the product 90 and hence the adduct 91. The transition state 92 gives the correct stereochemistry.15... 

The reaction of carbonyl groups produces the opposite regioselectivity. The reaction of (41c) with cyclohexanone gives predominantly the a-adduct (a y = 71 29). The lithium salt of the trimethylsilyl derivative (41d) in THF-HMPA produces the a-adduct in reactions with a variety of aldehydes and ketones (98-100% regioselectivity). Mild acid hydrolysis of the product monosilyl ethers affords 3,4-dihydroxy-... 

Methylmagnesium iodide undergoes addition to pyrido[2.3-c/]pyridazine to give a mixture of the 5,6-adduct 9 (20 %) and the 7,8-adduct 10 (80 %). The corresponding reaction with methyl-lithium also gives a mixture of 9/10 in a 40 60 ratio.3... 

Since all the reactions were run in tetrahydrofuran, the fact that three out of four possible products can be generated selectively is solely due to the Lewis acid present While lithium as the countercation leads to the normal Michael adduct 98, titanium gives rise to the corresponding 1,2-adduct 97. Aluminum favors 1,4-addition again but employing the sulfur atom as the nucleophile (99). 

Diastereoselective Mannich reactions may result with TiCU as adjuvant (eq 26) transmetalation of the initial lithium alkoxide adduct and displacement by a lithium enolate gives a diastereos-electivity of 78%. ... 

In view of the facile oxidation of 10.13a-c it is not surprising that some metathetical reactions with metal halides result in redox behaviour. Interestingly, lithium halides disrupt the dimeric structures of 10.13a or 10.13c to give distorted cubes of the type 10.14, in which a molecule of the lithium halide is entrapped by a Ei2[E(N Bu)3] monomer. Similar structures are found for the MeEi, EiN3 and EiOCH=CH2 adducts of 10.13a. In the EiN3 adduct, the terminal... 

Preparation of cholesta-5,7-diene-ia,3/3-diol a solution of 500 mg of the 1,4-cyclized adduct of cholesta-5,7-dien-3/3-ol-ia,2a-epoxideand 4-phenyl-1,2,4-triazoline-3,5-dione in 40 ml of tetrahydrofuran is added dropwise under agitation to a solution of 600 mg of lithium aluminum hydride in 30 ml of THF. Then, the reaction mixture liquid Is gently refluxed and boiled for 1 hour and cooled, and a saturated aqueous solution of sodium sulfate is added to the reaction mixture to decompose excessive lithium aluminum hydride. The organic solvent layer is separated and dried, and the solvent Is distilled. The residue Is purified by chromatography using a column packed with silica gel. Fractions eluted with ether-hexane (7 3 v/v) are collected, and recrystallization from the methanol gives 400 mg of cholesta-5,7-diene-la, 3/3-diol. 

When 2-lithio-2-(trimethylsilyl)-l,3-dithiane,9 formed by deprotonation of 9 with an alkyllithium base, is combined with iodide 8, the desired carbon-carbon bond forming reaction takes place smoothly and gives intermediate 7 in 70-80% yield (Scheme 2). Treatment of 7 with lithium diisopropylamide (LDA) results in the formation of a lactam enolate which is subsequently employed in an intermolecular aldol condensation with acetaldehyde (6). The union of intermediates 6 and 7 in this manner provides a 1 1 mixture of diastereomeric trans aldol adducts 16 and 17, epimeric at C-8, in 97 % total yield. Although stereochemical assignments could be made for both aldol isomers, the development of an alternative, more stereoselective route for the synthesis of the desired aldol adduct (16) was pursued. Thus, enolization of /Mactam 7 with LDA, as before, followed by acylation of the lactam enolate carbon atom with A-acetylimidazole, provides intermediate 18 in 82% yield. Alternatively, intermediate 18 could be prepared in 88% yield, through oxidation of the 1 1 mixture of diastereomeric aldol adducts 16 and 17 with trifluoroacetic anhydride (TFAA) in... 

Tin(Il) shows considerable affinity towards nitrogen, therefore is expected to activate the imino group. The diastereoselective addition of tin(II) enolates derived from thioesters 1 to x-imino-esters 2 is reported12. This reaction proceeds smoothly to afford. vi w-/j-amino acid derivatives 3 (d.r. 95 5) in good yields. Lithium, magnesium, and zinc enolates do not react while titanium enolates give the adducts in low yield with preferential formation of the anti-isomer. 

Addition of 2-butenyl sulfone anions to 2-cyclopentenone and 2-cyclohexenone at low temperatures ( — 85 °C) gives mixtures of y-1, 4- and a-1,2-addition products. When these reactions are warmed to 1 2CC, then y-l,4-addition products predominate7,8. The lithium salts of the a-1,2-adducts rearrange to 1,4-adducts at 0°C. 

The reverse trend is observed with (Z)-enolates. The reaction of the lithium enolate of cyclohexanone with ( )-(2-nitroethenyl)benzene gives a 75 25 mixture of the syn- and anti-adducts. In contrast, the same enolate undergoes addition of ( )-5-(2-nitroethenyl)-l,3-benzo-dioxole to give exclusively the yymaddition product in 93% yield2. 

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