Stereoselective synthesis and cyclisation of the acyclic precursor to auripyrone A and B

Perkins, Michael V.; Sampson, Rebecca K; Joannou, John; Taylor, Max R.

doi:10.1016/j.tetlet.2006.03.096

Cited by 11 publications

(3 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We suspect the high ( E )-selectivity in these reactions originates from minimization of 1,3- syn -pentane interactions in the competing transition states . As shown in Figure , it is conceivable that BF 3 will coordinate to the lower lone pair of electrons (in blue) of the oxygen atom distal to the angular methyl group to minimize steric interactions .…”

supporting

confidence: 92%

Highly (E)-Selective BF₃·Et₂O-Promoted Allylboration of Chiral Nonracemic α-Substituted Allylboronates and Analysis of the Origin of Stereocontrol

Chen

Roush

2010

Org. Lett.

View full text Add to dashboard Cite

Abstractγ-Methyl substituted homoallylic alcohols 2 were prepared in 71-88% yield, E:Z > 30:1 and 93% to >95% e.e. via BF 3 ·Et 2 O-promoted allylboration with α-Me-allylboronate 1. The origin of high E selectivity is proposed.The asymmetric carbonyl allylboration reaction is a valuable method for C-C bond formation. In the vast majority of cases that have been described, the asymmetric induction derives from the use of chiral auxiliaries attached to boron.1 , 2 Although not as widely adopted in the literature, the addition of enantioenriched α-substituted allylboronates to carbonyl compounds is a useful alternative.3 -5 Pioneered by Hoffmann et al., carbonyl addition reactions of enantioenriched α-substituted allylboronates 3 proceed with near perfect chirality transfer.3 -4 A mixture of (Z)-and (E)-homoallylic alcohols 4, 5 can be generated from two competing transition states TS-3 and TS-4 (Figure 1). The ratio of the two homoallylic alcohols depends in part on the electronic property of the group at the α-position. When the α-substituent is a polar group,3 such as an alkoxy group or halogen atom, allylboration proceeds predominately via TS-3 to give (Z)-homoallylic alcohol 4. Although the exact origin of the high (Z)-selectivity remains unclear, several factors, including steric effects, dipolar effects, and stereoelectronic minimization of π-σ* delocalization in the transition states have been proposed3l and supported by computational studies.4s However, when the α-substitution is a nonpolar alkyl group,4 , 5 a mixture of (Z)-and (E)-homoallylic alcohols, 4 and 5, is often obtained. proven challenging to achieve with enantioenriched α-alkyl substituted allyl-or (E)-crotylboronates.5l-n , 9Lewis or Brønsted acid promoted allylboration with allylboronate reagents is an important emerging topic in carbonyl allylation chemistry.6 , 7 As demonstrated by Hall and coworkers, allylboration in the presence of catalytic amount of a chiral, nonracemic Lewis or Brønsted acid provides homoallylic alcohols in high yields and excellent enantioselectivities.8 However, Lewis or Brønsted acid promoted allylboration with enantioenriched, α-substituted allylboronates largely remains underdeveloped.9 Recently, Hall reported the enantioselective synthesis and Lewis acid promoted allylborations of α-TMSCH 2 substituted allylboronates that generate (E)-δ-TMSCH 2 -substituted homoallylic alcohols with excellent selectivities.9cIn connection with an ongoing problem in natural product synthesis, we had occasion to explore Lewis acid promoted allylborations of enantioenriched α-substituted allylboronates. We found and report herein that (E)-δ-methyl-homoallylic alcohols 2 are obtained in good yields and excellent enantioselectivities from BF 3 ·Et 2 O promoted allylboration reactions of 1.10 In addition, we have found that δ-chloro-substituted homoallylic alcohols 14 can also be obtained in good yield and 3-6:1 (E)-selectivity from BF 3 ·Et 2 O promoted allylboration reactions of 13. The origin of (E)-selectivity in these reactions is...

show abstract

supporting

confidence: 92%

Highly (E)-Selective BF₃·Et₂O-Promoted Allylboration of Chiral Nonracemic α-Substituted Allylboronates and Analysis of the Origin of Stereocontrol

Chen

Roush

2010

Org. Lett.

View full text Add to dashboard Cite

show abstract

“…However, if one or both reactants are racemic (or simply not enantiopure), up to eight adducts are possible: four each from the like and unlike combinations of reactant enantiomers (Figure ) . These reactions can occur with KR (one racemic reactant) or with mutual kinetic enantioselection (MKE; both reactants racemic) . Both KR and MKE are a consequence of different rate constants for the like and unlike reactions.…”

Section: Introductionmentioning

confidence: 99%

Rational Design of Aldol Reactions That Proceed via Kinetic Resolution with Switchable Enantioselectivity

2009

View full text Add to dashboard Cite

The stereoselectivity of aldol reactions of chiral reactants can be factorized into to three stereocontrol elements: the diastereoface selectivities of the ketone enol(ate) and aldehyde and the relative topicity of the coupling. Application of the multiplicativity rule to these elements leads to the prediction that kinetic resolution (KR) should be possible if all three stereocontrol elements are strongly biased. As a corollary, the enantioselectivity of the kinetic resolution should be switchable by a change in the sense of selectivity of any of the stereocontrol elements. This hypothesis was tested using aldehyde and ketone reactants with high diastereoface selectivities and developing reaction conditions that strongly favor either syn or anti relative topicity. The aldehyde 2 undergoes aldol reactions with near-exclusive Felkin diastereoface selectivity, and hydroxy-protected derivatives of ketone 1 (R = MOM, Et(3)Si, or Ac) undergo aldol reactions with high diastereoface selectivity to give 3,5-trans adducts. High levels of anti and syn relative topicity were obtained with dicyclohexylboron enolates and Ti(O(i)Pr)(4)Li "ate" enolates, respectively. Using these enolates, aldol reactions of (+/-)-2 with (+/-)-1 gave two of the eight possible diastereomeric adducts (3 from a diastereoselective like combination of reactant enantiomers and 4 from a diastereoselective unlike combination) predominantly (>95% of the adducts) in ratios of 0.05-20:1; boron enolates favored the like reaction (3:4, 15-20:1) and Ti "ate" enolates favored the unlike reaction (3:4, 1:10-20). Under these conditions, the ratio of like and unlike products is a measure of the mutual kinetic enantioselection (MKE) and reflects the ratio of the rate constants for the competing like and unlike reactions. For each of the four diastereomers of 1, the reactions with the highest MKEs in favor of the like (3) or unlike products (4) were repeated using highly enantioenriched ketone. These reactions occurred with the expected KR (s = 10-20) allowing selective access to enantioenriched diastereomers of 3 or 4 from (+/-)-2. These adducts are useful for polypropionate synthesis, and this design strategy for KR should be applicable to related processes.

show abstract

“…In an important and influential series of papers, the Evans group reported on the stereoselectivities of aldol reactions of B, Li, Si, and Ti(IV) enolates of 5 with aldehydes 6a and 6b to give 7 (Pg′ = TBS or PMB) (Scheme ) . The diastereoface selectivities of aldehydes 6a and 6b were evaluated by reactions with the analogous enolates of 8 (R = i -Pr) to give 9a . − Similarly, the diastereoface selectivities of various enolates of 4a (R = i -Pr; Pg = TBS) were evaluated by reactions with 10a (R′ = i -Pr) to give 11a . , Others have investigated aldol couplings and diastereoface selectivities of some related substrates, , and these examples together with Evans’ results provide a database that demonstrates observed stereoselectivities can be qualitatively predicted according to the principles of the multiplicativity rule . With respect to the three stereocontrol elements, the summary conclusions from these and related studies are as follows: ,, …”

Section: Introductionmentioning

confidence: 99%

A Systematic Study of the Effects of Relative Configuration, Protecting Group, and Enolate Type on the Diastereoselectivities of Aldol Reactions of a Chiral Ethyl Ketone with 2-Methylpropanal

et al. 2014

View full text Add to dashboard Cite

The diastereoselectivities of aldol reactions of 2-methylpropanal with various enolates of 5-O-methoxymethyl and 5-O-triethylsilyl derivatives of the four racemic diastereomers of 6-(2-ethyl-1,3-dioxolan-2-yl)-5-hydroxy-4-methylheptan-3-one are reported. Reactions of the (E)-enol dicyclohexylborinates, (Z)-enol 9-BBN borinates (i.e., 9-((Z)-enoxy)-9-borabicyclo[3.3.1]nonanes), Li (E)-enolates, Li (Z)-enolates, and Ti(IV) (Z)-enolates were examined. Boron and Li enolates were prepared by standard methods, but Ti(IV) enolates were obtained via transmetalation of the Li (Z)-enolates by reaction with TiCln(Oi-Pr)(4-n) (n = 0-2). Aldol relative topicity (simple diastereoselectivity) was strongly correlated to the enolate geometry: anti aldols from (E)-enolates and syn aldols from (Z)-enolates. However, for each enolate type, the diastereoface selectivities varied widely (by factors of 5-400) with the relative configuration and nature of the C5 protecting group in the 8 starting ketones. Plausible transition state models are postulated to rationalize some of these observations. The relative configurations for the complete set of 16 diastereomeric 2-(2-ethyl-1,3-dioxolan-2-yl)-7-hydroxy-3-(methoxymethoxy)-4,6,8-trimethylnonan-5-one aldol adducts were confirmed by NMR analysis of 12 acetonide derivatives prepared from the corresponding 5,7-syn diols. Examination of the NMR data for the above set of aldol adducts revealed consistent trends that were exploited to assign the relative configurations of 13 diastereomeric 2-(2-ethyl-1,3-dioxolan-2-yl)-7-hydroxy-3-(triethylsilyloxy)-4,6,8-trimethylnonan-5-one aldol adducts.

show abstract

Stereoselective synthesis and cyclisation of the acyclic precursor to auripyrone A and B

Cited by 11 publications

References 21 publications

Highly (E)-Selective BF₃·Et₂O-Promoted Allylboration of Chiral Nonracemic α-Substituted Allylboronates and Analysis of the Origin of Stereocontrol

Highly (E)-Selective BF₃·Et₂O-Promoted Allylboration of Chiral Nonracemic α-Substituted Allylboronates and Analysis of the Origin of Stereocontrol

Rational Design of Aldol Reactions That Proceed via Kinetic Resolution with Switchable Enantioselectivity

A Systematic Study of the Effects of Relative Configuration, Protecting Group, and Enolate Type on the Diastereoselectivities of Aldol Reactions of a Chiral Ethyl Ketone with 2-Methylpropanal

Contact Info

Product

Resources

About

Stereoselective synthesis and cyclisation of the acyclic precursor to auripyrone A and B

Cited by 11 publications

References 21 publications

Highly (E)-Selective BF3·Et2O-Promoted Allylboration of Chiral Nonracemic α-Substituted Allylboronates and Analysis of the Origin of Stereocontrol

Highly (E)-Selective BF3·Et2O-Promoted Allylboration of Chiral Nonracemic α-Substituted Allylboronates and Analysis of the Origin of Stereocontrol

Rational Design of Aldol Reactions That Proceed via Kinetic Resolution with Switchable Enantioselectivity

A Systematic Study of the Effects of Relative Configuration, Protecting Group, and Enolate Type on the Diastereoselectivities of Aldol Reactions of a Chiral Ethyl Ketone with 2-Methylpropanal

Contact Info

Product

Resources

About

Highly (E)-Selective BF₃·Et₂O-Promoted Allylboration of Chiral Nonracemic α-Substituted Allylboronates and Analysis of the Origin of Stereocontrol

Highly (E)-Selective BF₃·Et₂O-Promoted Allylboration of Chiral Nonracemic α-Substituted Allylboronates and Analysis of the Origin of Stereocontrol