3-pentanone boron enolate

The following C2-symmetric bis-sulfonamide is a more efficient controller of stereoselectivity in aldol additions. The incorporation of this ligand into the bromodiazaborolane, subsequent generation of the boron enolate derived from 3-pentanone, and addition to achiral aldehydes preferentially leads to the formation of ijn-adducts (synjanti 94 6 to >98 2) with 95-98% ee. Chemical yields of 85-95% are achieved51. 

Achiral ketones, for example, 3-pentanone, can be converted predominantly into (Z)-boron enolates [(Z)/( )>97 3] by treatment with (- )-diisopinocampheylboron triflate. Subsequent addition to aldehydes, followed by an oxidative workup procedure, delivers /i-hydroxy ketones with a diastcrcomeric ratio of 95 5 to 98 2 (synjanli) and the xpn-products with 66 to 93% ee33. 

Z-Boron enolates can also be obtained from silyl enol ethers by reaction with the bromoborane derived from 9-BBN (9-borabicyclo[3.3.1]nonane). This method is necessary for ketones such as 2,2-dimethyl-3-pentanone, which give E-boron enolates by other methods. The Z-stereoisomer is formed from either the Z- or E-silyl enol ether.20... 

Little steric differentiation is observed with either the lithium or boron enolates of 2-methyl-2-pentanone.102... 

The is-boron enolates of some ketones can be preferentially obtained with the use of dialkylboron chlorides.17 The data in Table 2.3 pertaining to 3-pentanone and 2-methyl-3-pentanone illustrate this method. Use of boron triflates with a more hindered amine favors the Z-enolate. The contrasting stereoselectivity of the boron triflates and chlorides has been discussed in terms of reactant conformation and the stereoelectronic requirement for perpendicular alignment of the hydrogen being removed with the carbonyl group.18 The... 

The synthesis starts with the thioester 64 to get the cis boron enolate 75 we need for the syn product Once the adduct 76 has been made, the sulfur has done its work and can be removed. Transesterification with MeOH and HgCl2 and straightforward steps lead to iodide 78. Once this iodide has reacted with the enolate of pentanone, there will be no trace of the carbonyl that originally allowed the aldol chemistry to be performed. 

Following an early lead from the Meyers group [94,95], Paterson used the readily available diisopinocampheyl (Ipc) boron triflate to make Z(0)-boron enolates of 3-pentanone [93] and other ketones [96], which add to aldehydes to produce syn adducts in 83 - 96% es (Scheme 5.16 and Table 5.6). Based on molecular mechanics calculations [55,56], the transition structure analysis shown in Scheme 5.16 was suggested to rationalize the enantioselectivity. The axial boron ligand rotates so that the C-H bond is over the top of the Zimmerman-Traxler six-membered ring, and the equatorial ligand orients with its C-H bond toward the... 

In a pioneering investigation, the lithium enolate derived from 3-methyl-2-pentanone was added to aldehydes. Only moderate diastereoselectivity was obtained, however [119]. Exceptionally high induced stereoselectivity was observed when camphor-derived ketone 69 was converted into the lithium enolathe and subsequently added to aldehydes. a-Cleavage at the carbonyl group enabled the formation of y -hydroxy aldehydes and acids in high enantiomeric excess (Eq. (31)) [60]. The work on the aldol addition of methyl ketones led to a variety of stereoselective variants which rely mainly on boron enolates and will be discussed in Chapter 3 of Part I of this book. 

In the absence of chelation, comparison of the destabilizing syw-pentane interactions recently encouraged Evans and coworkers to use the Comforth model to justify the exalted 3,4-anti selectivity observed for a series of chiral a-oxygenated aldehydes reacting with the Z(O) boron and lithium enolates of 2-methyl-3-pentanone (Scheme 117)568. Comple-mentarily, the corresponding E(O) isomers showed, as expected, a striking difference in their 2,3-selectivities, while the 3,4 anti-selectivity was lowered in both cases a finding inconsistent with the PFA model. 

For example, condensation of silyl enol ether (3.21) of 3-pentanone with 2-methylbutanal in the presence of TiC gives the Ti-complex 3.22, which on hydrolysis yields an aldol product, manicone (4,6-dimethyl-4-octen-3-one) (3.23), an alarm pheromone. Treatment of 3-pentanone with LDA results in the formation of an enolate, which is trapped with chlorotrimethylsilane to give 3.21. Other Lewis acids such as tin tetrachloride (SnCU) and boron trifluoride etherate (BF3-OEt2) can also be used. 

Paterson et have prepared the enolate of 3-pentanone, an achiral ketone, with (-( )- or (-)-IpcaBOTf and have found that its aldol reactions with various aldehydes proceed with high syn.anti ratios (>9 1) and respectable enantioselectivities (5 1-20 1) (Scheme 44). High degrees of asymmetric induction are noted with unhindered aldehydes, llie combination of the chiral ethyl ketone (104) and (-t-)-Ipc2BOTf constitutes a matched pair, which enhances the diastereofacial selectivity of the resulting enolate (compared to that obtained with an achiral boron reagent), and provides via aldol reactions high... 

When the alkylboranes formed by reaction with an alkene are oxidized with Na0H/H202, the product is an alcohol. When the vinylborane unit is similarly oxidized in 115 (or 114), replacement of boron with the OH gives an enol product, 117 or 116, which tautomerizes to the corresponding carbonyl derivative (see Section 10.4.5 for the similar reaction in oxymercuration). Enol 116 tautomerizes to 2-pentanone (118) and 117 to butanal (118). Because vinylborane 115 is the most prevalent vinylborane, aldehyde 119 is the major isolated product after oxidation. Note the anti-Markovnikov orientation of the boron and the oxygen, analogous to the regioselectivity shown by hydroboration of alkenes. 

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