Allylsilanes stereoselection

Synthesis of Allylsilanes. TMSCu reacts with a variety of allylic substrates to form allylsilanes stereoselectively and in good to excellent yields. Thus the reagent reacts readily with primary allylic halides, " sulfonates from secondary and tertiary alcohols, and primary and secondary allylic phosphates to yield a variety of allylsilanes. Representative examples of these reactions are shown in eqs 1-3. This methodology seems particularly attractive for the S3Uithe-sis of 3-trimethylsilyl-l-alkenes which are presently unavailable... 

The diastereoselectivity of these reactions was initially explained in terms of acyclic, an-tiperiplanar transition states23, although a synclinal process has since been proposed on the basis of the stereoselectivity of Lewis acid induced intramolecular allylsilane- aldehyde cycliza-tions56. 

The reaction between a-alkoxyaldehydes and allylsilanes is highly stereoselective in favor of chelation-controlled products if tin(IV) chloride is used as the Lewis acid, whereas boron trifluoride gives modest stereoselectivity in favor of the nonchelation-controlled product58. 

Chelation control has been invoked to explain the stereoselectivity of the reaction between 2-methoxycyclohexanone and trimethyl(2-propenyl)silane promoted by titanium(IV) chloride59, and has been observed for addition of allylsilanes to a-amidoaldehydes60, although the stereoselectivity is very dependent upon the amount of Lewis acid used and the structure of the substrate, particularly when the Lewis acid can bind to more than one site61. 

Of particular interest are reactions between a-hydroxy ketones and allyl(trifluoro)silanes which proceed with participation of the hydroxy group via a pentacoordinated allylsilane, with intramolecular delivery of the allyl group to the ketone. Excellent stereoselectivity is obtained at up to three contiguous stereogenic centers66. 

Chelation control of the intramolecular reaction between an allylsilane and an aldehyde or ketone has been carefully investigated. Excellent stereoselectivity was found for cyclization of B-oxo esters using titanium(IV) chloride as the Lewis acid, less good selectivity for cyclization of /l-diketones70. 

Optically active (Z)-l-substituted-2-alkenylsilanes are also available by asymmetric cross coupling, and similarly react with aldehydes in the presence of titanium(IV) chloride by an SE process in which the electrophile attacks the allylsilane double bond unit with respect to the leaving silyl group to form ( )-s)vr-products. However the enantiomeric excesses of these (Z)-allylsilanes tend to be lower than those of their ( )-isomers, and their reactions with aldehydes tend to be less stereoselective with more of the (E)-anti products being obtained74. 

The addition of 2-propenyltris(diethylamino)titanium to 2-(dibenzylamino)alkanals, readily prepared from amino acids, yields the anti-amino alcohols with high stereoselectivity and free of racemization91. Allylsilanes, with Lewis acids under the conditions of chelation control, lead to the iyn-diastereomers91. 

The amidoalkylation of certain allylsilanes with a glycine cation equivalent shows low stereoselectivity 84. 

The stereoselectivity is higher, however, in the amidoalkylation of the allylsilane 4 only one isomer, of unknown configuration, is observed85. 

In the intramolecular amidoalkylation of certain (Z)-allylsilanes, piperidine derivatives (n = 2) are formed less stereoselectively than the corresponding pyrrolidines (n = 1). The complete regiocontrol is induced by the /3-effect of the silicon atom. 

An example of a completely stereoselective cyclization of an allylsilane, leading to a seven-mem-bered ring in excellent yield, is known158. Treatment of the hydroxy compound with methanesulfonyl chloride and triethylamine in acetonitrile gives a single isomer of the bicyclic compound via cyclization of the (T )-iminium ion. 

The results described can fully explain the stereoselectivity observed in the titanium(IV) chloride promoted additions of allylsilanes. In all cases, the additions of the allylsilanes followed the stereoelectronically favored pathway. 

The stereoselective addition of allylsilanes to enones was used to control the relative C-3-C-5 configuration in total syntheses of lycopodium alkaloids and of fawcettimine29,30. 

Stereoselective Ring Annulations by Intramolecular 1,6-Addition of an Allylsilane Function... 

Extensive studies (/ /) of such SE- reactions of allylsilanes have demonstrated a high degree of anti stereoselectivity with the majority of electrophiles, except in cases where steric effects play a dominant role. 

Intermolecular allylation of aldehydes with 1 -trialkylsilyl-1,3-dienes 22 in the presence of a stoichiometric amount of triethylsilane and a catalytic amount of Ni(cod)2 and PPI13 shows novel regio- and stereoselectivity (Scheme 6) [20-22], When a toluene solution of a 1-silyl-1,3-diene and an aldehyde is refluxed in the presence of trialkylsilane under the catalysis of Ni(cod)2 and PPh3, ( )-allylsilane (E)-23 is obtained exclusively. On the other hand, when the reaction is carried out in THF upon heating at 50 °C as... 

Recently, a new multicomponent condensation strategy for the stereocontrolled synthesis of polysubstituted tetrahydropyran derivatives was re-published by the Marko group, employing an ene reaction combined with an intramolecular Sakurai cyclization (IMSC) (Scheme 1.14) [14]. The initial step is an Et2AlCl-promoted ene reaction between allylsilane 1-50 and an aldehyde to afford the (Z)-homoallylic alcohol 1-51, with good control of the geometry of the double bond. Subsequent Lewis acid-media ted condensation of 1-51 with another equivalent of an aldehyde provided the polysubstituted exo-methylene tetrahydropyran 1-53 stereoselectively and... 

Substituted (5R,6A,)-6-(dimethyl(phenyl)silyl)-2-phenyldihydropyrazolo[l,2- ][l,2,4]triazole-l,3(2//,5//)-dione 716, synthesized via the [3+2] annulation of a-substituted allylic silanes 715 with PTAD, were oxidized to the corresponding hydroxy substituted urazoles 717. This work shows that allylsilanes with a single substituent at the allylic carbon undergo exclusive stereoselective [3+2] annulation (Scheme 114) <2007TL6671>. 

An interesting application of the cydization of alkenyl thioacetals is the stereoselective preparation of olefmic diols. Thus, oxidative cleavage of the silicon—carbon bond [32] in the ring-closed metathesis products, i.e. cyclic allylsilanes such as 35 and 36, affords (Z)-alk-2-ene-1,5-diols 37 and 38 (Scheme 14.18) [33],... 

Another interesting example of a photochemi-cally induced domino process is the combination of the photocyclization of aryl vinyl sulfides with an intramolecular addition as described by Dittami et al. [901 as intermediate a thiocarbonyl ylide can be assumed. The domino-Norrish I-Knoevenagel-allyl-silane cyclization developed by us allows the efficient stereoselective formation of 1,2-trans-subsituted five- and six-membered carbocycles.1911 A photochemical cycloaddition of enamino-aldehydes and enamino-ketones with the intermediate formation of an iminium salt followed by addition to allylsilanes gives access to novel bicyclic heterocy-des. New examples of photochemically induced... 

Pyrrolo[l,2-c][l,3]oxazin-l-one 248 has been obtained by reaction of allylsilanes with a pyrrolidine-lV-acyliminium ion 247 (Scheme 32), formed by addition of a Lewis acid on compound 244. The /3-silyl carbocation formed by the reaction with allylsilane 246 reacted with the oxygen of the N-15OC group followed by the loss of 2-methylpropene. The reaction was not very stereoselective when trimethylsilane was used, whereas with larger group on the silicon the selectivity was increased <1997J(P1)2163>. 

Fig. 43 Stereoselective intramolecular coupling of enolether with allylsilane [201, 202].

The class of 3-silyl-substituted reagents provides, upon addition with aldehydes, allylic silanes that offer many options for further derivatization. Oxidative processes are described in previous sections (see the sections on Preparation of 1,2-Diols and 1,4-Diols). If the appropriate silicon substituents are chosen, formal [3+2] cycloadditions with aldehydes can be promoted under Lewis acid catalysis. For example, the mismatched addition of the Z-3-propyl-3-benzhydryldimethyl allylsilane 183 to an a-benzyloxy aldehyde proceeds with low diastereofacial selectivity in favor of product 184 however, after protection of the secondary alcohol, an efficient [3+2] annulation provides the polysubsubstituted furan 185 in good yield and acceptable stereoselectivity (Scheme 24). ° The latter is brought forward to a tricyclic unit found in the antitumor natural product angelmicin B. 

Maeda K, Shinokubo H, Oshima K (1997) Lewis acid-induced chemo- and stereoselective allylation of a-iodo mixed acetal with allylsilane. J Org Chem 62 6429-6431... 

In a related strategy, the dihydropiperidine skeleton of the macrocyclic alkaloid cannabisativine (208) (Fig. 1.6), isolated from the leaves and roots of the common cannabis plant, was prepared with regio- and stereoselectivity using an intramolecular allylsilane-nitrone cycloaddition reaction as a key step (260). 

The cross-coupling route to allylsilanes is effective with either aromatic or aliphatic a-silylated Grignard reagents16, and palladium catalysts are more reactive and stereoselective than the corresponding nickel complexes. Unsubstituted or i+monosubstituted alkenyl bromides work well but the Z-substituted bromides give lower yields and an inferior enantiomeric excess. The enantiomeric excess increases quite markedly with decreasing temperature, and optimum results are obtained at 0 C or below. 

Scheme 5 Olefin stereoselectivity based on allylsilane substituents.

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