Boron enol ethers synthesis

The addition of carboxylic acids to alkynes affords enol esters which are useful as intermediates in organic synthesis.470 As in the addition to alkenes, a catalyst is usually required for high conversions of alkynes to enol esters. Simple acid catalysis has been employed (equation 279),471 but the more common catalysts are Lewis acids, such as boron trifluoride etherate,472 silver nitrate,473 zinc acetate474 and zinc oxide (equations 280 and 281),47S-476... 

Asymmetric induction in the aldol reaction of enolsilane and metal enolate nucleophiles with yS-substituted aldehydes gives rise to both excellent yields and good diastereoselectivities (equation 128)507. The best diastereoselectivity was obtained using a trimethylsilyl enolate in the presence of boron trifluoride-etherate (92 8 anti. syn). The key step in the synthesis of the N-terminal amino acid analogue of nikkomycin B and Bx (nucleoside peptide antibiotics) has been performed using this type of methodology508. 

In the total synthesis of (+)-trienomycins A and F, Smith et al. used an Evans aldol reaction technology to construct a 1,3-diol functional group8 (Scheme 2.1i). Asymmetric aldol reaction of the boron enolate of 14 with methacrolein afforded exclusively the desired xyn-diastereomer (17) in high yield. Silylation, hydrolysis using the lithium hydroperoxide protocol, preparation of Weinreb amide mediated by carbonyldiimidazole (CDI), and DIBAL-H reduction cleanly gave the aldehyde 18. Allylboration via the Brown protocol9 (see Chapter 3) then yielded a 12.5 1 mixture of diastereomers, which was purified to provide the alcohol desired (19) in 88% yield. Desilylation and acetonide formation furnished the diene 20, which contained a C9-C14 subunit of the TBS ether of (+)-trienomycinol. 

With catalytic amounts of rare earth metal triflates, heterocarbonyl compounds, e.g. acylhy-drazones, are also successfully activated. From the latter and silyl enolates (Scheme 4), the coupling products are obtained directly or in a one-pot synthesis in the presence of 5 mol% of Sc(OTf)3 or Yb(OTf)3 in 45-96% yield. For example, compound 17 was isolated in 92 % yield and was subsequently cyclized with base to the corresponding pyrazolone (Scheme 4) [16]. In comparison with typical Lewis acids, such as SnCl4, (10% yield) and boron trifluoride etherate (42 % yield), Sc(OT03 proved to be superior. 

Enol ethers 28 are easily converted to selenoacetals 29 by treatment with benzeneselenol in the presence of boron trifluoride etherate (Scheme 31) [53]. When cyclic enol ethers are employed, the corresponding open-chain products are formed. The selenoacetals obtained are considered to be important intermediates in organic synthesis [54]. 

C-C bonds. It needs only to be emphasized that, in addition to the silyl enol ethers shown in the scheme, modem organic synthesis extensively employs enolates of boron, tin, titanium, zirconium, and other elements, as their utilization offers additional opportunities to achieve higher efficiency and exert control over the selectivity of the corresponding reactions. 

Silyl enol ethers react with aldehydes in the presence of chiral boranes or other additives " to give aldols with good asymmetric induction (see the Mukaiyama aldol reaction in 16-35). Chiral boron enolates have been used. Since both new stereogenic centers are formed enantioselectively, this kind of process is called double asymmetric synthesis Where both the enolate derivative and substrate were achiral, carrying out the reaction in the presence of an optically active boron compound ° or a diamine coordinated with a tin compound ° gives the aldol product with excellent enantioselectivity for one stereoisomer. Formation of the magnesium enolate anion of a chiral amide, adds to aldehydes to give the alcohol enantioselectively. 

The Nicholas reaction was used to synthesize the p-lactam precursor of thienamycin in the laboratory of P.A. Jacobi and thereby accomplish its formal total synthesis. The necessary p-amino acid was prepared by the condensation of a boron enolate (derived from an acylated oxazolidinone) with the cobalt complex of an enantiopure propargylic ether. The resulting adduct was oxidized with ceric ammonium nitrate (CAN) to remove the cobalt protecting group from the triple bond, and the product was obtained with a 17 1 anti.syn selectivity and in good yield. 

Given this problem, the attachment of the butanone synthon to aldehyde 74 prior to the methyl ketone aldol reaction was then addressed. To ovenide the unexpected. vTface preference of aldehyde 74, a chiral reagent was required and an asymmetric. syn crotylboration followed by Wacker oxidation proved effective for generating methyl ketone 87. Based on the previous results, it was considered unlikely that a boron enolate would now add selectively to aldehyde 73. However, a Mukaiyama aldol reaction should favour the desired isomer based on induction from the aldehyde partner. In practice, reaction of the silyl enol ether derived from 87 with aldehyde 73, in the presence of BF3-OEt2, afforded the required Felkin adduct 88 with >97%ds (Scheme 9-29). This provides an excellent example of a stereoselective Mukaiyama aldol reaction uniting a complex ketone and aldehyde, and this key step then enabled the successful first synthesis of swinholide A. 

As previously mentioned, certain methyl ketone aldol reactions enable the stereocontrolled introduction of hydroxyl groups in a, 5-anti relationship (Scheme 9-7) [9], and this was now utilized twice in the synthesis. Hence, methyl ketones 48 and 98 were converted to their respective Ipc boron enolates and reacted with aldehydes 97 and 99 to give almost exclusively the, 5-anti aldol adducts 100 and 101, respectively (Scheme 9-34). In the case of methyl ketone 48, the j -silyl ether leads to reduced stereoinduction however, this could be boosted to >97%ds with the use of chiral ligands. In both examples, the y9-stereocenter of the aldehyde had a moderate reinforcing effect (1,3-syn), thus leading to triply matched aldol reactions. Adducts 100 and 101 were then elaborated to the spiro-acetal containing aldehyde 102 and ketone 103, respectively. 

Hoffmann and co-workers completed the first synthesis of both denticulatins via a C9-C10 aldol bond construction (Scheme 9-70) [87], In this case, aldehyde 266 was assembled using asymmetric crotylboration reactions to introduce the C4-CS stereocenters. The (Z)-boron enolate 267 was then reacted with aldehyde 266 to afford the desired anh-Felkin adduct with 80% selectivity where the minor diastereomer resulted from reaction of the enantiomer of the starting ketone. Unfortunately, the C5-PMB ether protecting group could not be removed without epi-merization at C o, and denticulatins A and B were formed in equimolar amounts. 

In our synthesis, iterative aldol reactions of dipropionate reagent (R)-18 allowed for the control of the C3-C10 stereocenters (Scheme 9-72) [89]. Hence, a tin-mediated, syn aldol reaction followed by an anti reduction of the aldol product afforded 270. Diol protection, benzyl ether deprotection and subsequent oxidation gave aldehyde 271 which reacted with the ( )-boron enolate of ketone (/ )-18 to afford anti aldol adduct 272. While the ketone provides the major bias for this reaction, it is an example of a matched reaction based on Felkin induction from the... 

These two milestone syntheses were soon followed by others, and activity in this field continued to be driven by interest in the biologically active esters of cephalotaxine. In 1986, Hanaoka et al. (27) reported the stereoselective synthesis of ( )-cephalotaxine and its analog, as shown in Scheme 4. The amide acid 52, prepared by condensation of ethyl prolinate with 3,4-dimethoxyphenylacetyl chloride, followed by hydrolysis of the ethyl ester, was cyclized to the pyrrolobenzazepine 53 by treatment with polyphos-phoric acid, followed by selective O-alkylation with 2,3-dichloropropene (54) in the presence of sodium hydride. The resulting enol ether 55 underwent Claisen rearrangement on heating to provide C-allylated compound 56, whose reduction with sodium borohydride yielded the alcohol, which on treatment with 90% sulfuric acid underwent cationic cyclization to give the tetracyclic ketone 57. Presumably, this sequence represents the intramolecular version of the Wichterle reaction. On treatment with boron tribromide, ketone 57 afforded the free catechol, which was reacted with dibromometh-ane and potassium fluoride to give methylenedioxy derivative 58, suited for the final transformations to cephalotaxine. Oxidation of ketone 58... 

Introduction and stereochemical control syn,anti and E,Z Relationship between enolate geometry and aldol stereochemistry The Zimmerman-Traxler transition state Anti-selective aldols of lithium enolates of hindered aryl esters Syn-selective aldols of boron enolates of PhS-esters Stereochemistry of aldols from enols and enolates of ketones Silyl enol ethers and the open transition state Syn selective aldols with zirconium enolates The synthesis of enones E,Z selectivity in enone formation from aldols Recent developments in stereoselective aldol reactions Stereoselectivity outside the Aldol Relationship A Synthesis ofJuvabione A Note on Stereochemical Nomenclature... 

Acetylenic cobalt complexes greatly facilitate the heterolytic cleavage of adjacent alcohols or ethers. On treatment with Lewis acids, these complexes afford cobalt stabilized carbenium ions, which can be captured by nucleophiles such as enolates. Jacobi and Zheng have employed chiral boron enolates of Evans s oxa-zolidinone 6.91 (R = i-Pr). After removal of the chiral auxiliary, they obtained anti adds 11.43 with a high selectivity [1677] (Figure 11.9). The reaction can be extended to the boron enolates of related oxazolidinones and to a-branched propargyl derivatives. This reaction has been applied to the synthesis of P-aminoacids after Curtius rearrangement and oxidation of the triple bond [1677]. 

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