Enol Borinates Research Articles

Regiospecific Addition of Alkyl and Allyl Groups to α,β-Unsaturated Carbonyl Compounds with Trialkylboranes through the Palladium Catalyst

Trialkylboranes were well known to transfer an alkyl group to the β-position of α,β-unsaturated aldehydes and ketones through radical chain mechanism. It is reported that trialkylborane reacted with acrolein, α-methylacrolein, α-bromolacrolein, methyl vinyl ketone, 2methylcycloalkanones and isopropenyl methyl ketone to generate 1,4-addition products via hydrolysis of enol borinate intermediate with water. Mukaiyama reported for preparation of β-hydroxyketones by the reaction of vinyloxyboranes and carbonyl compounds. Quite recently, Yamamoto reported β-alkyl-α-allylation of benzylidenmalononitrile using trialkylboranes and π-allylpalladium. However such enol borinates were used only limited scope as a synthetic intermediates. In this paper, we wish to report that the generated enol borinate with α,β-unsaturated carbonyl compounds can be used as good nucleophiles for the reaction with π-allylpalladium intermediates. The alkyl radical from 2 undergo 1,4-addition at the β-position of olefins and form an enol borinate. And generated enol borinate intermediate added to the π-allylpalladium of allyl compound and palladium. The reaction gave the β-alkyl and α-allylated derivatives of the activated olefins in a direct process, with high to good yields (eq 1). The results are summarized in Table 1.

ChemInform Abstract: Computer‐Assisted Design and Synthetic Applications of Chiral Enol Borinates: Novel, Highly Enantioselective Aldol Reagents

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Computer-Assisted Design and Synthetic Applications of Chiral Enol Borinates: Novel, Highly Enantioselective Aldol Reagents

We have recently described the development of a quantitative transition state model for the prediction of stereoselectivity in the boron-mediated aldol reaction. This model provides qualitative insights into the factors contributing to the stereochemical outcome of a variety of reactions of synthetic importance. The force field model was used to assist the design and preparation of new chiral boron ligands derived from menthone. The chiral boron enolates were employed in various stereoselective processes, including the addition to chiral aldehydes and the reagent-controlled total synthesis of (3S,4S)-statine. The chiral enolates derived from alpha-halo and alpha-oxysubstituted thioacetates were added to aldehydes and imines. Addition to imines leads to the enantioselective synthesis of chiral aziridines, a formal total synthesis of (+)-thiamphenicol, and a new highly efficient synthesis of the paclitaxel (taxol®) C-13 side-chain and taxol semisynthesis from baccatin III. The stereochemical outcome of the addition to imines was rationalised with the aid of computational studies. Enantioselective addition reactions of the chiral boron enolate derived from thioacetate have successfully been applied to solid phase bound aldehydes to give aldol products in comparable yields and enantioselectivities to the usual solution conditions.

ChemInform Abstract: Rationally Designed Chiral Enol Borinates: Powerful Reagents for the Stereoselective Synthesis of Natural Products

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1,5-Asymmetric Induction in Methyl Ketone Aldol Addition Reactions

In the addition of enol derivatives to â-alkoxy aldehydes, the influence of the â-heteroatom substituent may be regulated by the nature of the aldol process selected (eq 1). For example, good levels of 1,3-anti induction may be realized in the Lewis acid-promoted addition with enol silanes. In contrast, this same substituent possesses no control over the analogous enol borinate nucleophilic additions.2 We have speculated that the principal bias exerted by the â-alkoxy substituent is electrostatic in nature. Given the importance of these remote effects on the π-facial selectivity of aldehyde electrophiles, we have now probed the analogous polar effect of a â-heteroatom substituent on the enolate facial bias in these acetate aldol processes (eq 2).3,4 In this paper, methyl ketone enolates that undergo highly 1,5-diastereoselective aldol addition are identified, and the integration of this control element into double-stereodifferentiating aldol reactions is presented. This study was initiated with an examination of the aldol reactions of unsubstituted ketone enolates 1 (M ) TMS, Li, BR2) that contain a â-alkoxy substituent (Table 1). To isolate the contribution of electrostatic effects to the diastereoselectivity of these addition processes, enolates 1 were selected bearing â-substituents of similar steric size (-OCH2Ar vs -CH2CH2Ar) but different electronic properties. Unlike our previous study on 1,3induction (eq 1),2 the dialkylboron enolates5 displayed good levels of asymmetric induction with dihydrocinnamaldehyde, consistently favoring the 1,5-anti diol product 2 (Table 1, entries 1-5). Due to the similar steric requirements of the â-substituents, electrostatic effects might be at least partially responsible for enolate face selectivity. The enolate facial bias may be further enhanced by a decrease in reaction temperatures (Table 1, entry 5). In contrast to our previous study on 1,3induction (eq 1),2 the Lewis acid-mediated aldol reaction in this system demonstrated no asymmetric induction (Table 1, entry 6).6 Similarly, the aldol reactions of metal enolates capable of internal chelation with the â-heteroatom were also nonselective (Table 1, entry 7).7 (1) For general approaches to the synthesis of 1,3-diol relationships in conjunction with C-C bond formation see: (a) Rychnovsky, S. D.; Hoye, R. C. J. Am. Chem. Soc. 1994, 116, 1753-1765. (b) Mora, Y.; Asai, M.; Okumura, A.; Furukawa, H. Tetrahedron 1995, 51, 52995314. (c) Knochel, P.; Brieden, W.; Rozema, M. J.; Eisenberg, C. Tetrahedron Lett. 1993, 34, 5881-5884. (2) (a) Evans, D. A.; Duffy, J. L.; Dart, M. J. Tetrahedron Lett. 1994, 35, 8537-8540. (b) Evans, D. A.; Dart, M. J.; Duffy, J. L.; Yang, M. G. J. Am. Chem. Soc., 1996, 118, 4322-4343. (3) (a) Blanchette, M. A.; Malamas, M. S.; Nantz, M. H.; Roberts, J. C.; Somfai, P.; Whritenour, D. C.; Masamune, S. J. Org. Chem. 1989, 54, 2817-2825. (b) Seebach, D.; Misslitz, U.; Uhlmann, P. Angew. Chem., Int. Ed. Engl. 1989, 28, 472-473. (4) For 1,4-induction in acetate aldol reactions see: (a) Zibuck, R.; Liverton, N. J.; Smith, A. B. J. Am. Chem. Soc. 1986, 108, 2451-2453. (b) Braun, M. Angew. Chem., Int. Ed. Engl. 1987, 26, 24-37. (c) Paterson, I.; Goodman, J. M.; Isaka, M. Tetrahedreon Lett. 1989, 30, 7121-7124. (d) Trost, B. M.; Urabe, H. J. Org. Chem. 1990, 55, 39823983. (e) Roush, W. R.; Bannister, T. D. Tetrahedron Lett. 1992, 33, 3587-3590. (f) Lagu, B. R.; Liotta, D. C. Tetrahedron Lett. 1994, 35, 4485-4488. (5) Evans, D. A.; Nelson, J. V.; Vogel, E.; Taber, T. R. J. Am. Chem. Soc. 1981, 103, 3099-3111. The regiochemistry (CH3 vs CH2) of the enolization process with Bu2BOTf and Chx2BCl with these methyl ketone substrates is high (>95:5). In certain cases, 9-BBNOTf is nonselective in this enolization process. Table 1. 1,5-Induction with Various Metal Enolates

Rationally designed chiral enol borinates: Powerful reagents for the stereoselective synthesis of natural products

Abstract

Synthesis of the central C18–C30 core of the phorboxazole natural products

A direct synthesis of the central C18C30 core of the phorboxazole natural products has been developed. This involves construction of an acyclic acrylate using Paterson's ( E)-enol borinate aldol methodology followed by an intramolecular hetero-Michael addition to form the central pyran ring of the natural products.

ChemInform Abstract: The Rational Design and Systematic Analysis of Asymmetric Aldol Reactions Using Enol Borinates: Applications of Transition State Computer Modelling

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The rational design and systematic analysis of asymmetric aldol reactions using enol borinates: Applications of transition state computer modelling

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Enolboration. 7. Dicyclohexyliodoborane, a Highly Stereoselective Reagent for the Enolboration of Tertiary Amides. Effects of Solvent and Aldolization Temperature on Stereochemistry in Achieving the Stereoelective Synthesis of either Syn or Anti Aldols

Abstract : A highly stereoselective enolboration of tertiary amides has been accomplished for the first time with dicyclohexyliodoborane, Chx2BI. A systematic study of the enolboration of representative N,N-dialkylpropionamides (CH3CH2CONR2) with Chx2BI in the presence of various tertiary amines of variable steric requirements revealed an unusual aldol stereoselectivity in different solvents and at different aldolization temperatures. Both the nature of solvent and the aldolization temperature influence the stereochemistry of enolboration with the solvent effect being greater than that of the temperature. Aliphatic and alicyclic hydrocarbon solvents favor formation of the syn aldols from the enol borinates by aldolization at lower temperature (-78 deg C), whereas most of the other solvents examined, such as aromatic and chlorinated aliphatic solvents, favor formation of the anti aldols by aldolization at relatively higher temperatures (0 or 25 deg C). The remarkable effects of both temperature and solvent in the case of tertiary amides raise a question about the validity of the previously assumed constancy of the Z to syn and E to anti relationship, suggesting either a possible isomerization of enol borinates with temperature or a different aldolization transition state with different solvent. jg

Enolboration. 6. Dicyclohexyliodoborane, a Versatile Reagent for the Stereoselective Synthesis of Either Z or E Enolates from Representative Esters

Abstract : A smooth, rapid, quantitative and highly stereoselective synthesis of either Z or E enolates from representative esters has been achieved with dicyclohexyliodo-borane, Chx2BI, in the presence of a suitable tertiary amine, such as triethylamine or N,N-diisopropylethylamine. A systematic investigation of the enolboration of ethyl propionate and ethyl phenylacetate, as model esters, by the various Chx2BX and B-X-9-BBN reagents (X = OMs, I, and Br) established Chx2BI as the preferred reagent in terms of yield and selectivity. Further study of representative esters (RCH2COOR') with Chx2BI established that both the steric requirements of the alkyl group (R) at the (alpha-position and the alkoxy group (OR') play a significant role in controlling the enolate geometry. The steric requirements of the amine (R 3N) also contribute considerably to the stereoselectivity of the reaction. The present study provides a simple procedure for the synthesis of Z or E enol borinates from representative esters (RCH2COOR') using the combined stereodirecting effects of the alkyl (R) and the alkoxy (OR') groups. These enol borinates are highly reactive with aldehydes at temperatures as low as -78 deg C and are exceptionally stereoselective even at 0 deg C. In this exploratory study, the synthesis of stereoselective enolates from representative esters (RCH2COOR') using Chx2BI/R 3N is discussed, with special emphasis on the effects of the steric requirements of R and OR'in controlling the enolate geometry.

Studies in marine macrolide synthesis: Boron and silicon-mediated coupling strategies for Swinholide A

Reaction of aldehyde 6 with enol borinates 7 gives adduct 10 preferentially, whereas the allylsilane 18 provides the epimeric adduct 11 with 95% ds. Aldehyde 2 reacts mainly by si-face attack with simple Z enol borinates, which can be overturned by reagent control from (+)- 25.

Computer-assisted design of chiral boron enolates: The role of ate complexes in determining aldol stereoselectivity.

Transition-state modelling for the aldol reaction of chiral Z and E enol borinates ( 1 and 2, Scheme 1) bearing mixed ligands (L 1 = Ipc, L 2 = 9) predicted higher enantioselectivities than those calculated and experimentally tested with C 2 symmetric systems (L 1 = L 2 = Ipc, L 1 = L 2 = 9). Reagent 8 was prepared and used to generate E enol borinates 24, which reacted with aldehydes to give the anti aldol products 25–28 with substantially lower enantiomeric excesses than predicted. This unexpected suggested that ate complex formation may be an important factor in controlling the selectivity of the boron-mediated aldol reaction. In particular, the presence of two different ligands on boron makes it a prostereogenic centre, and two diastereomeric ate complexes ( 29 and 30) can be formed on aldehyde complexation. These ate complexes are calculated to display different re: si face selectivities. The experimental results are similar to the ones predicted if the aldol reaction proceeds via the less selective ate complex 29.

Enolboration. 5. An examination of the effects of amine, solvent, and other reaction parameters on the stereoselective enolboration of ketones with various Chx2BX reagents. An optimized procedure to achieve the stereoselective synthesis of E enol borinates from representative ketones using Chx2BCl/Et3N

Abstract : The effects of amine, solvent, concentration, temperature and other reaction parameters in controlling the enolate geometry have been systematically investigated in the present study. A IIB NMR study of the interaction of representative tertiary amines of variable steric requirements with dicyclohexylchloroborane, Ch(x)2BCl, suggests that the smaller amines coordinate strongly with Ch(x)2BCl, while the more bulky amines do not. These amines have also been examined for the enolboration of diethyl ketone with Ch(x)2BCl, in order to understand the effect of the steric requirements of the amine on the enolate geometry. While the smaller amines favor formation of E enol borinate, the more hindered amines favor formation of the isomeric Z enol borinate. Triethylamine and NN-diisopropylethylamine, the best amines selected in terms of yield and selectivity, have also been compared for the enolboration of two model ketones, diethyl ketone and propiophenone, using various Ch(x)2BX reagents (X = Cl, Br, I, OMs and OTf) to understand their effect with different ketones and reagents. Detailed studies for the enolboration of diethyl ketone with Ch(x) 2BCl/Et3N, with the hope of understanding the various effects on the enolate geometry and of improving the E enolate selectivity, suggest that formation of the E enolates are highly favored

ChemInform Abstract: Enolboration. Part 4. An Examination of the Effect of the Leaving Group X on the Stereoselective Enolboration of Ketones with Various R2BX/Et3N. New Reagents for the Selective Generation of Either Z or E Enol Borinates from Representative Ketones.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Origins of π‐Face Selectivity in the Aldol Reactions of Chiral E‐ Enol Borinates: A Computational Study Using Transition State Modelling.

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Enolboration. 4. An examination of the effect of the leaving group (X) on the stereoselective enolboration of ketones with various R2BX/triethylamine. New reagents for the selective generation of either Z or E enol borinates from representative ketones

Abstract : A smooth, rapid, quantitative and stereoselective enolboration of representative ketones to either Z or E enol borinates is achieved with many new R2BX/Et3N reagents. Representative B - X-9-BBN and Chx2BX reagents with various leaving groups, such as triflate, mesylate, iodide, bromide, and chloride, have been examined with representative ethyl ketones, such as diethyl ketone, ethyl isopropyl ketone, ethyl tert-butyl ketone, and propiophenone, as model ketones, in order to attain an understanding of the effect of the leaving group in controlling the enolate geometry. R2BX reagents with better leaving groups, such as triflate, mesylate, and iodide, favor the formation of Z enol borinates, whereas those with relatively poorer leaving groups, such as bromide, and chloride, favor the formation of E enol borinates. The steric requirements of R in R2BX and R'in C2H5COR' also contribute substantially to the control of enolate geometry. An unusual behavior of the iodide reagents, favoring the exclusive formation of the Z enol borinates, has been observed in the enolboration of EtCOt-Bu and EtCOPh. The achievement of an understanding of this important effect of the leaving group in R2BX, as well as the effects of steric requirements of the substituents on boron and ketone in controlling the enolate geometry, and also the discovery of new R2BX reagents for the stereoselective generation of either Z or E enol borinates from representative ethyl ketones, are emphasized in this exploratory study.

New methods and strategies for the stereocontrolled synthesis of polypropionate-derived natural products

Abstract

Stereocontrolled, two-directional, chain synthesis using the Boron Aldol reaction and double Ireland-Claisen rearrangement.

Long-chain, (4 E,9 E)-unsaturated, diesters can be prepared efficiently by double Ireland-Claisen rearrangements, as in 4 → 5 → 6. By combination with appropriate E ot Z enol borinate aldol reactions, a high level of stereocontrol can be achieved at the four chiral centres and two trisubstituted double bonds in 11, 15, 30, 31 and 32.

Enol Borinates in Organic Synthesis: Regioselective α-Sulphenylation and α-Selenenylation of Ketones

Enol Borinates in Organic Synthesis: Regioselective α-Sulphenylation and α-Selenenylation of Ketones