Crotyl silanes

Fig. 5. Synclinal approach of crotyl silanes onto oxocarbenium ions...

In the synthesis shown in Scheme 13.15, racemates of both erythro- and threo-juvabione were synthesized by parallel routes. The isomeric intermediates were obtained in greater than 10 1 selectivity by choice of the E- or Z-silanes used for conjugate addition to cyclohexenone (Michael-Mukaiyama reaction). Further optimization of the stereoselectivity was achieved by the choice of the silyl substituents. The observed stereoselectivity is consistent with synclinal TSs for the addition of the crotyl silane reagents. 

Panek et al. based their total synthesis of (+)-Macbecin I 78 [39], Epothilone A 81 [40, 41] and Rutamycin B 84 [42] on a sequence of SMS reactions using the optically pure crotyl silane 74. This allylsilane is readily obtained by kinetic resolution using a PAK lipase. 

Crotyl silanes are powerful reagents in stereoseleetlve synthesis... 

Crotyl silanes offer the possibility of diastereoselectivity in reactions with aldehydes in the same way as the corresponding boranes. The mechanism is completely different because crotyl trialkylsilanes react via an open transition state as the silicon is not Lewis acidic enough to bind the carbonyl oxygen of the electrophile. Instead, the aldehyde has to be activated by an additional Lewis acid or by conversion into a reactive oxonium ion by one of the methods... 

Better results (80 % ee) have been reported by Mikami, Nakai and co-workers [3c] for the addition of crotyl silane also catalyzed by complex 1. Yamamoto and co-workers [3b] used chiral acyl-oxy boranes to catalyze the Sakurai-Hosomi-reac-tion. While an excellent 96 % ee was obtained for the addition of 2,3 -disubstituted allyl groups, the conversion with parent allyl silane was low (46 %) and the asymmetric induction mediocre (55 % ee). Gauthier and Carreira [5] then made a big leap forward by using the difluorotita-nium-binaphthol complex 3. The catalyst 3 is prepared in situ via the TiF4-binaphthol adduct 4 and formal HF elimination mediated by allyl silane 5. The addition of 5 to aldehydes 6 ( 7) catalyzed by 10 % of 3 proceeds with 61 - 94 % < e and good yields (69-93 %), the best results being observed for aldehydes with tertiary alkyl residues (Scheme 1). 

Key Chemistry Stereoselective Crotylation of Aldehydes with Chiral Crotyl Silanes... 

The reaction of aldehydes 3 with crotyl silanes (e.g. 5) yields 3-methylated homoallylic products such as 6 and 9. Since crotyl silanes are only weak nucleophiles, the carbonyl compound 3 must be activated. This can be done by addition of a Lewis acid (LA) to form the C2ixhony -Lewis acid complex 4. After addition of 5 and aqueous workup, the homoallylic alcohol 6 is obtained. An alkyl-oxo-carbenium ion 8 is available when treating an acetal 7 with acid or when the aldehyde 3 reacts with a silyl ether 10 in the presence of a Lewis or a Brousted acid (multicomponent crotylation). Crotylation of this alkyl-oxocarbenium ion 8 yields homoallylic ethers 9. 

In organic syntheses, good syn/anti diastereoselectivities are important, but it is crucial to use methods to obtain the syn or anti dia-stereomer in its enantiopure form. Panek and coworkers have developed chiral crotyl silanes such as ( S)-12 that show remarkable induced selectivities in crotylation reactions. ... 

High levels of enantioselectivity are achieved when the stereochemistry-inducing group is fixed in the transition state, thereby preventing one side of the molecule from attacking the carboxenium ion. Because of steric and electronic effects, the crotyl silane confor-m ations are stabilized when the dihedral angle between the C-Si bond and the ally lie double bond is about 120°. This structural element is still relevant in the transition state of the attack of 12 to a carboxenium ion such as 4 or 8. Therefore, attack cannot come fi om conformation III, but only from conformations I or II. Conformation II, however, is disfavored over conformation I because of 1,3-allylic strain. The bulky silyl group in conformation I then demands that the attack to the electrophile comes from the opposite si face. 

Here, complex 25 is obtained in the first step. Then, the acetal in 25 is cleaved with BF3 OEt2 to form the corresponding methylaldehyde ion 26 which is attacked by the chiral crotyl silane 12 to form 27 selectively. 

In their 2001 paper, the authors assume that transition state B is the favored transition state leading to the syn product. In that transition state, the carboxenium double bond and the crotyl silane double bond adopt a antiperiplanar orientation. However, the more recent theoretical paper by Tietze et al. suggests that the eclipsed transition state A explains the enhanced diastereoselectivity. 

The two stereogenic centers of the target compound were concomitantly introduced by a diastereo- and enantio selective crotylation technique employing a chiral crotyl silane. The syn/anti selectivity of this reaction was improved dramatically by converting the propargylic starting material into the corresponding hexacarbonyldicobalt complex. 

In contrast with the more reactive crotyl reagents discussed above, crotyl-silanes, -stannanes and -boronates can be prepared in isomerically pure cis and trans forms for use in imine and aldehyde addition reactions. However, isomerization of these reagents under certain reaction conditions, particularly those requiring the presence of Lewis acids, cannot be ruled out. Nonetheless, in connection with a study involving aldehyde additions, Yamamoto et al. have shown that frans-crotyltri-n-butylstannane is stable to BF.vEt20 at -78 C. ... 

An interesting extention of this methodology using chiral crotyl silane 474 produces tetrahydrofurans directly as a result of 1,2-silicon migration and heterocyclization [152]. Under boron trifluoride etherate catalysis (non-chelation controlled conditions), cis-2,5-disubstituted tetrahydrofuran (475) is produced in 50% yield, whereas tin tetrachloride (chelation control) gives the ra 5-2,5-disubstituted tetrahydrofuran (476) in 75% yield. Stereoselectivities in both cases exceed 40 1. 

When the enantiomeric crotyl silane 477 is added to 464 with aluminum chloride catalysis, virtually no tetrahydrofuran products are produced. Instead, octenoic acid derivative 478 (with the syn- diol configuration) is formed as a single diastereomer. 

An unusual case of diastereoselectivity occurs in condensation reactions using jS-methyl crotyl silanes or stannanes. In the absence of a jS-substituent, reaction of 492 with 464 under chelation-controlled conditions gives the expected aW-syn homoallylic alcohol 493 (R=H) as the predominant isomer. However, when a j -methyl group is introduced into 492, the stereochemical outcome of the reaction changes to favor the a /-isomer 494 [157]. 

The o, )-unsaturated ester 7 can be transformed reductively into the p,Y-unsaturated system 8 in high yield using magnesium in methanol J Reaction of the chiral crotyl silane 9 with various aldehydes and acetals offers a diastereoselective approach to branched P,Y-unsatuiated esters, as in the example in Scheme 2, and, as indicated, stereospecific allylic rearrangement gave the a,p-unsaturated system. Similar reactions were also described using the C-2 epimer of 9. ... 

Nucleophile = Allyl/crotyl silanes, Allyl/crotyl stannanes, Silyl enol ethers, Silyl ketene acetals, Silyl hydrides. Metal cyanides. Alkyl zincs... 

FIGURE 10.9. Examples of enantiomerically pure allyl and crotyl silanes. 

---