Silyl ketene acetals cyclization

Few examples of intramolecular enol silyl ether or silyl ketene acetal cyclizations to oc,3-enones have been reported. Notable, as exemplified in Scheme 34, is the iodotrimethylsilane-mediated intramolecular cyclization of 5-(iodoacetoxy)-a,3-enones (211) to 5-lactones (214). These cyclizations proceed with in situ generated silyl ketene acetals (212) arising from iodotrimethylsilane reduction of the iodoacetoxy moiety.87... 

Additions of silylated ketene acetals to lactones such as valerolactone in the presence of triphenylmethyl perchlorate in combination with either allyltrimethylsilane 82, trimethylsilyl cyanide 18, or triethylsilane 84b, to afford substituted cyclic ethers in high yields have already been discussed in Section 4.8. Aldehydes or ketones such as cyclohexanone condense in a modified Sakurai-cyclization with the silylated homoallylic alcohol 640 in the presence of TMSOTf 20, via 641, to give unsaturated cyclic spiro ethers 642 and HMDSO 7, whereas the 0,0-diethyllactone acetal 643 gives, with 640, the spiroacetal 644 and ethoxytrimethylsilane 13b [176-181]... 

Chiral trms-fi-lactams. The silyl ketene acetal (1), derived from (1S,2R)-N-methylephedrine, reacts in the presence of TiCl, with benzylideneaniline (2) to give as the major products anti- and syn-3 in the ratio >10 1. Cyclization of the mixture gives the trans-p-lactam (4) in 95% ee. 

The silyl ketene acetal 2, prepared from ethyl 3-hydroxybutanoate, undergoes a similar condensation with benzylideneaniline but with syn-selectivity. The product cyclizes to a cis-fl-lactam (4). 

Similar results were obtained when diphenylnitrenium ion was trapped with various silylenol ethers and silyl ketene acetals (e.g., 116). In these experiments, a distribution of N-(117), p- (118), and o- (119) adducts were generated (Fig. 13.55). The ortho adducts underwent a cyclization reaction, producing an indolone derivative. 

Intramolecular Mukaiyama aldol condensation.5 The silyl ketene acetal 1 cyclizes to the tetrahydrofuran 2 in 32% yield on exposure to TiCl4 (1 equiv.) in CH2C12 at 0°. The product is convertible into 3, an analog of cycloleucine. 

When the same silyl ketene acetal is reacted with benzylide-neaniline in the presence of TiCU, the anti-p-amino ester is obtained (anti/syn> lO/l). Cyclization of the p-amino ester affords the trani-p-lactam in 95% ee (eq 4). ... 

Conjugate additions. Cyclopentaneacetic esters are readily prepared by cyclization of -iodo-a,P-unsaturated esters. The Michael reaction of silyl ketene acetals with enones (and Mukaiyama aldol reaction) can be promoted by Sml,. " However, thermodynamic enolsilylation of carbonyl compounds under similar conditions is noted. 

Two short syntheses of racemic ipalbidine ( )-(842) are shown in Scheme 109. The synthesis by Jefford et al. commenced with conjugate addition between pyrrole and Ae atropate ester 849 followed by homologation of the acid 850 with diazomethane and rhodium-induced intramolecular carbene cyclization of the resulting diazoketone 851 (574). The bicyclic product 852 was converted into ( )-842 in a further four steps. The approach taken by Danishefsky and Vogel centered on acid-catalyzed cyclocondensation between the silyl ketene acetal 853 and A -pyrroline (854) to give indolizidinone 855 (575). Reduction of the lactam and cleavage of the aryl ether completed the synthesis of ( )-842. 

In an extension of their earlier work, Ojima and coworkers have described analogous reactions using vinyl silyl ketene acetals (160 equation 19). 9 xhe carbon-carbon bond forming step in these reactions occurs exclusively at the terminal carbon of the vinyl silyl ketene acetal (160) to give cyclized 5,6-dihy-dro-2-pyridones (162), methyl 5-amino-2-pentenoates (163), or mixtures. Steric and electronic factors play an important role in the formation of cyclized products, which are favored by the lack of an a-sub-stituent (R ) and the presence of an N-alkyl group on the imine (R ). Formation of (162) and (163) proceeds by a common metalated intermediate, since in reactions that form cyclized products (162), quenching at -50 °C leads to acyclic products. Yields are good to excellent when corrected for recovered imine (161), but a 100% excess of vinyl silyl ketene acetal (160) must be employed. It is curious to note that these reactions require much lower initial temperatures (-100 C) than those of silyl ketene acetals. 

The rearrangement of the 15-membered silyl ketene acetals 12 indicates a high relative asymmetric induction with the preferred formation of 16 from the ( )-substrates through the chairlike and 17 from the (Z)-substrates through the boatlike transition state. The rearranged product 14 obtained from the 14-membered silyl ketene acetal 13 immediately undergoes cyclization to give the tetrahydronaphthalene derivative 15018. 

McIntosh et al. have applied the Ireland-Claisen rearrangement of bis-allyl silyl ketene acetals in studies directed toward the synthesis of the eupomatilones (Scheme 4.135) [128]. The 1,2-transposition of the alkene, which occurred in the rearrangement afforded a reactive vinyl epoxide (cf Scheme 4.83). Stereoselective cyclization of the carboxylic acid onto the vinyl epoxide generated the 5-aryl lactone, which was further manipulated to the putative structure of 5-epi-eupoma-tilone-6. 

In a series of reports, banger s group studied the synthesis of pulvinic acids via a TMSOTf-catalyzed [3-f2] cyclization of l,3-bis-(trimethylsilyloxy)-l,3-dienes (e.g., 83) with oxalyl chloride followed by Suzuki couphng of product triflates (Scheme 1.11) [64]. banger s versatile method was apphed to the synthesis of almost all natural pulvinic acids (e.g., xerocomic acid 29), including norbadione A (37) by be Gall et al. [65]. In a modification of banger s protocol, Mioskowski dimerized simple silyl ketene acetals (e.g., 85) to obtain symmetrical pulvinic acids via an uncatalyzed reaction with (COCl)2 (Scheme 1.11) [66]. 

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