Enol silanes

The pioneering discovery by Mukaiyama in 1974 of the Lewis acid mediated aldol addition reaction of enol silanes and aldehydes paved the way for subsequent explosive development of this innovative method for C-C bond formation. One of the central features of the Mukaiyama aldol process is that the typical enol silane is un-reactive at ambient temperatures with typical aldehydes. This reactivity profile allows exquisite control of the reaction stereoselectivity by various Lewis acids additionally, it has led to the advances in catalytic, enantioselective aldol methodology. Recent observations involving novel enol silanes, such as enoxy silacyclobutanes and O-si-lyl M(9-ketene acetals have expanded the scope of this process and provided additional insight into the mechanistic manifolds available to this versatile reaction. 

---

Q Chiral racemic y-alkyl-substituted enones the titanium(IV) chloride mediated addition of enol silanes and silylketene acetals to 7 shows high induced diastereoselection (diastereomeric ratios from 89 11 to more than 97 3) and the major isomer 8 results from addition of the enolsilane with ul topicity288. Re face attack on the S enantiomer of 7.)... 

The checkers found considerable variation in the rate of the reaction in different runs, the time required for its completion ranging from 3 to 10 hours. It is therefore advisable to monitor the progress of the reaction. For this purpose small aliquots (ca. 0.05 ml.) were withdrawn from the flask with a syringe and hydrolyzed by injection into a vial containing ether and saturated ammonium chloride. The relative amoimts of enol silane and cyclopropoxy sdane were determined by gas chromatography on an 0.6 cm. X 3.7 m. column of 3% OV-17 coated on 100-120 mesh Chromosorb W. With a column temperature of 120° and a carrier gas flow rate of 20 ml. per minute, the retention times for the enol silane and the cyclopropoxy silane are ca. 1.9 and 2.3 minutes, respectively. 

Conversion of ketone 80 to the enol silane followed by addition of lithium aluminum hydride to the reaction mixture directly provides the allylic alcohol 81 [70]. Treatment of crude allylic alcohol 81 with tert-butyldimethylsilyl chloride followed by N-b ro m o s u cc i n i m i de furnishes the a-bromoketone 82 in 84 % yield over the two-step sequence from a.p-unsaturated ester 80. Finally, a one-pot Komblum oxidation [71] of a-bromoketone 82 is achieved by way of the nitrate ester to deliver the glyoxal 71. It is worth noting that the sequence to glyoxal 71 requires only a single chromatographic purification at the second to last step (Scheme 5.10). 

Intermolecular cross aldolization of metallo-aldehyde enolates typically suffers from polyaldolization, product dehydration and competitive Tishchenko-type processes [32]. While such cross-aldolizations have been achieved through amine catalysis and the use of aldehyde-derived enol silanes [33], the use of aldehyde enolates in this capacity is otherwise undeveloped. Under hydrogenation conditions, acrolein and crotonaldehyde serve as metallo-aldehyde enolate precursors, participating in selective cross-aldolization with a-ketoaldehydes [24c]. The resulting/ -hydroxy-y-ketoaldehydes are highly unstable, but may be trapped in situ through the addition of methanolic hydrazine to afford 3,5-disubstituted pyridazines (Table 22.4). 

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],... 

J0rgensen and co-workers (230) reported the aldol reaction between enolsilanes and ketomalonate esters. Catalyst 269c proved to be nearly nonselective in these reactions. Optimal conditions involve the use of < /-269d in Et20 at -78°C. The reactions are quite sluggish under these conditions. Benzosubarone-derived enol-silane affords the aldol adduct in 93% ee, Eq. 200, while propiophenone enolsilane provides the aldol product in 90% ee under identical conditions, Eq. 201. Other nucleophiles are less selective. No model was advanced to account for the observed enantioselectivities. 

KH/18-crown-6, HMPA "- 13 Scheme 8 Addition of triarylgermanes to alkenes and enol silanes... 

SPIROANNELATION OF ENOL SILANES 2-OXO-5-METHOXYSPIRO[5.4]DECANE (Spiro[4.5]decan-1-one, 4-methoxy-)... 

Energy loss spectroscopy, 30 305-306, 308 a, P-Enoates, Michael reaction of silyl ketene acetal, 38 275 Enol silanes... 

Palladium-catalyzed conversion of enol silanes to enones, also known as the Saegusa enone synthesis. 

Song and co-workers have taken a variety of aldehydes 344 and treated them with A -adamantyl carbene 1 and trimethylsilyl ketene acetal 345 to produce Mukaiyama aldol products 346 in good yield (Eq. 34) [170], The carbene presumably acts as a Lewis base to activate the silicon - oxygen bond in order to promote reactivity of the enol silane. The catalyst loading can be reduced to as low as 0.05 mol% without a change in yield. 

Electron-rich as well as electron-deficient olefinds undergo aziridination by decomposition of [A/-(/ -tolylsulfonyl)imino]phenyliodinane (19) with a catalytic amount of the soluble Cu(I) and Cu(II) triflate and perchlorate salts (Eq. 8) (91JOC6744 94JA2742). Phenyliodinane 19 acts as nitrene precursor. The Cu(I) catalyzed aziridination when applied to enol silanes... 

In 2000, Tanino and his co-workers developed the novel [5- -2]-cycloaddition reaction of a propargyiic cation equivalent bearing allylic silane 17 with enol silane 18 to give the corresponding cycloheptyne complexes 19 in good yields with an excellent diastereoselectivity (Scheme 3). While ceric ammonium nitrate (CAN) is generally used to... 

In 1993, Nicholas and his co-worker developed the stereospecific propargylic alkylation of chiral propargylic alcohols 30 with enol silanes 31 by using a stoichiometric amount of [Co2(CO)5L] (L = phosphite), but separation procedures of the produced diastereoisomers are necessary twice on the way to obtain the compounds specifically alkylated at the propargylic position 32 (Scheme 5). In 2001, Montana and his co-worker reported the diastereo-selective Nicholas alkylation of propargylic acetal complexes 33 bearing a chiral auxiliary with various enol silanes 34 (Equation (14)). A high diastereoselectivity is observed, but unfortunately, only low to moderate enantioselec-tivities are achieved in all cases. 

Recently, analogues of nucleosides [60], natural products Huperzine-A [61] and Hydroartemisinin [62], and inhibitors of metallo-/ -lactamases have been synthesised [63]. With acylsilane electrophiles, the initial adducts undergo Brook rearrangement which is interrupted by -Si bond fission with loss of fluoride anion (Eq. 16), leading to the formation of extremely useful difluoro-enol silanes [64]. Of the various fluoride sources employed, the tetrabutylam-monium triphenyldifluorostannate described by Gingras appears to be particularly effective. The numerous other methods for trifluoromethylation formed the subject of an exhaustive review [65]. More recently, the Olah group described a chlorodifluoromethyl trimethylsilane which is expected to have a rich chemistry [66]. 

TiC14j ArH, enol silane or (R02C)2CH2 [R = Ai, CH2COR or CH(C02R)2]... 

For reactions with enol silanes and Lewis acids, see... 

---