Aldehydes allylic stannanes

Cram erythro-products" (G.E. Keck, 1984 A, B, C). [3-(Silyloxy)allyl]stannanes and O-pro-tected a- or y -hydroxy aldehydes yield 1,2,3- or 1,2,4-triols with three chiral centres with high regio- and diastereoselectivity (G.E. Keck, 1987). 

As with the silanes, the most useful synthetic procedures involve electrophilic attack on alkenyl and allylic stannanes. The stannanes are considerably more reactive than the corresponding silanes because there is more anionic character on carbon in the C-Sn bond and it is a weaker bond.156 The most useful reactions in terms of syntheses involve the Lewis acid-catalyzed addition of allylic stannanes to aldehydes.157 The reaction occurs with allylic transposition. 

With chiral aldehydes, reagent approach is generally consistent with a Felkin model.163 This preference can be reinforced or opposed by the effect of other stereocenters. For example, the addition of allyl stannane to l,4-dimethyl-3-(4-methoxybenzyloxy)pentanal is strongly in accord with the Felkin model for the anti stereoisomer but is anti-Felkin for the syn isomer. 

A. y-Oxygen-Substituleel Stannanes. Oxygenated allylic stannanes have been synthesized and used advantageously in several types of syntheses. Both a- and y-alkoxy and silyloxy stannane can be prepared by several complementary methods.177 C-y-Alkoxy and silyloxy allylic stannanes react with aldehydes to give primarily syn... 

Certain S- and e-oxygenated allylic stannanes have been found to transmetallate with SnCU to give chiral pentacoordinated chloro stannane intermediates which add stereos-electively to aldehydes (Scheme 31)74. These reactions proceed with net 1,5-and 1,6-asymmetric induction. 

D. P. Curran, Z. Luo, Rapid, Parallel Synthesis of Homo-allylic Alcohols by Lewis Acid Mediated Allylations of Aldehydes with New Fluorous Allyl Stannanes , Med Chem. Res. 1998, 8,261. 

AT-Boc group, was followed by reductive debenzylation of 30 and Yamaguchi lactonization of the resultant hydroxy acid to provide macrodiolide 31 in 25% yield accompanied by a dimer. Finally, removal of the N-Boc group and reductive N-methylation yielded pamamycin-607 (lb). In total, ca. 40 steps were required to access the target from ester 4, aldehyde 22, and allyl stannanes 10 and ent-lO. 

These reagents are also useful for the preparation of 1,2-diols. Upon exposure to Lewis acids such as boron trifluoride etherate (BFa-OEta), the a-alkoxy and oc-siloxyallyl stannanes undergo a stereospecific, intermolecular 1,3-isomerization to give y-alkoxy- and y-siloxy allylic stannanes.3. .7 When tert-butyldimethylsilyl trifluoromethanesulfonate is substituted for chloromethyl methyl ether in the above procedure, the isomeric -y-siloxy allylic stannane can be obtained directly with no loss of enantioselectivity.6 These stannanes can then be added to various aldehydes to give monoprotected 1,2-diols with high diastereoselectivity.8... 

The effectiveness of various substituted BINOL ligands 12-16 in the Zr(IV)-or Ti(IV)-catalyzed enantioselective addition of allyltributyltin to aldehydes was also investigated by Spada and Umani-Ronchi [21], The number of noteworthy examples of asymmetric allylation of carbonyl compounds utilizing optically active catalysts of late transition metal complexes has increased since 1999. Chiral bis(oxazolinyl)phenyl rhodium(III) complex 17, developed by Mo-toyama and Nishiyama, is an air-stable and water-tolerant asymmetric Lewis acid catalyst [23,24]. Condensation of allylic stannanes with aldehydes under the influence of this catalyst results in formation of nonracemic allylated adducts with up to 80% ee (Scheme 3). In the case of the 2-butenyl addition reac-... 

Elemental antimony is known to mediate the Barbier-type allylation of aldehydes by allylic halides.35 The active intermediates are believed to be allylic antimony(m) species, which are generated from the antimony(O) and the halides. In fact, allylic dichlorostibanes, produced by metathesis of SbCl3 with the corresponding allylic stannanes, react with benzaldehyde to give homoallyl alcohols, where the C-C bond is constructed with -selectivity (Equation (l)).36 Fluoride salts such as KF, NaF, RbF, and CsF accelerate the Sb-mediated Barbier-type allylation with allyl bromide in aqueous media (Equation (2)).37 In the absence of the fluoride ion, no allylation occurs. Although aromatic and aliphatic aldehydes are allylated in good yields by a combined use of Sb-KF, acetophenone, cyclohexanone, and methyl pyruvate remain untouched. 

Indium trichloride-mediated addition of (i )-a-(methoxymethoxy)allylic stannane (>95% ee) to cyclohexanecarbox-aldehyde affords the anti-adduct predominantly (anti syn = 98 2) and stereoselectively (>95%ee) (Equation (12)). Production of a transient allylic indium reagent is postulated via a stereosepecific anti-Se2 transmetallation. This a-(methoxymethoxy)allylic stannane reacts without allylic inversion, whereas the reaction of crotylstannane in Equation (5) (Section 9.14.3.3.1) proceeds with net allylic inversion. <5-Oxygenated allylic stannane also undergoes transmetallation with InCl3, and in situ addition to a-ODPS acetaldehyde leads mainly to the //-adduct, which is a potential precursor to D-(+)-altrose (Scheme 31).149,150... 

Transformations involving chiral catalysts most efficiently lead to optically active products. The degree of enantioselectivity rather than the efficiency of the catalytic cycle has up to now been in the center of interest. Compared to hydrogenations, catalytic oxidations or C-C bond formations are much more complex processes and still under development. In the case of catalytic additions of dialkyl zinc compounds[l], allylstan-nanes [2], allyl silanes [3], and silyl enolethers [4] to aldehydes, the degree of asymmetric induction is less of a problem than the turnover number and substrate tolerance. Chiral Lewis acids for the enantioselective Mukaiyama reaction have been known for some time [4a - 4c], and recently the binaphthol-titanium complexes 1 [2c - 2e, 2jl and 2 [2b, 2i] have been found to catalyze the addition of allyl stannanes to aldehydes quite efficiently. It has been reported recently that a more active catalyst results upon addition of Me SiSfi-Pr) [2k] or Et2BS( -Pr) [21, 2m] to bi-naphthol-Ti(IV) preparations. 

MCPBA oxidation of an allylic stannane is a key stq> in the overall converaon of an a,p-unsaturated aldehyde to an ( )>p-bromo-a-enone, as shown in equation (8). ... 

Optically active allyl stannanes thus obtained were treated with a-alkoxy aldehydes to give useful substrates for the synthesis of carbohydrates13. 

As noted in the introduction, the first addition of an allylic stannane to carbonyl compounds was reported over thirty years ago and involved allyl triethyltin and mainly aromatic aldehydes at elevated temperatures without solvent (Table 1) [1], In these experiments the triethylstannyl ether of the alcohol adduct was isolated by distillation before conversion to the final product. 

Additions of allylic stannanes to aldehydes can also be effected imder high pressure without an added catalyst or promoter [12]. Interestingly, and in apparent contradiction to the thermal additions, mixtures of syn and anti adducts are formed from both (E)- and (Z)-allylic stannanes (Table 3). Moreover, the proportion of (E) syn and (Z) — anti products actually increases as the pressure is increased in contrast with what might have been expected from the thermal reactions. These findings have been interpreted as reflecting reduced activation volumes in the boat vs chair transition states, as illustrated in Eq. (10). The effect is also observed with propanal, 2-ethylbu-tanal, and 2-phenylpropanal. 

The first studies on Lewis acid promotion of allylic stannane additions were conducted with BF3 OEt2 (Table 4) [13]. Aldehydes were found to be more reactive than ketones and methyl ketones were more reactive than internal ketones. Addition to 4-fert-butylcyclohexanone favored equatorial allylation by 85 15. 

In contrast with the thermal reactions, jyn-homoallylic alcohols were found to be the major adducts of both ( )- and (Z)-allylic stannanes (Table 5). These findings were interpreted by assuming an acychc transition state for the addition in which steric interactions between the aldehyde substituent R and the Me substituent of the stannane were the controlling factor (Fig. 1) [14]. An antiperiplanar arrangement was initially proposed, but later work has implicated synclinal arrangements in certain cases. It has also been found that anti products may result as the major or exclusive isomers from such additions. The issue is a complex one and multiple factors, including orbital overlap, may be operative. 

A parallel trend is observed for MgBr2-promoted additions of cis- and trans-crotyl tributylstannanes to a-benzyloxy aldehydes but the effect is much smaller (Table 9) [18], In such reactions the orientation of the allylic stannane and the chelated aldehyde is governed by steric effects in which the vinylic y-hydrogen orients over the five-membered chelate (Fig. 4). Support for this picture is provided by competition experiments in which y3,)8-dimethylallyl tributyltin was found to be markedly slower than the crotyl or allyl derivatives in additions to a-benzyloxypropanal. The observed rate decrease was attributed to the disfavored relationship of a vinylic methyl substituent with the chelate ring resulting in unfavorable steric interactions. 

Several 3,3-disubstituted allylic stannanes were examined in BF3 OEtz-promoted additions to aldehydes [20]. The ( ) isomers afforded mainly the syn adducts whereas the (Z) isomers led to the anti adducts as major products (Tables 10 and 11). These results differ sharply from those obtained with simple 3-substituted allylic stannanes where both ( ) and (Z) isomers tend to favor syn adducts, with exceptions as noted. 

Table 10. Addition of ( )-3,3-disubstituted allylic stannanes to aldehydes promoted by BF3 OEta-...

Both Sc(OTf)3 and Yb(OTf)3 have been employed as Lewis acid catalysts for additions of allylic stannanes to aldehydes. Reactions with the former catalyst can be conducted in a variety of solvents and are not sensitive to water [24]. All four allyl groups of tetraallyltin are consumed in the addition (Table 13). The latter reaction is performed with allyl tributyltin in CH2CI2 (Eq. 16) [25]. 

Bis-pi-allyl Pd and Pt complexes have been found to catalyze the addition of allyl tributyltin to aldehydes [26]. These catalysts are formed in situ from Pd- and PtCl2-phosphine complexes and the allylstannanes (Fig. 7, step 1). The allylation step is depicted as a metallocene reaction of the aldehyde and an his-allylmetal complex (Fig. 7, step 3). The catalyst is regenerated by attack of the allylic stannane on the alcoholate-palladium complex formed in step 3. Representative additions of allyl and methallyl tributyltin to aldehydes with the pi-allyl platinum catalyst are summarized in Table 14. 

When Lewis acids such as SnCU and TiCU are used to promote additions of allylic trialkyltin reagents to aldehydes several reaction outcomes are possible, depending on stoichiometry and the mode of addition. If the Lewis acid is added to the aldehyde followed by the allylic stannane, the typical product (syn for crotylstannanes) derived from an acyclic transition state is formed. If, however, the stannane and Lewis acid are premixed and left to equilibrate, metathesis can occur forming the allylic halome-tal compound which reacts with the subsequently added aldehyde to give products (anti for crotyl) consistent with a cyclic transition state (Eq. 22). The initially formed allylic halostannane gives rise to the linear adduct, but if aldehyde addition is delayed, this initial secondary allylic metal halide can equilibrate to the primary isomer which then reacts with the aldehyde to afford the branched product. 

Table 23. Additions of allylic stannanes to aldehydes promoted by SnCl2.

Additions of Achiral and Racemic Oxygenated Allylic Stannanes to Aldehydes... 

Both a- and y-oxygenated allylic stannanes add to aldehydes under thermal or Lewis-acid-promoted conditions. These reagents are less reactive and more acid-labile than their non-oxygenated counterparts. Consequently, the best results are obtained with relatively reactive aldehydes. Strong Lewis acids cannot be used because they tend to cause decomposition of the stannanes. Initial studies employed thermal conditions to effect the additions. Thus, the frans-a-OMOM crotylstannane, prepared from crotonaldehyde by addition of BuaSnLi and etherification of the alcohol adduct, afforded the anti-(Z) adduct upon treatment with benzaldehyde under reflux in toluene (Eq. 28) [46]. 

Hydrostannation of methoxyallene affords a mixture of cis- and trans-y-methoxy allylic stannanes, among other products [48]. These stannanes can be separated by chromatography. Treatment with aldehydes in the presence of BF3 OEta affords the s yn-l,2-diol methyl ethers as major products (Table 31). Formation of the syn adduct from both the cis and trans allylic stannanes is consistent with an acyclic transition state (see Fig. 1). 

Table 31. BF3-promoted additions of y-methoxy allylic stannanes to aldehydes.

Several racemic a- and /3-oxygenated aldehydes were examined under chelation-con-trolled conditions in which MgBra OEt2 served as the chelating Lewis acid. Reaction of a c -y-OTBS allylic stannane with a-benzyloxybutyraldehyde was highly selective for the syn, syn adduct (Eq. 31). /3-Oxygenated butyraldehydes were somewhat less selective. In these additions, the anti, syn adducts predominated by 4 1 (Table 33). 

Initial efforts in this area involved the addition of BuaSnLi to fratw-crotonaldehyde and conversion of the racemic hydroxy stannane adduct to diastereomeric (-)-menthyloxy-methyl ethers by reaction with (-)-menthyloxymethyl chloride (Eq. 32) [52]. These dia-stereomers could be separated by careful chromatography. They formed diastereomeric anti, (Z) adducts with aldehydes upon heating to 130 °C. The results parallel those seen for the racemic OMOM allylic stannanes (Table 25). Formation of the (Z) double bond in these adducts is attributed to steric interactions between the allylic OR substituent and the adjacent stannane butyl groups in a chair-like transition state as pictured in Eq. (9). The excellent stereoselectivity of these additions is suggestive of a highly ordered transition state. 

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