Microwave assisted synthesis of enantiomerically pure allylboronates

Tetrahedron 66 (2010) 6550e6564

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Microwave assisted synthesis of enantiomerically pure allylboronates

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Vesna Cmrecki , Nils C. Eichenauer , Wolfgang Frey , Jorg Pietruszka

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Institut für Bioorganische Chemie, Heinrich-Heine-Universitat Düsseldorf, Forschungszentrum Jülich, Stetternicher Forst Geb. 15.8, 52428 Jülich, Germany

Institut für Organische Chemie, Universitat Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany

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Article history:

Stable allylboronates with a stereogenic centre

for stereoselective synthesis of homoallylic alcohols. Use of microwave irradiation in desilylation and

sigmatropic rearrangement reactions allows rapid synthesis of -chiral allylboronates utilized in the

highly diastereo- and enantioselective synthesis of (Z)-conﬁgured homoallylic a-hydroxy esters by allyl

additions to ethyl glyoxylate.

a to the boronic ester moiety represent versatile reagents

Received 24 February 2010

Received in revised form

15 April 2010

Accepted 22 April 2010

Available online 29 April 2010

a

Keywords:

Asymmetric synthesis

Sigmatropic rearrangement

Microwave chemistry

Allyl addition

Boronic esters

1. Introduction

chromatography still remains an issue and can conﬁne utilization of

the triﬂuoroborates.

During the last two decades, the application of microwave ir-

radiation has become increasingly popular and widespread in all

sectors of organic chemistry due to the beneﬁts in comparison with

conventional heating methods. Diversity- as well as target-directed

synthetic organic chemistry proﬁts from increased reaction rates,

higher yields, less formation of by-products and simpliﬁed pro-

cedures for a multitude of reactions.^1e3Among these, microwave

assisted synthesis has found numerous application in sigmatropic

rearrangements, due to the signiﬁcance of thermal conditions for

the outcome of the reaction.^4,5Nonetheless, to the best of our

knowledge no microwave assisted procedures of sigmatropic

rearrangements furnishing

a-chiral allylboronates have yet been

presented. The conditions reported herein provide a fast and con-

venient way for the synthesis of the title compounds via Johnson

rearrangement of boronate-substituted allylic alcohols.

The key to the successful synthesis of bench-stable and enan-

tiomerically pure a-chiral allylboronates was the development of

a new chiral auxiliary and protective group for boronic acids 1

(Scheme 1).⁶The necessity of orthogonal protection of the boronic

acid moiety and stable boronic acid equivalents has ﬁrst been

served by Genêt’s triﬂuoroborates,^7,8which have been studied in-

tensively and have found numerous applications in synthetic

chemistry. However, the puriﬁcation of the triﬂuoroborates via

Scheme 1. Diol 1: chiral auxiliary and protective group for boronic acids.

Camphor (Hoffmann⁹) or tartrate (Roush¹⁰) derived dioxabor-

olanes were widely used in the synthesis of enantiomerically pure

homoallylic alcohols, though difﬁculties in preparation of enantio-

merically pureallylboronates, instabilityand arduoushandling were

reported as a major drawback.¹¹Recently, we developed a newchiral

auxiliary 1 as a protecting group for boronic acids.^6,12,13This did not

* Corresponding author. Fax: þ492461616196; e-mail address: j.pietruszka@

fz-juelich.de (J. Pietruszka).

doi:10.1016/j.tet.2010.04.100

V. Cmrecki et al. / Tetrahedron 66 (2010) 6550e6564

6551

only provide access to enantiomerically pure allylboronates, but also

made them easy to store and handle.^14e16Diol 1 was ﬁrst synthe-

sized by Nakayama and Rainier,¹²and the procedure was continu-

ously improved by Pietruszka et al.^6,17The auxiliary 1 was

successfully applied in the asymmetric synthesis of amino acids by

Zhang et al.¹⁸While lowselectivity in DielseAlder reactions resulted

in no further investigation,¹⁹very good selectivity was observed in

the addition of enolates to furyl aldehydes bearing an adjacent

boronate group.²⁰The diol 1 has been applied by the Pietruszka group

in a manifold of reactions (Scheme 1). Therein, it was not just utilized

as a source of chiral information, its application as an extraordinarily

stable protective group for boronic acids allowed the performance of

unprecedented transformations like cyclopropanations^21e25or car-

bonyl allylations²⁶of allyl alcohol 2 furnishing homoallyl alcohols 3

(Scheme 1). The auxiliary 1 also enabled [3,3]-sigmatropic rear-

rangements of boron-containing allyl alcohol 2 leading to enantio-

and diastereomerically pure allylboronic esters 4 with a stereogenic

(Scheme 2).^6,37After protection of hydroxyl groups as a PMP-acetal

(PMP: p-methoxyphenyl), acetal 7 was subjected to exhaustive

Grignard addition with phenylmagnesium bromide in Me-THF. The

newly generated hydroxyl groups of diol 8 were methylated using

NaH/MeI giving ether 9. Afterward, the acetal 9 was cleaved oxi-

datively utilizing a mixture of NaBrO₃/Na₂S₂O₄,⁶followed by the

reduction of ester 10 with LiAlH₄: free diol 1 was obtained. The

intermediates shown were all used without any puriﬁcation, ﬂash

column chromatography on silica gel was performed only after the

last step in order to isolate pure product 1 (64% yield over four

steps).

As a major difference to previously published results,⁶THF was

replaced throughout by 2-methyl tetrahydrofuran (Me-THF) as

solvent of choice thus considerably simplifying the work-up pro-

cedure. This proved to be especially advantageous for the Grignard

reaction when using a commercially available solution of phenyl-

magnesium bromide in Me-THF. Therewith, the reaction time was

shortened and a better separation of layers during work-up was

accomplished. None the less, the choice of solvent did not inﬂuence

the reaction outcome. The diol 8 could be isolated by ﬂash column

chromatography in 88% yield for Me-THF and 92% for THF. Diethyl

ether seemed to be rather inappropriate due to the low solubility of

substrate 7, and agglutination of the reaction mixture was observed

temporarily while adding the Grignard reagent. Nevertheless,

suspension of the substrate in a threefold amount of solvent ﬁnally

led to the isolation of 71% of alcohol 8 after chromatography.

centre inthea

-positiontotheboronicestermoiety.^14e16Furthermore,

highly selective allyl additions of allylboronic esters led to enantio-

merically pure homoallylic alcohols with a (Z)-double bond (Scheme

13).²⁷The general need for a protective group, which would allow

a multitude of transformations in presence of a boronate moiety, can

be measured by the attention paid to MIDA (N-methyliminodiacetic

acid) protected boronates developed in 1986 by Wrackmayer²⁸and

recently elegantly applied by Gillis and Burke.^29,30

Herein, the potential of the auxiliary 1 and its unprecedented

stability was proven one more time utilizing microwave assisted

conversions in the presence of the corresponding dioxaborolane.

Furthermore, we wished to extend the scope of allylboronates

obtained after [3,3]-sigmatropic rearrangements (4 and 5) by

adding the reagents to ethyl glyoxylate. In doing so, the synthesis of

2.2. Synthesis of allyl alcohols 2

In order to obtain (E)-conﬁgured allyl alcohols, two well estab-

lished steps were performed:¹⁵First, the corresponding TBS-pro-

tected propargylic alcohols 10^16,38e40were submitted to a one-pot

hydroboration,^16,41oxidation, and transesteriﬁcation sequence,

furnishing silyl-protected allyl alcohols 11, which were directly

used in the next step without any further puriﬁcation (Scheme 3).

Cleavage of the silyl protective group under the acidic conditions

yielded free allyl alcohols 2. Besides known allyl alcohols 2a (R¼H),

2b (R¼Me), and 2c (R¼Ph), the hydroboration was extended to new

enantiomerically pure boron-containing allyl alcohols (S)-2d and

(R)-2d (R¼n-Pe: 82% and 67% yield, respectively).

(Z)-conﬁgured esters of homoallylic

a-hydroxy acids would be

feasable, a motif present in a number of natural products and ap-

plied in the synthesis of related substructures.^31e36

2. Results and discussion

2.1. Synthesis of chiral auxiliary and protective group 1

The synthesis of protective group 1 for the boronic acids was

further optimized commencing from (þ)-dimethyl tartrate

6

Scheme 3. Conditions: (i) (a) 1 equiv BH₃$SMe₂, 2 equiv cyclohexene; 1 equiv 11, DME,

rt, 1 h; (b) 2 equiv Me₃NO; (c) 1 equiv 1, rt; (ii) 0.1 M HCl, CH₂Cl₂/MeOH, rt, up to 24 h.

The deprotection of the silyl group of 12 under acidic conditions

was successful, but rather slow; for the n-pentyl-derivative 12d the

reaction time exceeded 20 h. The addition of more equivalents of

0.1 M HCl did not accelerate the reaction considerably. Therefore,

microwave (MW) assisted closed vessel desilylation was attempted

and it was found that microwave irradiation accelerated the

Scheme 2. Conditions: (i) 5.6 equiv PhMgBr, Me-THF, 0 ^ꢀC to rt, 1 h; (ii) 3 equiv NaH,

3 equiv MeI, Me-THF, rt, 3 days; (iii) 3 equiv NaBrO₃, 3 equiv Na₂S₂O₄, H₂O/EtOAc, 0 ^ꢀ

to rt, 2 h; (iv) LiAlH₄, Me-THF, 0 ^ꢀC to rt, over night (64% over four steps).

C

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V. Cmrecki et al. / Tetrahedron 66 (2010) 6550e6564

cleavage. For silyl-protected alcohols 12a and 12b, full conversion

was detected after only 15 min stirring at 60 ^ꢀC at 200 W releasing

the corresponding free alcohol 2a and (S)-2b in 84% and 78% yield

(Scheme 4), respectively. For the deprotection of ether 12a on larger

scale, a microwave assisted open vessel protocol was employed

without decreasing the yield (2a: 82%).

13dunder the best conditions found (entry 7)din good yield (78%)

and as a 1:1 mixture of diastereoisomers in 9 min, only. The same

conditions were applied for the Johnson rearrangement of sec-

ondary allyl alcohols (S)- and (R)-2d furnishing only one di-

astereoisomer (S)-14 (87%) and (R)-14 (75%), respectively. The

obtained allylboronic esters were air- and moisture-stable colorless

solids that were separated and puriﬁed via MPLC.

The rearrangement of the secondary allyl alcohols 2bed with

triethylortho propionate allowed the introduction of an additional

methyl group in 2-position of ester 15. All conducted Johnson

rearrangements elapsed in a very good yield (79e89%), both under

conventional conditions as well as under microwave irradiation

(Scheme 6, entries 1e6): The rearrangement of the (R)-allyl alco-

hols 2b and 2d furnished the expected 1:1 mixtures of di-

astereoisomers (3S)-15b and (3S)-15d independent of the method

applied. Improved diastereoselectivity was observed for the cor-

responding alcohols (S)-2b, (S)-2d, and (R)-2c, respectively, fur-

nishing (3R)-15bed allylboronic esters. Unfortunately all attempt

to separate the mixtures of diastereoisomers via MPLC failed.

As expected, Johnson rearrangement of 2a with triethylortho

propionate (Scheme 6, entry 1) afforded a complex mixture in-

cluding the desired four isomers. After extensive attempts to purify

the crude product, we were fortunate to obtain a small sample of

the pure diastereoisomer (2S,3R)-15a whose conﬁguration was

conﬁrmed after cross metathesis with styrene to yield enantio-

merically pure allylboronic ester (2S,3R)-15c (Scheme 7): X-ray

analysis of ester (2S,3R)-15c enabled the unequivocal assignment of

the absolute conﬁguration also conﬁrming our assumption of 1,3-

chirality transfer when using (R)-2c as substrate for the rear-

rangement.⁴²On the basis of this result, we succeeded to assign the

conﬁguration of all diastereoisomers from the mixtures 15bed (see

Experimental section) by comparison of the NMR data. It was found

that the coupling constant ³J_2,3in ¹H NMR (w10 Hz for syn-15; ³J_2,3

w5 Hz for anti-15) and the chemical shifts of the 2-CH₃in the ¹³C

Scheme 4. Conditions (MW): 0.1 M HCl, CH₂Cl₂/MeOH, 60 ^ꢀC, 200 W, 15 min.

2.3. [3,3]-Sigmatropic rearrangements

With allyl alcohols 2 in hand, [3,3]-sigmatropic rearrangements

were performed. Besides conventional conditions already estab-

lished in the group for the Johnson reaction,¹⁴requiring relatively

long reaction times and strict exclusion of moisture, a microwave

assisted closed vessel protocol was employed in the synthesis of a-

chiral allylboronates (Scheme 5). The procedure was optimized for

the transformation of allyl alcohol 2a (Scheme 5, entry 1: conven-

tional conditions, 72% yield, 4 h): We were pleased to observe that

under almost identical conditions (triethylortho acetate, cat. pro-

pionic acid, 135 ^ꢀC) the rearrangement was also possible in the

microwave, albeit not in high yield (entry 2þ3). Increasing the

temperature to 160 ^ꢀC (entries 4e7) furnished allylboronic esters

Scheme 6. Conditions: A 7 equiv EtC(OEt)₃, cat. EtCO₂H, 135 ^ꢀC, 4 h; B 7 equiv EtC

(OEt)₃, cat. EtCO₂H, DMF, 160 ^ꢀC, 200 W, 9 min. [a] The yield was not determined since

a complex mixture (including four diastereoisomers) was formed.

Scheme 5. Microwave assisted Johnson rearrangement with triethylortho acetate.

V. Cmrecki et al. / Tetrahedron 66 (2010) 6550e6564

6553

conventional reaction conditions (conditions A: toluene, 80 ^ꢀC) the

diastereomerically pure allylboronic esters 16aed were formed in

good yield and perfect selectivityafter 36 h. As previously reported,¹⁵

the rearrangement of the alcohol 2a (R¼H) afforded a 1:1 mixture of

diastereoisomers (entry 1; the isomers are separable by MPLC). All

attempts at utilizing the microwave reactor (conditions B: 80 ^ꢀC,

200 W in DMF) were unsuccessful (entry 2), no conversion was

detected.

The conﬁguration of allylboronates 16bed was ﬁrst assumed on

the basis of the already known 1,3-chirality transfer (vide supra). In

order to conﬁrm the results, allyl additions to benzaldehyde were

performed with new reagents (R)- and (S)-16b. As expected, (Z)-

homoallyl alcohols 17 were formed in 45e70% yield as essentially

single enantiomers (ee >97%; Scheme 9). The absolute conﬁgura-

tion was proven by chemical correlation: ozonolysis of homoallyl

alcohols (R,R)-17 and (S,S)-17 furnished (after reductive work-up)

the corresponding known diols 18 (X-ray analysis). Based on the

reported^13,43,44optical rotation not only their conﬁguration was

determined, but also the corresponding reagents 16b could be

assigned. The rational behind it can be explained in full agreement

with the ﬁndings of Hoffmann,^45,46by assuming a transition state

(Fig. 1) with the side chain X in 19 being in axial position.¹⁴The

results were later further substantiated by successful X-ray struc-

ture analyses of reagents (S)-16b and (S)-16c (Figs. 2 and 3).

Scheme 7. Conditions: (i) 0.1 equiv Grubbs II catalyst, 2.0 equiv styrene, CH₂Cl₂, 40 ^ꢀC,

21 h, 66%; (ii) 7.0 equiv EtC(OEt)₃, cat. EtCO₂H, 135 ^ꢀC, 4 h, syn:anti¼72:28, 79%. Crystal

structure analysis⁴²from allylboronate (2S,3R)-15c obtained by cross metathesis from

alcohol (2S,3R)-15a.

NMR [2-CH₃

Δd w2 ppm (syn-15-anti-15)] are diagnostic for the

assignment of the absolute conﬁguration and especially the syn/

anti relationship between 2-H and 3-H of the allylboronic esters 15.

Next, the Eschenmoser rearrangement of allyl alcohols 2aed was

investigated furnishing the corresponding diastereo- and enantio-

merically pure allylboronic esters 16aed (Scheme 8): Under

Scheme 9. Conditions: (i) 1.2 equiv PhCHO, CH₂Cl₂, 0 ^ꢀC to rt; (ii) a O₃, CH₂Cl₂, ꢁ78 ^ꢀC,

8 min; b Me₂S, rt; c LiAlH₄, THF, ꢁ78 ^ꢀC to rt, 1 h.

To conclude, microwave assisted closed vessel conditions

allowed temperatures above the boiling points of the reagents thus

enabling the accelerated synthesis of the desired allylboronates via

the Johnson albeit not via the Eschenmoser rearrangement. For the

ﬁrst case, comparing conventional conditions and microwave

Scheme 8. Conditions: A 2 equiv MeC(OMe)₂NMe₂, toluene, 80 ^ꢀC, 36 h; B: 2 equiv

MeC(OMe)₂NMe₂, toluene, DMF, 80 ^ꢀC, 200 W 10 min. s.m.¼starting material.

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V. Cmrecki et al. / Tetrahedron 66 (2010) 6550e6564

Figure 1. Favored transition state 19 for allyl additions of allylboronic esters 16 to

aldehydes.

Scheme 10. Conditions: (i) 1.2 equiv 22, CH₂Cl₂, 0 ^ꢀC to rt.

Figure 2. Crystal structure analysis of amide (S)-16b.⁴²

Scheme 11. Conditions: (i) 1.2 equiv 22, CH₂Cl₂, 0 ^ꢀC to rt.

Figure 3. Crystal structure analysis of amide (S)-16c.⁴²

12). As a matter of fact, the addition of allylboronate (R)-13 to al-

dehyde 22 was signiﬁcantly faster compared with the conventional

transformation (from to 2 days to 3 h); at the same time the yields

of homoallyl alcohol (2R)-23a were comparable (rt: 83%; MW:

77%). Unfortunately selectivity decreased from 99% ee to 89% ee

(Fig. 4): For comparison, the allyl addition was also performed at

65 ^ꢀC using an oil bath as heating device for 3 h furnishing highly

enriched product (2R)-23a (99% ee!), albeit still contaminated with

some starting material (yield not determined). The stated conﬁg-

uration of the ethyl glyoxylate adducts 23a was deduced in analogy

to our previous ﬁndings.

synthesis showed that there are no major differences considering

yield or selectivity. The conﬁguration of all new reagents could be

assigned either by correlation or from the X-ray structure analysis.

2.4. Allyl additions

In order to gain access to acyclic (Z)-conﬁgured homoallylic a-

hydroxy esters, we investigated the applicability of the synthesized

allylboronates 13, 16b, 20e21^14,16,27in allyl addition using ethyl

glyoxylate (22) as electrophile (Schemes 10 and 11). To our delight,

all additions yielded exclusively the desired (Z)-homoallyl alcohols

23 (up to 85% yield). The selectivity given was always determined

from the crude NMR spectrum of the intermediate 24 before

chromatography was performed. Hydrolysis of the chiral boron

auxiliary was accomplished during the chromatographic puriﬁca-

tion of intermediate 24 on silica gel to yield enantiomerically pure

(Z)-homoallyl alcohols 23 (HPLC analysis). It should be noted that

the auxiliary was recovered by reduction of all diol-containing

boron residues with LiAlH₄and was reused.

In the last step, it was again attempted to shorten the reaction

time of the allyl addition by means of microwave heating (Scheme

Scheme 12. Allyl additionsdeffect of microwave irradiation.

V. Cmrecki et al. / Tetrahedron 66 (2010) 6550e6564

6555

using a Büchi Melting Point B-540 and are not corrected. Optical

rotation was measured with a tempered polarimeter PerkineElmer

(241 MC or precisely 341) at

l

¼589 nm (sodium-D-line) and 20 ^ꢀC

in a cell of 1 dm length. Infrared spectra were recorded on FTIR

from PerkineElmer (SpectrumOne). Samples were measured either

as a solution in CHCl₃or neat on the ATR-sample head. The posi-

tions of the absorption bands are given in cm^ꢁ1. Mass spectra were

measured at the Zentralabteilung für chemische Analysen des

Forschungszentrums Jülich or using the following instruments

(IBOC): ESI (LC/MS)dFinnigan MAT LC-Q; GC/MS (EI)dHewlett

Packard HP6890, HP5973; ESI (LC/MS-MS)dApplied Biosystems

QTrap 4000. Elemental analyses were performed at the For-

schungszentrums Jülich or at the Institute of Organic Chemistry,

Stuttgart. NMR Spectra were recorded at 300 K using the following

instruments: Bruker ARX 300; Bruker Advance/DRX 600. The

chemical shifts

d are given in parts per million relative to the in-

Figure 4. HPLC trace of the allyl addition of allylboronic ester 23 to ethyl glyoxylate 22,

utilizing (a) a 1:1 mixture of (S)-13 and (R)-13, (b) (S)-13 (0 ^ꢀC to rt), (c) (R)-13 (0 ^ꢀC to

rt), (d) (R)-13 (MW, 65 ^ꢀC), (e) (R)-13 (oil bath, 65 ^ꢀC).

ternal standard TMS (¹H: 0.00 ppm) or relative to the resonance of

the solvent (e.g., ¹H: CHCl₃, 7.26 ppm; ¹³C: CHCl₃, 77.0 ppm). J is

given in hertz; in spectra of higher order the ds and Js were not

corrected. The NMR signals were assigned by means of DEPT-,

HeH-, and CeHeCOSY spectra.

3. Conclusion

The following compounds were synthesized according to liter-

ature procedures.^6,14e16,272a, (R)-2b, (R)-2c, (S)-2b, (S)-2c, 7, 11a,

(R)-11b, (R)-11c, (S)-11b, 12a, (R)-12b, (R)-12c, (S)-12b, (R)-13, (S)-

13, (R)-16a, (S)-16a, (R)-20, (S)-20; (R)-21, (S)-21.

In summary, we have successfully applied diol 1 in the synthesis

of allylboronates 13e16, proving the surprisingly high stability by

utilizing microwave assisted transformations in their presence.

Noteworthy are not only the successful desilylations, but especially

the [3,3]-sigmatropic rearrangements toward allylboronic esters

13e15. En route the synthesis of auxiliary 1 was improved, the

conﬁgurations of the reagents were assigned, and the formation of

4.1.1. General procedure 1: introduction of silyl-protecting groups. In

a Schlenk-ﬂask equipped with a magnetic stirrer bar and a septum,

the corresponding alcohol (1.00 equiv) was dissolved in abs CH₂Cl₂

(0.75 mL/mmol alcohol) under an inert atmosphere of argon. The

solution was cooled to 0 ^ꢀC before imidazole (1.10 equiv) and

subsequently TBSCl (1.00 equiv) was added. A colorless precipitate

was formed and the reaction mixture was stirred at room tem-

perature over night. Hydrolysis with water was followed by ex-

traction with n-pentane. The combined organic layer was washed

with brine and dried over MgSO₄. The solvents were evaporated

under reduced pressure and the crude product was puriﬁed either

by ﬂash column chromatography on silica gel or by distillation as

indicated.

essentially enantiomerically pure (Z)-conﬁgured homoallylic

hydroxy esters 23 was achieved.

a-

4. Experimental section

4.1. General methods and materials

All reagents (including Me-THF) were used as purchased from

commercial suppliers without any further puriﬁcation, if not in-

dicated differently. The reactions were carried out using Schlenk

techniques under an atmosphere of dry argon or nitrogen. Glass-

ware was oven-dried at 120 ^ꢀC over night prior to use. Solvents

were dried and puriﬁed by conventional methods prior to use.

Toluene, dichloromethane (CH₂Cl₂), tetrahydrofuran (THF), and

diethyl ether (Et₂O) were dried in a Solvent Puriﬁcation System:

MBraun, MB SPS-800. O₃/O₂mixtures were generated with Ozon-

Generator 500 from Fischer Technology with an oxygen stream of

150 L/h at the maximum power of the instrument. Solvent evapo-

ration under reduced pressure was performed on rotary evapora-

tors at 40 ^ꢀC (water bath), if not indicated differently. Microwave

syntheses were performed using a CEM Discover^ÒLabMateTH/

ExplorerPLS^Òmonomode reactor. Reaction time under MW con-

ditions corresponds to the actual reaction time at given tempera-

ture without ramp time needed to reach the desired temperature.

High pressure liquid chromatography was performed on Gynkotek

and Dionex systems using chiral columns Chiralcel OD, Chiralcel

OD-H, Chiralpak IC, and Chiralpak IA (Daicel). As eluent, mixtures of

n-heptane or n-hexane and i-propanol (i-PrOH) were used. Pre-

parative Medium Pressure Liquid Chromatography (MPLC on silica

4.1.2. General procedure 2: hydroboration of alkynes. In a Schlenk-

ﬂask equipped with a stirrer bar and a septum were placed abs

cyclohexene (2.00 equiv) and abs 1,2-dimethoxyethane (DME)

(2 mL/mmol alkyne) under an atmosphere of dry nitrogen. The

mixture was treated at 0 ^ꢀC with 10 M BH₃$SMe₂(1.00 equiv);

a colorless precipitate formed within 30 min. The reaction mixture

was warmed to room temperature before the corresponding alkyne

(1.00 equiv) was added. Stirring was continued for 1 h at room

temperature; the precipitate dissolved within the hour. The re-

action mixture was treated with Me₃NO$2H₂O (1.90 equiv), stirred

for 1 h, and diol 1 (1.00 equiv) was added. After complete con-

sumption of the starting material was indicated by TLC, the solvent

was removed under reduced pressure and the crude product was

puriﬁed by ﬂash column chromatography on silica gel as indicated.

4.1.3. General procedure 3: deprotection of silyl-protected allyl al-

cohols with HCl. The corresponding silyl ether was dissolved in

a minimum amount of CH₂Cl₂and ethanol or methanol (7.64 mL/

mmol of silyl ether) before it was treated with a solution of concd

gel 15e25 mm, 60 Å; UV detection at 254 nm) was performed on

Labomatic instruments. Mixtures of petroleum ether (PE) and ethyl

acetate (EtOAc) were used as eluent. Flash column chromatography

was performed using silica gel 0.040e0.063 mm (400e230 mesh)

from Macherey/Nagel. Crystal structure analyses were performed

at the Institute for Organic Chemistry, Stuttgart using Nicolet P 3

Refractometer with graphite-monochromator, Mo- or Cu- cathode.

The program SHELXS-97 was used. Melting points were measured

hydrochloric acid (159 mL/mmol silyl ether, w2.30 mmol) in etha-

nol or methanol (1.43 mL/mmol silyl ether). The reaction mixture

was stirred at room temperature; the reaction was quenched with

NaHCO₃(aq) after complete consumption of starting material (as

judged by TLC). The volume of the solvent was reduced under re-

duced pressure and water was added. The aqueous layer was

extracted three times with Et₂O. The combined organic layer was

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V. Cmrecki et al. / Tetrahedron 66 (2010) 6550e6564

washed with brine and dried over MgSO₄. The solvents were re-

moved under reduced pressure and the crude product was puriﬁed

by ﬂash column chromatography on silica gel as indicated.

product was puriﬁed by ﬂash column chromatography on silica gel

and MPLC as indicated.

4.1.8. General procedure 8: allyl addition. In

a Schlenk-ﬂask

4.1.4. General procedure 4: deprotection of silyl-protected allyl al-

cohols in a microwave reactor. In a microwave vessel equipped with

a stirrer bar and a septum the corresponding silyl ether (1.00 equiv)

was dissolved in a minimum amount of CH₂Cl₂and methanol

(7.64 mL/mmol of silyl ether) before it was treated with a solution

equipped with a stirrer bar and a septum, the corresponding

allylboronic ester (1.00 equiv) was dissolved in CH₂Cl₂(0.50 mL/

mmol ester) under an atmosphere of dry argon. The solution was

treated with the appropriate aldehyde (1.10e1.50 equiv) at 0 ^ꢀC

and was warmed over night to room temperature. The progress of

the reaction was monitored by TLC. After the complete conversion

was determined, the solvent was removed under reduced pres-

sure. The diastereomeric ratio of the crude product was de-

termined by ¹H and ¹³C NMR spectroscopy. The crude product was

puriﬁed by ﬂash column chromatography on silica gel as

indicated.

of concd hydrochloric acid (159 mL/mmol silyl ether, w1.92 mmol)

in ethanol (1.43 mL/mmol silyl ether). The reaction was carried out

according to the closed vessel method at 60 ^ꢀC, 200 W for 15 min in

a CEM Microwave. After cooling to room temperature, the reaction

was quenched by addition of saturated NaHCO₃(aq) and the vol-

ume of the solvent was reduced under reduced pressure. Water was

added and the aqueous layer was extracted three times with Et₂O.

The combined organic layer was washed with brine and dried over

MgSO₄. The solvents were removed under reduced pressure and

the crude product was puriﬁed by ﬂash column chromatography on

silica gel as indicated.

4.2. Synthesis of chiral auxiliary and protective group (1)

4.2.1. (4R,5R)-(2-(4-Methoxyphenyl)-1,3-dioxolane-4,5-diyl)bis(di-

phenylmethanol) (8). A 500 mL Schlenk ﬂask was charged with

dicarboxylate 7⁶(10.0 g, 33.8 mmol) and Me-THF (60 mL) and

cooled to 0 ^ꢀC. A solution of phenylmagnesium bromide in Me-THF

(45%, 68 mL, 197 mmol) was added via a double-tipped cannula to

the stirred solution. After removal of the ice-bath stirring was

continued for 1 h at room temperature; TLC indicated complete

conversion of diester 7. The mixture was diluted with Me-THF

(40 mL) and quenched by adding 75% satd aqueous NH₄Cl (260 mL).

The two layers were separated and the aqueous layer was extracted

with Me-THF (5ꢂ40 mL). The combined organic layer was washed

with brine (140 mL) and dried over MgSO₄. The solvent was

evaporated under reduced pressure to yield 20.2 g of crude bis

(diphenylmethanol) 8 as a yellow foam, which was used in the next

step without further puriﬁcation.

4.1.5. General procedure 5: microwave assisted Johnson re-

arrangement. In a microwave vessel equipped with a stirrer bar and

a septum the corresponding allyl alcohol (1.00 equiv) was dissolved

in triethyl orthoacetate (7.10 equiv) or triethyl orthopropionate

(7.10 equiv) containing

a catalytic amount of propionic acid

(4.34 L/mmol allyl alcohol) and N,N-dimethylformamide (DMF)

m

(1.35 mL/mmol allyl alcohol). The reaction was carried out

according to the closed vessel method at 160 ^ꢀC, 200 W for 9 min in

a CEM Microwave. After cooling to room temperature, the solvent

was removed under reduced pressure (10^ꢁ3hPa). The di-

astereomeric ratio of the crude product was determined by ¹H and

¹³C NMR spectroscopy. The crude sample was puriﬁed by ﬂash

column chromatography on silica gel as indicated.

Solvent screening for 2-Me-THF, THF, and diethyl ether:

A 100 mL Schlenk ﬂask was charged with dicarboxylate 7⁶

(1.5 g, 5.06 mmol) and the appropriate solvent (Me-THF and

THF: 8.5 mL; Et₂O: 25.5 mL). The stirred solution/suspension was

cooled to 0 ^ꢀC and a solution of phenylmagnesium bromide (Me-

THF 45%; Et₂O 45%; THF 17%) (28.35 mmol) was added. The

cooling bath was removed and after 45 min (Me-THF/THF) or 2 h

(Et₂O), the reaction was quenched by addition of 75% satd

aqueous NH₄Cl (8 mL/mmol PhMgBr). The aqueous layer was

extracted with the solvent used (5ꢂ10 mL), the combined organic

layer was washed with brine (25 mL) and dried over MgSO₄. Flash

column chromatography (90% PE/EtOAc to 80% PE/EtOAc) yielded

2.42 g (Me-THF: 4.44 mmol, 88%), 2.54 g (THF: 4.66 mmol, 92%),

and 1.97 g (Et₂O: 3.62 mmol, 71%) of compound 8 as a colorless

foam. All spectroscopic data are in full agreement with literature

data.¹²

4.1.6. General procedure 6: Johnson rearrangement (standard con-

ditions). In a round-bottom ﬂask equipped with a magnetic stirrer

bar, Claisen condenser and a drying tube, the corresponding allyl

alcohol (1.00 equiv) was dissolved in triethyl orthopropionate or

triethyl orthoacetate (7.10 equiv) containing a catalytic amount of

propionic acid (4.34 mL/mmol allyl alcohol) under an atmosphere

of dry nitrogen. The reaction mixture was then heated (exactly

135 ^ꢀC) for up to 4 h. During the ﬁrst 2 h of the reaction, the at-

tached Claisen condenser was heated to accelerate the removal of

the formed ethanol (EtOH). The progress of the reaction was

monitored by TLC. After complete conversion was determined, the

reaction mixture was cooled to room temperature and the solvent

was removed under reduced pressure (10^ꢁ3hPa). The di-

astereomeric ratio of the crude product was determined by ¹H and

¹³C NMR spectroscopy. The crude product was puriﬁed by ﬂash

column chromatography on silica gel and MPLC as indicated.

4.2.2. (4R,5R)-4,5-Bis(methoxydiphenylmethyl)-2-(4⁰-methox-

yphenyl)-1,3-dioxolane (9). A ﬂame dried 500 mL Schlenk-ﬂask

equipped with a magnetic stirrer bar and a rubber septum was

charged with crude bis(diphenylmethanol) 8 (20.2 g) obtained in

the previous step and Me-THF (75 mL). After the addition of NaH

(95%; 2.53 g, 100.1 mmol) at 0 ^ꢀC, the solution was stirred at room

temperature for 30 min, then MeI (6.2 mL, 100 mmol) was added

and stirred at room temperature over night. NaH (2.53 g,

100.1 mmol) and MeI were added, and after stirring for 2 days at

room temperature the same amount of NaH and MeI was added

once more. After stiring over night, the reaction mixture was di-

luted with 85 mL of Me-THF and quenched carefully by initially

adding H₂O (85 mL) dropwise. The aqueous layer was extracted

with Me-THF (3ꢂ85 mL), and the combined organic layer was

washed with H₂O (5ꢂ65 mL), brine (70 mL), and dried over MgSO₄.

Evaporation of the solvent yielded the crude product 9 (19.0 g) as

4.1.7. General procedure 7: Eschenmoser rearrangement. In a round-

bottom ﬂask equipped with a magnetic stirrer bar, Claisen con-

denser and

a drying tube, the corresponding allyl alcohol

(1.00 equiv) was dissolved in toluene (2.00 mL/mmol allyl alcohol)

under an atmosphere of dry nitrogen. The solution was treated with

a

90% solution of N,N-dimethylacetamide dimethyl acetal

(2.00 equiv) and was then heated (exactly 80 ^ꢀC) for 24e36 h.

During the ﬁrst 2 h of the reaction, the attached Claisen condenser

was heated to accelerate the removal of the formed methanol. The

progress of the reaction was monitored by TLC. After the complete

conversion was determined, the reaction mixture was cooled to

room temperature and the solvent was removed under reduced

pressure (10^ꢁ3hPa). The diastereomeric ratio of the crude product

was determined by ¹H and ¹³C NMR spectroscopy. The crude

V. Cmrecki et al. / Tetrahedron 66 (2010) 6550e6564

6557

a yellow foam. The product was used in the next step without

further puriﬁcation.

³J 6.8 Hz, CH₃), 1.26e1.45 (6H, m, CH₃CH₂CH₂CH₂CH₂), 1.66 (2H, m,

CH₃CH₂CH₂CH₂CH₂), 2.37 (1H, d, ⁴J 2.1 Hz, C^CH), 4.33 (1H, td, ³J

6.5 Hz, ⁴J 2.1 Hz, CHOTBS); ¹³C NMR (CDCl₃, 151 MHz) ꢁ5.0 (CH₃Si),

ꢁ4.6 (CH₃Si), 14.0, 18.2 ((CH₃)₃CSi), 22.5 (CH₃), 24.7, 25.7, 31.4, 38.5

(CH₃CH₂CH₂CH₂CH₂), 62.7 (CHOTBS), 71.8, 85.7 (CHC^CH); GC/MS

(EI, 70 eV, H₂): t_ret7.7 min, m/z 183 (10) [(C₁₀H₁₉OSi)^þ], 169 (12)

[(C₉H₁₇OSi)^þ], 113 (100), 107 (5), 83 (45), 75 (100), 55 (10).

4.2.3. (2R,3R)-3-Hydroxy-1,4-dimethoxy-1,1,4,4-tetraphenylbutan-2-

yl 4-methoxybenzoate (10). A 250 mL round-bottom ﬂask equipped

with a magnetic stirrer bar and a pressure-equalizing addition

funnel was charged with crude dimethyl ether 9 (19.0 g) and EtOAc

(65 mL). A solution of NaBrO₃(15.1 g, 100 mmol in 50 mL H₂O) was

added within 15 min. The two-phase mixture was cooled to 0 ^ꢀC

and a solution of Na₂S₂O₄(17.4 g, 100 mmol in 50 mL H₂O) was

added dropwise while stirring continuously. Upon complete addi-

tion of the dithionite solution the deep red color vanished, and

more of the NaBrO₃solution (5.00 g, 33.1 mmol in 20 mL H₂O) was

added. The red color persisted and after 2 h of vigorous stirring at

room temperature TLC indicated complete conversion of the

starting material. The mixture was diluted with EtOAc (65 mL) and

the aqueous layer was extracted with EtOAc (3ꢂ85 mL). The com-

bined organic layer was washed with aqueous 2 M Na₂S₂O₃solu-

tion (12ꢂ60 mL) and brine (2ꢂ60 mL), dried over MgSO₄, and

concentrated to yield the crude product 10 as a yellow foam. It was

dissolved in CH₂Cl₂(130 mL) and reﬂuxed with charcoal (1.3 g) for

1 h. The mixture was cooled to room temperature and ﬁltered

through a pad of Celite^Ò. The solvent was removed under reduced

pressure. The resulting pale yellow foam was used in the next step

without further puriﬁcation.

4.3.2. (E,4⁰R,5⁰R)-3-[4⁰,5⁰-Bis(methoxydiphenylmethyl)-1⁰,3⁰,2⁰-dioxa-

borolan-2⁰-yl]prop-2-en-1-ol (2a). According to general procedure

4 silyl ether 12a^14,17(250 mg, 0.39 mmol) was dissolved in a mini-

mum amount of CH₂Cl₂and solution of concd hydrochloric acid

(97 mL, approx. 1.18 mmol) in methanol (0.56 mL) was added. The

mixture was irradiated and worked up as described. Flash column

chromatography (90% PE/EtOAc to 70% PE/EtOAc) yielded 172.4 mg

(0.33 mmol, 84%) of compound 2a as a colorless foam.

Open vessel protocol: A 100 mL round-bottom ﬂask was charged

with a stirrer bar and silyl ether 12a^14,17(11.70 g, 18.37 mmol) was

dissolved in a minimum amount of CH₂Cl₂. A solution of concd

hydrochloric acid (4.56 mL, 55.1 mmol) in methanol (26.3 mL) was

added. The ﬂask was placed in a microwave reactor and equipped

with a reﬂux condenser. The reaction mixture was irradiated for

6 min with a ﬁxed power of 200 W, reaching a measured tempera-

ture of 68 ^ꢀC. The mixture was cooled down and saturated aqueous

NaHCO₃was added until neutral. The layers were separated and the

aqueous phase was extracted with diethyl ether (4ꢂ150 mL). The

combined organic layer was dried over MgSO₄and evaporated to

give the crude product. Flash column ﬂash chromatography (90% PE/

EtOAc to 70% PE/EtOAc) yielded 7.85 g (15.08 mmol, 82%) of title

4.2.4. (2R,3R)-1,4-Dimethoxy-1,1,4,4-tetraphenylbutane-2,3-diol

(1). A 250 mL Schlenk-ﬂask equipped with a magnetic stirrer bar

and a rubber septum was charged with 4-methoxybenzoate 10

and Me-THF (140 mL). The mixture was cooled to 0 ^ꢀC, LiAlH₄

(3.8 g, 100.1 mmol) was added and stirred over night. The mix-

ture was diluted with Me-THF (35 mL), the reductant was hy-

drolyzed by addition of H₂O (3.7 mL), aqueous 15% NaOH

(3.7 mL), and H₂O (3.7 mL). The formed precipitate was removed

by ﬁltration through a pad of Celite^Ò, and the ﬁlter cake was

thoroughly washed with Me-THF. The ﬁltrate was dried over

MgSO₄and concentrated under reduced pressure to yield the

crude compound 1 as a yellowish resin. Flash column chroma-

compound 2a as a colorless foam. [

a

]

²⁰ꢁ81 (c 1.0, CHCl₃). All spec-

D

troscopic data are in full agreement with those previously

published.¹⁴

4.3.3. (3S,E,4⁰R,5⁰R)-4-[4⁰,5⁰-Bis(methoxydiphenylmethyl)-1⁰,3⁰,2⁰-di-

oxaborolan-2⁰-yl]but-3-en-2-ol [(S)-2b]. According to general pro-

cedure 3 silyl ether (S)-12b¹⁶(6.29 g, 9.70 mmol, 1.00 equiv) was

dissolved in a minimum amount of CH₂Cl₂and methanol (74.0 mL)

was added; the mixture was treated with a solution of concd

hydrochloric acid (1.84 mL, 22.3 mmol, 2.30 equiv) in methanol

(14.0 mL) for 4 h. The crude product was puriﬁed by ﬂash column

chromatography on silica gel (85% PE/EtOAc) affording alcohol (S)-

2b as a colorless foam (2.14 g, 3.98 mmol, 41%).

tography (93% PE/EtOAc) of the crude product led to the isolation

20

of 9.8 g (21.56 mmol, 64%) of diol 1 as a colorless foam. [a]

D

þ60.0 (c 1.0, CHCl₃) All spectroscopic data are in full agreement

with those previously published.⁶

According to general procedure 4 silyl ether (S)-12b¹⁶(68.9 mg,

0.11 mmol, 1.0 equiv) was dissolved in a minimum amount of

CH₂Cl₂and methanol (0.80 mL), and treated with a solution of

4.3. Synthesis of allyl alcohols (2)

4.3.1. (S)- and (R)-tert-Butyldimethyl(oct-1-yn-3-yloxy)silane [(S)-

11d] and [(R)-11d]. According to general procedure 1 (S)-1-octyn-

3-ol (800 mg, 6.34 mmol, 1.00 equiv) in abs CH₂Cl₂(13.0 mL) was

treated with imidazole (453 mg, 6.65 mmol, 1.10 equiv) and TBSCl

(1.11 g, 6.97 mmol, 1.00 equiv) at 0 ^ꢀC. The reaction mixture was

stirred at room temperature for 6 h. The crude product was puriﬁed

by ﬂash column chromatography on silica gel (98% n-pentane/Et₂O)

to yield ether (S)-11d as a light yellow liquid (1.41 g, 6.21 mmol,

98%). Enantiomer (general procedure 1): (R)-(þ)-1-octyn-3-ol

(952 mg, 7.54 mmol, 1.0 equiv) in abs CH₂Cl₂(15.0 mL) was treated

with imidazole (565 mg, 8.29 mmol, 1.1 equiv) and TBSCl (1.14 g,

7.54 mmol, 1.0 equiv). The reaction mixture was stirred at room

temperature for 5 h. The crude product was puriﬁed by ﬂash col-

umn chromatography on silica gel (98% n-pentane/Et₂O) to yield

(R)-11d as a yellow liquid (1.54 g, 6.41 mmol, 85%). The analytical

data are in full agreement to those reported in the literature.^38e40

[Found: C, 69.82; H, 11.81. C₁₄H₂₈OSi requires C, 69.93; H, 11.74%];

concd hydrochloric acid (16.9 mL) in methanol (0.15 mL). The crude

product was puriﬁed by ﬂash column chromatography on silica gel

(85% PE/EtOAc) affording alcohol (S)-2b as a colorless foam

(44.2 mg, 0.08 mmol, 78%). The analytical data are in full agreement

with those reported in the literature.^47,16[Found: C, 76.30; H, 6.65.

20

C₃₄H₃₅BO₅requires C, 76.41; H, 6.60%]; R_f(85% PE/EtOAc) 0.11; [a]

D

ꢁ74 (c 1.02, CHCl₃); mp¼80e95 ^ꢀC; m/z (ESI, positive ion, N₂) 557

(18) [(MþNa)^þ], 197 (100) [(CPh₂OMe)^þ], 167 (10) [(C₁₃H₁₁)^þ], 105

(18) [(PhCO)^þ].

4.3.4. (3S,E,4⁰R,5⁰R)-1-[4⁰,5⁰-Bis(methoxydiphenylmethyl)-1⁰,3⁰,2⁰-di-

oxaborolan-2⁰-yl]oct-1-en-3-ol [(S)-2d]. According to general pro-

cedure 2 a mixture of abs cyclohexene (1.52 mL, 1.23 g, 14.9 mmol,

2.0 equiv) and abs DME (15.0 mL) was treated with 10 M BH₃$SMe₂

(0.79 mL, 569 mg, 7.48 mmol, 1.0 equiv). Alkyne (S)-11d (1.80 g,

7.48 mmol, 1.0 equiv) was added at room temperature. After 1 h the

reaction mixture was treated with trimethylamine N-oxide dihy-

drate Me₃NO$2H₂O (1.66 g, 14.9 mmol, 2.0 equiv) and was stirred

for 1 h. Diol 1 (3.40 g, 7.48 mmol, 1.0 equiv) was added and stirring

was continued for 2 days. After solvent evaporation, a yellow foam

of boronic ester (S)-12d was obtained, which was used in the

R_f(90% PE/EtOAc) 0.84; [

a

]

D

²⁰ꢁ41 [c 1.20, CHCl₃, (S)-11d]; [

a

]

D

²⁰þ41

[c 1.06, CHCl₃, (R)-11d]; n_max(liquid ﬁlm): 3313, 2960, 2860, 1472,

1253, 1120, 1092, 839, 778 cm^ꢁ1

;

¹H NMR (CDCl₃, 300 MHz) 0.11

(3H, s, CH₃Si), 0.13 (3H, s, CH₃Si), 0.91 (9H, s, (CH₃)₃CSi), 1.20 (3H, t,

6558

V. Cmrecki et al. / Tetrahedron 66 (2010) 6550e6564

following step without any further puriﬁcation. R_f(85% PE/EtOAc)

0.69.

(CH]CH-B

*

); m/z (ESI, positive ion, N₂) 608 (100) [(MþH₂O)^þ], 558

(20) [(MꢁCH₃O)^þ], 529 (20) [(Mꢁ2CH₃O)^þ], 197 (12) [(CPh₂OMe)^þ],

According to general procedure 3 silyl ether (S)-12d (4.24 g,

6.01 mmol, 1.00 equiv) was dissolved in a minimum amount of

CH₂Cl₂and ethanol (40.0 mL), followed by treatment with a solu-

tion of concd hydrochloric acid (1.16 mL, 13.9 mmol, 2.91 equiv) in

ethanol (7.37 mL). The reaction mixture was stirred for 24 h. Flash

column chromatography on silica gel (85% PE/EtOAc) afforded the

pure product (S)-2d as a colorless solid (2.91 g, 4.93 mmol, 82% over

67 (12) [(C₁₃H₁₁)^þ].

4.4. [3,3]-Sigmatropic rearrangements

4.4.1. (3S)-Ethyl 3-[4⁰,5⁰-bis(methoxydiphenylmethyl)-1⁰,3⁰,2⁰-dioxa-

borolan-2⁰-yl]pent-4-enoate [(S)-13] and (3R)-ethyl 3-[4⁰,5⁰-bis(me-

thoxydiphenylmethyl)-1⁰,3⁰,2⁰-dioxaborolan-2⁰-yl]pent-4-enoate [(R)-

13]. According to general procedure 5 a 10 mL microwave vessel

equipped with a stirrer bar was charged with allyl alcohol 2a

(250 mg, 0.48 mmol), triethylortho acetate (625

3.41 mmol), propionic acid (2.1 L, 2.1 mg, 28.5 mol), and DMF

(649 L). The vessel was exposed to microwave irradiation for

two steps). [Found: C, 76.90; H, 7.39. C₃₈H₄₃BO₅requires C, 77.28; H,

20

7.34%]; R_f(85% PE/EtOAc) 0.17; [

a

]

ꢁ53 (c 1.06, CHCl₃); mp

), 3083, 3058, 3012

), 2970, 2932, 2855, 2830 (aliph. CeH- ), 1642 (olef.

), 1598, 1494 (arom. C]C- ), 1446, 1398, 1369, 1347, 1284,

1234, 1196, 1177, 1075 (CeOeC), 1032, 1015, 993, 966, 917, 895, 846,

D

68e71 ^ꢀC; n_max(liquid ﬁlm): 3551 (br, OeH-

(arom CeH-

C]C-

n

mL, 553 mg,

n

m

n

m

9 min, reaching a temperature of 160 ^ꢀC. After removal of volatile

compounds in vacuo and subsequent ﬂash column chromatography

(90% PE/EtOAc to 75% PE/EtOAc) 222.6 mg (0.38 mmol, 78%) of (S)-

13 and (R)-13 were isolated as a 1:1 mixture of diastereomers. The

diastereomers (S)-13 and (R)-13 were separated by means of MPLC

794, 757 (Ph, CeH-d_out

_plane), 732, 695 cm^{ꢁ1 1}H NMR (CDCl₃,

;

of

600 MHz) 0.86 (3H, t, ³J 7.1 Hz, CH₃), 1.21e1.41 (8H, m,

CH₃CH₂CH₂CH₂CH₂), 1.29 (1H br, OH), 2.98 (6H, s, OCH₃); 3.99 (1H,

m, CHOH), 5.22 (1H, dd, ³J 18.1 Hz, ⁴J 1.3 Hz, CH]CH-B

*

), 5.35 (2H, s,

), 7.24e7.35

20

CHCPh₂OMe), 6.16 (1H, dd, ³J 18.1, 5.3 Hz, CH]CH-B

*

(98% PE/EtOAc). (S)-13: [

a

]

ꢁ108.6 (c 1.0, CHCl₃); (R)-13: [

a]

D

(20H, m, arom. CH); ¹³C NMR (CDCl₃, 151 MHz) 14.0 (CH₃), 22.6,

ꢁ97.1 (c 1.0, CHCl₃). All spectroscopic data are in full agreement

24.7, 31.7, 36.5 (CH₃CH₂CH₂CH₂CH₂), 51.8 (OCH₃), 77.6

with those previously reported.^14,16,27

(CHCPh₂OMe), 83.3 (CPh₂OCH₃), 116.8 (CH]CH-B ), 127.2, 127.3,

*

127.5, 127.8, 128.4, 129.6 (arom. CH), 141.0, 141.3 (arom. C_ipso), 154.8

4.4.2. (3S,4E,4⁰R,5⁰R)-Ethyl

3-[4⁰,5⁰-bis(methoxydiphenylmethyl)-

(CH]CH-B

*

); m/z (ESI, positive ion, N₂) 608 (100) [(MþH₂O)^þ], 564

1⁰,3⁰,2⁰-dioxaborolan-2⁰-yl]dec-4-enoate [(S)-14]. According to

general procedure 5 alcohol (S)-2d (500 mg, 0.85 mmol, 1.0 equiv),

triethyl orthoacetate (1.80 mL, 5.92 mmol, 7.0 equiv), a catalytic

(48), 167 (17) [(C₁₃H₁₁)^þ].

4.3.5. (3R,E,4⁰R,5⁰R)-1-[4⁰,5⁰-Bis(methoxydiphenylmethyl)-1⁰,3⁰,2⁰-di-

oxaborolan-2⁰-yl]oct-1-en-3-ol ((R)-2d). According to general pro-

cedure 2 a mixture of abs cyclohexene (1.30 mL, 1.04 g, 12.7 mmol,

2.05 equiv) and abs DME (6.40 mL) was treated with 10 M

BH₃$SMe₂(0.68 mL, 535 mg, 6.34 mmol, 1.02 equiv). Alkyne (R)-

11d (1.49 g, 6.18 mmol, 1.00 equiv) was added at room temperature,

followed by treatment with trimethylamine N-oxide dihydrate

Me₃NO$2H₂O (953 mg, 12.7 mmol, 2.05 equiv) after 1 h. After stir-

ring for 1 h, diol 1 (2.88 g, 6.34 mmol, 1.02 equiv) was added. The

yellow oily crude product (R)-12d obtained after 25 h was used in

the next step without further puriﬁcation. R_f(85% PE/EtOAc) 0.70;

¹H NMR (CDCl₃, 300 MHz) ꢁ0.09 [9H, s, (CH₃)₃CSi], ꢁ0.06 (3H, s,

CH₃Si), ꢁ0.04 (3H, s, CH₃Si), 0.85 (3H, t, ³J 6.8 Hz, CH₃), 1.16e1.49

(8H, m, CH₃CH₂CH₂CH₂CH₂), 2.96 (6H, s, OCH₃), 3.91 (1H, m,

amount of propionic acid (3.67 mL), and DMF (1.14 mL) were heated

in a microwave. ¹H and ¹³C NMR of the crude product proved the

diastereomeric ratio to be >99:1. The crude sample was puriﬁed by

ﬂash column chromatography (95% PE/EtOAc) to yield boronic ester

(S)-14 as a colorless foam (486 mg, 0.735 mmol, 87%). [Found: C,

76.40; H, 7.51. C₄₂H₄₉BO₆requires C, 76.36; H, 7.48%]; R_f(85% PE/

EtOAc) 0.49; [

3027 (arom. CeH-

a

]

²⁰ꢁ72 (c 2.18, CHCl₃); n_max(liquid ﬁlm): 3088, 3058,

D

n), 2951, 2929, 2860, 2830 (aliph. CeH-n), 1735

(C]O-

n

), 1494, 1461, 1446 (arom. C]C-n), 1369, 1330, 1274, 1229,

1198, 1138, 1076 (CeOeC), 1033, 1016, 967; 917, 895, 844, 758, 733,

703 cm^ꢁ1; ¹H NMR (CDCl₃, 600 MHz) 0.79 (3H, t, ³J 7.2 Hz, CH₃), 1.13

(3H, t, ³J 7.2 Hz, CO₂CH₂CH₃),1.08e1.26 (6H, m, CH₃CH₂CH₂CH₂CH₂),

1.84 (3H, m, CH-B

, n-BuCH₂CH), 1.94 (1H, dd, ²J 15.5 Hz, ³J 10.6 Hz,

*

CH_2aCOEt), 2.06 (1H, dd, ²J 15.5 Hz, ³J 4.5 Hz, CH_2bCOEt), 2.99 (6H, s,

OCH₃), 3.93 (2H, q, ³J 7.2 Hz, CO₂CH₂CH₃), 5.09 (2H, m, 2H, CH]CH),

5.28 (2H, s, CHCPh₂OMe), 7.23e7.31 (20H, m, arom. CH); ¹³C NMR

(CDCl₃, 151 MHz) 13.9 (CH₃), 14.2 (CO₂CH₂CH₃), 22.4, 29.1, 31.1

CHOTBS), 5.10 (1H, dd, ³J 17.9 Hz, ⁴J 1.3 Hz, CH]CH-B

*

), 5.22 (2H, s,

), 7.20e7.34

CHCPh₂OMe), 6.08 (1H, dd, ³J 17.9, 5.5 Hz, CH]CH-B

(20H, m, arom. CH).

*

According to general procedure 3 silyl ether (R)-12d (3.20 g,

4.54 mmol, 1.0 equiv) was dissolved in a minimum amount of

CH₂Cl₂and ethanol (43.0 mL), and treated with a solution of concd

(CH₃CH₂CH₂CH₂CH₂), 23.8 (CH-B ), 32.5 (CH₃CH₂CH₂CH₂CH₂), 34.3

*

(CH₂COEt), 51.7 (OCH₃), 59.9 (CO₂CH₂CH₃), 77.9 (CHCPh₂OMe), 83.3

(CPh₂OCH₃), 128.4 (CH]CH), 127.3, 127.3, 127.5, 127.8, 129.4, 129.7

(arom. CH); 141.1, 141.2 (arom. C_ipso), 173.2 (CO₂OEt); m/z (ESI, pos-

itive ion, N₂) 678 (100) [(MþH₂O)^þ], 683 (40) [(MþNa)^þ], 403 (19),

197 (5) [(CPh₂OMe)^þ].

hydrochloric acid (877 mL) in ethanol (8.00 mL). The reaction mix-

ture was stirred for 21 h. Flash column chromatography on silica gel

(85% PE/EtOAc) afforded the pure product (R)-2d as a colorless

foam (1.80 g, 3.04 mmol, 67%; 50% over two steps). [Found: C,

77.22; H, 7.35. C₃₈H₄₃BO₅requires C, 77.28; H, 7.34%]; R_f(85% PE/

4.4.3. (3R,4E,4⁰R,5⁰R)-Ethyl 3-[4⁰,5⁰-bis(methoxydiphenylmethyl)-

1⁰,3⁰,2⁰-dioxaborolan-2⁰-yl]dec-4-enoate [(R)-14]. According to the

20

EtOAc) 0.23; [

a]

ꢁ60 (c 0.11, CHCl₃); mp 66e73 ^ꢀC; n_max(liquid

D

ﬁlm): 3402 (br, OeH-

n

), 3083, 3063, 3022 (arom CeH-

n), 2968,

general procedure

5

alcohol (R)-2d (500 mg, 0.85 mmol,

2926, 2825 (aliph. CeH-

n

), 1643 (olef. C]C-n), 1494 (arom. C]C-n),

1.00 equiv), triethyl orthoacetate (1.8 mL, 5.92 mmol, 7.00 equiv),

1446, 1400, 1367, 1350, 1317, 1282, 1237, 1181, 1074 (CeOeC), 1032,

1011, 995, 967, 938, 917, 895, 844, 757 (Ph, CeH-d_{out of plane}),733,

a catalytic amount of propionic acid (3.67 mL), and DMF (1.14 mL)

were heated in a microwave. ¹H and ¹³C NMR of the crude product

proved the diastereomeric ratio to be >99: 1. The crude sample was

puriﬁed by ﬂash column chromatography (95% PE/EtOAc) to yield

698, 668 cm^ꢁ^{1 1}H NMR (CDCl₃, 600 MHz) 0.87 (3H, t, ³J 7.1 Hz,

;

CH₃),1.21e1.29 (6H, m, CH₃CH₂CH₂CH₂CH₂), 1.32 (1H, br, OH), 1.38

(2H, m, CH₃CH₂CH₂CH₂CH₂), 2.99 (6H, s, OCH₃), 3.98 (1H, m,

boronate (R)-14 as a colorless foam (419 mg, 0.63 mmol, 75%). R_f

20

CHOH), 5.19 (1H, dd, ³J 18.1 Hz, ⁴J 1.5 Hz, CH]CH-B

*

), 5.35 (2H, s,

), 7.24e7.36

(85% PE/EtOAc) 0.46; [

a

]

D

þ70 (c 1.99, CHCl₃); n_max(liquid ﬁlm):

CHCPh₂OMe), 6.17 (1H, dd, ³J 18.1, 5.7 Hz, CH]CH-B

*

3093, 3058, 3027 (arom. CeH-

CeH- ), 1736 (C]O- ), 1494, 1461, 1446 (arom. C]C-n

n

), 2951, 2929, 2855, 2830 (aliph.

), 1368, 1327,

(20H, m, arom. CH); ¹³C NMR (CDCl₃, 151 MHz) 14.0 (CH₃), 22.6,

n

24.7, 31.7, 36.4 (CH₃CH₂CH₂CH₂CH₂), 51.8 (OCH₃), 73.6

1278, 1230, 1201, 1139, 1076 (CeOeC), 1033, 1014, 967, 915, 895,

842, 794, 758, 733, 698 cm^ꢁ1; ¹H NMR (CDCl₃, 600 MHz) 0.84 (3H, t,

³J 7.1 Hz, CH₃), 1.15 (3H, t, ³J 7.1 Hz, CO₂CH₂CH₃), 1.12e1.28 (6H, m,

(CHCPh₂OMe), 83.3 (CPh₂OCH₃), 116.5 (CH]CH-B

*

), 127.2, 127.3,

127.5, 127.8, 128.4, 129.6 (arom. CH), 141.0, 141.3 (arom. C_ipso), 154.8

V. Cmrecki et al. / Tetrahedron 66 (2010) 6550e6564

6559

CH₃CH₂CH₂CH₂CH₂), 1.80e1.85 (3H, m, CH-B

*

, CH₃CH₂CH₂CH₂CH₂),

75.73; H, 7.01%]; R_f(85% PE/EtOAc) 0.52; n_max(liquid ﬁlm): 3457

(br), 3083, 3053, 3022 (arom. CeH- ), 2977, 2937, 2830, (aliph.

CeH- ), 1732 (C]O- ), 1600, 1580 (arom. C]C- ), 1489, 1446, 1376,

1.98 (1H, dd, ²J 15.5 Hz, ³J 10.9 Hz, CH_bH_aCOEt), 2.05 (1H, dd, ²J

15.5 Hz, ³J 4.5 Hz, CH_aH_bCOEt), 2.99 (6H, s, OCH₃), 3.99 (2H, q, ³J

7.1 Hz, CO₂CH₂CH₃), 4.94 (1H, ddt, ³J 15.3 Hz, ³J 8.3 Hz, ⁴J 1.5 Hz,

n

1350, 1332, 1282, 1233, 1177, 1150, 1076 (CeOeC), 1033, 1014, 1001,

967 (CH]CH₂, CeH-d_{out of plane}), 920, 900, 859, 842, 791, 758, 730,

703, 698 cm^ꢁ1; ¹H NMR [CDCl₃, 600 MHz, (2R,3S)-15b] 0.67 (3H, d,

³J 6.8 Hz, CH₃CHCO₂Et),1.12 (3H, m, CO₂CH₂CH₃),1.46 (3H, dd, ³J 6.4,

CH]CHCHB

), 5.08 (1H, dtd, ³J 15.3 Hz, ³J 6.8 Hz, ⁴J 1.1 Hz, CH₂CH]

*

CH), 5.28 (2H, s, 2H, CHCPh₂OMe), 7.23e7.31 (20H, m, arom. CH);

¹³C NMR (CDCl₃, 151 MHz) 14.1 (CH₃), 14.2 (CO₂CH₂CH₃), 22.5, 29.2,

31.1 (CH₃CH₂CH₂CH₂CH₂), 24.4 (CH-B

34.9 (CH₂COEt), 51.7 (OCH₃),59.9 (CO₂CH₂CH₃), 77.7 (CHCPh₂OMe),

83.3 (CPh₂OCH₃), 127.5 (CH]CHCHB ), 130.1 (CH]CHCHB ), 127.2,

*

); 32.5 (CH₃CH₂CH₂CH₂CH₂),

1.5 Hz, CH₃CH]CH), 1.58 (1H, dd, ³J 10.5, 9.6 Hz CH-B

), 2.28 (1H,

*

qd, ³J 6.8, 10.5 Hz, CHCO₂Et), 2.98 (6H, s, OCH₃), 3.94 (2H, m,

CO₂CH₂CH₃), 4.93 (1H, ddq, ³J 15.1, 9.6 Hz, ⁴J 1.5 Hz, MeCH]CH),

5.07 (1H, dq, ³J 15.1 6.4 Hz, MeCH]CH), 5.29 (2H, s, CHCPh₂OMe),

7.25e7.35 (20H, m, arom. CH); ¹H NMR [CDCl₃, 600 MHz, (2S,3S)-

15b] 0.77 (3H, d, ³J 7.2 Hz, CH₃CHCO₂Et), 1.12 (3H, m, CO₂CH₂CH₃),

1.51 (3H, dd, ³J 6.4, 1.5 Hz, CH₃CH]CH), 1.90 (1H, dd, ³J 9.4, 4.9 Hz,

*

127.3, 127.7, 128.1, 128.4, 129.7 (arom. CH), 141.3 (arom. C_ipso), 173.2

(CO₂OEt); m/z (ESI, positive ion, N₂) 678 (100) [(MþH₂O)^þ], 645

(20) [(MꢁCH₃)^þ], 403 (17), 197 (8) [(CPh₂OMe)^þ]. HRMS (ESI, pos-

itive ion): MNa^þ, found 683.35138. C₄₂H₄₉BO₆Na requires

683.35199.

CH-B

), 2.17 (1H, qd, ³J 7.2, 4.9 Hz, CHCO₂Et), 2.98 (6H, s, OCH₃), 3.94

*

(2H, m, CO₂CH₂CH₃), 4.95 (1H, ddq, ³J 15.1, 9.6 Hz, ⁴J 1.5 Hz, MeCH]

CH), 5.07 (1H, dq, ³J 15.1, 6.4 Hz, MeCH]CH), 5.31 (2H, s,

CHCPh₂OMe), 7.25e7.35 (20H, m, arom. CH); ¹³C NMR [CDCl₃,

151 MHz, mixture of syn-(2R,3S)-15b and anti-(2S,3S)-15b] 13.9

(CH₃CHCO₂Et-anti), 14.1, 14.2 (CO₂CH₂CH₃), 16.4 (CH₃CHCO₂Et-syn),

4.4.4. (2R,3S,E,4⁰R,5⁰R)-Ethyl 3-[4⁰,5⁰-bis(methoxydiphenylmethyl)-

1⁰,3⁰,2⁰-dioxaborolan-2⁰-yl]-2-methylpent-4-enoate [(2S,3R)-15a].

According to general procedure 6 alcohol 2a (500 mg, 0.96 mmol,

1.0 equiv), triethyl orthopropionate (1.34 mL, 1.19 g, 6.73 mmol,

7.0 equiv), and a catalytic amount of propionic acid (4

mL) were

18.0, 18.1 (CH₃CH]CH), 31.4 (CH-B

*

-anti), 32.7 (CH-B -syn), 39.3

*

heated at 135 ^ꢀC for 4 h. After work-up a complex mixture of

slightly impure diastereoisomers (405 mg, w70%) was obtained.

After extensive chromatographic puriﬁcation [ﬂash column chro-

matography (95% PE/EtOAc)/MPLC (98% PE/EtOAc)] a small sample

of the allylboronic ester (2S,3R)-15a was isolated: [Found: C, 75.20;

H, 6.84. C₃₈H₄₁BO₆requires C, 75.50; H, 6.48%]; R_f(85% PE/EtOAc)

(CHCO₂Et-anti), 41.1 (CHCO₂Et-syn), 51.8, 51.9 (OCH₃), 59.6, 59.8

(CO₂CH₂CH₃), 77.7, 77.8 (CHCPh₂OMe), 83.4, 83.5 (CPh₂OCH₃),

125.3, 126.8, (MeCH]CH), 126.6 (MeCH]CH-anti), 128.5 (MeCH]

CH-syn), 127.1, 127.2, 127.3, 127.4, 127.4, 127.5, 127.7, 128.6, 129.7

(arom. CH), 141.2, 141.3, 141.4, 141.5 (arom. C_ipso), 175.6 (CO₂CH₂CH₃-

anti), 175.9 (CO₂CH₂CH₃-syn), m/z (ESI, positive ion, N₂) 636 (100)

[(MþH₂O)^þ], 361 (47) [(C₂₈H₂₅)^þ], 197 (8) [(CPh₂OMe)^þ].

0.43; [

a

]

D

²⁰ꢁ116 (c 1.10, CHCl₃); n_max(liquid ﬁlm): 3083, 3063, 3022

(arom CeH-n), 2978, 2936, 2906, 2834 (aliph. CeH-n), 1732 (C]O-

n

), 1636, 1600, 1577, 1494, 1446 (arom. C]C-

n

), 1368, 1332, 1347,

4.4.6. (2S,3R,E,4⁰R,5⁰R)- and (2R,3R,E,4⁰R,5⁰R)-Ethyl 3-[4⁰,5⁰-bis(me-

thoxydiphenylmethyl)-1⁰,3⁰,2⁰-dioxaborolan-2⁰-yl]-2-methylhex-4-

enoate [(3R)-15b]. According to general procedure 5 alcohol (S)-

2b¹⁶(100 mg, 0.19 mmol, 1.0 equiv), triethyl orthopropionate

1231, 1198, 1186, 1076 (CeOeC), 1051, 1033, 1015, 967 (CH]CH₂,

CeH-d_{out of plane}), 907, 857, 794, 757, 703, 698 cm^ꢁ1; ¹H NMR (CDCl₃,

600 MHz) 0.69 (3H, d, ³J 6.9 Hz, CH₃CHCO₂Et), 1.10 (3H, dd, ³J 7.1,

7.1 Hz, CO₂CH₂CH₃), 1.77 (dddd, ³J 9.6, 9.1 Hz, ⁴J 1.2, 0.8 Hz, CH-B

*

),

(264

mL, 234 mg, 1.33 mmol, 7.1 equiv), a catalytic amount of pro-

2.24 (dq, ³J 9.6, 6.9 Hz, CHCO₂Et), 2.99 (6H, s, OCH₃), 3.85 (1H, dq, ²J

pionic acid (0.82

m

L), and DMF (0.26 mL) were heated in a micro-

10.8 Hz, J 7.1 Hz, CO₂CH_bH_aCH₃), 3.89 (1H, dq, ²J 10.8 Hz, ³J 7.1 Hz,

wave reactor. ¹H and ¹³C NMR of the crude product proved the

diastereomeric ratio to be 63:37. The crude product was puriﬁed by

ﬂash column chromatography (95% PE/EtOAc) and MPLC (98% PE/

EtOAc) to yield a 63:37 mixture of diastereoisomers (2S,3R)- and

(2R,3R)-15b (99.8 mg, 0.16 mmol, 87%) as a colorless solid.

3

CO₂CH_aH_bCH₃), 4.70 (1H, ddd, ³J 17.1 Hz, ²J 1.8 Hz, ⁴J 0.8 Hz, CH]

CH_EH_Z), 4.74 (1H, ddd, ³J 10.3 Hz, ²J 1.8 Hz, ⁴J 1.2 Hz, CH]CH_ZH_E),

5.31 (2H, s, CHCPh₂OMe), 5.50 (1H, ddd, ³J 17.1, 10.3 Hz, ³J 9.1 Hz,

CH]CH₂), 7.23e7.36 (20H, m, arom. CH); ¹³C NMR (CDCl₃,

151 MHz) 14.1 (CO₂CH₂CH₃), 16.3 (CH₃CHCO₂Et), 33.6 (CH-B

*

), 40.3

According to general procedure 6 alcohol (S)-2b¹⁶(500 mg,

0.94 mmol, 1.0 equiv), triethyl orthopropionate (1.30 mL, 1.15 g,

6.55 mmol, 7.0 equiv), and a catalytic amount of propionic acid

(CHCO₂Et), 51.7 (OCH₃), 59.8 (CO₂CH₂CH₃), 77.7 (CHCPh₂OMe), 83.4

(CPh₂OCH₃), 114.4 (CH]CH₂), 127.3, 127.4, 127.5, 127.7, 128.5, 129.7

(arom. CH), 136.9 (CH]CH₂), 141.3, 141.3 (arom. C_ipso), 175.9

(CO₂Et); m/z (ESI, positive ion, N₂) 627 (100) [(MþNa)^þ].

(4.05 m

L) were heated at 135 ^ꢀC for 4 h. ¹H and ¹³C NMR of the crude

product proved the diastereomeric ratio to be 86:14. The crude

product was puriﬁed by ﬂash column chromatography (95% PE/

EtOAc) and MPLC (98% PE/EtOAc) to yield a 86:14 mixture of di-

astereoisomers (2S,3R)- and (2R,3R)-15b (509 mg, 0.82 mmol, 88%)

as a colorless solid. [Found: C, 75.51; H, 6.99. C₃₉H₄₃BO₆requires C,

75.73; H, 7.01%]; R_f(85% PE/EtOAc) 0.47; n_max(liquid ﬁlm): 3457

4.4.5. (2R,3S,E,4⁰R,5⁰R)- and (2S,3S,E,4⁰R,5⁰R)-Ethyl 3-[4⁰,5⁰-bis(me-

thoxydiphenylmethyl)-1⁰,3⁰,2⁰-dioxaborolan-2⁰-yl]-2-methylhex-4-

enoate [(3S)-15b]. According to general procedure 5 alcohol (R)-

2b¹⁶(150 mg, 0.28 mmol, 1.00 equiv), triethyl orthopropionate

(308

pionic acid (1.22

m

L, 351 mg, 1.99 mmol, 7.10 equiv), a catalytic amount of pro-

(br), 3083, 3048, 3027 (arom CeH-

n

), 2970, 2936, 2834, (aliph.

), 1446,

mL), and DMF (0.38 mL) were heated in a micro-

CeH- ), 1736 (C]O- ), 1590, 1570, 1519, 1494 (arom. C]C-n

n

wave reactor. ¹H and ¹³C NMR of the crude product proved the

diastereomeric ratio to be 50:50. The crude product was puriﬁed by

ﬂash column chromatography (95% PE/EtOAc) and MPLC (98% PE/

EtOAc) to yield a 1:1 mixture of the diastereoisomers (2R,3S)- and

(2S,3S)-15b (152 mg, 0.25 mmol, 88%) as a colorless solid.

1366, 1355, 1266, 1229, 1217, 1204, 1155, 1075 (CeOeC), 1032, 1014,

1001, 966 (CH]CH₂, CeH-d_{out of plane}), 921, 901, 857, 839, 795, 758,

734, 698 cm^ꢁ1; ¹H NMR [CDCl₃, 600 MHz, (2S,3R)-15b] 0.65 (3H, d,

³J 6.9 Hz, CH₃CHCO₂Et), 1.09 (3H, t, ³J 7.2 Hz, CO₂CH₂CH₃), 1.48 (3H,

m, CH₃CH]CH), 1.65 (1H, dd, ³J 9.3, 9.8 Hz, CH-B ), 2.18 (1H, qd, ³

J

*

According to general procedure 6 alcohol (R)-2b¹⁶(1.00 g,

1.87 mmol, 1.00 equiv), triethyl orthopropionate (2.64 mL, 2.34 g,

13.3 mmol, 7.10 equiv), and a catalytic amount of propionic acid

6.8, 9.8 Hz, CHCO₂Et), 2.97 (6H, s, OCH₃), 3.86 (2H, m, CO₂CH₂CH₃),

5.08 (1H, ddq, ³J 15.1, 9.3 Hz, ⁴J 2.1 Hz, MeCH]CH), 5.12 (1H, dq, ³J

15.1, 6.8 Hz, MeCH]CH), 5.29 (2H, s, CHCPh₂OMe), 7.23e7.35 (20H,

m, arom. CH); ¹³C NMR [CDCl₃, 151 MHz (2S,3R)-15b] 14.2

(8.12 m

L) were heated at 135 ^ꢀC for 4 h. ¹H and ¹³C NMR of the crude

product proved the diastereomeric ratio to be 50:50. The crude

product was puriﬁed by ﬂash column chromatography (85% PE/

EtOAc) and MPLC (98% PE/EtOAc) to yield a 1:1 mixture of di-

astereoisomers (2R,3S)- and (2S,3S)-15b (0.99 g, 1.61 mmol, 86%) as

a colorless solid. [Found: C, 75.73; H, 7.01. C₃₉H₄₃BO₆requires C,

(CO₂CH₂CH₃), 16.4 (CH₃CHCO₂Et), 17.8 (CH₃CH]CH), 32.7 (CH-B ),

*

41.1 (CHCO₂Et), 51.7 (OCH₃), 59.8 (CO₂CH₂CH₃), 77.7 (CHCPh₂OMe),

83.4 (CPh₂OCH₃),125.2 (MeCH]CH),127.2,127.3,127.5,127.7,128.6,

129.7 (arom. CH), 129.1 (MeCH]CH), 141.3, 141.4 (arom. C_ipso), 176.1

(CO₂Et); ¹H NMR [CDCl₃, 600 MHz, (2R,3R)-15b] 0.69 (3H, d, ³J

6560

V. Cmrecki et al. / Tetrahedron 66 (2010) 6550e6564

6.8 Hz, CH₃CHCO₂Et), 1.21 (3H, t, ³J 7.2 Hz, CO₂CH₂CH₃), 1.49 (3H, m,

CH₃CH]CH), 1.84 (1H, dd, ³J 9.8, 4.9 Hz, CH-B ), 2.30 (1H, qd, ³J 6.9,

CH), 7.13e7.35 (25H, m, arom. CH); ¹³C NMR [CDCl₃, 151 MHz syn-

(2S,3R)-15c] 14.2 (CO₂CH₂CH₃), 16.5 (CH₃CHCO₂Et), 33.1 (CH-B ),

*

5.1 Hz, CHCO₂Et), 2.98 (6H, s, OCH₃), 3.86 (2H, m, CO₂CH₂CH₃), 5.04

(1H, ddq, ³J 15.1, 9.8 Hz, ⁴J 1.5 Hz, MeCH]CH), 5.13 (1H, ddq, ³J 15.1,

6.8 Hz, ⁴J 0.8 Hz MeCH]CH), 5.29 (2H, s, CHCPh₂OMe), 7.23e7.35

(20H, m, arom. CH); ¹³C NMR [CDCl₃, 151 MHz, (2R,3R)-15b] 13.9

40.9 (CHCO₂Et), 51.8 (OCH₃), 59.9 (CO₂CH₂CH₃), 77.9 (CHCPh₂OMe),

83.5 (CPh₂OCH₃), 125.9, 126.5, 127.3, 127.4, 127.5, 127.8, 128.2, 128.6,

129.3 (arom. CH),129.3 (PhCH]CH), 130.0 (PhCH]CH),138.0, 141.1,

141.3 (arom. C_ipso); 175.9 (CO₂Et); m/z (ESI, positive ion, N₂) 698 (52)

[(MþH₂O)^þ], 719 (25) [(MþK)^þ], 423 (21) [(C₂₈H₂₂O₄)^þ].

(CH₃CHCO₂Et), 14.2 (CO₂CH₂CH₃), 18.0 (CH₃CH]CH), 31.4 (CH-B ),

*

39.3 (CHCO₂Et), 51.7 (OCH₃), 59.7 (CO₂CH₂CH₃), 77.8 (CHCPh₂OMe),

83.3 (CPh₂OCH₃),125.2 (MeCH]CH),127.2,127.3,127.4,127.7,128.5,

129.6 (arom. CH), 127.0 (MeCH]CH), 141.1, 141.3 (arom. C_ipso), 176.0

(CO₂Et); m/z (ESI, positive ion, N₂) 636 (100) [(MþH₂O)^þ], 361 (50)

[(C₂₈H₂₅)^þ], 197 (9) [(CPh₂OMe)^þ].

4.4.8. (2R,3S,E,4⁰R,5⁰R)- and (2S,3S,E,4⁰R,5⁰R)-Ethyl 3-[4⁰,5⁰-bis(me-

thoxydiphenylmethyl)-1⁰,3⁰,2⁰-dioxaborolan-2⁰-yl]-2-methyldec-4-

enoate [(3S)-15d]. According to general procedure 5 alcohol (R)-2d

(100 mg, 0.17 mmol, 1.0 equiv), triethyl orthopropionate (240

mL,

212.6 mg,1.19 mmol, 7.1 equiv), a catalytic amount of propionic acid

4.4.7. (2S,3S,E,4⁰R,5⁰R)- and (2S,3R,E,4⁰R,5⁰R)-Ethyl 3-[4⁰,5⁰-bis(me-

thoxydiphenylmethyl)-1⁰,3⁰,2⁰-dioxaborolan-2⁰-yl]-2-methyl-5-phe-

nylpent-4-enoate [(3R)-15c]. According to general procedure 6

alcohol (R)-2c¹⁶(1.16 g, 1.94 mmol, 1.0 equiv), triethyl orthopropi-

onate (1.30 mL,1.15 g, 6.55 mmol, 7.0 equiv), and a catalytic amount

(0.73 mL), and DMF (0.23 mL) were heated in a microwave reactor.

¹H and ¹³C NMR of the crude product proved the diastereomeric

ratio to be 50:50. The crude product was puriﬁed by ﬂash column

chromatography (95%, PE/EtOAc) to yield a 1:1 mixture of di-

astereoisomers (2R,3S)- and (2S,3S)-15d (101 mg, 0.15 mmol, 89%)

as a colorless foam.

of propionic acid (1.58 m

L) were heated at 135 ^ꢀC for 3 h. ¹H and ¹³C

NMR of the crude product proved the diastereomeric ratio to be

72:28. The crude product was puriﬁed by ﬂash column chroma-

tography (95% PE/EtOAc) and MPLC to yield a 1:1 mixture of di-

astereoisomers (2S,3R)- and (2R,3R)-15c (1.04 g,1.53 mmol, 79%) as

According to general procedure 6 alcohol (R)-2d (1.19 g,

2.02 mmol, 1.0 equiv), triethyl orthopropionate (2.85 mL, 2.53 g,

14.3 mmol, 7.1 equiv), and a catalytic amount of propionic acid

(8.8 m

L) were heated at 135 ^ꢀC for 4 h. ¹H and ¹³C NMR of the crude

a colorless solid. [Found: C, 77.21; H, 6.62. C₄₄H₄₅BO₆requires C,

product proved the diastereomeric ratio to be 50:50. The crude

product was puriﬁed by ﬂash column chromatography (85% PE/

EtOAc) and MPLC (98% PE/EtOAc) to yield a 1:1 mixture of di-

astereoisomers (2R,3S)- and (2S,3S)-15d (1.18 g, 1.74 mmol, 86%) as

a colorless foam. [Found: C, 76.31; H, 7.57. C₄₃H₅₁BO₆requires C,

76.55; H, 7.62%]; R_f(85% PE/EtOAc) 0.47; n_max(liquid ﬁlm): 3457

20

77.64; H, 6.66%]; R_f(85% PE/EtOAc) 0.15; [

n_max(liquid ﬁlm): 3458 (br), 3083, 3027, 3002 (arom CeH- ), 2970,

a

]

ꢁ50 (c 1.04, CHCl₃);

D

n

2941 (aliph. CeH- ), 1734 (C]O- ), 1489 (arom. C]C-n), 1446,

n

1408, 1375, 1365, 1229, 1217, 1203, 1165, 1150, 1087, 1075 (CeOeC),

1032, 1012, 965 (CH]CH₂, CeH-d_{out of plane}), 903, 895, 795, 755,

733, 698, 668 cm^ꢁ1

;

¹H NMR [CDCl₃, 600 MHz (2R,3R)-15c] 0.79

(br), 3093, 3058, 3027 (arom CeH-

(aliph. CeH- ), 1733 (C]O- ), 1598, 1577, 1494 (arom. C]C-

1447, 1374, 1330, 1279, 1231, 1188, 1148, 1076 (CeOeC), 1033, 1014,

n

), 2956, 2932, 2850, 2830

(3H, d, ³J 7.2 Hz, CH₃CHCO₂Et), 1.03 (3H, t, ³J 7.2, CO₂CH₂CH₃), 2.05

n

n),

(1H, dd, ³J 9.4, 5.3 Hz, CH-B ), 2.39 (1H, qd, ³J 7.2, 5.3 Hz, CHCO₂Et),

*

2.99 (6H, s, OCH₃), 3.83 (2H, m, CO₂CH₂CH₃), 5.34 (2H, s,

CHCPh₂OMe), 5.80 (1H, dd, ³J 15.6, 9.4 Hz, PhCH]CH), 6.10 (1H, d, ³J

15.8 Hz, PhCH]CH), 7.11e7.35 (25H, m, arom. CH); ¹³C NMR [CDCl₃,

151 MHz (2R,3R)-15c] 14.2 (CO₂CH₂CH₃), 14.4 (CH₃CHCO₂Et), 31.7

967 (CH]CH₂, CeH-d_out

_plane), 915, 897, 839, 794, 728, 705,

of

665 cm^ꢁ1; ¹H NMR [CDCl₃, 600 MHz syn-(2R,3S)- and anti-(2S,3S)-

15d] 0.70 (3H, ³J 6.8 Hz, CH₃CHCO₂Et-syn), 0.80 (3H, d, ³J 7.2 Hz,

CH₃CHCO₂Et-anti), 0.87 (3H, t, ³J 7.2 Hz, CH₃CH₂CH₂CH₂CH₂),

1.11e1.27 (6H, m, CH₃CH₂CH₂CH₂CH₂), 1.13 (3H, t, ³J 7.2 Hz,

(CH-B ), 39.2 (CHCO₂Et), 51.8 (OCH₃), 60.0 (CO₂CH₂CH₃), 78.0

*

(CHCPh₂OMe), 83.4, 83.5 (CPh₂OCH₃), 125.9, 126.6, 127.3, 127.5,

127.7, 128.3, 128.5, 129.6, 129.7 (arom. CH), 126.8 (PhCH]CH), 131.6

(PhCH]CH), 141.0, 141.2 (arom. C_ipso), 175.7 (CO₂Et); m/z (ESI,

positive ion, N₂) 703 (100) [(MþNa)^þ], 698 (55) [(MþH₂O)^þ], 719

(20) [(MþK)^þ], 423 (18) [(C₂₈H₂₂O₄)^þ]. The analytical data of

(2S,3R)-15c are described below.

Synthesis via cross metathesis: Under an atmosphere of dry

nitrogen in a 25 mL Schlenk-ﬂask equipped with a magnetic stirrer

bar and a reﬂux condenser, the allylboronic ester (2S,3R)-15a

(300 mg, 0.49 mmol, 1.00 equiv) was dissolved in abs CH₂Cl₂

CO₂CH₂CH₃), 1.56 (1H, t, ³J 10.2 Hz, CH-B

BuCH₂CH), 1.86 (1H, ³J 9.8, 5.6 Hz, CH-B

*

-syn), 1.78 (2H, m, n-

*

-anti), 2.28 (1H, qd, ³J 10.9,

6.8 Hz, CHCO₂Et-syn), 2.29 (1H, qd, ³J 7.5, 5.6 Hz, CHCO₂Et-anti),

2.98 (6H, s, OCH₃), 3.93 (2H, q, ³J 7.2 Hz, CO₂CH₂CH₃), 4.87 (1H, ddt,

³J 15.3, 9.6 Hz, ⁴J 1.3 Hz, n-PeCH]CH-syn), 5.07 (1H, dtd, ³J 15.3,

6.4 Hz, ⁴J 0.8 Hz, n-PeCH]CH-syn), 4.91 (1H, ddt, ³J 15.1, 10.2 Hz, ⁴J

1.3 Hz, n-PeCH]CH-anti), 5.10 (1H, dtd, ³J 15.1, 6.8 Hz, ⁴J 0.8 Hz, n-

PeCH]CH-anti), 5.28 (2H, s, CHCPh₂OMe), 7.23e7.34 (20H, m,

arom. CH); ¹³C NMR [CDCl₃, 151 MHz mixture of syn-(2R,3S)-15d

and anti-(2S,3S)-15d] 14.5 (CH₃CHCO₂Et-anti), 14.0, 14.0

(CH₃CH₂CH₂CH₂CH₂), 14.1, 14.2 (CO₂CH₂CH₃), 17.0 (CH₃CHCO₂Et-

syn), 22.3, 22.5, 29.0, 29.1, 22.4, 22.5 (CH₃CH₂CH₂CH₂CH), 31.0 (CH-

(5.00 mL). The solution was treated with styrene (114

0.99 mmol, 2.00 equiv) and the Grubbs II catalyst (42.1 mg,

49.6

mol, 0.10 equiv); the mixture was stirred for 21 h at 40 ^ꢀC.

mL, 103.4 mg,

m

B

*

-anti), 33.1 (CH-B -syn), 32.4 (n-BuCH₂-syn), 32.5 (n-BuCH₂-anti),

*

After cooling to room temperature, the solvent was evaporated

under reduced pressure and the crude product was puriﬁed by ﬂash

column chromatography on silica gel (98% PE/EtOAc) to yield

(2S,3R)-15c as a colorless solid (223 mg, 0.33 mmol, 66%). An X-ray

crystal structure analysis of a single diastereoisomer (2S,3R)-15c

was obtained.⁴²[Found: C, 77.64; H, 6.66. C₄₄H₄₅BO₆requires C,

39.3 (CHCO₂Et-anti), 40.9 (CHCO₂Et-syn), 51.8, 53.4 (OCH₃), 59.6

(CO₂CH₂CH₃-syn), 59.8 (CO₂CH₂CH₃-anti), 77.6, 77.8 (CHCPh₂OMe),

83.3, 83.4 (CPh₂OCH), 127.1, 127.2, 127.3, 127.4, 127.4, 127.4, 127.7,

127.7, 128.5, 128.5, 129.6, 129.7 (arom. CH), 125.7 (n-PeCH]CH-

anti), 127.3 (n-PeCH]CH-syn), 131.3 (n-PeCH]CH-syn), 132.5 (n-

PeCH]CH-anti), 141.3, 141.3, 141.4, 141.4 (arom. C_ipso), 175.8 (CO₂Et

-anti), 176.5 (CO₂Et-syn); m/z (ESI, positive ion, N₂) 697 (80)

[(MþNa)^þ], 729 (100) [(Mþ3H₂O)^þ].

77.27; H, 6.68%]; R_f(85% PE/EtOAc) 0.44; [

a]

²⁰ꢁ44 (c 1.00, CHCl₃);

D

n_max(liquid ﬁlm): 3458 (br), 3083, 3027, 3002 (arom CeH-n), 2970,

2941 (aliph. CeH-n),1739 (C]O-n),1489 (arom. C]C-n), 1447,1413,

1375, 1365, 1229, 1217, 1208, 1165, 1150, 1092, 1077 (CeOeC), 1034,

4.4.9. (2S,3R,E,4⁰R,5⁰R)- and (2R,3R,E,4⁰R,5⁰R)-Ethyl 3-[4⁰,5⁰-bis(me-

thoxydiphenylmethyl)-1⁰,3⁰,2⁰-dioxaborolan-2⁰-yl]-2-methyldec-4-

enoate [(3R)-15d]. According to general procedure 5 alcohol (S)-2d

1008, 963 (CH]CH₂, CeH-d_out

_plane), 903, 895, 757, 733,

of

700 cm^ꢁ1; ¹H NMR [CDCl₃, 600 MHz syn-(2S,3R)-15c] 0.73 (3H, d, ³J

6.8 Hz, CH₃CHCO₂Et),1.03 (3H, t, ³J 7.2 Hz, CO₂CH₂CH₃),1.90 (1H, dd,

(100 mg, 0.17 mmol, 1.0 equiv), triethyl orthopropionate (240

213 mg, 1.20 mmol, 7.1 equiv), a catalytic amount of propionic acid

(0.73 L), and DMF (0.23 mL) were heated in a microwave reactor.

¹H and ¹³C NMR of the crude product proved the diastereomeric

mL,

³J 9.8, 9.4 Hz, CH-B ), 2.33 (1H, qd, ³J 9.8, 6.8 Hz, CHCO₂Et), 2.98 (6H,

*

s, OCH₃), 3.83 (2H, m, CO₂CH₂CH₃), 5.29 (2H, s, CHCPh₂OMe), 5.84

m

(1H, dd, ³J 15.6, 9.4 Hz, PhCH]CH), 6.05 (1H, d, ³J 15.8 Hz, PhCH]

V. Cmrecki et al. / Tetrahedron 66 (2010) 6550e6564

6561

ratio to be 60:40. The crude product was puriﬁed by ﬂash column

chromatography (95% PE/EtOAc) and MPLC (98% PE/EtOAc) to yield

a 60:40 mixture of diastereoisomers (2S,3R)-15d and (2R,3R)-15d

(101.4 mg, 0.15 mmol, 89%) as a colorless solid.

9.2 Hz, CH_bH_aCONMe₂), 1.96 (1H, dd, ²J 14.8 Hz, ³J 5.5 Hz, CH_aH_b

-

CONMe₂), 2.01 (1H, m, CHB ), 2.69 (3H, s, NCH_a3), 2.75 (3H, s,

*

NCH_b3), 2.99 (6H, s, OCH₃), 5.08 (1H, dqd, ³J 15.3, 6.1 Hz, ⁴J 1.13 Hz,

CH₃CH]CH), 5.15 (1H, ddq, ³J 15.3, 6.9 Hz, ⁴J 1.5 Hz, CH₃CH]CH),

5.29 (2H, s, 2H, CHCPh₂OMe), 7.24e7.32 (20H, m, arom. CH); ¹³C

According to general procedure 6 alcohol (S)-2d (500 mg,

0.86 mmol, 1.0 equiv), triethyl orthopropionate (1.18 mL, 1.05 g,

5.93 mmol, 7.0 equiv), and a catalytic amount of propionic acid

NMR (CDCl₃, 151 MHz) 18.1 (CH₃CH), 23.4 (CHB ), 32.1

*

(CH₂CONMe₂), 35.4, 37.3 [(NCH₃)₂], 51.8 (OCH₃), 77.9 (CHCPh₂OMe),

83.4 (CPh₂OCH₃), 123.1 (CH₃CH]CH), 127.2, 127.3, 127.5, 127.8,

128.6, 129.7 (arom. CH), 130.5 (CH₃CH]CH), 141.0, 141.2 (arom.

C_ipso), 172.6 (CONMe₂); m/z (ESI, positive ion, N₂) 626 (35)

[(MþH₂O)^þ], 603 (30) [M^þ], 346 (100) [(C₂₂H₁₈O₄)^þ].

(3.74 m

L) were heated at 135 ^ꢀC for 4 h. ¹H and ¹³C NMR of the crude

product proved the diastereomeric ratio to be 77:23. The crude

product was puriﬁed by ﬂash column chromatography (95% PE/

EtOAc) and MPLC (98% PE/EtOAc) to yield a 77:23 mixture of di-

astereoisomers (2S,3R)-15d and (2R,3R)-15d (506 mg, 0.75 mmol,

87%) as a colorless solid. Even though the MPLC separation was not

completely successful, a small amount of enriched diastereoisomer

(2S,3R)-15d was isolated. [Found: C, 76.31; H, 7.57. C₄₃H₅₁BO₆re-

quires C, 76.55; H, 7.62%]; R_f(85% PE/EtOAc) 0.47; n_max(liquid ﬁlm):

4.4.11. (3R,4E,4⁰R,5⁰R)-3-[4⁰,5⁰-Bis(methoxydiphenylmethyl)-1⁰,3⁰,2⁰-

dioxaborolan-2⁰-yl]-N,N-dimethylhex-4-enamide ((R)-16b). Accord-

ing to general procedure 7 alcohol (R)-2b¹⁶(200 mg, 0.37 mmol,

1.0 equiv) dissolved in abs toluene (0.75 mL) was treated with a 90%

3457 (br); 3093, 3058, 3027 (arom CeH-

(aliph. CeH- ), 1733 (C]O- ), 1598, 1577, 1494 (arom. C]C-

1374, 1330, 1279, 1231, 1188, 1148, 1076 (CeOeC), 1033, 1014, 967

n

), 2956, 2932, 2850, 2830

solution of N,N-dimethylacetamide dimethyl acetal (122 mL,111 mg,

n

n), 1447,

0.74 mmol, 2.0 equiv). The reaction mixture was stirred at 80 ^ꢀC for

22 h. ¹H and ¹³C NMR of the crude product proved the di-

astereomeric ratio to be >99:1. The crude product was puriﬁed by

ﬂash column chromatography (85% PE/EtOAc with a gradient to

70% PE/EtOAc) to yield (R)-16b as a yellow oil (194 mg, 0.32 mmol,

86%). [Found: C, 75.61; H, 7.02; N, 2.22. C₃₈H₄₂BNO₅requires C,

(CH]CH₂, CeH-d_{out of plane}), 915, 897, 839, 794, 728, 705, 665 cm^ꢁ1

;

¹H NMR [CDCl₃, 600 MHz, (2S,3R)-15d] 0.66 (3H, d, ³J 6.9 Hz,

CH₃CHCO₂Et), 0.85 (3H, t, ³J 7.2 Hz, CH₃CH₂CH₂CH₂CH₂), 1.10 (3H, t,

³J 7.2, CO₂CH₂CH₃), 1.13e1.27 (6H, m, CH₃CH₂CH₂CH₂CH₂), 1.67 (3H,

t, ³J 9.8, CH-B

*

), 1.81 (2H, m, n-BuCH₂), 2.18 (1H, qd, ³J 6.9, 9.8 Hz,

75.62; H, 7.01; N, 2.32%]; R_f(60% PE/EtOAc) 0.19; [

CHCl₃); n_max(liquid ﬁlm): 3083, 3063, 3022 (arom. CeH-n), 2980,

a

]

²⁰ꢁ91 (c 1.00,

D

CHCO₂Et), 2.98 (6H, s, OCH₃), 3.87 (2H, m, CO₂CH₂CH₃), 5.06 (2H, m,

n-PeCH]CH), 5.28 (2H, s, 2H, CHCPh₂OMe), 7.23e7.34 (20H, m,

arom. CH); ¹H NMR [CDCl₃, 600 MHz, (2R,3R)-15d] 0.71 (3H, d, ³J

6.8 Hz, CH₃CHCO₂Et), 0.79 (3H, t, ³J 7.2 Hz, CH₃CH₂CH₂CH₂CH₂), 1.11

(3H, t, ³J 7.2, CO₂CH₂CH₃), 1.13e1.27 (6H, m, CH₃CH₂CH₂CH₂CH₂),

2937, 2915, 2855, 2820 (aliph. CeH-

1446 (arom. C]C- ), 1390, 1381, 1370, 1353, 1319, 1266, 1232, 1198,

1158, 1130, 1076 (CeOeC), 1033, 1019, 1001, 967 (CH]CH₂, CeH-

d_{out of plane}), 938, 923, 901, 857, 826, 796, 759, 733, 700 cm^{ꢁ1 1}H

NMR (CDCl₃, 600 MHz) 1.50 (3H, ddd, ³J 6.0 Hz, ⁴J 1.3 Hz, ⁵J 0.8 Hz,

n), 1648 (C]O-n), 1494, 1466,

n

;

1.81 (2H, m, n-BuCH₂), 1.84 (3H, t, ³J 9.4, ³J 5.3 Hz,CH-B

), 2.29 (1H,

*

qd, ³J 6.8, 5.3 Hz, CHCO₂Et), 2.98 (6H, s, OCH₃), 3.87 (2H, m,

CO₂CH₂CH₃), 5.00 (1H, ddt, ³J 15.1, 9.4 Hz, ⁴J 1.3 Hz, n-PeCH]CH),

5.10 (1H, dt, ³J 15.1, 6.8 Hz, n-PeCH]CH), 5.30 (2H, s, 2H,

CHCPh₂OMe), 7.23e7.34 (20H, m, arom. CH); ¹³C NMR [CDCl₃,

151 MHz mixture of syn-(2S,3R)-15d and anti-(2R,3R)-15d] 13.9

(CH₃CHCO₂Et-anti), 14.0, 14.0 (CH₃CH₂CH₂CH₂CH₂), 14.1, 14.2

(CO₂CH₂CH₃), 16.4 (CH₃CHCO₂Et-syn), 22.3, 22.5, 29.1, 29.1, 31.0, 31.1

CH₃CH), 1.96 (2H, m, CH_bH_aCONMe₂, CHB

), 2.08 (1H, dd, ²J 15.8 Hz,

*

³J 11.7 Hz, CH_aH_bCONMe₂), 2.82 (3H, s, NCH_a3), 2.84 (3H, s, NCH_b3),

2.98 (6H, s, 6H, OCH₃), 5.01 (1H, ddq, ³J 15.3, 7.7 Hz, ⁴J 1.3 Hz,

CH₃CH]CH), 5.06 (1H, dqd, ³J 15.3, 6.0 Hz, ⁴J 0.8 Hz, CH₃CH]CH),

5.29 (2H, s, CHCPh₂OMe), 7.24e7.35 (20H, m, arom. CH); ¹³C NMR

(CDCl₃, 151 MHz) 18.1 (CH₃CH), 24.0 (CHB ), 33.1 (CH₂CONMe₂),

*

35.4, 37.3 [(NCH₃)₂], 51.8 (OCH₃), 77.9 (CHCPh₂OMe), 83.4

(CPh₂OCH₃), 124.1 (CH₃CH]CH), 127.2, 127.3, 127.5, 127.6, 128.5,

129.7 (arom. CH), 129.8 (CH₃CH]CH); 141.2, 141.3 (arom. C_ipso),

172.4 (CONMe₂); m/z (ESI, positive ion, N₂) 626 (10) [(MþH₂O)^þ],

604 (30) [(Mþ1)^þ], 346 (100) [(C₂₂H₁₈O₄)^þ], 168 (22) [(C₁₃H₁₁₂)^þ].

(CH₃CH₂CH₂CH₂CH₂), 32.3 (CH-B

*

-syn), 32.6 (CH-B -anti), 32.4, 32.6

*

(n-BuCH₂), 39.1 (CHCO₂Et-anti), 41.1 (CHCO₂Et-syn), 51.7, 53.4

(OCH₃), 59.7, 59.7 (CO₂CH₂CH₃), 77.6, 77.8 (CHCPh₂OMe), 83.3, 83.4

(CPh₂OCH), 127.2, 127.2, 127.3, 127.3, 127.4, 127.4, 127.7, 127.7, 127.8,

128.5, 129.6, 129.7 (arom. CH), 125.2, 132.6 (n-PeCH]CH -anti),

*

128.1, 130.6 (n-PeCH]CH-syn), 141.2, 141.3, 141.4, 141.4 (arom. C_ipso),

176.0 (CO₂Et -anti), 176.2 (CO₂Et-syn); m/z (ESI, positive ion, N₂) 692

(100) [(MþH₂O)^þ], 197 (6) [(CPh₂OMe)^þ].

4.4.12. (3S,4E,4⁰R,5⁰R)-3-[4⁰,5⁰-Bis(methoxydiphenylmethyl)-1⁰,3⁰,2⁰-

dioxaborolan-2⁰-yl]-N,N-dimethyl-5-phenylpent-4-enamide

[(S)-

16c}. According to general procedure 7 alcohol (R)-2c¹⁶(145 mg,

0.24 mmol,1.0 equiv) dissolved in abs toluene (0.50 mL) was treated

with a 90% solution of N,N-dimethylacetamide dimethyl acetal

4.4.10. (3S,4E,4⁰R,5⁰R)-3-[4⁰,5⁰-Bis(methoxydiphenylmethyl)-1⁰,3⁰,2⁰-

dioxaborolan-2⁰-yl]-N,N-dimethylhex-4-enamide [(S)-16b]. Accord-

ing to general procedure 7 alcohol (S)-2b¹⁶(1.00 g, 1.87 mmol,

1.0 equiv) was dissolved in abs toluene (3.60 mL) and treated with

a 90% solution of N,N-dimethylacetamide dimethyl acetal (0.61 mL,

497 mg, 3.74 mmol, 2.0 equiv). The reaction mixture was stirred at

80 ^ꢀC for 45 h. ¹H and ¹³C NMR of the crude product proved the

diastereomeric ratio to be >99:1. The crude product was puriﬁed by

ﬂash column chromatography (80% PE/EtOAc to 70% PE/EtOAc) to

yield (S)-16b as a yellowish oil (880 mg, 1.46 mmol, 78%). From the

(78.8 mL, 64.6 mg, 0.48 mmol, 2.0 equiv). The reaction mixture was

stirred at 80 ^ꢀC for 24 h.¹H and ¹³C NMR of the crude product proved

the diastereomeric ratio to be >99:1. The crude product was puriﬁed

by ﬂash column chromatography (85% PE/EtOAc) to yield product

(S)-16c as a light brown solid (99.9 mg, 0.15 mmol, 62%). From the

allylboronic ester (S)-16c

obtained.⁴²R_f(85% PE/EtOAc) 0.20; [

58e75 ^ꢀC; n_max(liquid ﬁlm): 3083, 3058, 3032 (arom. CeH-

2967, 2946, 2901, 2855, 2830 (aliph. CeH- ), 2324, 2298 (OCH₃,

CeH- ), 1744, 1635 (C]O- ), 1595, 1524, 1491, 1466, 1458, 1443

(arom. C]C- ), 1390, 1373, 1350, 1319, 1264, 1231, 1198, 1158, 1148,

1075 (CeOeC), 1031, 1021, 1001, 963 (CH]CH₂, CeH-d_{out of plane}),

a crystal structure analysis was

20

a]

ꢁ46 (c 1.01, CHCl₃); mp

D

n

), 2980,

n

allylboronic ester (S)-16b

a

crystal structure analysis was

n

obtained.⁴²[Found: C, 75.19; H, 7.02; N, 2.23. C₃₈H₄₂BNO₅requires

n

20

C, 75.62; H, 7.01; N, 2.32%]; R_f(70% PE/EtOAc) 0.27; [

a

]

ꢁ100 (c

D

1.02, CHCl₃); softening range 47e62 ^ꢀC; n_max(liquid ﬁlm): 3091,

3058, 3029 (arom. CeH- ), 2980, 2958, 2937, 2915, 2857, 2825

(aliph. CeH- ), 1643 (C]O- ), 1494, 1466, 1446 (arom. C]C- ),

938, 923, 900, 887, 834, 799, 758, 735, 700 cm^ꢁ^{1 1}H NMR (CDCl₃,

;

n

600 MHz) 2.05 (1H, dd, ²J 14.7 Hz, ³J 7.9 Hz, CH_bH_aCONMe₂), 2.08

(1H, dd, ²J 14.7 Hz, ³J 6.49 Hz, 1H, CH_aH_bCONMe₂), 2.27 (1H, m,

n

1390, 1381, 1370, 1354, 1319, 1267, 1230, 1196, 1158, 1130, 1076

CHB ), 2.67 (3H, s, NCH_a3), 2.76 (3H, s, NCH_b3), 3.01 (6H, s, OCH₃),

*

(CeOeC), 1033, 1019, 1001, 967 (CH]CH₂, CeH-d_{out of plane}), 938,

5.30 (2H, s, CHCPh₂OMe), 5.94 (1H, dd, ³J 15.9, 7.2 Hz, PhCH]CH),

6.06 (1H, d, ³J 15.9 Hz, PhCH]CH), 7.09e7.39 (5H, m, arom. CH),

923, 901, 857, 826, 796, 757, 734, 705, 662 cm^ꢁ^{1 1}H NMR (CDCl₃,

;

600 MHz) 1.50 (3H, d, ³J 6.0 Hz, CH₃CH),1.93 (1H, dd, ²J 14.8 Hz, ³J

7.25e7.39 (20H, arom. CH); ¹³C NMR (CDCl₃, 151 MHz) 24.4 (CHB

),

*

6562

V. Cmrecki et al. / Tetrahedron 66 (2010) 6550e6564

31.9 (CH₂CONMe₂), 35.5, 37.4 [(NCH₃)₂], 51.8 (OCH₃), 78.1

(CHCPh₂OMe), 83.4 (CPh₂OCH₃), 128.1 (PhCH]CH), 125.9, 126.4,

127.3, 127.4, 127.6, 127.8, 128.3, 128.6, 129.7 (arom. CH), 130.9

(PhCH]CH), 138.2, 140.9, 141.1 (arom. C_ipso), 172.2 (CONMe₂); m/z

(ESI, positive ion, N₂) 666 (20) [(Mþ1)^þ]. HRMS (ESI, positive ion):

MNa^þ, found 688.32035. C₄₃H₄₄BNO₅Na requires 688.32102.

141.3, 141.4 (arom. C_ipso), 172.5 (CONMe₂); m/z (ESI, positive ion, N₂)

682 (30) [(MþK)^þ], 698 (100) [(MþNa)^þ].

4.5. Allyl additions

4.5.1. (5R,6R,Z)- and (5S,6S,Z)-6-Hydroxy-N,N-dimethyl-5,6-diphe-

nylhex-3-enamide [(R,R)-17] and [(S,S)-17]. According to general

4.4.13. (3S,4E,4⁰R,5⁰R)-3-[4⁰,5⁰-Bis(methoxydiphenylmethyl)-1⁰,3⁰,2⁰-

dioxaborolan-2⁰-yl]-N,N-dimethyldec-4-enamide [(S)-16d]. Accord-

ing to general procedure 7 (S)-2d (500 mg, 0.85 mmol, 1.00 equiv)

dissolved in abs toluene (1.70 mL) was treated with a 90% solution

procedure

1.0 equiv) was treated with benzaldehyde (14.1

0.14 mmol, 1.2 equiv) in abs CH₂Cl₂(258 L). The reaction mixture

8

allylboronic ester (R)-16b (70.0 mg, 0.12 mmol,

mL, 14.8 mg,

m

wasstirred for 7 days.¹H and ¹³C NMRof the crude product conﬁrmed

the (Z)/(E) diastereomeric ratio to be >99:1. The crude product was

puriﬁed by ﬂash column chromatography on silica gel (40% PE/EtOAc)

to yield (R,R)-17 as a colorless oil (19.9 mg, 0.08 mmol, 70%).

According to general procedure 8 allylboronic ester (S)-16b

(272 mg, 0.45 mmol, 1.0 equiv) was treated with benzaldehyde

of N,N-dimethylacetamide dimethyl acetal (275 mL, 225 mg,

1.70 mmol, 2.00 equiv). The reaction mixture was stirred at 80 ^ꢀC

for 24 h. ¹H and ¹³C NMR of the crude product proved the di-

astereomeric ratio to be >99:1. The crude product was puriﬁed by

ﬂash column chromatography (70%PE/EtOAc) to yield (S)-16d as

a colorless solid (440 mg, 0.67 mmol, 79%). [Found: C, 76.35; H,

(54.6 mL, 57.3 mg, 0.54 mmol, 1.2 equiv) in abs CH₂Cl₂(1.10 mL). The

7.67; N, 2.17. C₄₂H₅₀BNO₅requires C, 76.47; H, 7.64; N, 2.12%]; R_f

reaction mixture was stirred for 7 days. ¹H and ¹³C NMR of the

crude product conﬁrmed the (Z)/(E) diastereomeric ratio to be

>99:1. The crude product was puriﬁed by ﬂash column chroma-

tography on silica gel (60% PE/EtOAc with a gradient to 30% PE/

EtOAc) to yield (S,S)-17 as a colorless oil (50.5 mg, 0.20 mmol, 45%).

[Found: C, 72.50; H, 8.53; N, 5.55. C₁₅H₂₁NO₂requires C, 72.84; H,

8.56; N, 5.55%]. HRMS (ESI, positive ion): [MþNa]^þ, found

270.14648; [MꢁOH]^þ, found 230.15396. [MþNa]^þ, requires

20

(50% PE/EtOAc) 0.56; [

a

]

ꢁ94 (c 1.05, CHCl₃); n_max(liquid ﬁlm):

D

3457 (br), 3091, 3053, 3012 (arom. CeH-

2836 (aliph. CeH- ), 1643 (C]O- ), 1493, 1463, 1446 (arom. C]C-

), 1392, 1368, 1317, 1264, 1228, 1198, 1153, 1130, 1075 (CeOeC),

1032, 1017, 966 (CH]CH₂, CeH-d_{out of plane}), 922, 901, 827, 796, 758,

733, 698 cm^ꢁ^{1 1}H NMR (CDCl₃, 600 MHz) 0.79 (3H, t, ³J 7.1 Hz,

CH₃CH₂CH₂CH₂CH₂), 1.14 (6H, m, CH₃CH₂CH₂CH₂CH₂), 1.81 (2H, m,

n), 2958, 2928, 2876, 2854,

n

;

n-BuCH₂), 1.95 (2H, m, CH₂CONMe₂), 2.02 (1H, m, CHB

*

), 2.66 (3H, s,

270.14645; [MꢁOH]^þ, requires 230.15394; R_f(50% PE/EtOAc) 0.06;

20

NCH_a3), 2.72 (3H, s, NCH_b3), 2.99 (6H, s, OCH₃), 5.07 (1H, dtd, ³J 15.5,

6.1 Hz, ⁴J 1.1 Hz, n-PeCH]CH), 5.13 (1H, ddt, ³J 15.5, 6.8 Hz, ⁴J 1.1 Hz,

n-PeCH]CH), 5.28 (2H, s, CHCPh₂OMe), 7.23e7.36 (20H, m, arom.

CH); ¹³C NMR (CDCl₃, 151 MHz) 14.0 (CH₃CH₂CH₂CH₂CH₂), 22.4,

R_f(30% PE/EtOAc) 0.14; [

a]

þ181 [c 1.04, CHCl₃, (R,R)-17]; [a]_D²⁰

D

ꢁ153 [c 1.44, CHCl₃, (S,S)-17]; n_max(liquid ﬁlm): 3442 (br), 3367

(OeH-

2860 (aliph. CeH-

C]C- ), 1450, 1435, 1366, 1259, 1216, 1228, 1203, 1144, 1092, 1074,

n

, br), 3070, 3040, 3026 (arom. CeH-

n), 2970, 2940, 2926,

n

), 1739 (C]O- ), 1625 (olef. C]C-

n

), 1492 (arom.

27.5, 29.2 (CH₃CH₂CH₂CH₂CH₂), 24.2 (CHB

*

), 31.1 (n-BuCH₂), 32.6

n

(CH₂CONMe₂), 35.4, 35.7 [(NCH₃)₂], 51.7 (OCH₃), 77.9

(CHCPh₂OMe), 83.3 (CPh₂OCH₃), 128.2 (n-PeCH]CH), 129.2 (n-

PeCH]CH), 127.2, 127.3, 127.5, 127.7, 127.8, 129.6 (arom. CH), 141.0,

141.6 (arom. C_ipso), 172.8 (CONMe₂); m/z (ESI, positive ion, N₂) 682

(100) [(MþNa)^þ], 659 (20) [M^þ], 629 (9), 403 (38), 224 (7).

1054, 1024, 988, 932, 907, 824, 799, 762 (Ph, CeH-d_{out of plane}), 720,

700 cm^ꢁ1; ¹H NMR (CDCl₃, 600 MHz) 0.80 (3H, d, ³J 6.4 Hz, CHCH₃),

2.73 (1H, m, CHCH₃), 2.96 (3H, s, NCH_3a), 3.03 (3H, s, NCH_3b), 3.13

(2H, dd, ³J 7.2, 1.1 Hz, CH₂CONMe₂), 3.65 (1H, br, OH), 4.28 (1H, d, ³J

8.3 Hz, CHOH), 5.58 (1H, td, ³J 10.1 Hz, ⁴J 1.5 Hz, CH]CHCH₂), 5.71

(1H, dtd, ³J 10.1, 7.2 Hz, ⁴J 0.8 Hz, CH]CHCH₂), 7.24e7.36 (5H, m,

arom. CH); ¹³C NMR (CDCl₃, 151 MHz) 17.4 (CHCH₃), 32.1

(CH₂CONMe₂), 35.7 (NCH_3a), 37.4 (NCH_3b), 40.8 (CHCH₃), 78.6

(CHOH), 123.5 (CH]CHCH₂), 126.9, 127.4, 128.1 (arom. CH), 136.3

(CH]CHCH₂), 143.2 (arom. C_ipso), 171.5 (CONMe₂); m/z (ESI, positive

ion, N₂) 248 (100) [(MþH)^þ], 230 (30) [(MꢁOH)^þ]; HPLC (Chiracel

OD-H, 90% n-hexane/i-PrOH, ﬂow rate 0.5 mL/min, detection UV

220 nm) t_R(R,R)-17 33.1 min, ee >97%; t_R(S,S)-17 27.7 min, ee

>99%.

4.4.14. (3R,4E,4⁰R,5⁰R)-3-[4⁰,5⁰-Bis(methoxydiphenylmethyl)-1⁰,3⁰,2⁰-

dioxaborolan-2⁰-yl]-N,N-dimethyldec-4-enamide ((R)-16d). Accord-

ing to general procedure 7 alcohol (R)-2d (200 mg, 0.34 mmol,

1.0 equiv) dissolved in abs toluene (0.70 mL) was treated with a 90%

solution of N,N-dimethylacetamide dimethyl acetal (110 mL,

100.2 mg, 0.68 mmol, 2.0 equiv). The reaction mixture was stirred at

80 ^ꢀC for 21 h. ¹H and ¹³C NMR of the crude product proved the di-

astereomeric ratio to be >99:1. The crude product was puriﬁed by

ﬂash column chromatography (90% PE/EtOAc with the gradient to

70% PE/EtOAc) to yield (R)-16d as a yellowish oil (197 mg, 0.29 mmol,

88%). [Found: C, 76.01; H, 7.65; N, 2.11. C₄₂H₅₀BNO₅requires C, 76.47;

4.5.2. (1R,2R)- and (1S,2S)-2-Methyl-1-phenylpropane-1,3-diol [(R,

R)-18] and [(S,S)-18]. In a Schlenk tube homoallylic alcohol (R,R)-17

or (S,S)-17 (49.5 mg, 0.20 mmol) was dissolved in abs CH₂Cl₂

(20.0 mL) under an atmosphere of dry argon. Ozone was passed

through the solution at ꢁ78 ^ꢀC and the reaction progress was

monitored by TLC. After 8 min the excess of the ozone was removed

by passing a continuous stream of argon through the solution. After

the reductive work-up with Me₂S (2.0 mL), the reaction mixture was

warmed to room temperature and the solvent was removed under

reduced pressure. The residue was dissolved in abs THF (20 mL)

under an atmosphere of dry argon and was treated with LiAlH₄

(200 mg, 5.28 mmol) at ꢁ78 ^ꢀC. The mixture was warmed to room

temperature. After 1 h it was diluted with Et₂O (20.0 mL) and

H, 7.64; N, 2.12%]; R_f(70% PE/EtOAc) 0.20; [

n_max(liquid ﬁlm): 3457 (br), 3091, 3053, 3026 (arom. CeH-n), 2957,

a

]

²⁰þ92 (c 1.00, CHCl₃);

D

2929, 2876, 2856, 2836 (aliph. CeH-n), 1641 (C]O-n), 1522, 1493,

1463, 1446 (arom. C]C- ), 1392, 1366, 1265, 1229, 1217, 1205, 1198,

n

1153,1075(CeOeC),1033,1014, 966(CH]CH₂, CeH-d_{out of plane}), 920,

900, 725, 758, 733, 698, 670 cm^ꢁ1; ¹H NMR (CDCl₃, 600 MHz) 0.84

(3H, t, ³J 7.2 Hz, CH₃CH₂CH₂CH₂CH₂), 1.20 (6H, m,

CH₃CH₂CH₂CH₂CH₂), 1.81 (2H, dt, ³J 6.8, 6.8 Hz, n-BuCH₂), 1.94 (1H,

ddt, ³J 11.5, 7.9, 3.2 Hz, CHB ), 2.00 (1H, dd, ²J 15.1 Hz, ³J 3.5 Hz,

*

CH_bH_aCONMe₂), 2.1 (1H, dd, ²J 15.1 Hz, ³J 10.9 Hz, CH_aH_bCONMe₂),

2.82 (3H, s, NCH_a3), 2.83 (3H, s, NCH_b3), 2.99 (6H, s, 6H, OCH₃), 4.98

(1H, ddt, ³J 15.1, 8.3 Hz, ⁴J 1.3 Hz, n-PeCH]CH), 5.07 (1H, dtd, ³J 15.1,

5.7 Hz, ⁴J 0.9 Hz, n-PeCH]CH), 5.30 (2H, s, CHCPh₂OMe), 7.23e7.34

(20H, m, arom. CH); ¹³C NMR (CDCl₃, 151 MHz) 14.1

(CH₃CH₂CH₂CH₂CH₂), 22.5, 29.2, 31.2 (CH₃CH₂CH₂CH₂CH₂), 24.4

quenched at 0 ^ꢀC with H₂O (242

H₂O (716 L). After stirring for approximately 30 min, the formed

mL), 15% NaOH (aq) (242 mL), and

m

precipitate was ﬁltered off and washed thoroughly. The ﬁltrate was

dried over MgSO₄and the solvent was removed under reduced

pressure. The crude product was puriﬁed by ﬂash column chro-

matography on silica gel (60% PE/EtOAc) to yield diol (R,R)-18

(28.5 mg, 0.17 mmol, 86%) as a colorless solid, and (S,S)-18 (17.2 mg,

(CHB ), 32.5 (n-BuCH₂), 33.3 (CH₂CONMe₂), 35.4, 37.4 [(NCH₃)₂], 51.8

*

(OCH₃), 77.8 (CHCPh₂OMe), 83.4 (CPh₂OCH₃), 128.6 (n-PeCH]CH),

130.1 (n-PeCH]CH),127.2,127.3,127.5,127.8,128.5,129.7 (arom. CH),

V. Cmrecki et al. / Tetrahedron 66 (2010) 6550e6564

6563

0.10 mmol, 52%), respectively. The analytical data are in full agree-

ment with those reported in the literature.^14,16,44A crystal structure

4.5.4. (2S,Z)- and (2R,Z)-Ethyl 2,7-dihydroxyhept-4-enoate [(2S)-

23b] and [(2R)-23b]. According to general procedure 8 allylboro-

nate (S)-20 or (R)-20 (400 mg, 0.73 mmol) was dissolved in CH₂Cl₂

(365

(50%, 188 mL, 0.95 mmol, 1.3 equiv) was added. After 3 days stirring

analysis of (S,S)-18 was obtained.⁴²[Found: C, 71.91; H, 8.46.

20

C₁₀H₁₄O₂requires C, 72.26; H, 8.46%]; R_f(50% PE/EtOAc) 0.28; [

a

]

m

L) at 0 ^ꢀC, before a solution of ethyl glyoxylate (22) in toluene

D

þ49 [c 0.50, CHCl₃, (R,R)-18]; [a]²_D⁰ꢁ45 [c 0.50, CHCl₃, (S,S)-18]; n_max

(liquid ﬁlm): 3333 (OeH-

n, br), 3083, 3063, 3027 (arom. CeH-

n

),

), 1454, 1431,

1378,1340,1276,1198,1084,1064,1020, 976, 928, 912, 761 (Ph, CeH-

d_{out plane}), 698 cm^{ꢁ1 1}H NMR (CDCl₃, 600 MHz) 0.71 (3H, t, ³J

at room temperature and removal of solvents under reduced

pressure, ester (2S)-23b was isolated by ﬂash column chromatog-

raphy (70% PE/EtOAc to 30% PE/EtOAc) (115.4 mg, 0.61 mmol, 84%,

ee 98%) as a clear liquid; ester (2R)-23b was obtained in 77%

(105.4 mg, 0.56 mmol, ee 99%). [Found: C, 57.27; H, 8.50. C₉H₁₆O₄

2956, 2926, 2879 (aliph. CeH-n), 1489 (arom. C]C-n

;

of

7.2 Hz, CH₃), 2.06 (1H, m, CHMe), 2.82 (2H, br, OH), 3.73 (1H, dd, ²J

10.9 Hz, ³J 7.6 Hz, CH_aH_b), 3.78 (1H, d, ²J 10.9 Hz, CH_bH_a), 4.56 (1H, d,

³J 8.3 Hz, CHOH), 7.27e7.38 (5H, m, arom. CH); ¹³C NMR (CDCl₃,

151 MHz) 13.8 (CH₃), 41.7 (CHCH₃), 67.9 (CH₂), 80.8 (CHOH), 126.7,

127.8, 128.4 (arom. CH), 143.3 (arom. C_ipso); HPLC (Chiralpak IC, 90%

n-hexane/i-PrOH, ﬂow rate 1.0 mL/min, detection UV at 220 nm) t_R

(R,R)-18 14.8 min, ee >97%; t_R(S,S)-18 11.4 min, ee >99%.

requires C, 57.43; H, 8.57%] R_f(30% PE/EtOAc) 0.14; [

a

]

²⁰ꢁ30.2 [c 1.1,

D

20

CHCl₃, (2S)-23b]; [

a

]

þ30.4 [c 1.1, CHCl₃, (2R)-23b]; n_max(liquid

D

ﬁlm) 3600e3050 (br), 2982, 2938, 2901,1730,1267,1199,1111,1083,

1034, 862, 721 cm^ꢁ^{1 1}H NMR (CDCl₃, 600 MHz) 1.26 (3H, t, ³J

;

7.1 Hz, OCH₂CH₃), 2.36 (2H, ddd, ³J 7.5, 6.2 Hz, ⁴J 1.2 Hz, CH₂CH₂OH),

2.49 (1H, ddd, ²J 14.5 Hz, ³J 7.5 Hz, ⁴J 1.2 Hz, CH(OH)CH_aH_b), 2.53

(1H, s br, OH), 2.57 (1H, ddd, ²J 14.5 Hz, ³J 7.5 Hz, ⁴J 1.2 Hz, CH(OH)

CH_aH_b), 3.45 (1H, s br, OH), 3.67 (2H, t, ³J 6.2 Hz, CH₂OH), 4.20 (2H,

q, ³J 7.1 Hz, OCH₂CH₃), 4.22 (1H, m, CH(OH)), 5.51 (1H, dtt, ³J 11.0 Hz,

³J 7.5 Hz, ⁴J 1.2 Hz, CHC]CHCH₂CH₂OH), 5.57 (1H, dtt, ³J 11.0, 7.5 Hz,

⁴J 1.2 Hz, CHC]CHCH₂CH₂OH); ¹³C NMR (CDCl₃, 151 MHz) 14.2

(OCH₂CH₃), 30.61 (CH₂CH₂OH), 32.06 (C(OH)HCH₂), 61.69 (CH₂OH),

61.71 (OCH₂CH₃), 70.0 (C(OH)H), 126.3 (CHC]CHCH₂CH₂OH), 130.0

(CHC]CHCH₂CH₂OH), 174.4 (CO₂Et). HRMS (ESI): [MþNa]^þ, found

211.0942. C₉H₁₆O₄²³Na [MþNa]^þ, requires 211.0941; HPLC (Chiracel

OD-H, 90% n-hexane/i-PrOH, ﬂow rate 0.5 mL/min, detection

202 nm) t_R(2S)-23b 17.0 min, t_R(2R)-23b 29.4 min.

4.5.3. (2S,Z)- and (2R,Z)-Diethyl 2-hydroxyhept-4-enedioate [(2S)-

23a] and [(2R)-23a]. According to general procedure 8 allylboro-

nate (S)-13 or (R)-13 (400 mg, 0.68 mmol) was dissolved in CH₂Cl₂

(340

(50%, 175

m

L) at 0 ^ꢀC, before a solution of ethyl glyoxylate (22) in toluene

mL, 0.88 mmol) was added. After 2 days stirring at room

temperature solvents were removed under reduced pressure. Re-

peated ﬂash column chromatography (90% PE/EtOAc to 80 PE/

EtOAc) furnished diester (2S)-23a (132.8 mg 0.58 mmol, 85%, ee

>99%) and (2R)-23a (128.9 mg 0.56 mmol, 83%, ee >99%) as a clear

liquid.

Microwave assisted addition: A 10 mL microwave vessel equip-

ped with a stirrer bar was charged with allylboronate (R)-13

(200 mg, 0.34 mmol), a solution of ethyl glyoxylate (22) in toluene

4.5.5. (2S,Z)- and (2R,Z)-Ethyl 7-(tert-butyldimethylsilyloxy)-2-hy-

droxyhept-4-enoate [(2S)-23c] and [(2R)-23c]. According to general

procedure 8 allylboronate (S)-21 or (R)-21 (440.0 mg, 0.66 mmol)

(50%, 134 mL, 0.68 mmol), and 0.51 mL CH₂Cl₂. The vessel was

closed with an IntelliVent^Óseptum and heated to a temperature of

65 ^ꢀC using a microwave reactor. Herein, the power was limited to

150 W, the ‘cooling’ function was on permanently. After 3 h of ir-

radiation, all volatile compounds were removed under reduced

pressure. After repeated ﬂash column chromatography (90% PE/

EtOAc to 80% PE/EtOAc) product (2R)-23a (60.3 mg, 0.26 mmol,

77%, 89% ee) was isolated as a colorless liquid.

was dissolved in CH₂Cl₂(330

m

L) at 0 ^ꢀC before a solution of ethyl

L, 0.86 mmol, 1.3 equiv) was

glyoxylate (22) in toluene (50%, 171

m

added. After 4 days stirring at room temperature, the solvents were

removed under reduced pressure. Repeated ﬂash column chro-

matography (95% PE/EtOAc to 80% PE/EtOAc) yielded (2S)-23c as

a clear liquid (84.0 mg 0.28 mmol, 42%, ee 97%); ester (2R)-23c was

obtained in 59% (119.4 mg 0.39 mmol, ee 92%). [Found: C, 59.35; H,

9.86. C₁₅H₃₀O₄Si requires C, 59.56; H, 10.00%]; R_f(80% PE/EtOAc)

Thermal conditions: A 10 mL microwave vessel equipped with

a stirrer bar was charged with allylboronate (R)-13 (200 mg,

0.34 mmol) and 0.51 mL CH₂Cl₂. It was closed with an IntelliVent^Ó

septum and heated to 65 ^ꢀC in an oil bath. After 30 min a solution of

0.30; [

a

]

²⁰ꢁ0.2 [c 0.7, CHCl₃, (2S)-23]; [

a

]

²⁰þ0.1 [c 0.9, CHCl₃, (2R)-

D

23c]; n_max(liquid ﬁlm) 3550e3200 (br), 2930, 2891, 2858, 1734,

1254, 1201, 1189, 1035, 832, 775, 737 cm^ꢁ^{1 1}H NMR (CDCl₃,

;

ethyl glyoxylate (22) in toluene (50%, 134

m

L, 0.68 mmol) was added

600 MHz) 0.06 (3H, s, Si(CH₃)), 0.06 (3H, s, Si(CH₃)), 0.89 (9H, s, C

to the closed vessel through a cannula. After stirring for 3 h, the

vessel was removed from the oil-bath and freed from all volatile

compounds under reduced pressure. NMR of the crude product in-

dicated incomplete conversion; a sample of (2R)-23a was isolated by

ﬂash column chromatography (90% n-pentane/MTBE to 70% n-pen-

tane/MTBE) and submitted to HPLC: 99% ee. [Found: C, 57.63; H, 7.74.

(CH₃)₃), 1.30 (3H, t, ³J 7.2 Hz, OCH₂CH₃), 2.28 (1H, dddd, ²J 14.2 Hz, ³J

7.4, 6.7 Hz, ⁴J 1.4 Hz, CH_aH_bCH₂OTBS), 2.32 (1H, dddd, ²J 14.2 Hz, ³

7.4, 6.7 Hz, ⁴J 1.4 Hz, CH_aH_bCH₂OTBS), 2.43 (1H, dddd, ²J 14.6 Hz, ³

J

7.5, 6.9 Hz, ⁴J 1.4 Hz, CH(OH)CH_aH_b), 2.52 (1H, dddd, ²J 14.6 Hz, ³J

7.5, 6.9 Hz, ⁴J 1.4 Hz, CH(OH)CH_aH_b), 2.88 (1H, d, ³J 6.2 Hz, OH), 3.57

(2H, t, ³J 6.7 Hz, CH₂OTBS), 4.24 (1H, ddd, ³J 6.9, 6.2 Hz, ⁴J 0.7 Hz, CH

(OH)), 4.24 (2H, dq, ³J 7.2 Hz, ⁴J 0.7 Hz, OCH₂CH₃), 5.44 (1H, dtt, ³J

10.9, 7.5 Hz, ⁴J 1.5 Hz, CH]CHCH₂C(OH)H), 5.53 (1H, dtt, ³J 10.9,

7.4 Hz, ⁴J 1.4 Hz, CH]CHCH₂C(OH)H); ¹³C NMR (CDCl₃, 151 MHz),

ꢁ5.3 (Si(CH₃)₂), 14.2 (OCH₂CH₃), 18.4 (SiC(CH₃)₃), 26.0 (SiC(CH₃)₃),

31.1 (CH₂CH₂OTBS), 32.3 (CH(OH)CH₂), 61.6 (OCH₂CH₃), 62.7

(CH₂OTBS), 70.2 (CHOH), 124.8 (CH]CHCH₂C(OH)H), 130.1 (CH]

CHCH₂C(OH)H), 174.5 (COOEt). HRMS (ESI): [MþNa]^þ, found

325.1805. C₁₅H₃₀O₄²³Na²⁸Si [MþNa]^þ, requires 325.1806; HPLC

(Chiracel OD-H, 98% n-hexane/i-PrOH, ﬂow rate 0.5 mL/min, de-

tection 210 nm) t_R(2S)-23c 11.1 min, t_R(2R)-23c 13.1 min.

C₁₁H₁₈O₅requires C, 57.38; H, 7.88%]; R_f(80% PE/EE) 0.09; [

a]

²⁰þ1.0

D

[c 1.4, CHCl₃, (2S)-23a]; [

a

]

²⁰ꢁ1.1 [c 1.2, CHCl₃, (2R)-23a]; n_max(liquid

D

ﬁlm) 3650e3200 (br), 2983, 2937, 2906,1734,1254, 1196, 1180,1105,

1031, 860, 704 cm^ꢁ1; ¹H NMR (CDCl₃, 600 MHz) 1.26 (3H, t, ³J 7.1 Hz,

b

-OCH₃CH₂),1.30 (3H, t, ³J 7.1 Hz,

a-OCH₃CH₂), 2.46e2.60 (2H, m_c, CH

(OH)CH₂), 3.11 (1H, ddd, ²J 15.5 Hz, ³J 7.3 Hz, ⁴J 1.5 Hz, CH_aH_bCOOEt),

3.12 (1H, ddd, ²J 15.5 Hz, ³J 7.3 Hz, ⁴J 1.5 Hz, CH_aH_bCOOEt), 4.15 (2H, q,

³J 7.1 Hz,

b-OCH₂CH₃), 4.22e4.28 (3H, m, CHOH and a-OCH₂CH₃),

5.63 (1H, dtt, ⁴J 1.5 Hz, ³J 10.8, 7.5 Hz, CH]CHCH₂COOEt), 5.77 (1H,

dtt, ⁴J 1.5 Hz, ³J 10.8, 7.3 Hz, CH]CHCH₂COOEt); ¹³C NMR (CDCl₃,

151 MHz) 14.2 (a‑OCH₂CH₃), 14.2 (b-OCH₂CH₃), 32.3 (CH(OH)CH₂),

33.1 (CH₂COOEt), 60.8 (

b

-OCH₂CH₃), 61.8 (

a

-OCH₂CH₃), 69.9 (CHOH),

4.5.6. (2R,3R,Z)- and (2S,3S,Z)-Ethyl 7-(dimethylamino)-2-hydroxy-

3-methyl-7-oxohept-4-enoate [(R,R)-23d] and [(S,S)-23d]. Accord-

ing to general procedure 8 allylboronic ester (R)-16b or (S)-16b

124.9 (CH]CHCH₂COOEt), 126.7 (CH]CHCH₂COOEt), 171.7 (b-

COOEt), 174.3 (

a

-COOEt). HRMS (ESI): [MþNa]^þ, found 253.1048.

23

C₁₁H₁₈O₅Na [MþNa]^þ, requires 253.1047; HPLC (Chiracel OD-H,

90% n-hexane/i-PrOH, ﬂow rate 0.5 mL/min, detection 210 nm) t_R

(2S)-23a 14.6 min; t_R(2R)-23a 17.3 min.

(150 mg, 0.25 mmol,1.0 equiv) was dissolved in abs CH₂Cl₂(124

and treated with a 50% solution of ethyl glyoxylate (22) in toluene

(54.2 L, 27.9 mg, 0.27 mmol, 1.1 equiv). The reaction mixture was

mL)

m

6564

V. Cmrecki et al. / Tetrahedron 66 (2010) 6550e6564

stirred for 2 days. ¹H and ¹³C NMR of the crude product conﬁrmed

the (Z)/(E) diastereomeric ratio to be >99:1. The crude product was

puriﬁed by ﬂash column chromatography on silica gel (85% PE/

EtOAc) to yield amide (R,R)-23d as a colorless oil (33.8 mg,

0.14 mmol, 56%); amide (S,S)-23d was obtained in 58% (40.1 mg,

0.16 mmol). The product could even at 0 ^ꢀC not be stored longer

than 2 months. [Found: C, 59.41; H, 8.63; N, 5.71. C₁₂H₂₁NO₄requires

C, 59.246; H, 8.70; N, 5.71%]; R_f(50% PE/EtOAc) 0.04; R_f(30% n-Pe/

9. Hoffmann, R. W.; Dresely, S. Chem. Ber. 1989, 122, 903e909.

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20

Et₂O) 0.02; [

CHCl₃, (S,S)-23d]; n_max(liquid ﬁlm): 3397 (OeH-

2875 (aliph. CeH- ), 1737 (C]O- ), 1628 (olef. C]C-

1399, 1370, 1262, 1223, 1204, 1145, 1112, 1027, 991, 732 cm^ꢁ1

a

]

þ12 [c 1.26, CHCl₃, (R,R)-23d]; [

a

]

þ12 [c 1.02,

D

n

, br), 2971, 2931,

), 1499, 1453,

¹H

n

;

NMR (CDCl₃, 600 MHz) 1.08 (3H, d, ³J 6.8 Hz, CH₃), 1.29 (3H, t, ³J

7.2 Hz, COCH₂CH₃), 2.72 (1H, br, OH), 2.92 (1H, m, CHCH₃), 2.95 (3H,

s, NCH₃), 3.03 (3H, s, NCH₃), 3.07 (1H, ddd, ²J 15.8 Hz, ³J 6.8 Hz, ⁴J

1.5 Hz, CH_aH_b), 3.18 (1H, ddd, ²J 15.8 Hz, ³J 7.2 Hz, ⁴J 1.5 Hz, CH_bH_a),

4.04 (1H, d, ³J 4.9 Hz, CHOH), 4.22 (2H, m, COCH₂CH₃), 5.54 (1H, ddt,

³J 10.9, 7.3 Hz, ⁴J 1.5 Hz, CH]CHCH₂), 5.65 (1H, dtd, ³J 10.9, 7.2 Hz, ⁴J

0.8 Hz, CH]CHCH₂); ¹³C NMR (CDCl₃, 151 MHz) 14.2 (COCH₂CH₃),

16.9 (CH₃), 32.6 (CH₂), 35.6 (NCH₃), 36.4 (CHCH₃), 37.3 (NCH₃), 61.5

(CO₂CH₂CH₃), 74.6 (CHOH),123.5 (CH]CHCH₂),132.7 (CH]CHCH₂),

171.1,173.9 (CO₂Et, CO₂NMe₂); m/z (GC/MS, EI, 70 eV) 243 (0.2) [M^þ],

223 (8), 205 (5), 149 (100); m/z (ESI, positive ion, N₂) 244 (100)

[(MþH)^þ]; HPLC (Chiracel OD-H, 90% n-hexane/i-PrOH, ﬂow rate

0.5 mL/min, detection UV 220 nm) t_R(R,R)-23d 45.2 min, ee >99%;

t_R(S,S)-23d 28.8 min, ee >99%.

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€

ref. 14 and Pietruszka, J.; Schone, N. Synthesis 2006, 24e30.

Acknowledgements

Scheme 13. Conditions: (i) 2.00 equiv DiBAlH, ꢁ78 ^ꢀC to rt, CH₂Cl₂, 2 h; (ii) 1.10 equiv

TBSCl, 1.05 equiv imidazole, CH₂Cl₂, 0 ^ꢀC to rt, over night.

We gratefully acknowledge the Deutsche Forschungs-

gemeinschaft and the Ministry of Innovation, Science, Research and

Technology of the German federal state of North Rhine-Westphalia

for the generous support of our projects. Donations from the BASF

AG, the Chemetall GmbH, and the Wacker AG were greatly appre-

ciated. Furthermore, we thank the analytical departments at the

University of Stuttgart and the FZ Jülich as well as Verena Doum,

Monika Gehsing, Rainer Goldbaum, Birgit Henßen, Christoph Lor-

enz, Erik Kranz, Vera Ophoven, Bea Paschold, and Truc Pham for

their ongoing support. We are grateful for the preliminary experi-

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Supplementary data

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Supplementary data associated with this article can be found in

the online version at doi:10.1016/j.tet.2010.04.100.

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Microwave assisted synthesis of enantiomerically pure allylboronates

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