Tin enolates synthesis

The second approach for the synthesis of 2-amino-3-hydroxycarboxylic acids starts with a chiral isothiocyanate which is added, via the tin enolate, to aldehydes. The initially formed adducts are immediately derivatized to the heterocycles, from which. yj 7-2-amino-3-hy-droxycarboxylic acids result after a three-step procedure. The diastereomeric ratios of the intermediate bis-heterocyclic products range from 93 7 to 99 1 (desired isomer/sum of all others)104. 

In Step D another thiazoline chiral auxiliary, also derived from cysteine, was used to achieve double stereodifferentiation in an aldol addition. A tin enolate was used. The stereoselectivity of this reaction parallels that of aldol reactions carried out with lithium or boron enolates. After the configuration of all the centers was established, the synthesis proceeded to P-D lactone by functional group modifications. 

Bicyclic alkaloids. Nagao et al. have developed a general synthesis of chiral bicyclic alkaloids with a nitrogen atom at the ring juncture, such as pyrrolizidines [5.5], quinolizidines [6.6], and indolizidines [6.5], based on a highly diastereose-lective alkylation of 3-a>-chloroacyl-(4S)-isopropyl-l,3-thiazolidine-2-thiones (1, m = 1,2) with 5-acetoxy-2-pyrrolidinone (2, n = 1) or 6-acetoxy-2-piperidinone (2, n = 2). Thus the tin enolate of 1 (m = 1), prepared with Sn(OTf) and N-... 

The direct coupling of the tin enolate (175 Scheme 25) with (30) gives complex (176) in good yield (87%). Fortuitously, the bond formation gives approximately a 5 1 mixture in favor of the diastereomer required for trichothecene synthesis. Further elaboration of the major isomer leads to (i)-trichodiene (167), representing an eight step diastereoselective total synthesis of the natural product from p-methyl-anisole, which compares very favorably with previous methods.32-36... 

Low-temperature NMR studies of the reaction of 2-methoxycyclohexanone with SnCU in the presence of a base confirm the formation of a chelated tin enolate (Equation (84)). A synthetic application, a high stereoselective synthesis of sanfetrinem, has been described.239... 

The tin enolates are useful in organic synthesis as a mild source of the nucleophilic enolate group in its reaction with alkyl or acyl halides, aldehydes or enones. The tin enolates are less basic than the lithium enolates, and more reactive though rather less easy to handle than the silicon enolates.105-113... 

Further, a highly enantioselective synthesis of 2-substituted malates is achieved by application of this reaction. The divalent tin enolate of 3-acetylthiazolidme-2-thione reacts with various a-ketoesters to afford the corresponding aldol-type products, generally in greater than 95% e.e. (Table 16) . 

Table 7 Synthesis of a,3-Epoxy Ketones via Divalent Tin Enolates ...

A delocalized 0-stannyl radical anion can also be generated from the reaction of an a,/ -unsaturated ketone or aldehyde with tributyltin hydride and radical initiator AIBN [3, 4, 5a, 5b]. Thus, a,/ -unsaturated carbonyl compound 4 (R or R = H or alkyl), can be reacted with wBu SnH under standard free-radical conditions to give allylic O-stannyl ketyl species (5 6), shown in Scheme 2. After hydrogen atom transfer to the -position of 6, a synthetically useful tin(IV) enolate is produced [5b, 5d, 5g. Allylic 0-stannyl ketyls have both one- (radical) and two-electron (anionic) sites for reactivity. These reactions can proceed in a sequential manner - a rapidly-evolving methodology in organic synthesis [2, 5, 8j. If the one-electron reactivity in 6 is used with a radicophile, then the tin enolate or two-electron reactivity can be used in reactions with suitable electrophiles (E ). Note that the carbonyl species. 

A synthesis of 0-lactams from volves reaction of tin enolates. 

In the synthesis of hapalindole Q, an indolylterpene isolated from algae, coupling was achieved under Heck conditions with a tin enolate (Equation (117)) <93JA3499>. 

In analogy t 0 the Cu(II) complex systems, the silver(I) -catalyzed aldol reaction is also proposed to proceed smoothly through a Lewis acidic activation of carbonyl compounds. Since Ito and co-workers reported the first example of the asymmetric aldol reaction of tosylmethyl isocyanide and aldehydes in the presence of a chiral silver(I)-phosphine complex (99,100), the catalyst systems of sil-ver(I) and chiral phosphines have been applied successfully in the aldol reaction of tin enolates and aldehydes (101), Mukaiyama aldol reaction (102), and aldol reaction of alkenyl trichloroacetates and aldehydes (103). In the Ag(I)-disphosphine complex catalyzed aldol reaction, Momiyama and Yamamoto have also examined an aldol-type reaction of tin enolates and nitrosobenzene with different silver-phosphine complexes (Scheme 15). The catalytic activity and enantioselectivity of AgOTfi(f )-BINAP (2 1) complex that a metal center coordinated to one phosphine and triflate were relay on solvent effect dramatically (Scheme) (104). One catalyst system solves two problems for the synthesis of different O- and AT-nitroso aldol adducts under controlled conditions. 

Scheme 28 shows a stereoselective epoxide synthesis, which proceeds by way of a tin enolate. Similarly, the tin enolates derived from triphenyltin chloride and lithium enolates, R HC=C(OLi)R react with alkyl and aryl aldehydes R CHO without the necessity for a catalyst to give mainly the erythro-products (139) in good yield. ... 

Much tvork in the field of aldol reactions of ketones tvas performed by Evans to enable the synthesis of polypropionate natural products. They demonstrated that j5-ketoimides like 159 vere selectively and completely enolized at the C4 position rather than the potentially labile methyl-bearing C2 position, most probably because steric factors prohibited alignment of the carbonyl groups necessary to activate the C2 proton. As sho vn in Table 2.29, it vas demonstrated that these compounds vould react vith aldehydes to provide syn-syn product 161, via titanium enolates, vith good yield and excellent selectivity, and the corresponding syn-anti product 162 could be favored by use of a tin enolate reaction [58]. They invoked the chelated transition state assembly 160 to explain the product stereochemistry observed, in vhich the C2-methyl group directs diastereofacial selectivity. Interestingly, reduction vith Zn(BH4)2 provided the syn diol diastereoselec-tively. 

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