Allylic halides, diastereoselective

C-Alkylations of l,4-dihydro-27/-pyrazino[2,l-A]quinazoline-3,6-diones at positions C-l and CM were studied in detail. Compounds of type 57 could be alkylated diastereoselectively at C-l, owing to the geometry of the piperazine ring, which is locked in a flat boat conformation with the R4 or R1 substituent in a pseudoaxial position to avoid steric interaction with the nearly coplanar C(6)-carbonyl group. Alkylation of 57 (R2 = Me, Bn, R4 = Me) in the presence of lithium hexamethyldisilazide (LHMDS) with benzyl and allyl halides resulted, under kinetic control, in the 1,4-trans-diastereomer 59 as the major product, with retention of the stereocenter at CM (Scheme 5). 

Allylic chromium species can also add to aldehydes. In this regard, an efficient catalytic enantioselective variant using allylic halides as substrates and manganese as co-oxidant has been described recently (Eq. 117). This method provides high enantiomeric excesses in the simple allylation of a wide range of aliphatic, aromatic, and heteroaromatic aldehydes. Crotylation examples are also very enantioselective, albeit with modest anti/syn diastereoselectivity. 

As shown in equation 53, when the zincated hydrazone, prepared from hydrazone by treatment with 2 equivalents of f-butyllithium and zinc(II) bromide, is treated with alkenylborane, the a-borylorganozinc is obtained with high diastereoselectivity. This pseudo-gem-dimetal species reacts with allyl halide stereospecifically. Through the transformation, three stereogenic centers are constructed diastereoselectively77. 

SCHEME 38. Threo/erythro diastereoselectivity in the photooxygenation of allylic halides, sulphones, carboxylic acids and esters... 

The products were obtained in satisfactory to good yields (up to 85%) and enantio-selectivity for the trans isomer was up to 90% ee. Diastereoselectivity was high for branched allyl halides, with d.r. (trans/cis) up to >50 1, whereas for unbranched allyl halides the diastereomeric ratio was only modest - 2.3 1 to 2.8 1. Selected examples are shown in Scheme 6.93. The methylallyl iodide or bromide was found to be the preferred allyl halide in terms of diastereoselectivity and enantioselectiv-... 

A second route involves preforming first the allylic halide addition to form the iminium salt arising from the alkylation on the highly nucleophic sulfur atom. Subsequent treatment with triethylamine provided the S-allyl thioimidoester which was usually not observed but underwent a deprotonation and a fast [3,3] sigmatropic transposition to give the a-allyl thioamide. With pyroglutamate derivatives no diastereoselectivity was found. An analogous sequence [197] was used with a thioacyl proline derivative, with some stereoselectivity. 

Stereoselective synthesis of the 1,3-amino alcohol moiety is possible starting from N-tert-butyldimethylsilyloxycarbonyl derivatives of allylic halides 5 through a ScN cyclization. Thus, methyl ( )-2-tm-butyldimethylsilyloxycarboiiylamino-6-chloro-4-hexenoatc (5, R = COOCH3), treated with 2 equivalents of silver fluoride in acetonitrile, gives a mixture of the cis- and trans-tetrahydro-2//-l,3-oxazin-2-oncs 6 in 65% yield, although in moderate diastereoselectivity,9c. 

When dialkylcopperzinc reagents R2CuZnCl couple with allylic halides, almost complete allylic rearrangement occurs (Sn2 )> and the reaction is diastereoselective if the allylic halide contains a 8 alkoxy group. Another type of copper reagent... 

The syn-hydroxy sulphones (280) are available in a highly diastereoselective fashion by the zinc-promoted addition of 2-(phenylsulphonyl)allylic halides to aldehydes. The susceptibility... 

Allylation. Allyl halides are converted to allyltitanium compounds by r-PrMgBr/jr-PrOj Ti, which can be used for allylation of carbonyl compounds and aldimines. With imines derived from a chiral a-phenethylamine, the reaction is highly diastereoselective following the Cram pattern exhibiting a 1,3-asymmetric induction. 

Readily available functionalized aryl siloxanes are also viable cross-coupling partners for Pd(dba)2-catalyzed allylic arylations. A mixture of 5% Pd(dba)2, allylic halide, and in situ-generated aryl zinc reagent produces allylated arenes in high yield. Aryl boronic acids have been converted to allylated arenes as well. Diastereoselective intramolecular Stille-type coupling of two allylic moieties (aUylic acetate and allylic stannane) has been performed in high yield to produce the key intermediate in the synthesis of racemic 10-ep/-elemol (eq 19). ... 

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