Anti-allylsilane

The same reaction was studied by Roush et al. [50]. However, in this case, the cyclization of anti-allylsilane 126 resulted in the production of only cis-2,6-disubstituted dihydropyrans 127. No trans-2,6-disubstituted dihydropyrans 128 were formed. Moreover, significant amounts of adducts 129 and 130 were observed (Scheme 13.45). These products probably originate from a side-chain exchange process (vide infra). 

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. 

Tricyclic compounds can be obtained directly by annulation on to cyclic allylsilanes, using either ethylaluminum dichloride or titanium(IV) chloride as Lewis acids57. The stereochemical outcome of this particular cyclization is controlled by the relative configuration of the cyclic allylsilane. The reaction follows the usual anti" SE2 process for reactions of allylsilanes with electrophiles. Thus, the reaction was stereospecific, which makes it very useful for stereocon-trolled syntheses of complex ring systems57. 

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. 

The addition reaction of allylsilane to acetaldehyde with BF3 as the Lewis acid has been modeled computationally.95 The lowest-energy TSs found, which are shown in Figure 9.2, were of the synclinal type, with dihedral angles near 60°. Although the structures are acyclic, there is an apparent electrostatic attraction between the fluorine and the silicon that imparts some cyclic character to the TS. Both anti and syn structures were of comparable energy for the model. However, steric effects that arise by replacement of hydrogen on silicon with methyl are likely to favor the anti TS. 

Fig. 9.2. Most favorable transition structures for reaction of allylsilane with acetaldehyde-fluoroborane (left) anti synclinal (right) syn synclinal. Reproduced from J. Am. Chem. Soc., 119, 12131 (1997), by permission of the American Chemical Society.

The mechanism of this new reaction is shown in Scheme 14. Coordination of the diene to palladium(II) makes the diene double bond electrophilic enough to be attacked by the allylsilane. The attack by the allylsilane takes place on the face of the diene opposite to that of the palladium (anti). This is the first example of an anti attack by an allylsilane on a 7T-(olefin)metal complex. Benzoquinone (BQ)-induced anti attack by chloride ion produces the product 58. 

The bromoallene (-)-kumausallene (62) was isolated in 1983 from the red alga Laurencia nipponica Yamada [64a], The synthesis of the racemic natural product by Overman and co-workers once again employed the SN2 -substitution of a propargyl mesylate with lithium dibromocuprate (Scheme 18.22) [79]. Thus, starting from the unsymmetrically substituted 2,6-dioxabicyclo[3.3.0]octane derivative 69, the first side chain was introduced by Swern oxidation and subsequent Sakurai reaction with the allylsilane 70. The resulting alcohol 71 was protected and the second side chain was attached via diastereoselective addition of a titanium acetylide. The synthesis was concluded by the introduction of two bromine atoms anti-selective S -substitution of the bulky propargyl mesylate 72 was followed by Appel bromination (tetrabromo-methane-triphenylphosphine) of the alcohol derived from deprotection of the bromoallene 73. 

The C-glycosylation of pentose glycals with silylacetylenes or allylsilanes through oxocarbenium ion intermediates proceeds with high regio- and stereo-selectivity, giving the 1,4-anti compounds as the main products. ... 

Additions to carbon-carbon multiple bonds initiated by electrophiles are generally governed by the Markovnikov rule. However, the rule must be modified to accom-ipodate such substrates as vinylsilanes. The so-called anti-Markovnikov hydro-halogenation [105] is to be contrasted to the Markovnikov addition for allylsilanes. In fact, when one recognizes the acceptor role of the silicon atom and applying the polarity alternation rule, the puzzling results become self-consistent. 

The Lewis acid catalyzed conjugate addition of allylsilanes (140) to (142) and allylstannanes (154) and (155) to ot,0-enones, described by Sakurai,68a,68b is highly efficient and experimentally simple in contrast to the allylcuprate additions. Various substituents can be incorporated into the allylsilanes (allylstannanes), e.g. alkoxy, alkoxycarbonyl and halogen, some of which are incompatible with cuprate reagents 69 In addition, Heathcock and Yamamoto report that diastereoselectivity is correlated to the alkene geometry of both the allylmetals and the acceptor units for example, allylation of ( )-enones (143) and (146) affords predominantly the syn adducts (144) and (147), while (Z)-enone (149) gives predominantly the anti adduct (150 Scheme 25).680 On the other hand, with cyclohexen-2-one the (Z)-silane (141) affords predominantly the threo adduct (152), while (142) affords erythro adduct (ISS).686 The more reactive allylstannanes (154) and (155) also afford similar diastereoselectivity.68e,f... 

In most cases, open-chain allylsilanes react with electrophiles with anti stereoselectivity156-162. The simple explanation for this observation follows from the probable conformation of the allylsilane. The preferred conformation 129 will have the small substituent H eclipsing the double bond. 

Treatment of vinylsilane epoxides with nucleophiles followed by acid promoted anti-elimination or base-promoted syn elimination gives the corresponding Z- or E-alkenes 174, respectively (equation 148)262,263. A similar approach has been employed for the synthesis of exo-brevicomin 175 (equation 149)264. Allylsilanes are obtained stereoselectively under similar conditions when Li2Cu(CN)(CH2SiMe3)2 is employed as the nucleophile265. 

Claisen-Ireland rearrangement of 239 followed by DIBALH reduction gives a mixture of syn and anti isomers 240 (equation 194)34-347. In a similar manner, orthoester Claisen rearrangements of 241 give stereoselectively the corresponding chiral allylsilanes 242 (equation 195)348. 

The chiral allylsilanes (3b) were used to determine the stereochemistry of the electrophilic substitution reactions (SE1). Typical results are shown in equations (II) it rid (III). The (Z)-allylsilanes give products of (R)-configuration and the (E)-allylsilanes give the (S)-isomers. In each case, the electrophile attacks the double bond anti to the leaving group.6... 

This side reaction, which complicates the condensation of allylsilanes anti-126, was suppressed by using a-acetoxy acetals such as anti-131 as the oxonium cation precursor. Under these conditions, the desired cis-2,6-disubstituted dihydropyran 132 was isolated in moderate yields but high diastereoselectivity (dr = 94 6 Scheme 13.46). 

Diastereoselective reaction of allylsilanes with o-amino aldehydes. The dia-stereoselectivity of the reaction of allylsilane with the protected a-amino aldehyde 1 depends on the quantity of TiCl4 used. Thus anti-selectivity predominates when 1 equiv. of TiCU is used, but syn-selectivity obtains with less than 1 equiv. The a-amino aldehyde 3 shows syn-selectivity with stoichiometric or catalytic amounts of TiCU. These results suggest that aldehydes such as 1 can form both 1 1 and 2 1 complexes with TiCU-... 

The /3-lactone was formed by the cyclization of a 3-hydroxycarboxylic acid with sulfonyl chloride. An alternative synthesis attempted to control all stereochemical relationships in the molecule using the properties of silyl moieties attached to substrates and reagents <20040BC1051>. Stereoselective reactions of this type included the use of silyl groups in enolate alkylations, hydroboration of allylsilanes, and an anti Se2 reaction of an allenyl silane with an aldehyde and ry -silylcupration of an acetylene. The /3-lactone was again formed by the standard sulfonyl chloride cyclization method. 

This outcome is rational since the (/ )-allylsilanes 74 and 75 are expected to exist in conformation 78 (Scheme 11), in which the C-Si bond overlaps with the Jt bond. This conformation maximizes the ct-tc interaction between the C-Si bond and the 7t system84 (see also later section on allylsilanes). Attack of the electrophile from the opposite face to the trimethylsilyl group in 78 gives the carbenium ion intermediate 79, which is stabilized by a interaction with the C-Si bond substituent12,37,38 loss of silicon from this intermediate gives the E olefin products. Anti selectivity has also been observed in the trifluoroacetolysis of 2-cyclohexenyl-silanes, germanes, and stannanes.85... 

The effects of the cr—JT interaction on the ground-state properties of allyltrimethylmetal compounds are paralleled by the effect on reactivity towards electrophilic reagents. Mayr demonstrated that allyltrialkylsilanes, allyltrialkyl-germanes, and trialkylstannanes react with diphenylcarbenium ions at rates 105,5.6 x 105, and 109, respectively, relative to propene.158 The reaction rates were also found to be sensitive to the inductive effects of the other substituents attached to the metal. A theoretical evaluation of the factors determining the regiochemistry and stereochemistry of electrophilic addition to allylsilanes and other allyl systems is reported by Hehre et al.159 They predict a preference for electrophilic attack anti with respect to the silane substituent, a prediction that is supported by many experimental studies.82,160... 

The allylation reaction between ketones and allylsilanes was achieved in 2005. Yamamoto and Wadamoto developed the asymmetric allylation reaction in the presence of AgF-Difluorphos (Scheme 9.6).12 The reaction of ketones and allyltrimethoxysilane in the presence of AgF and Difluorophos afforded the corresponding tertiary homoallyhc alcohols with high enantioselectivities. Additionally, a,(3-unsaturated ketones could be used as substrates, and this catalytic system could be applied for the asymmetric crotylation reaction to obtain anti adducts preferentially (Schemes 9.7 and 9.8). When a,p-unsaturated ketones were used as substrates, 1,2-addition products were obtained exclusively. As described before, the anti adducts were obtained predominately, regardless of the geometry of crotyltrimethoxysilane. 

Chiral (acyloxy)borane (CAB) is known as an effective chiral Lewis acid catalyst for enantioselective allylation of aldehydes. Marshall applied the CAB complex 1 to the addition of crotylstannane to achiral aldehydes and found that the CAB catalyst gives higher syn/anti selectivity than BINOL/Ti catalysts in the reaction [4]. CAB complex 2 was utilized in asymmetric synthesis of chiral polymers using a combination of dialdehyde and bis(allylsilane) [5] or monomers possessing both formyl and allyltrimethylsilyl groups [6]. 

AUylsilanes. The Se2 reaction of the cuprate (2) derived from 1 with tertiary allylic acetates results in stereospecific anti-reaction to provide allylsilanes. Similar stereospecificity is observed in reaction of 2 with propargyl acetates to form allenylsilanes. Examples ... 

Epoxidation of the allylsilane (14) is diastereospecific (equation 6). The favored confonnation of (14) is (14a) the peroxy acid approaches the double bond horn the face anti to the bulky silyl group. The epoxides (16) and (17) obtained from the acetonide (15 equation 7) can be readily separated in gram quantities using standard chromatographic techniques. The presence of the conformationally rigid acetonide moie in the epoxides (16) and (17) facilitates their separation the corresponding epoxy diols cannot be separated by chromatography. The racemic epoxide (19), an intermediate for the synthesis of maytansine has been synthesized from (18 equation 8)."... 

There thus exists a preference for anti (or antara) hydroxylation in these cyclohexenylstannanes, where electrophilic substitutions are known to proceed faitiifully with allylic rearrangement. A more likely padiway is shown in Scheme 4, which is supported by results with optically active allylsilanes, whidi require anti attack by MCPBA on the silane conformation maximizing C—Si tr nr interaction. 

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