Enol silanes cyclic

Silyltitanation of 1,3-dienes with Cp2Ti(SiMe2Ph) selectively affords 4-silylated r 3-allyl-titanocenes, which can further react with carbonyl compounds, C02, or a proton source [26]. Hydrotitanation of acyclic and cyclic 1,3-dienes functionalized at C-2 with a silyloxy group has been achieved [27]. The complexes formed undergo highly stereoselective addition with aldehydes to produce, after basic work-up, anti diastereomeric (3-hydroxy enol silanes. These compounds have proved to be versatile building blocks for stereocontrolled polypropionate synthesis. Thus, the combination of allyltitanation and Mukayiama aldol or tandem aldol-Tishchenko reactions provides a short access to five- or six-carbon polypropionate stereosequences (Scheme 13.15) [28],... 

Mikami has carried out a number of investigations aimed at elucidating mechanistic aspects of this Si-atom transfer process. In particular, when the aldol addition reaction was conducted with a 1 1 mixture of enoxysilanes 60 and 62, differentiated by the nature of the 0-alkyl and 0-silyl moieties, only the adducts of intramolecular silyl-group transfer 63 and 64 are obtained (Scheme 8B2.6). This observation in addition to results obtained with substituted enol silanes have led Mikami to postulate a silatropic ene-like mechanism involving a cyclic, closed transition-state structure organized around the silyl group (Scheme 8B2.6). 

Kocienski and coworkers [98] have reported the synthesis of 8-membered cyclic ketones by intramolecular aldol reaction of enol silanes and acetals mediated by Lewis acid. 

Oxazaborolidenes. Corey has reported the use of a novel oxazaborolidene complex 41 prepared from borane and A-tosyl (5)-tryptophan. This complex functions in a catalytic fashion in enantioselective, Mukaiyama aldol addition reactions (Scheme 8-3) [17]. The addition of ketone-derived enol silanes 42-43 gives adducts in 56-100% yields and up to 93% ee. The use of 1-trimethylsilyloxycyclo-pentene 43 in the addition reactions to benzaldehyde affords adducts 46 as a 94 6 mixture of diastereomers favoring the syn diastereomer in 92% ee. Addition reactions with dienol silanes 44 furnishes products 47 in up to 82% ee. Corey also demonstrated the use of these adducts as important building blocks for the synthesis of corresponding dihydropyrones treatment of 47 with trifluoroacetic acid affords the cyclic product in good yields. 

The most intensely studied aldol addition mechanisms are those beUeved to proceed through closed transition structures, which are best understood within the Zimmerman-Traxler paradigm (Fig. 5) [Id]. Superposition of this construct on the Felkin-Ahn model for carbonyl addition reactions allows for the construction of transition-state models impressive in their abiUty to account for many of the stereochemical features of aldol additions [50a, 50b, 50c, 51]. Moreover, consideration of dipole effects along with remote non-bonding interactions in the transition-state have imparted additional sophistication to the analysis of this reaction and provide a bedrock of information that may be integrated into the further development and refinement of the corresponding catalytic processes [52a, 52b]. One of the most powerful features of the Zimmerman-Traxler model in its application to diastereoselective additions of chiral enolates to aldehydes is the correlation of enolate geometry (Z- versus E-) with simple di-astereoselectivity in the products syn versus anti). Consequently, the analyses of catalytic, enantioselective variants that display such stereospecificity often invoke closed, cyclic structures. Further studies of these systems are warranted, since it is not clear to what extent such models, which have evolved in the context of diastereoselective aldol additions via chiral auxiliary control, are applicable in the Lewis acid-catalyzed addition of enol silanes and aldehydes. 

A second distinct process disclosed by Denmark involves the Lewis base-catalyzed addition of enol trichlorosilanes 36 to aldehydes (Eq. 3) [30b]. Remarkably, despite the fact that the imcatalyzed addition of such enol silanes to aldehydes is rapid at -78 C, the use of optically active phosphoramides substantially accelerates the addition reaction and leads to the formation of optically active products. As a consequence of stereochemical studies involving substituted enol trichlorosilanes, Denmark has proposed a hexacoordinated silicon atom as the organizational locus about which enolate and aldehyde are arranged in a cyclic array 37. 

When R3 is replaced by a smaller group, and R2 is large (TMS, Bu1), then both Ai and S.i (gauche interaction between R and R2) are disfavored compared to Si, and the syn isomers are obtained (Table 1 entries 14-17). The same analysis applies to several other cases ketene bis(trimethylsilyl) acetals (R3 = OTMS) are anti selective when R2 is Me (anti 86-89%) and syn selective when R2 is Bu1 (syn 70-89%) 24 silyl ketene acetal (3) derived from butyrolactone is anti (R Ji ) selective when R = H (anti 70%) and syn (R, S ) selective when R = TMS (single isomer, equation 2) 25a c S-trimethylsilyl S,N-acetals (4) are anti selective when R = Me (anti 60-87%) and syn selective when R = Pr (syn 60%, equation 3).22 Cyclic enol silanes usually show poor selectivity,2 1026 apart from isolated cases where good anti. syn ratios were obtained by carefully choosing reagents and Lewis acids. Fair anti preferences were observed with the cyclopentenone-derived silyl enol ether and TiCU (equation 4 R = Pr1, Bn anti (R Ji ) syn(R, S ) >90 10)27 and with 2-trimethylsilyloxyfuran (5 equation 5 anti (R, R ) syn(R, S ) 76—88 24—12).17-27... 

Shibata successfully adapted the asymmetric transfer fluorination to cyclic silyl enol ethers, cyclic allyl silanes and oxindoles, illustrated in Schemes 13.1-13.3, as a catalytic method (Scheme 13.6) [16]. Similar reaction conditions were identified for all three substrates, including the use of stoichiometric NFSI as the electrophilic fluorine source and a stoichiometric inorganic base additive. It was observed that bis-Cinchona alkaloid (DHQ)2PHAL was best for cyclic silyl enol ethers (X = 0), (DHQ)2PYR (Scheme 13.2) was best for cyclic allyl silanes (X = CH2), while (DHQD)2AQN was best for oxindoles. A similar method was applied to cyclic enol ethers, providing products in modest ee s [17]. 

In investigations of double diastereodifferentiating Mukaiyama aldol reactions, Evans demonstrated that the coupling of end silane 195 either to aldehyde 196 or to aldehyde 198 affords the Felkin products 197 and 199, respectively, with excellent diastereoselectivity (Scheme 4.21) [36]. Because of the involvement of open transition states in these aldol reactions, no direct correlation was found between the starting end silane geometry and the observed simply selectivity (syn versus anti). This contrasts with the simple diastereoselectivity typically observed for cis- and trans-metal enolates that react through cyclic Zimmerman-Traxler transition states. By this strategy, the addition of enol silane 201 to 200 provided an advanced intermediate 202 in the synthesis of 6-deoxyerythronolide B (187, Scheme 4.22) [97]. 

The ring-opening of the cyclopropane nitrosourea 233 with silver trifiate followed by stereospecific [4 + 2] cycloaddition yields 234 [129]. (Scheme 93) Oxovanadium(V) compounds, VO(OR)X2, are revealed to be Lewis acids with one-electron oxidation capability. These properties permit versatile oxidative transformations of carbonyl and organosilicon compounds as exemplified by ring-opening oxygenation of cyclic ketones [130], dehydrogenative aroma-tization of 2-eyclohexen-l-ones [131], allylic oxidation of oc,/ -unsaturated carbonyl compounds [132], decarboxylative oxidation of a-amino acids [133], oxidative desilylation of silyl enol ethers [134], allylic silanes, and benzylic silanes [135]. 

With aldehydes 73 and 74 in hand, two alternatives were considered for the completion of the synthesis of preswinholide A, i.e. carrying out the butanone aldol reaction on either the methyl or the ethyl side first (see Scheme 9-24). Initially, the former option was investigated. While the reaction of the kinetic boron enolate of butanone with aldehyde 73 did not favour the desired Felkin adduct 83, the addition of allyl silane 84 (a masked butanone equivalent) proved selective in the desired sense (Scheme 9-27). This change in selectivity indicates the stereochemical reversal possible when switching from a cyclic to an acyclic transition state. 

---