Syntheses of new chiral phosphane ligands by diastereoselective conjugate addition of phosphides to enantiomerically pure acceptor-substituted olefins from the chiral pool

FULL PAPER

Syntheses of New Chiral Phosphane Ligands by Diastereoselective Conjugate

Addition of Phosphides to Enantiomerically Pure Acceptor-Substituted Olefins

from the Chiral Pool

Burkhard Wiese,^[a]Guido Knühl,^[a]Dietmar Flubacher,^[a]Jan W. Prieß,^[a]

Bolette Ulriksen (nee Laursen),^[a]Kerstin Brödner,^[a]and Günter Helmchen*^[a]

Keywords: Asymmetric synthesis / Phosphanes / Diastereoselectivity / Michael addition / Terpenoids

A variety of new chiral phosphanes were prepared by highly

diastereoselective additions of phosphanes to α,β-unsatu-

rated carbonyl compounds and related acceptor-substituted

phorus are described. In addition diphosphanes were pre-

pared by a highly diastereoselective double conjugate ad-

dition of a secondary diphosphane.

olefins derived from myrtenal as ex chiral pool source. Mono- (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,

phosphanes with astereogenic as well as stereogenic phos-

Germany, 2005)

Jansen and Feringa who employed this approach for a syn-

thesis of the ligand chiraphos using as key steps diastereo-

selective addition of lithium diphenylphosphide to a γ-al-

koxybutenolide and trapping of the resulting enolate with

PPh₂Cl (Scheme 2).^[6]

Introduction

In modern organic synthesis, a variety of enantioselective

reactions are successfully applied that are promoted by

transition metal catalysts containing chiral ligands.^[1]Espe-

cially phosphane ligands are extremely valuable as they are

highly variable both with respect to their electronic and ste-

ric properties.^[2]Therefore, the development of new meth-

ods or strategies for the synthesis of enantiomerically pure

phosphanes is of great importance.^[3]So far, phosphorus is

most often introduced by nucleophilic substitution reac-

tions with alkali phosphides.^[4]Far less attention has been

paid to the conjugate addition of phosphanes to electron-

deficient olefins, especially to α,β-unsaturated carboxylic

acid derivatives according to Scheme 1, leading to poten-

tially useful phosphane ligands with one or two additional

functional groups.

Scheme 2. Asymmetric synthesis of chiraphos via conjugate ad-

dition.

Afterwards, the concept of the diastereoselective conju-

gate addition of phosphides as a simple route to novel li-

gands was further elaborated in our group. In contrast to

Jansen and Feringa we directly used the addition products

as ligands and selected the chiral starting materials from ex

chiral pool sources in order to assure enantiomeric purity

and relative configuration of the new phosphane ligands. In

this way it was possible to obtain enantiomerically pure

trans-3-(diphenylphosphanyl)myrtanic acid^[7]in only two

steps: addition of lithium diphenylphosphide to tert-butyl

myrtenate which is easily accessible from commercial, cheap

myrtenal followed by cleavage of the ester (Scheme 3).^[8]In

the meantime related diastereoselective conjugate additions

to EWG-substituted olefins to give enantiomerically pure

P,N-ligands were described by Knochels group.^[9]Further-

Scheme 1. Conjugate additions of phosphanes.

There are several reports on the preparation of achiral

or racemic phosphanes via conjugate addition to achiral en-

oates.^[5]However, prior to our work reactions with chiral,

enantiomerically pure substrates were only carried out by

[a] Organisch-Chemisches Institut der Universität Heidelberg,

Im Neuenheimer Feld 270, 69120 Heidelberg, Germany

Fax: +49-6221-544205

E-mail: en4@ix.urz.uni-heidelberg.de

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DOI: 10.1002/ejoc.200500144

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New Chiral Phosphane Ligands

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more, enantioselective additions of phosphanes under con-

2. The scope of the stereoselective conjugate addition of

trol of asymmetric catalysts have been achieved by Togni et phosphides to carboxylic acid derivatives was examined.

al.^[10]

The reaction was possible with a α,β–unsaturated amide,

the nitrile as well as oxazolines derived from myrtenic acid.

Further transformation of the acceptor groups by reduction

gave hydroxy- and amino-phosphanes. Thus, chiral mono-

and bidentate ligands with sterically and electronically vari-

able functionalities are accessible.

3. Addition of diphosphanes [HP(R)CH₂CH₂P(R)H] as

well as unsymmetrically substituted phosphanes (HRRЈP)

allows the generation of polydentate ligands and the fine

tuning of the steric and electronic properties of the phos-

phanyl group.

In this report, syntheses with α,β–unsaturated carboxylic

acid derivatives derived from myrtenal are described. The

conjugate addition of the phosphanes under a variety of

conditions as well as derivatizations of the resulting phos-

phanylcarboxylic esters will be presented. As mentioned

above, applications of trans-3-(diphenylphosphanyl)myrtan-

ate in catalysis were already reported.^[8,11]Syntheses of

phosphane ligands with a menthane and a camphane

skeleton and asymmetric syntheses with the new phosphane

ligands will be reported separately.

Scheme 3. Synthesis of trans-3-(diphenylphosphanyl)myrtanic acid,

an excellent ligand for Pd-catalyzed allylic substitutions, by diaster-

eroselective conjugate addition.

trans-3-(Diphenylphosphanyl)myrtanic acid is an excel-

lent ligand for Pd-catalyzed allylic substitutions.^[11]Minami

et al. described an alternative approach to enantiomerically

pure β-phosphanylcarboxylic acids via a multi-step synthe-

sis of a racemate followed by enantiomer resolution by

crystallization of diastereomeric salts.^[12]

Both the butenolide-derived as well as the myrtane-based

system impressively demonstrate that phosphane additions

on such rigid, cyclic cores proceed with a high degree of

diastereoselectivity and at a high reaction rate. The almost

unlimited availability of a large variety of enantiomerically

pure enones, enoates and enals, therefore, offers the pos-

sibility to generate libraries of structurally diverse ligands.

This consideration and the high efficiency of trans-3-(di-

phenylphosphanyl)myrtanic acid as ligand in Pd-catalyzed

allylic alkylation reactions^[8]prompted us to examine the

conjugate addition more thoroughly. To begin with, the fol-

lowing aspects were most relevant:

Results and Discussion

1. Synthesis of the Requisite α,β-Unsaturated Carboxylic

Acid Derivatives

The synthesis of myrtenic acid (3) (Scheme 5) followed a

1. The torsion angle between the phosphanyl and the car- route described by Semmler,^[13]starting from commercially

boxyl group of phosphanylcarboxylic acids can be system- available (1R)-myrtenal (1) by oxime formation, dehydrati-

atically varied by choosing appropriate conjugated ac- sation of this to give the nitrile 2 and subsequent hydrolysis.

ceptors. As shown in Scheme 4 phosphanylcarboxylic acids For the hydrolysis of nitrile 2 to give acid 3 we obtained

with torsion angles between 0° and 120° could be realized superior results by modifying the original procedure and

starting from camphor, menthone and myrtenal as cheap use of alkaline aqueous hydrogen peroxide solution under

ex chiral pool compounds.

reflux (97% yield).

Scheme 4. β-Phosphanylcarboxylic acids with different torsion angles (HOOC)–C–C–P.

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G. Helmchen et al.

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carboxylic acid 3 in quantitative yield using trifluoroacetic

acid.

The amide 5 was prepared by activation of the acid 3

with oxalyl chloride followed by reaction with dimethyl-

amine, or in one step by in situ activation with 2-(1H-

benzotriazol-1-yl)-1,1,3,3- tetramethyluronium tetrafluo-

roborate (TBTU) and subsequently reaction with dimethyl-

amine (Scheme 6). Dihydrooxazoles 7a–7d were obtained

via amides 6a–6d which were cyclized in a one-pot pro-

cedure by treatment with tosyl chloride and base.^[16]

Alternatively, the synthesis of dihydrooxazoles was car-

ried out by transforming nitrile 2 to an imidate^[17]and con-

densation of this with the amino alcohol (Scheme 7). The

dihydrooxazole 7a was obtained in 33% yield using this pro-

cedure.

Scheme 5. Synthesis of myrtenic acid (3) and myrtenic acid esters

4a and 4b.

Esters 4a and 4b were prepared from acid 3 by reaction

with trifluoroacetic acid anhydride according to Kuivila^[14]

followed by in situ reaction either with methanol or tert-

butyl alcohol (Scheme 5). The methyl ester 4a could also be

obtained directly from myrtenal by oxidation with MnO₂/

NaCN under Corey conditions.^[15]For large scale synthesis

(100–200 g), however, the stepwise synthesis was preferred

as it avoids the handling of large amounts of cyanides. The

enantiomeric purity of the tert-butyl ester 4b could be en-

hanced to Ͼ99% ee by crystallization from cold n-pentane.

The ester 4b was transformed to the enantiomerically pure

Scheme 7. One-pot synthesis of dihydrooxazole 7a.

2. Addition of Diphenylphosphane

The rate of addition of diphenylphosphane (8a) to the

various α,β-unsaturated carboxylic acid derivatives differs

considerably; thus, variation of reaction conditions and op-

timization are required. The reaction of lithium diphenyl-

phosphide with the esters 4a and 4b at –78 °C proceeded

with quantitative yield (Scheme 8). For easier purification

and storage, the phosphanylcarboxylic acid esters 9a and 9b

were transformed into the oxidation-stable borane adducts

9a·BH₃and 9b·BH₃.

Scheme 8. Synthesis of phosphanyl carboxylic acid esters 9a·BH₃

and 9b·BH₃and of the phosphanyl carboxylic acid 10·BH₃.

The corresponding phosphanylcarboxylic acid 10·BH₃

can be obtained as follows (Scheme 8). Treatment of the

tert-butyl ester 9b·BH₃with trifluoroacetic acid initially

gives the complex 10·BH₂(OOCCF₃) according to ³¹P

Scheme 6. Synthesis of myrtenic acid amide 5 and the dihydroox-

azoles 7a–7d.

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NMR monitoring. Upon treatment with aqueous KOH

during work-up 10 is produced which is treated with

BH₃·THF to furnish 10·BH₃in 75% yield. Alkaline saponi-

fication of the methyl ester 9a·BH₃gives the phosphane 10

in 70% yield, i.e., this reaction also proceeds with loss of

the BH₃group. In addition, the formation of 11% each of

myrtenic acid and HPPh₂signifies accompanying elimi-

nation, most likely of HPPh₂BH₃which further reacts.

The configuration of 10 was confirmed by X-ray analysis

of the phosphane oxide 10·oxide (Figure 1). A noteworthy

feature of this structure is an envelope conformation of the

six-membered ring. As a consequence a very large torsion

angle (HOOC)–C–C–P of 110° is found in the X-ray struc-

ture.

Scheme 10. Conjugate addition of diphenylphosphane to dihy-

drooxazole derivatives of myrtenic acid (3).

Figure 2. Stereoview of the X-ray crystal structure of phosphane

12.

Figure 1. Stereoview of the X-ray crystal structure of phosphane

oxide 10·oxide.

3. Phosphanes Obtained by Functional Group

Interconversion

Lithium diphenylphosphide did not yield an addition

Due to the presence of the carboxyl group, the phos-

product with the dihydrooxazoles 7a-7d and amide 5. The phanes described above could be easily modified and, there-

addition proceeded smoothly with diphenylphosphane at fore, generation of further ligands was possible. Thus, trans-

room temperature under catalysis with tetraethylammo- formation of 10·BH₃to the acid chloride and reaction of

nium hydroxide (Scheme 9, Scheme 10).^[18]The configura- this with anhydreous ammonia gave the amide 14·BH₃, and

tion of the phosphane 12 was confirmed by X-ray analysis the N-methyl-amide 15·BH₃was obtained under DCC

(Figure 2). In the case of the dihydrooxazole 7a it was dem- coupling conditions (Scheme 11). However, under the same

onstrated by ³¹P NMR that the addition also proceeds un- reaction conditions, attempted DCC coupling of 10·BH₃

der acidic conditions with camphorsulfonic acid as catalyst. with the secondary amine piperidine did not yield the de-

sired amide but the corresponding N-acyl urea resulting

from rearrangement.

Scheme 9. Conjugate addition of diphenylphosphane to myrtenic

acid derivatives.

Excepting the formation of dihydrooxazole 7d, the ad-

ditions proceeded with diastereoselectivities Ͼ95:5 (¹H

NMR, ³¹P NMR). In the course of the synthesis of the

phosphanyl dihydrooxazole 13d slow epimerization of the

benzylic position of the dihydrooxazole ring occurred be-

cause of the basic reaction conditions. This led to contami-

nation of the desired product 13d by its epimer 13c (13d/

13c Ϸ 20:1). Attempts to separate the isomers by crystalli-

zation or MPLC were not successful.

Scheme 11. Preparation of derivatives of the phosphanyl carboxylic

acid 10·BH₃.

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Reduction of ester 9a·BH₃and nitrile 11 with lithium crystallization from PE/ethyl acetate. Similarly, in the case

aluminium hydride gave the alcohol 16·BH₃in 94% and the of 21·BH₃only diastereomerically pure (R_P)-21·BH₃could

ammonium salt 17 in 52% yield, respectively.

be obtained by chromatography. Ester (R_P)-21·BH₃was

converted to carboxylic acid (R_P)-22·BH₃by treatment with

trifluoroacetic acid.

Configurations of the borane-protected epimers of the

phosphanyl carboxylic esters 19·BH₃, 20·BH₃and 21·BH₃

were determined by X-ray crystal structure analysis (Fig-

ure 3). Tentative assignment of the configuration of the P-

epimers of 18 is based on comparison of ³¹P NMR chemi-

cal shifts with those of the epimers of 19 and 20 (Table 1).

4. Addition of Unsymmetric Secondary Phosphanes and

Diphosphanes

Encouraged by the results obtained in the addition of

diphenylphosphane (8a) to myrtenic esters, additions of the

unsymmetric secondary phosphanes (2-biphenyl)-phenyl-

phosphane (8b), (1-naphthyl)-phenylphosphane (8c) and

methyl-phenylphosphane (8d) were examined (Scheme 12).

The phosphanes were prepared by known procedures.^[19]

Their additions to esters 4 were relatively slow and revers-

ible, presumably because of the steric bulk of these phos-

phanes. It was important to add the lithium phosphide at

–78 °C and hydrolyze the resultant enolate at –78 °C with a

pre-cooled solution of methanol in THF. The crude phos-

phanyl carboxylic esters were transformed into the air-

stable borane adducts. For 20·BH₃this was possible by di-

rectly adding BH₃·THF to the reaction mixture. In the case

of 18·BH₃and 19·BH₃, however, complexation only oc-

curred after removal of salts from the crude phosphanes by

filtration through silica.

In all the reactions described above, only two dia-

stereomers were formed in every case according to ³¹P

NMR analysis of the crude products. These were P-epimers

which were formed with a low degree of diastereoselectivity

(Scheme 12). On the other hand, all additions proceeded

highly diastereoselectively in favor of the trans-isomers (dr

Ͼ 95:5 according to ³¹P NMR).

Figure 3. Stereoviews of the X-ray crystal structures of borane-pro-

tected phosphanyl carboxylic esters: (a) (S_P)-19·BH₃, (b) (S_P)-

20·BH₃, (c) (R_P)-21·BH₃.

Whilst (R_P)- and (S_P)-diastereomers of borane adducts

Propensities of phosphanes^[20](S_P)-18, (S_P)-19 and (S_P)-

18·BH₃and 19·BH₃could be separated by flash chromatog- 20 towards P-epimerization were assessed by ³¹P NMR

raphy, this was not possible in the case of 20·BH₃; only spectroscopy. In the temperature range room temp. –100°C,

diastereomerically pure (S_P)-20·BH₃could be isolated, by spectra of toluene solutions were recorded at 10°C intervals

Scheme 12. Synthesis of phosphanyl carboxylic esters with stereogenic phosphorus (2-Bp = 2-biphenyl). Yields refer to the sum of the

pure diastereomers, the ratio refer to ³¹P integration.

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Table 1. ³¹P NMR chemical shifts of phosphanes 18–21.

(a) Deprotonation of 8e with two equivalents of nBuLi

at –78°C, followed by addition of two equivalents of 4b;

(b) Addition of 8e to 4b catalyzed by tetraethylammo-

nium hydroxide at room temperature according to the

method Blinn et al.^[18]

Compound (S_P)-18/(R_P)-18

(S_P)-19/(R_P)-19 (S_P)-20/(R_P)-20 (R_P)-21

δ [ppm]

–4.7/ –1.4

32.1/30.2^[a]

–5.1/ –1.5

32.0/29.1^[a]

–8.5/ –4.5

–12.1

[a] Chemical shifts of borane complexes.

In both cases the resultant diphosphanes were trans-

formed into the air stable borane adducts 23·BH₃. Under

both conditions, P-diastereoisomeric products 23a-c and

corresponding borane adducts were formed with a remark-

ably high degree of diastereoselection. Thus, from the reac-

tion according to method (a) (R_P,S_P)-23a·BH₃, (S_P,S_P)-

23b·BH₃and (R_P,R_P)-23c·BH₃were obtained pure (flash

chromatography) in 45, 3 and Ͻ 1% yield, respectively.

Similarly, the reaction according to method (b) gave the

three isomers in 43, ca. 5 and 0.6% yield, respectively. The

mono addition product was not observed under either con-

ditions.

over a time period of 5 min at every stage. The diarylphos-

phanes were configurationally stable up to 80°C; at tem-

peratures higher than 90°C isomerization became apparent.

The dialkylmonoarylphosphane (R_P)-21 did not isomerize

(15 h at 110°C, toluene) under these conditions.

5. Double Conjugate Addition of Secondary Diphosphanes

Stimulated by the encouraging results described above,

the preparation of diphosphane ligands by double conju-

gate addition of secondary diphosphanes was examined.

The requisite diphosphane 8e was prepared according to

Brookham et al. by reductive cleavage of dppe with lithium

at 0°C (Scheme 13).^[21]In the reaction between the dianion

of 8e and the enoate, the diphosphide could not be used in

excess because of the formation of the undesired monoaddi-

tion product. Good results were obtained using either of

the following methods:

For preparation of (S_P,S_P)-23 and (R_P,R_P)-23 in substan-

tial amounts, crude phosphanes were isomerized by heating

at 110°C for eight hours. Epimers were obtained in the ratio

(R_P,S_P)-23:(S_P,S_P)-23:(R_P,R_P)-23 = 32:39:29 (³¹P NMR).

Borane adducts of the isomers were separated by standard

flash chromatography. Investigation of the rate of P-epi-

merization of phosphanes 22 showed that these compounds

are configurationally stable up to a temperature of 100°C.

Relative configurations of the isomers as given above

were determined by X-ray crystal structure analysis and

NMR spectroscopy as follows. The C₁-symmetric dia-

stereomer (R_P,S_P)-23a·BH₃displays two sets of signals both

1

in the H NMR as well as in the ³¹P NMR spectrum. The

configurations of the two C₂-symmetric epimers could be

assigned by X-ray structure analysis of (S_P,S_P)-23·BH₃(Fig-

ure 4).

Experimental Section

General Methods: All reactions requiring anhydrous conditions

were carried out in dried flasks under a positive pressure of argon

or nitrogen. Melting points were determined in open glass capillar-

ies and are not corrected. If not stated otherwise, ¹H and ¹³C NMR

spectra were recorded on a Bruker Advance 500 [500 MHz (¹H),

125 MHz (¹³C)], or a Bruker Avance 300 spectrometer [300 MHz

(¹H), 75 MHz (¹³C)], ³¹P NMR and ¹¹B NMR spectra were re-

corded on a Bruker AC-200 spectrometer [81 MHz (³¹P), 64 MHz

(¹¹B), CDCl₃]. Chemical shifts are reported in δ (ppm) relative to

Scheme 13. Synthesis of 23·BH₃by double conjugate addition to

acceptor 8e. Methods a and b see text.

Figure 4. X-ray crystal structure of (S_P,S_P)-23b·BH₃.

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tetramethylsilane (TMS). High resolution MS were obtained on a

vacuum Generators ZAB 2F (EI) or JEOL JMS-700 (FAB) spec-

trometer. Optical rotations were measured with a Perkin–Elmer PE

241 polarimeter. For TLC Machery–Nagel PolygramSil G/UV₂₅₄

plates were used with spot detection by I₂vapour, UV light or

phosphomolybdic acid in ethanol followed by heating. If not stated

otherwise, ICN Kieselgel S (0.032–0.063 mm) was used for flash

chromatography. For MPLC columns of type C (N = 10000) ac-

cording to Helmchen and Glatz^[22]were used.

CHCl₃(8 mL) pTsCl (1.1 mmol) was added. The reaction mixture

was allowed to warm to room temp. and stirred until TLC indi-

cated complete conversion. The mixture was then cooled to 0°C

and a catalytic amount of DMAP and water (3.0 mmol) were

added. After stirring overnight the solution was washed success-

ively with 1 n HCl, 1 n NaOH and brine, dried over Na₂SO₄, fil-

tered and the solvent was removed under reduced pressure. The

dihydro-1,3-oxazoles were purified by flash chromatography.

(–)-(1R)-6,6-Dimethylbicyclo[3.1.1]hept-2-ene-2-carbonitrile

(2):

Materials: Commercially available reagents were used without fur-

ther purification. (–)-(1R)-Myrtenal was purchased from Acros or

Aldrich,^[23]borane-THF complex from Aldrich, nBuLi from

Metallgesellschaft. Petroleum ether (PE) and ethyl acetate (Merck,

Darmstadt) were distilled through a 1 m Vigreux column. Diethyl

ether, dioxane and THF were dried by distillation from sodium/

benzophenone. Methylene chloride and chloroform were distilled

from CaH₂. All anhydrous solvents were stored under nitrogen over

4-Å molecular sieves. For reactions and work-up involving phos-

phanes carefully deoxygenated solvents and reagents were used.

NH₂OH·HCl (50.7 g, 729 mmol) was added in small portions to a

solution of NaHCO₃(61.3 g, 729 mmol) in water (50 mL). When

the evolution of CO₂had ceased water (64 mL) was added, the

solution was cooled to 0°C and a solution of (–)-(1R)-myrtenal (1)

(97.0 g, 646 mmol) in ethanol (1250 mL) was added. The mixture

was heated at reflux for 20 h, then most of the ethanol was removed

in vacuo and 2 n HCl was added (pH Ͻ 2). The residual aqueous

mixture was extracted with diethyl ether (4×200 mL). The com-

bined organic layers were dried (Na₂SO₄) and the solvent removed

in vacuo to give crude crystalline oxime. This was treated with ace-

tic acid anhydride (165.1 g, 1615 mmol) and sodium acetate (53.2 g,

646 mmol) and the mixture was stirred for 5 d at 100°C. The reac-

tion mixture was then neutralized by addition of 2 n NaOH

(900 mL) and extracted with diethyl ether (5×150 mL). The com-

bined organic layers were dried over Na₂SO₄and the solvent was

removed in vacuo. Kugelrohr distillation of the crude product [95–

98°C/10 mbar (ref.^[13b]95–98°C, 8.5 Torr)] gave the nitrile 2 (67.9 g,

72%) as colorless oil. [α]²_D²= –55.2 (c = 1.00, CHCl₃) (ref.^[13b][α]_D

General Procedure for Conjugate Addition of Lithium Phosphides

Derived from Secondary Phosphanes (GP 1): Under nitrogen, nBuLi

(1.9 mmol, 1.6 m in hexane) was added dropwise to a solution of

the phosphane (2.0 mmol) in anhydrous THF (1.5 mL) at –78°C.

After stirring at –78°C for 30 min, a cold (–78°C) solution of the

acceptor-substituted olefin (1.0 mmol) in anhydrous THF (2.5 mL)

was added via double-ended needle transfer. The mixture was

stirred at –78°C and conversion was monitored by TLC and ³¹P

NMR spectroscopy.^[24]Work-up was initiated by adding at –78°C

a cold (–78°C) deoxygenated solution of methanol (3 mmol) in

THF (1.5 mL).^[25]Subsequently borane adducts were formed as

described below for individual compounds.

1

= 55, neat). H NMR (CDCl₃, 300 MHz): δ = 0.87 (s, 3 H, 8-H),

1.24 (d, J_7a,7b= 9.3 Hz, 1 H, 7-H_a), 1.32 (s, 3 H, 9-H), 2.16 (m_c, 1

H, 5-H), 2.39–2.42 (m, 3 H, 4-H, 7-H_b), 2.54 (m, 1 H, 1-H), 6.55

(m_c, 1 H, 3-H). ¹³C NMR (CDCl₃, 75 MHz): δ = 20.96 (q, C-8),

25.64 (q, C-9), 31.26, 32.63 (2t, C-4, C-7), 38.18 (s, C-6), 39.84,

44.56 (2d, C-1, C-5), 118.46 (s, C-2), 120.96 (s, CN), 142.06 (d, C-

3).

General Procedure for Conjugate Addition of Secondary Phosphanes

by Use of Catalytic Amounts of Et₄NOH (GP 2): All operations

were carried out under strict exclusion of oxygen. To a degassed

solution of Et₄NOH (15 drops, 40% in water) in degassed acetoni-

trile (2 mL) the acceptor-substituted olefin (1.0 mmol) was added.

After addition of the phosphane (1.0 mmol) the mixture was stirred

at room temp. for 1–4 days. Conversion was monitored by TLC

and ³¹P NMR and was Ͼ90% in all cases. For work-up, the solvent

was removed under reduced pressure, water was added and the pro-

duct was extracted with CH₂Cl₂. The combined organic layers were

washed three times with water at 0°C and dried over deoxygenated

Na₂SO₄. After filtration, the solvent was removed in vacuo and the

product purified.

(–)-(1R)-6,6-Dimethylbicyclo[3.1.1]hept-2-ene-2-carboxylic Acid (3):

Nitrile 2 (10.00 g, 67.9 mmol) was added at 0°C to a stirred solu-

tion of sodium hydroxide (8.00 g, 200 mmol) in aqueous hydrogen

peroxide (10%, 150 mL). After stirring for 3 h at room temperature

the solution was heated at reflux for 4 d. After cooling to room

temperature the mixture was extracted with diethyl ether and the

organic phase discarded. The aqueous layer was acidified (pH Ͻ 2)

and extracted three times with diethyl ether (400 mL). The combind

organic layers were dried (Na₂SO₄) and the solvent was removed.

Kugelrohr distillation [160°C /4 mbar (ref.^[13b]149–152°C, 9 Torr)]

of the residue gave 3 (10.99 g, 97%) as slightly yellow oil.

General Procedure for Amide Formation (GP 3): Oxalyl chloride

(1.5 mmol) was added to a cooled (0°C) solution of the carboxylic

acid (1.0 mmol) and a catalytic amount of anhydrous DMF

(2 drops) in anhydrous toluene (2 mL) and the mixture was stirred

overnight at room temp. The mixture was evaporated down under

reduced pressure and the residue was repeatedly dissolved in tolu-

ene (2 mL) and concentrated in vacuo in order to remove traces of

oxalyl chloride. The crude acid chloride was then dissolved in diox-

ane (1 mL) and the solution added to a solution of the amino

alcohol (1.2 mmol) and NEt₃(5 mmol) in dioxane (1 mL) at 10°C.

After stirring overnight water (1 mL) was added and the mixture

concentrated in vacuo. The residue was extracted with CH₂Cl₂or

ethyl acetate. The combined organic layers were successively

washed with 1 n HCl, 1 n NaOH and brine, dried over Na₂SO₄,

filtered and the solvent was removed in vacuo.

Trifluoroacetic acid (5.93 mL) was added to the tert-butyl ester 4b

(1.00 g, 4.50 mmol) in a pre-dried flask, and the reaction mixture

was stirred for 30 min under argon atmosphere. Excess of trifluoro-

acetic acid was removed in vacuo, and the residue was treated with

an aqueous solution of potassium hydroxide (5.93 mL, 3 m). The

aqueous phase was extracted with diethyl ether (2×30 mL) and the

organic phase discarded. The aqueous phase was acidified with

HCl (6 m) to pH 2 and extracted with diethyl ether (4×40 mL).

The combined organic phases were dried over Na₂SO₄, filtered and

concentrated in vacuo. The carboxylic acid 3 (755.1 mg, 100%) of

was isolated as pale yellow oil. [α]²_D²= –40.2 (c = 1.01, CHCl₃),

[α]²_D²= –47.1 (c = 4.22, EtOH) [ref.^[14][α]²_D²= –60.4 (c = 4.36,

EtOH)]. ¹H NMR (CDCl₃, 300 MHz): δ = 0.79 (s, 3 H, 8-H), 1.12

(d, J_7a,7b= 9.2 Hz, 1 H, 7-H_a), 1.33 (s, 3 H, 9-H), 2.13 (m_c, 1 H,

General Procedure for Cyclization of β-Hydroxy Amides to Dihydro- 5-H), 2.36–2.53 (m, 3 H, 4-H, 7-H_b), 2.78 (ddd, J = 5.6, J = 5.6,

1,3-oxazoles (GP 4): To a cold (0°C) solution of the β-hydroxy

amide (1.0 mmol) and NEt₃(5.0 mL) in anhydrous CH₂Cl₂or

J_1,3= 1.5 Hz, 1 H, 1-H), 6.99 (m, 1 H, 3-H), 11.4 (br. s, 1 H,

COOH). ¹³C NMR (CDCl₃, 75 MHz): δ = 20.91 (q, C-8), 25.83

3252

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New Chiral Phosphane Ligands

FULL PAPER

(q, C-9), 31.24, 32.35 (2t, C-4, C-7), 37.67 (s, C-6), 40.25, 40.90 washed with an aqueous solution of NaHSO₄(3×10 mL),

(2d, C-1, C-5), 139.39 (d, C-3), 139.71 (s, C-2), 171.55 (s, COOH). NaHCO₃(3×10 mL), brine (10 mL), and dried over Na₂SO₄, fil-

tered and concentrated in vacuo. The residue was purified by flash

chromatography (pre-dried silica gel, n-pentane/diethyl ether, 1:1)

(–)-(1R)-Methyl 6,6-Dimethylbicyclo[3.1.1]hept-2-ene-2-carboxylate

(4a): Diazomethane in diethyl ether was added to a solution of 3

(500 mg, 3.01 mmol) in diethyl ether (20 mL) until the yellow color

to afford the amide 5 (818.5 mg, 93%) as a pale yellow oil. B.p. =

1

100–120°C, 0.01 mbar. [α]²_D¹= –44.5 (c = 2.18, CHCl₃). H NMR

persisted, and excess diazomethane was destroyed by addition of

(300 MHz, CDCl₃): δ = 0.90 (s, 3 H, 8-H), 1.24 (d, J_7a,7b= 8.8 Hz,

acetic acid. Then 2 n NaOH was added and the solution was ex-

1 H, 7-H_a), 1.28 (s, 3 H, 9-H), 2.09–2.15 (m, 1 H, 5-H), 2.28–2.41

tracted with diethyl ether (3×50 mL), and the combined organic

(m, 3 H, 1-H, 4-H), 2.48 (ddd, J_7a,7b= 8.8, J_1,7b= 5.6, J_5,7b= 5.6

layers were dried over Na₂SO₄. Kugelrohr distillation at 160°C/

Hz, 1 H, 7-H_b), 2.95 [bs, 6 H, N(CH₃)₂; at –50°C: 2.91, 2.98 [2s,

10 mbar gave 4a (520 mg, 96%) as colorless liquid. [α]²_D²= –35.4 (c

each 3 H, N(CH₃)₂], 5.79–5.82 (m, 1 H, C=CH). ¹³C NMR

= 1.29, CHCl₃) [ref.^[14][α]²_D²= –45.8 (c = 1.71, CHCl₃)]. H NMR

(CDCl₃): δ = 21.09 (q, C-8), 25.93 (q, C-9), 31.53, 31.65 (2t, C-4,

(CDCl₃, 300 MHz): δ = 0.76 (s, 3 H, 8-H), 1.08 (d, J_7a,7b= 9.0 Hz,

C-7), 34.92, [bq, N(CH₃)₂], 37.79 (s, C-6), 38.23 [bq, N(CH₃)₂],

1 H, 7-H_a), 1.29 (s, 3 H, 9-H), 2.06–2.10 (m, 1 H, 5-H), 2.36–2.47

40.36 (d, C-5), 44.23 (d, C-1), 125.81 (d, C=CH), 143.67 (s, C=CH),

(m, 3 H, 4-H, 7-H_b), 2.76 (ddd, J = 5.7, J = 5.7, J = 1.5 Hz, 1 H,

171.20 (s, C=O). C₁₂H₁₉NO (193.32): calcd. C 74.55, H 9.93, N

1-H), 3.69 (s, 3 H, OCH₃), 6.80 (m_c, 1 H, 3-H). ¹³C NMR (CDCl₃,

7.25; found C 74.28, H 9.89, N 7.20.

1

75 MHz): δ = 20.69 (q, C-9), 25.65 (q, C-8), 31.08, 31.92 (2t, C-4,

C-7), 37.41 (s, C-6), 40.07, 41.02 (2t, C-1, C-5), 51.25 (q, CO-

OCH₃), 136.23 (d, C-3), 139.85 (s, C-2), 166.47 (s, COOCH₃).

(–)-(1R)-N-(2-Hydroxyethyl)-6,6-dimethylbicyclo[3.1.1]hept-2-ene-2-

carboxamide (6a): Carboxylic acid 3 (14.0 g, 84.2 mmol) and 2-

aminoethanol (6.18 g, 101 mmol) were transformed into the title

compound according to GP 3 [TLC: PE/iPrOH, 9:1, R_f(3) = 0.46,

R_f(6a) = 0.21]. The crude product was purified by flash chromatog-

raphy (silica gel, CH₂Cl₂/MeOH, 95:5) to give 6a (16.2 g, 92%) as

(–)-(1R)-tert-Butyl

6,6-Dimethylbicyclo[3.1.1]hept-2-ene-2-carb-

oxylate (4b): Trifluoroacetic anhydride (100.9 g, 0.480 mol) was

added to a solution of 3 (20.0 g, 0.120 mol) in anhydrous benzene

(170 mL). After stirring for 40 min at room temperature tBuOH

(143.1 g, 1.929 mol) was added. Conversion was monitored by TLC

[PE/EE, 10:1, R_f(3) = 0.09, R_f(4b) = 0.57]. After 3.5 h aqueous

NaOH (15%, 110 mL) was added. The organic layer was separated

and the aqueous layer was extracted with diethyl ether

(3×200 mL). The combined organic phases were dried over

Na₂SO₄. The solvent was removed in vacuo and the product was

purified by chromatography (500 g of silica gel, PE/diethyl ether,

10:1). Kugelrohr distillation gave 4b (23.2 g, 87%) as colorless oil.

B.p. 160°C, 10 mbar. [α]²_D¹= –32.1 (c = 1.00, CHCl₃, 96% ee),

[ref.^[14][α]²_D¹= –34.1 (c = 3.25, CHCl₃)]. GC: column Chrompac

Permethyl-β-CD (50 m×0.25 mm), oven temp.: 110°C, He (1 bar),

injector temp.: 250°C, detector temp.: 250°C, t_R[(1R)-4b] = 26.8

min, t_R[(1S)-4b] = 28.0 min. The oil crystallized after some time.

Crystallization from a saturated solution in ether or n-pentane by

cooling with a dry ice bath and removal of the mother liquor with

a syringe gave material of Ͼ99% ee in 55% yield. M.p. 34–34.5°C.

colorless oil [α]²_D³= –37.7 (c = 1.37, CHCl₃). H NMR (300 MHz,

1

CDCl₃): δ = 0.75 (s, 3 H, 8-H), 1.07 (d, J_7a,7b= 9.0 Hz, 1 H, 7-

H_a), 1.27 (s, 3 H, 9-H), 2.08–2.15 (m, 1 H, 5-H), 2.28–2.39 (m, 2

H, 4-H), 2.45 (ddd, J_7a,7b= 9.0, J_1,7b= 5.7, J_5,7b= 5.7 Hz, 1 H, 7-

H_b), 2.62 (ddd, J_1,5= 5.5, J_1,7b= 5.5, J_1,3= 1.5 Hz, 1 H, 1-H), 3.44

(q, J = 5.0 Hz, 2 H, CH₂N; after H/D exchange: t, 5.0 Hz), 3.70

(t, J = 5.0 Hz, 2 H, CH₂O), 3.80 (br. s, 1 H, OH, H/D), 6.38–6.45

(m, 1 H, C=CH), 6.48–6.58 (m, 1 H, NH, H/D). ¹³C NMR

(CDCl₃): δ = 20.70 (q, C-8), 25.71 (q, C-9), 31.17 (t, C-7), 31.52 (t,

C-4), 37.51 (s, C-6), 40.16 (d, C-5), 41.66 (d, C-1), 42.33 (t, CH₂N),

61.85 (t, CH₂O), 129.59 (d, C=CH), 143.03 (s, C=CH), 168.23 (s,

C=O). C₁₂H₁₉NO₂(209.32): calcd. C 68.85, H 9.17, N 6.69; found

C 68.62, H 9.16, N 6.58.

(–)-(1R)-N-(2-Hydroxy-1,1-dimethylethyl)-6,6-dimethylbicyclo-

[3.1.1]hept-2-ene-2-carboxamide (6b): Carboxylic acid 3 (3.50 g,

21.1 mmol) and 2-amino-2-methylpropanol (2.23 g, 25.0 mmol)

were transformed into the title compound according to GP 3 [TLC:

PE/iPrOH, 95:5, R_f(3) = 0.31, R_f(6b) = 0.14]. The crude product

was purified by flash chromatography (silica gel, PE/ethyl acetate,

95:5) and crystallized from ethyl acetate/hexane to give 6b (3.41 g,

68%) as colorless needles. M.p. 83.5–84.5°C. [α]²_D⁰= –38.2 (c =

1.30, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 0.80 (s, 3 H, 8-

H), 1.13 (d, J_7a,7b= 9.0 Hz, 1 H, 7-H_a), 1.30 [s, 6 H, NC(CH₃)₂],

1.32 (s, 3 H, 9-H), 2.09–2.15 (m, 1 H, 5-H), 2.28–2.46 (m, 2 H, 4-

H), 2.45 (ddd, J_7a,7b= 9.0, J_1,7b= 5.9, J_5,7b= 5.9 Hz, 1 H, 7-H_b),

2.59 (ddd, J_1,5= 5.5, J_1,7b= 5.5, J_1,3= 1.8 Hz, 1 H, 1-H), 3.57 (d,

J = 6.0 Hz, 2 H, CH₂O; after H/D exchange: s), 5.07 (t, J = 5.9

Hz, 1 H, OH, H/D), 5.75 (br. s, 1 H, NH, H/D), 6.29–6.37 (m, 1

H, C=CH). ¹³C NMR (CDCl₃): δ = 20.68 (q, C-8), 24.46, 24.55

[2d, NC(CH₃)₂], 25.69 (d, C-9), 31.15, 31.42 (2t, C-4, C-7), 37.51

(s, C-6), 40.11 (d, C-5), 41.89 (d, C-1), 55.73 [s, NC(CH₃)₂], 70.68

(t, CH₂O), 128.88 (d, C=CH), 143.81 (s, C=CH), 168.01 (s, C=O).

C₁₄H₂₃NO₂(237.38): calcd. C 70.83, H 9.79, N 5.90; found C

70.81, H 9.68, N 5.87.

1

[α]²_D¹= –38.9 (c = 1.13, CHCl₃). H NMR (CDCl₃, 300 MHz): δ =

0.76 (s, 3 H, 8-H), 1.08 (d, J_7a,7b= 8.8 Hz, 1 H, 7-H_a), 1.30 (s, 3

H, 9-H), 1.46 [s, 9 H, C(CH₃)₃], 2.08 (m, 1 H, 5-H), 2.33–2.45 (m,

3 H, 4-H, 7-H_b), 2.73 (ddd, J = 6.9, J = 6.9, J_1,3= 1.5 Hz, 1-H),

6.67 (m_c, 1 H, 3-H). ¹³C NMR (CDCl₃, 75 MHz): δ = 20.85 (q, C-

8), 25.93 (q, C-9), 28.14 [q, C(CH₃)₃], 31.29, 31.96 (2t, C-4, C-7),

37.58 (s, C-6), 40.37, 41.16 (2d, C-1, C-5), 79.69 [s, C(CH₃)₃],

134.84 (d, C-3), 141.67 (s, C-2), 165.62 [s, COOC(CH₃)₃].

(–)-(1R)-N,N,6,6-Tetramethylbicyclo[3.1.1]hept-2-ene-2-carboxamide

(5): Method A: According to GP 3, carboxylic acid 3 (10.0 g,

60.2 mmol) was converted into the acid chloride. This was dissolved

in anhydrous CHCl₃(20 mL) and the solution added dropwise to

a mixture of dimethylamine hydrochloride (7.36 g, 90.3 mmol) and

anhydrous NEt₃(40 mL, 289 mmol) in anhydrous CHCl₃(100 mL)

at –10°C. The resulting brown suspension was stirred overnight.

After aqueous work-up the crude product was purified by flash

chromatography (silica gel, PE/ethyl acetate, 7:3) and kugelrohr dis-

tillation afforded 5 (9.40 g, 81%) as colorless oil.

Method B: TBTU (1.60 g, 5.00 mmol) and NEt₃(1.92 mL, 13.6 (–)-(1R)-N-[2-Hydroxy-(1R)-phenylethyl]-6,6-dimethylbicyclo-

mmol) were added to a cooled (ice bath) solution of the carboxylic

acid 3 (755.1 mg, 4.54 mmol) and dimethylamine hydrochloride

(741 mg, 9.09 mmol) in anhydrous dichloromethane (14 mL), and

the suspension was stirred for 1 h at 0°C. The ice-bath was removed

and dichloromethane (70 mL) was added. The organic phase was

[3.1.1]hept-2-ene-2-carboxamide (6c): Carboxylic acid 3 (20.0 g,

120.3 mmol) and (R)-phenylglycinol (19.8 g, 144.3 mmol) were con-

verted into the title compound according to GP 3 [TLC: PE/iPrOH,

95:5, R_f(3) = 0.31, R_f(6c) = 0.18]. Crystallization of the crude pro-

duct from ethyl acetate gave 6c (26.4 g, 77%) as needles. M.p. 165–

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3253

G. Helmchen et al.

FULL PAPER

167°C. [α]²_D⁰= –46.5 (c = 3.10, MeOH). ¹H NMR (300 MHz,

CDCl₃): δ = 0.79 (s, 3 H, 8-H), 1.13 (d, J_7a,7b= 9.0 Hz, 1 H, 7-

(m, 3 H, 4-H, 7-H_b), 2.81 (td, J_1,5= 5.5, J_1,7b= 5.5, J_1,3= 1.5 Hz,

1 H, 1-H), 3.88 (s, 2 H, CH₂O), 6.37–6.39 (m, 1 H, C=CH). ¹³C

H_a), 1.31 (s, 3 H, 9-H), 2.12–2.19 (m, 1 H, 5-H), 2.30–2.43 (m, 2 NMR (CDCl₃): δ = 20.57 (q, C-8), 25.61 (q, C-9), 28.09, 28.16 [2q,

H, 4-H), 2.48 (ddd, J_7a,7b= 9.2, J_1,7b= 5.9, J_5,7b= 5.9 Hz, 1 H, 7-

H_b), 2.68 (ddd, J_1,5= 5.7, J_1,7b= 5.7, J_1,3= 1.5 Hz, 1 H, 1-H), 3.08

(br. s, 1 H, OH, H/D), 3.88 [m, 2 H, CH₂O; after H/D exchange:

3.85 (dd, J = 11.2, J = 4.2 Hz, 1 H, CH₂O)], 3.91 [dd, J = 11.2, J

= 5.7 Hz, 1 H, CH₂O], 5.09 (dd, J = 11.0, J = 5.8 Hz, 1 H, CHN;

after H/D exchange: t, J = 5.0 Hz), 6.38–6.48 (m, 2 H, C=CH,

NH, H/D; after H/D exchange: m, 1 H, C=CH), 7.23–7.39 (m, 5

H, Ph-H). ¹³C NMR (CDCl₃): δ = 20.73 (q, C-8), 25.70 (q, C-9),

31.19 (t, C-7), 31.55 (t, C-4), 37.57 (s, C-6), 40.22 (d, C-5), 41.78

(d, C-1), 55.96 (d, CHN), 66.62 (t, CH₂O), 126.47, 127.61, 128.68

(3d, Ph-C), 129.47 (d, C=CH), 139.04 (s, Ph-C), 143.30 (s, C=CH),

167.60 (s, C=O). C₁₈H₂₃NO₂(285.42): C 75.74, H 8.14, N 4.91;

found C 75.54, H 8.07, N 4.85.

NC(CH₃)₂], 31.21 (t, C-7), 31.79 (t, C-4), 37.45 (s, C-6), 40.26 (d,

C-5), 42.14 (d, C-1), 66.85 [s, NC(CH₃)₂], 78.23 (t, CH₂O), 130.48

(d, C=CH), 136.73 (s, C=CH), 161.48 (s, C=N). C₁₄H₂₁NO

(219.36): calcd. C 76.65, H 9.67, N 6.39; found C 76.45, H 9.83, N

6.24.

(+)-2-[(1R)-6,6-Dimethyl-bicyclo[3.1.1]hept-2-en-2-yl]-(4R)-phenyl-

4,5-dihydro-1,3-oxazole (7c): According to GP 4, 6c (1.60 g, 5.61

mmol) was converted into the dihydrooxazole 7c [TLC: PE/iPrOH,

95:5, R_f(6c) = 0.20, R_f(7c) = 0.39, R_f(TsCl) = 0.51]. Flash

chromatography (silica gel, PE/ethyl acetate, 95:5) and kugelrohr

distillation yielded 7c (1.12 g, 74%) as colorless oil. [α]¹_D⁹= +50.3

1

(c = 0.96, CHCl₃). H NMR (300 MHz, CDCl₃): δ = 0.87 (s, 3 H,

8-H), 1.20 (d, J_7a,7b= 9.0 Hz, 1 H, 7-H_a), 1.33 (s, 3 H, 9-H), 2.14–

2.21 (m, 1 H, 5-H), 2.38–2.56 (m, 3 H, 4-H, 7-H_b), 2.94 (ddd, J_1,5

= 5.5, J_1,7b= 5.5, J_1,3= 1.4 Hz, 1 H, 1-H), 4.11 (t, J = 8.2 Hz, 1

(–)-(1S)-N-[2-Hydroxy-(1S)-phenylethyl]-6,6-dimethylbicyclo-

[3.1.1]hept-2-ene-2-carboxamide (6d): The title compound was pre-

pared from carboxylic acid 3 (15.1 g, 90.8 mmol) and (S)-phenyl- H, CH₂O), 4.64 (dd, J = 10.0, J = 8.1 Hz, 1 H, CH₂O), 5.23 (dd,

glycinol (15.0 g, 109.3 mmol) according to GP 3 [TLC: PE/iPrOH,

9:1, R_f(3) = 0.31, R_f(6d) = 0.20]. Crystallization of the crude pro-

duct from ethyl acetate gave 6d (20.8 g, 80%) as colorless needles.

M.p. 121.5–122.0°C. [α]²_D⁰= –20.4 (c = 1.36, CHCl₃). ¹H NMR

(300 MHz, CDCl₃): δ = 0.79 (s, 3 H, 8-H), 1.10 (d, J_7a,7b= 9.0 Hz,

1 H, 7-H_a), 1.30 (s, 3 H, 9-H), 2.11–2.18 (m, 1 H, 5-H), 2.30–2.43

(m, 2 H, 4-H), 2.48 (ddd, J_7a,7b= 8.8, J_1,7b= 5.6, J_5,7b= 5.6 Hz, 1

H, 7-H_b), 2.63 (ddd, J_1,5= 5.5, J_1,7b= 5.5, J_1,3= 1.4 Hz, 1 H, 1-

H), 3.15 (br. s, 1 H, OH, H/D), 3.81–3.88 [m, 2 H, CH₂O; after H/

D exchange: 3.80 (d, J = 5.1 Hz)], 5.00–5.05 [m, 1 H, CHN; after

H/D exchange: 5.05 (t, J = 5.0 Hz)], 6.40–6.48 (m, 1 H, C=CH),

6.57 (bd, J = 6.7 Hz, 1 H, NH, H/D), 7.28–7.38 (m, 5 H, Ph-H).

¹³C NMR (CDCl₃, 75 MHz): δ = 20.98 (q, C-8), 25.95 (q, C-9),

31.42 (t, C-7), 31.77 (t, C-4), 37.79 (s, C-6), 40.40 (d, C-5), 41.92

(d, C-1), 56.01 (d, CHN), 66.49 (t, CH₂O), 126.67, 127.71, 128.80

(3d, Ph-C), 129.95 (d, C=CH), 139.39 (s, Ph-C), 143.32 (s, C=CH),

167.78 (s, C=O). C₁₈H₂₃NO₂(285.42): calcd. C 75.74, H 8.14, N

4.91; found C 75.55, H 8.04, N 4.85.

J = 10.0, J = 8.1 Hz, 1 H, CHN), 6.58–6.60 (m, 1 H, C=CH), 7.20–

7.38 (m, 5 H, Ph-H). ¹³C NMR (CDCl₃): δ = 20.97 (q, C-8), 25.90

(q, C-9), 31.52 (t, C-7), 32.21 (t, C-4), 37.79 (s, C-6), 40.52 (d, C-

5), 42.62 (d, C-1), 69.96 (d, CHN), 74.34 (t, CH₂O), 126.77, 127.48,

128.66 (3d, Ph-C), 131.81 (d, C=CH), 136.69 (s, C=CH), 142.57 (s,

Ph-C), 164.41 (s, C=N). C₁₈H₂₁NO (267.40): calcd. C 80.85, H

7.93, N 5.24; found C 80.83, H 7.92, N 5.28.

(–)-2-[(1R)-6,6-Dimethyl-bicyclo[3.1.1]hept-2-en-2-yl]-(4S)-phenyl-

4,5-dihydro-1,3-oxazole (7d): According to GP 4, 6d (18.3 g, 64.1

mmol) was converted into the dihydrooxazole 7d [TLC: PE/iPrOH,

95:5, R_f(6d) = 0.21, R_f(7d) = 0.39, R_f(pTsCl) = 0.51]. Flash

chromatography (silica gel, PE/ethyl acetate, 95:5) yielded 7d

(14.2 g, 83%) as crystalline compound. M. p. 70–71°C. [α]²_D¹

=

1

–119.1 (c = 1.27, CHCl₃). H NMR (300 MHz, CDCl₃): δ = 0.86

(s, 3 H, 8-H), 1.23 (d, J_7a,7b= 9.0 Hz, 1 H, 7-H_a), 1.33 (s, 3 H, 9-

H), 2.13–2.20 (m, 1 H, 5-H), 2.38–2.55 (m, 3 H, 4-H, 7-H_b), 2.94

(ddd, J_1,5= 5.5, J_1,7b= 5.5, J_1,3= 1.4 Hz, 1 H, 1-H), 4.11 (t, J =

8.3, 1 H, CH₂O), 4.64 (dd, J = 10.0, J = 8.3 Hz, 1 H, CH₂O), 5.23

(t, J = 9.0 Hz, 1 H, CHN), 6.63–6.70 (m, 1 H, C=CH), 7.23–7.39

(m, 5 H, Ph-H). ¹³C NMR (CDCl₃): δ = 20.97 (q, C-8), 25.90 (q,

C-9), 31.52 (t, C-7), 32.21 (t, C-4), 37.79 (s, C-6), 40.52 (d, C-5),

42.62 (d, C-1), 69.96 (d, CHN), 74.34 (t, CH₂O), 126.77, 127.48,

128.66 (3d, Ph-C), 131.81 (d, C=CH), 136.69 (s, C=CH), 142.57 (s,

Ph-C), 164.41 (s, C=N). C₁₈H₂₁NO (267.40): calcd. C 80.85, H

(–)-2-[(1R)-6,6-Dimethylbicyclo[3.1.1]hept-2-en-2-yl]-4,5-dihydro-

1,3-oxazole (7a): According to GP 4, 6a (7.10 g, 33.9 mmol) was

converted into crude dihydrooxazole 7a [TLC: PE/iPrOH, 9:1,

R_f(4b) = 0.22, R_f(7a) = 0.49, R_f(pTsCl) = 0.58]. This was purified

by flash chromatography (PE/ethyl acetate, 95:5, then 8:2) and kug-

elrohr distillation to give 7a (5.31 g, 82%) as colorless oil. [α]²_D¹

=

–26.5 (c = 1.61, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 0.79 (s, 7.93, N 5.24; found C 80.74, H 7.66, N 5.26.

3 H, 8-H), 1.13 (d, J_7a,7b= 9.0 Hz, 1 H, 7-H_a), 1.29 (s, 3 H, 9-H),

(–)-(1S,2R,3S)-Methyl 3-(Boranatodiphenylphosphanyl)-6,6-dimeth-

2.09–2.17 (m, 1 H, 5-H), 2.32–2.50 (m, 3 H, 4-H, 7-H_b), 2.80 (ddd,

J_1,5= 5.6, J_1,7b= 5.6, J_1,3= 1.2 Hz, 1 H, 1-H), 3.87 (t, J = 9.3 Hz,

2 H, CH₂N), 4.32 (t, J = 9.1 Hz, 2 H, CH₂O), 6.42–6.48 (m, 1 H,

C=CH). ¹³C NMR (CDCl₃): δ = 20.66 (q, C-8), 25.67 (q, C-9),

31.17 (t, C-7), 31.80 (t, C-4), 37.47 (s, C-6), 40.26 (d, C-5), 42.35

(d, C-1), 54.43 (t, CH₂N), 66.79 (t, CH₂O), 130.81 (d, C=CH),

136.42 (s, C=CH), 164.19 (s, C=N). C₁₂H₁₇NO (191.30): calcd. C

75.34, H 8.98, N 7.32; found C 75.15, H 9.04, N 7.29.

ylbicyclo[3.1.1]heptane-2-carboxylate (9a·BH₃): A solution of 4a

(9.00 g, 50.0 mmol) in degassed THF (75 mL) was reacted with

diphenylphosphane (8a) (18.64 g, 100.0 mmol) according to GP 1

(reaction time: 30 min). Conversion was monitored by TLC [PE/

ethyl acetate, 98:2, R_f(4) = 0.20, R_f(9a) = 0.14]. The mixture was

cooled to –78°C, BH₃·THF (1 m in THF, 150 mL, 150 mmol) was

added and conversion was monitored by TLC [PE/ethyl acetate,

95:5, R_f(9a) = 0.23, R_f(9a·BH₃) = 0.15]. The mixture was allowed

to warm to room temperature and excess borane was hydrolyzed

by addition of 1 n HCl (150 mL). The mixture was then extracted

with diethyl ether, the organic layer dried over Na₂SO₄, filtered and

(–)-2-[(1R)-6,6-Dimethylbicyclo[3.1.1]hept-2-en-2-yl]-4,4-dimethyl-

4,5-dihydro-1,3-oxazole (7b): According to GP 4, 6b (3.40 g, 14.3

mmol) was converted into crude dihydrooxazole 7b [TLC: PE/iPr-

OH, 95:5, R_f(6b) = 0.17, R_f(7b) = 0.40, R_f(pTsCl) = 0.51]. This was concentrated in vacuo. The residue was purified by flash

purified by flash chromatography (PE/CHCl₃, 6:4) and kugelrohr

chromatography (silica gel, PE/ethyl acetate/CH₂Cl₂, 85:7.5:7.5) to

distillation to give 7b (2.10 g, 68%) as colorless oil. [α]¹_D⁹= –22.4 (c

give 9a·BH₃(14.0 g, 74%) as colorless needles. M. p. 119–120°C.

1

= 2.35, CHCl₃). H NMR (300 MHz, CDCl₃): δ = 0.78 (s, 3 H, 8- [α]²_D⁰= –84.4 (c = 1.77, CHCl₃). H NMR (300 MHz, CDCl₃): δ =

H), 1.13 (d, J_7a,7b= 9.0 Hz, 1 H, 7-H_a), 1.23, 1.24 [2s, each 3 H,

0.96 (s, 3 H, 8-H), 1.17 (s, 3 H, 9-H), 1.58 (ddd, J_7a,7b= 9.9, J =

NC(CH₃)₂], 1.27 (s, 3 H, 9-H), 2.09–2.13 (m, 1 H, 5-H), 2.24–2.48 3.5, J = 3.5, 1 H, 7-H_a), 1.90 (m, 1 H, 5-H), 1.98–2.17 (m, 2 H, 4-

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New Chiral Phosphane Ligands

FULL PAPER

H), 2.30–2.34 (m, 2 H, 1-H, 7-Hb), 3.22 (ddd, J_2,P= 20.2, J = 6.8, alkaline (ATTENTION: gas evolution). After 40 min the reaction

J = 2.0 Hz, 1 H, CHCOOCH₃), 3.23 (s, 3 H, COOCH₃), 4.00 (m, mixture was extracted thrice with diethyl ether. The combined or-

1 H, CHP), 7.28–7.41 (m, 3 H, Ar-H), 7.44–7.54 (m, 3 H, Ar-H), ganic layers were washed with water, dried over Na₂SO₄and fil-

7.63–7.75 (m, 2 H, Ar-H), 7.93–7.99 (m, 2 H, Ar-H). ¹³C NMR

(CDCl₃): δ = 21.82 (q, C-8), 22.87 [dd, J(C,P) = 36.1 Hz, CHP],

tered. The filtrate was cooled to –78°C and treated with BH₃·THF

(1 m in THF) (220 mL, 220 mmol). After stirring for 1 h 1 n HCl

27.06 (q, C-9), 27.86 (td, J_C,P= 3.3 Hz, C-4), 29.61 (t, C-7), 38.99 (200 mL) was added and stirring was continued until gas evolution

(s, C-6), 40.47 (dd, J_C,P= 4.4 Hz, C-1 or C-2 or C-5), 44.30 (dd,

J_C,P= 5.2 Hz, C-1 or C-2 or C-5), 45.22 (dd, J_C,P= 4.4 Hz, C-1

or C-2 or C-5), 51.57 (q, COOCH₃), 127.86 (d, J_C,P= 58 Hz, Ar-

C), 128.05–133.41 (10 Ar-C), 174.64 (d, J_C,P= 2.7 Hz, COOCH₃).

³¹P NMR (CHCl₃): δ = +27. ¹¹B NMR (CDCl₃): δ = –39.

ceased. The aqueous layer was removed and extracted with diethyl

ether. The combined organic phases were washed with water to

remove HCl, dried and concentrated in vacuo. The residue was

purified by flash chromatography (silica gel, PE/ethyl acetate/

CH₂Cl₂, 84:8:8) to give 10·BH₃(19.6 g, 75 %) as colorless nee-

C

₂₃H₃₀O₂PB (380.28): calcd. C 72.65, H 7.95, P 8.15; found C dles.^[26]M.p. 172–173.5°C. [α]²_D⁰= –99.2 (c, 2.11, CHCl₃). ¹H NMR

72.68, H 8.01, P 8.18.

(300 MHz, CDCl₃): δ = 0.50–1.50 (br. s, 3 H, BH₃), 0.90 (s, 3 H,

8-H), 1.17 (s, 3 H, 9-H), 1.60 (d, J = 10.4 Hz, 1 H, 7-H_a), 1.89–

1.95 (m, 1 H, 5-H), 1.91–2.21 (m, 2 H, 4-H), 2.28–2.38 (m, 1 H, 7-

H_b), 2.40–2.47 (m, 1 H, 1-H), 3.19 (ddd, J_2,P= 20.2, J = 6.4, J =

2.7 Hz, 1 H, 2-H), 3.84–3.98 (m, 1 H, CHP), 7.24–7.37 (m, 3 H,

Ph-H_m,p), 7.48–7.58 (m, 3 H, Ph-H_m,p), 7.67–7.76 (m, 2 H, Ph-H_o),

7.91–8.00 (m, 2 H, Ph-H_o), 9.70 (br. s, 1 H, COOH, H/D). ¹³C

NMR (CDCl₃): δ = 21.35 (q, C-8), 22.03 (d, J_C,P= 36.1 Hz, CHP),

26.62 (q, C-9), 27.59 (td, J_C,P= 3.4 Hz, C-4), 28.81 (t, C-7), 38.81

(s, C-6), 39.95 (dd, J_C,P= 4.0 Hz, C-5), 43.92 (dd, J_C,P= 4.5 Hz,

C-1), 44.32 (dd, J_C,P= 4.0 Hz, C-2), 127.42 (dd, J_C,P= 55.4 Hz,

Ph-C_i), 127.90 (d, J_C,P= 9.6 Hz, Ph-C_m), 128.05 (d, J_C,P= 52.0

(–)-(1S,2R,3S)-tert-Butyl 3-(Boranatodiphenylphosphanyl)-6,6-di-

methylbicyclo[3.1.1]heptane-2-carboxylate (9b·BH₃): All reagents

and solvents were carefully dried and degassed. Under nitrogen, a

solution of nBuLi (1.6 m solution in n-hexane, 91 mL, 145 mmol)

was added dropwise over a period of 20 min to a stirred solution

of diphenylphosphane (8a) (27.9 g, 150 mmol) in THF (250 mL)

cooled to –78°C. The mixture was allowed to warm up to room

temperature and was 15 min later cooled again to –78°C. The re-

sultant cold, dark red solution was dropped via double-ended nee-

dle transfer into a cooled (–78 °C) solution of ester 4b (30.0 g,

135 mmol) in THF (300 mL). Conversion was monitored by TLC

[PE/ethyl acetate, 98:2, R_f(4b) = 0.23, R_f(9b) = 0.20]. The mixture

was stirred for 30 min at –78°C and was then treated with a cold

(–20°C) solution of methanol (9.0 g, 281 mmol) in THF (100 mL).

The cooling bath was removed for 20 min and then the mixture

was again cooled to –78°C and dropwise treated with BH₃·THF

(1 m solution in THF, 400 mL, 400 mmol) (ATTENTION: gas

evolution). The mixture was then stirred for 1 h at –78°C and 2 h

at 0°C. TLC showed that conversion was complete [PE/ethyl ace-

tate, 95:5, R_f(HPPh·BH₃) = 0.33, R_f(9b·BH₃) = 0.39]. Excess bo-

rane was destroyed by cautious addition of 1 n HCl (ca. 300 mL)

at 0°C (ATTENTION: gas evolution). The mixture was extracted

with diethyl ether and the organic layer washed with 1 n HCl, sat.

NaHCO₃solution and sat NaCl solution, dried over Na₂SO₄and

concentrated in vacuo. The residue was purified by flash

chromatography (silica gel, PE/ethyl acetate/CH₂Cl₂, 85:7.5:7.5) to

Hz, Ph-C_i), 128.68 (dd, J_C,P= 9.6 Hz, Ph-C_m), 130.92 (dd, J_C,P

=

2.8 Hz, Ph-C_p), 131.27 (dd, J_C,P= 2.2 Hz, Ph-C_p), 132.82 (dd, J_C,P

= 8.5 Hz, Ph-C_o), 133.98 (dd, J_C,P= 8.5 Hz, Ph-C_o), 179.87 (d,

J_C,P= 3.4 Hz, C=O). ³¹P NMR (CDCl₃): δ = +27.3. ¹¹B NMR

(CDCl₃, 64.21 MHz): δ = –39.9. C₂₂H₂₈O₂PB (366.25): calcd. C

72.15, H 7.70, P 8.46; found C 71.93, H 7.88, P 8.23.

(–)-(1S,2R,3S)-3-Diphenylphosphanyl-6,6-dimethylbicyclo[3.1.1]-

heptane-2-carbonitrile (11): Nitrile 2 [11.1 g (75.4 mmol)] was re-

acted with diphenylphosphane according to GP2 [TLC: PE/ethyl

acetate, 9:1, R_f(2) = 0.43, R_f(11) = 0.31, R_f(HPPh₂) = 0.66]. After

work-up nitrile 11 was obtained as an oil which slowly solidified

(21.0 g, 84%). M.p. 56.5–58.0°C. [α]²_D²= –50.9 (c = 1.78, CHCl₃).

¹H NMR (300 MHz, CDCl₃): δ = 1.28, 1.30 (2s, each 3 H, 8-H, 9-

H), 1.43 (d, J_7a,7b= 10.4 Hz, 1 H, 7-H_a), 1.78 (dddd, J = 18.7, J

= 14.0, J = 4.1, J = 4.1 Hz, 1 H, 4-H_a), 1.94–2.00 (m, 1 H, 5-H),

2.20–2.37 (m, 3 H, 1-H, 4-H_b, 7-H_b), 2.96 (ddd, J_2,P= 14.5, J =

give 9b·BH₃(41.2 g, 72%) as colorless glassy solid. [α]²_D⁰= –85 (c

1

= 1.4, CHCl₃). H NMR (300 MHz, CDCl₃): δ = 0.93 (s, 3 H, 8- 5.2, J = 2.7 Hz, 1 H, 2-H), 3.03–3.13 (m, 1 H, CHP), 7.34–7.39

H), 1.12 [s, 9 H, C(CH₃)₃], 1.17 (s, 3 H, 9-H), 1.64 (d, J_7a,7b= 10.0

Hz, 1 H, 7-H_a), 1.90 (m, 1 H, 5-H), 1.96–2.14 (m, 2 H, 4-H), 2.24–

2.34 (m, 2 H, 1-H, 7-H_b), 3.10 (ddd, J_2,P= 20.8, J = 6.3, J = 2.6

(m, 6 H, Ph-H_m,p), 7.54–7.67 (m, 4 H, Ph-H_o). ¹³C NMR (CDCl₃):

δ = 21.69 (q, C-8), 26.11 (q, C-9), 26.73 (dd, J_C,P= 11.5 Hz, CHP),

28.58 (td, J_C,P= 2.0 Hz, C-7), 30.60 (td, J_C,P= 18.3 Hz, C-4), 33.11

Hz, 1 H, CHCOOtBu), 4.05 (m, 1 H, CHP), 7.27–7.37 (m, 3 H, (dd, J_C,P= 23.7 Hz, C-2), 38.20 (d, J_C,P= 1.4 Hz, C-6), 40.01 (dd,

Ar-H), 7.46–7.51 (m, 3 H, Ar-H), 7.70–7.76 (m, 2 H, Ar-H), 7.94– J_C,P= 2.0 Hz, C-5), 43.80 (dd, J_C,P= 2.0 Hz, C-1), 122.76 (d, J_C,P

8.00 (m, 2 H, Ar-H). ¹³C NMR (CDCl₃): δ = 21.74 (dd, J_C,P

=

= 4.8 Hz, CN), 128.61 (dd, J_C,P= 6.8 Hz, Ph-C_m), 128.71 (dd, J_C,P

36.7 Hz, CHP), 21.80 (q, C-8), 27.19 (q, C-9), 27.73 [q, C(CH₃)₃], = 7.5 Hz, Ph-C_m), 129.15 (d, Ph-C_p), 129.87 (dd, J_C,P= 1.2 Hz,

27.83 (td, J_C,P= 3.9 Hz, C-4), 29.06 (t, C-7), 39.09 (s, C-6), 40.38

(dd, J_C,P= 4.0 Hz, C-1 or C-2 or C-5), 44.49 (dd, J_C,P= 4.5 Hz,

Ph-C_p), 133.29 (dd, J_C,P= 19.0 Hz, Ph-C_o), 134.02 (d, J_C,P= 20.3

Hz, Ph-C_o), 135.66 (d, J_C,P= 15.6 Hz, Ph-C_i), 136.05 (d, J_C,P

=

C-1 or C-2 or C-5), 45.76 (dd, J_C,P= 4.5 Hz, C-1 or C-2 or C-5), 13.5 Hz, Ph-C_i). ³¹P NMR (CDCl₃): δ = +6.1 (11), δ = +34.9 (11-

80.34 [s, C(CH₃)₃], 127.81–133.53 (12 Ar-C), 173.28 (d, J_C,P= 2.9

oxide). C₂₂H₂₄NP (333.44): calcd. C 79.24, H 7.27, N 4.20, P 9.29;

Hz, COOtBu). ³¹P NMR (CDCl₃): δ = +26.5. ¹¹B NMR (CDCl₃): found C 78.96, H 7.23, N 4.14, P 9.12.

δ = –39.5. HR-MS (EI+) C₂₆H₃₃O₂P (M⁺– BH₃) calcd. 408.2218;

found 408.2239.

(–)-(1S,2R,3S)-N,N,6,6-Tetramethyl-3-diphenylphosphanylbicyclo-

[3.1.1]heptane-2-carboxamide (12): Amide 5 (5.00 g, 25.9 mmol)

was reacted with diphenylphosphane according to GP 2. In the

course of the reaction the product precipitated and a thick suspen-

sion formed. For work-up, the reaction mixture was concentrated

to about 1/4 of its original volume and the remaining solvent was

removed with a syringe. The crystalline residue was suspended in

CH₃CN (3×5 mL) and the washing liquid removed each time with

a syringe. The residue was dissolved in CH₂Cl₂and the solution

treated as described in GP 2. Crystallization from CH₃CN gave 12

(–)-(1S,2R,3S)-3-(Boranatodiphenylphosphanyl)-6,6-dimethylbicy-

clo[3.1.1]heptane-2-carboxylic Acid (10·BH₃): All operations were

carried out under strict exclusion of oxygen. A solution of 9b·BH₃

(30.8 g, 73.0 mmol) in degassed trifluoroacetic acid (120 mL) was

stirred at room temperature for 1 h while strong evolution of gas

occurred. The solvent was removed in vacuo (0.01 Torr) and the

residue was dissolved in diethyl ether (100 mL). At 0°C first 2 m

KOH (40 mL) was added and then solid KOH until the mixture was

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G. Helmchen et al.

FULL PAPER

(5.61 g, 61%) as colorless needles. M.p. 158–160°C. [α]²_D¹= –124.5

7.55–7.62 (m, 2 H, Ph-H_o), 7.64–7.71 (m, 2 H, Ph-H_o). ¹³C NMR

1

(c = 1.94, CHCl₃). H NMR (300 MHz, CDCl₃): δ = 1.12 (s, 3 H, (CDCl₃): δ = 21.80 (q, C-8), 23.35 (dd, J_C,P= 7.9 Hz, CHP), 26.85

8-H), 1.14 (s, 3 H, 9-H), 1.24 (d, J_7a,7b= 9.9 Hz, 1 H, 7-H_a), 1.83 (q, C-9), 27.46, 27.49 [2q, NC(CH₃)₂], 28.70 (td, J_C,P= 2.8 Hz, C-

(dddd, J = 19.9, J = 14.0, J = 5.5, J = 3.0 Hz, 1 H, 4-H_a), 1.96– 7), 30.70 (td, J_C,P= 18.1 Hz, C-4), 38.81 (d, J_C,P= 2.3 Hz, C-6),

2.60 (m, 2 H, 1-H, 5-H), 2.34–2.43 (m, 2 H, 4-H_b, 7-H_b), 2.42, 2.55 40.95 (dd, J_C,P= 2.2 Hz, C-5), 42.88 (dd, J_C,P= 20.4 Hz, C-2),

[2bs, each 3 H, N(CH₃)₂], 2.98 (ddd, J_2,P= 16.5, J = 6.5, J = 1.8

Hz, 1 H, 2-H), 3.86–3.97 (m, 1 H, CHP), 7.20–7.25 (m, 3 H, Ph-

44.14 (dd, J_C,P= 3.4 Hz, C-1), 66.46 [s, NC(CH₃)₂], 78.63 (t,

CH₂O), 127.55 (dd, J_C,P= 7.4 Hz, Ph-C_m), 128.24 (dd, J_C,P= 6.8

H

_m,p), 7.30–7.40 (m, 3 H, Ph-H_m,p), 7.49–7.58 (m, 2 H, Ph-H_o), Hz, Ph-C_m), 128.49 (d, Ph-C_p), 128.85 (dd, J_C,P= 1.1 Hz, Ph-C_p),

7.63–7.70 (m, 2 H, Ph-H_o). ¹³C NMR (CDCl₃): δ = 22.43 (q, C-8),

133.81 (dd, J_C,P= 18.6 Hz, Ph-C_o), 134.70 (d, J_C,P= 19.2 Hz, Ph-

C_o), 137.20 (d, J_C,P= 13.5 Hz, Ph-C_i), 137.48 (d, J_C,P= 17.0 Hz,

Ph-C_i), 167.39 (d, J_C,P= 5.0 Hz, C=N). ³¹P NMR (CDCl₃): δ =

23.55 (dd, J_C,P= 5.5 Hz, CHP), 27.58 (q, C-9), 31.48 (td, J_C,P

22.1 Hz, C-4), 31.90 (t, C-7), 35.51, 36.33 [2bq, N(CH₃)₂], 38.83

=

(d, J_C,P= 1.7 Hz, C-6), 41.51 (dd, J_C,P= 4.0 Hz, C-5), 44.19 (dd, +9.6 (13b), δ = +37.5 (13b-oxide). C₂₆H₃₂NOP (405.56): calcd. C

J_C,P= 4.5 Hz, C-1), 46.73 (dd, J_C,P= 20.3 Hz, C-2), 127.29 (dd, 76.99, H 7.97, N 3.45, P 7.64; found C 76.81, H 7.94, N 2.32, P

J_C,P= 7.9 Hz, Ph-C_m), 128.11 (dd, J_C,P= 6.8 Hz, Ph-C_m), 128.49 7.71.

(d, Ph-C_p), 128.85 (dd, J_C,P= 1.1 Hz, Ph-C_p), 133.09 (dd, J_C,P

=

(–)-2-[(1S,2R,3S)-Diphenylphosphanyl-6,6-dimethylbicyclo[3.1.1]-

hept-2-yl]-(4R)-phenyl-4,5-dihydro-1,3-oxazol (13c): Dihydroox-

azole 7c (2.90 g, 10.8 mmol) was reacted with diphenylphosphane

according to GP 2. In the course of the reaction the product pre-

cipitated and acetonitrile (15 mL) was added to allow stirring. The

solid obtained after work-up (ca. 4.3 g) was suspended in n-hexane

(20 mL) under reflux, followed by slow addition of ethyl acetate

until a clear solution was obtained. Upon slow cooling in an oil

bath 2.60 g of 13c precipitated. Further crystallization from the

mother liquid yielded additional 1.31 g of 13c (80% overall yield)

as thick needles. M.p. 118–120°C. [α]²_D⁰= –47.6 (c = 0.90, CHCl₃).

¹H NMR (300 MHz, CDCl₃): δ = 1.04 (s, 3 H, 8-H), 1.21 (s, 3 H,

9-H), 1.69 (d, J_7a,7b= 10.1 Hz, 1 H, 7-H_a), 1.83 (dddd, J = 19.8, J

= 14.0, J = 3.7, J = 3.7 Hz, 1 H, 4-H_a), 1.96–2.03 (m, 1 H, 5-H),

2.28–2.55 (m, 3 H, 1-H, 4-H_b, 7-H_b), 3.08–3.19 (m, 1 H, 2-H), 3.73

18.1 Hz, Ph-C_o), 134.65 (dd, J_C,P= 20.3 Hz, Ph-C_o), 137.11 (d, J_C,P

= 15.8 Hz, Ph-C_i), 137.31 (d, J_C,P= 14.1 Hz, Ph-C_i), 172.80 (d,

J_C,P= 2.3 Hz, C=O). ³¹P NMR (CDCl₃): δ = +8.1 (12), δ = +35.8

(12-oxide). C₂₄H₃₀NOP (379.52): calcd. C 75.95, H 7.98, N 3.69, P

8.16; found C 75.89, H 7.99, N 3.61, P 8.20.

(–)-2-[(1S,2R,3S)-3-Diphenylphosphanyl-6,6-dimethylbicyclo[3.1.1]-

hept-2-yl]-4,5-dihydro-1,3-oxazole (13a): Dihydrooxazole 7a (2.75 g,

14.4 mmol) was reacted with diphenylphosphane according to GP

2. Under argon, the crude oil obtained after work-up was dissolved

in diethyl ether and filtered. The product crystallized upon standing

at 5°C for several days to give 13a (3.30 g, 58%) as large, octahe-

1

dral crystals. M.p. 102–104°C. [α]²_D¹= –88.7 (c = 1.76, CHCl₃). H

NMR (300 MHz, CDCl₃): δ = 1.02 (s, 3 H, 8-H), 1.15 (s, 3 H, 9-

H), 1.36 (d, J_7a,7b= 8.8 Hz, 1 H, 7-H_a), 1.80 (dddd, J = 18.2, J =

14.2, J = 4.1, J = 4.1 Hz, 1 H, 4-H_a), 1.92–1.98 (m, 1 H, 5-H), (dd, J = 9.6, J = 8.3 Hz, 1 H, CH₂O), 3.76–3.86 (m, 1 H, CHP),

2.27–2.43 (m, 3 H, 1-H, 4-H_b, 7-H_b), 2.84–2.96 (m, 1 H, 2-H), 3.26–

3.39 (m, 1 H, CH₂N), 3.49–3.61 (m, 1 H, CH₂N), 3.63–3.73 (m, 1

H, CHP), 3.78 (td, J = 10.5, J = 8.1 Hz, 1 H, CH₂O), 3.91 (td, J

= 10.3, J = 8.0 Hz, 1 H, CH₂O), 7.18–7.25 (m, 3 H, Ph-H_m,p), 7.30–

7.41 (m, 3 H, Ph-H_m,p), 7.50–7.57 (m, 2 H, Ph-H_o), 7.64–7.71 (m,

2 H, Ph-H_o). ¹³C NMR (CDCl₃): δ = 21.54 (q, C-8), 24.19 (dd,

J_C,P= 8.5 Hz, CHP), 26.98 (q, C-9), 29.73 (td, J_C,P= 1.7 Hz, C-

7), 30.94 (td, J_C,P= 18.0 Hz, C-4), 38.79 (d, J_C,P= 2.2 Hz, C-6),

41.00 (dd, J_C,P= 2.2 Hz, C-5), 43.00 (dd, J_C,P= 20.8 Hz, C-2),

4.39 (dd, J = 9.9, J = 8.4 Hz, 1 H, CH₂O), 4.97 (t, J = 9.8 Hz, 1

H, CHN), 6.89–6.94 (m, 2 H, Ph-H), 7.17–7.33 (m, 6 H, Ph-H),

7.34–7.42 (m, 3 H, Ph-H), 7.56–7.66 (m, 2 H, Ph-H_o), 7.68–7.72

(m, 2H Ph-H_o). ¹³C NMR (CDCl₃): δ = 21.21 (q, C-8), 23.81 (dd,

J_C,P= 9.0 Hz, CHP), 26.83 (q, C-9), 28.25 (td, J_C,P= 4.5 Hz, C-

7), 30.65 (td, J_C,P= 17.0 Hz, C-4), 38.78 (d, J_C,P= 2.3 Hz, C-6),

40.82 (dd, J_C,P= 1.7 Hz, C-5), 42.35 (dd, J_C,P= 20.4 Hz, C-2),

44.27 (dd, J_C,P= 2.8 Hz, C-1), 69.41 (d, CHN), 74.26 (t, CH₂O),

126.81, 127.21 (2d, Ph-C), 127.99 (dd, J_C,P= 6.8 Hz, Ph-C_m),

43.96 (dd, J_C,P= 4.0 Hz, C-1), 53.75 (t, CH₂N), 66.59 (t, CH₂O), 128.32 (dd, J_C,P= 6.8 Hz, Ph-C_m), 128.49 (d, Ph-C), 128.75 (dd,

127.41 (dd, J_C,P= 7.4 Hz, Ph-C_m), 128.32 (dd, J_C,P= 6.8 Hz, Ph-

C_m), 128.69 (dd, J_C,P= 1.1 Hz, Ph-C_p), 128.79 (d, Ph-C_p), 133.75

J_C,P= 1.1 Hz, Ph-C_p), 128.80 (d, Ph-C_p), 133.93 (d, J_C,P= 18.6

Hz, Ph-C_o), 134.50 (dd, J_C,P= 19.8 Hz, Ph-C_o), 137.11 (d, J_C,P

=

(dd, J_C,P= 18.6 Hz, Ph-C_o), 134.64 (dd, J_C,P= 19.2 Hz, Ph-C_o), 13.6 Hz, Ph-C_i), 137.58 (d, J_C,P= 17.5 Hz, Ph-C_i), 142.00 (s, Ph-

136.84 (d, J_C,P= 13.5 Hz, Ph-C_i), 137.40 (d, J_C,P= 16.4 Hz, Ph-

C), 170.98 (d, J_C,P= 5.6 Hz, C=N). ³¹P NMR (CDCl₃): δ = +9.2

C_i), 169.91 (d, J_C,P= 4.0 Hz, C=N). ³¹P NMR(CDCl₃): δ = +7.8 (13c), δ = +37.8 (13c-oxide). C₃₀H₃₂NOP (453.60): calcd. C 79.43,

(13a), δ = +36.6 (13a-oxide). C₂₄H₂₈NOP (377.50): calcd. C 76.35, H 7.13, N 3.09, P 6.83; found C 79.21, H 7.22, N 3.03, P 6.76.

H 7.49, N 3.71, P 8.20; found C 76.21, H 7.52, N 3.61, P 8.10.

(–)-2-[(1S,2R,3S)-3-Diphenylphosphanyl-6,6-dimethylbicyclo-

[3.1.1]hept-2-yl]-4,4-dimethyl-4,5-dihydro-1,3-oxazole (13b): Dihy-

drooxazole 7b (3.82 g, 17.4 mmol) was reacted with diphenylphos-

phane according to GP 2. The oil obtained after work-up crys-

tallized upon standing. The product was purified by suspending the

crystals at –78°C under argon in a small amount of n-hexane. The

residue was dissolved in diethyl ether, filtered and the solvent was

removed to give 13b (4.33 g, 61%) as needles. M.p. 91–92°C. [α]²_D⁰

[3.1.1]hept-2-yl]-(4S)-phenyl-4,5-dihydro-1,3-oxazole (13d): Dihy-

drooxazole 7d (390 mg, 1.46 mmol) was reacted with diphenylphos-

phane according to GP 2. After work-up, an oily mixture of dia-

stereomers, 13c/13d = 20:1 (398 mg, 60%) was obtained. [α]²_D⁰

=

–47.4 (c = 1.00, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 1.12 (s,

3 H, 8-H), 1.20 (s, 3 H, 9-H), 1.42 (d, J_7a,7b= 9.6 Hz, 1 H, 7-H_a),

1.78–1.88 (m, 1 H, 4-H_a), 1.96–2.03 (m, 1 H, 5-H), 2.33–2.53 (m,

3 H, 1-H, 4-H_b, 7-H_b), 2.93–3.37 (m, 1 H, 2-H), 3.65 (t, J = 8.5

Hz, 1 H, CH₂O), 3.73–3.86 (m, 1 H, CHP), 4.15 (dd, J = 10.3, J

= 8.1 Hz, 1 H, CH₂O), 4.60–4.69 (m, 1 H, CHN), 7.04–7.08 (m, 2

1

= –77.8 (c = 2.62, CHCl₃). H NMR (300 MHz, CDCl₃): δ = 0.94

[s, 3 H, NC(CH₃)₂], 0.99 (s, 3 H, 8-H), 1.07 [s, 3 H, NC(CH₃)₂],

1.16 (s, 3 H, 9-H), 1.55 (d, J_7a,7b= 9.5 Hz, 1 H, 7-H_a), 1.78 (dddd, H, Ph-H), 7.24–7.40 (m, 9 H, Ph-H), 7.58–7.64 (m, 2 H, Ph-H),

J = 20.2, J = 14.0, J = 3.7, J = 3.7 Hz, 1 H, 4-H_a), 1.92–1.98 (m,

7.66–7.71 (m, 2 H, Ph-H). ¹³C NMR (CDCl₃): δ = 22.15 (q, C-8),

1 H, 5-H), 2.27–2.43 (m, 3 H, 1-H, 4-H_b, 7-H_b), 2.92 (ddd, J_2,P24.17 (dd, J_C,P= 8.4 Hz, CHP), 27.11 (q, C-9), 30.06 (td, J_C,P

17.6 Hz J = 4.8 Hz J = 2.6 Hz, 1 H, 2-H), 3.48 (d, J = 7.7 Hz, 1 2.2 Hz, C-7), 31.20 (td, J_C,P= 18.6 Hz, C-4), 39.06 (d, J_C,P= 2.2

=

H, CH₂O), 3.62 (d, J = 7.7 Hz, 1 H, CH₂O), 3.60–3.74 (m, 1 H, Hz, C-6), 41.34 (dd, J_C,P= 1.7 Hz, C-5), 43.51 (dd, J_C,P= 20.9 Hz,

CHP), 7.18–7.25 (m, 3 H, Ph-H_m,p), 7.30–7.41 (m, 3 H, Ph-H_m,p), C-2), 44.58 (dd, J_C,P= 3.4 Hz, C-1), 69.64 (d, CHN), 74.07 (t,

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New Chiral Phosphane Ligands

CH₂O), 126.80, 127.34 (2d, Ph-C), 127.50 (dd, J_C,P= 7.4 Hz, Ph- = 37.3 Hz, CHP), 22.38 (q, C-8), 25.94 (q, NCH₃), 27.29 (q, C-9),

FULL PAPER

C_m), 128.34 (dd, J_C,P= 6.8 Hz, Ph-C_m), 128.51 (d, Ph-C), 128.80

(d, Ph-C_p), 128.86 (dd, J_C,P= 1.1 Hz, Ph-C_p), 133.73 (dd, J_C,P

27.57 (td, J_C,P= 4.1 Hz, C-4), 30.37 (t, C-7), 38.86 (s, C-6), 40.45

(dd, J_C,P= 5.1 Hz, C-5), 45.80 (dd, J_C,P= 6.2 Hz, C-1), 47.45 (dd,

=

18.6 Hz, Ph-C_o), 134.96 (dd, J_C,P= 19.8 Hz, Ph-C_o), 137.02 (d, J_C,PJ_C,P= 4.5 Hz, C-2), 128.03 (dd, J_C,P= 9.6 Hz, Ph-C_m), 128.30 (d,

= 14.1 Hz, Ph-C_i), 137.42 (d, J_C,P= 17.0 Hz, Ph-C_i), 142.46 (s, Ph-

C), 170.63 (d, J_C,P= 3.4 Hz, C=N). ³¹P NMR (CDCl₃): δ = +8.5

(13d), δ +36.3 (13d-oxide). C₃₀H₃₂NOP (453.60): calcd. C 79.43, H

7.13, N 3.09, P 6.83; found C 79.41, H 7.14, N 3.05, P 6.67.

J_C,P= 54.8 Hz, Ph-C_i), 128.39 (d, J_C,P= 52.0 Hz, Ph-C_i), 128.84

(dd, J_C,P= 9.6 Hz, Ph-C_m), 131.06 (dd, J_C,P= 2.3 Hz, Ph-C_p),

131.30 (dd, J_C,P= 2.3 Hz, Ph-C_p), 132.72 (dd, J_C,P= 8.5 Hz, Ph-

C_o), 133.50 (dd, J_C,P= 9.0 Hz, Ph-C_o), 173.61 (d, J_C,P= 2.3 Hz,

C=O). ³¹P NMR (CDCl₃): δ = +25.5. ¹¹B NMR (CDCl₃): δ =

–42.5. C₂₃H₃₁BNOP (379.33): calcd. C 72.82, H 8.25, N 3.69, P

8.16; found C 72.78, H 8.20, N 3.61, P 8.13.

(–)-(1R)-3-(Boranatodiphenylphosphanyl)-6,6-dimethylbicyclo-

[3.1.1]heptane-2-carboxamide (14·BH₃): Oxalyl chloride (320 mg,

2.52 mmol) was added dropwise to a cold (–20 °C) solution of

10·BH₃(780 mg, 2.13 mmol) and 3 drops of anhydrous DMF in

anhydrous toluene (5 mL). The mixture was allowed to warm to

r. t. and stirred for 3 h. Residual oxalyl chloride and the solvent

were removed in vacuo. The crude acid chloride was dissolved in

anhydrous dioxane (10 mL) and dry NH₃gas was introduced under

cooling with an ice-water bath. The solvent was removed and the

residue suspended in PE/ethyl acetate/iPrOH, 2:1:1. After filtration

the solvent was removed. The product was purified by flash

chromatography (silica gel, PE/ethyl acetate/iPrOH, 90:5:5) to give

14·BH₃(700 mg, 90%) as a colorless solid. M.p. 139–142°C. [α]²_D⁰

= –77.3 (c = 19.9, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 0.50–

1.50 (br. s, 3 H, BH₃), 1.02 (s, 3 H, 8-H), 1.17 (s, 3 H, 9-H), 1.64

(–)-(1S,2R,3S)-[3-(Boranatodiphenylphosphanyl)-6,6-dimethylbicy-

clo[3.1.1]hept-2-yl]methanol (16·BH₃): A solution of 9a·BH₃

(12.80 g, 33.7 mmol) in THF was added dropwise to a suspension

of LiAlH₄(4.00 g, 105.4 mmol) in THF (200 mL) at 0°C. Then the

mixture was warmed to room temperature and conversion moni-

tored by TLC [PE/ethyl acetate, 7:3, R_f(9a·BH₃) = 0.73, R_f(16·BH₃)

= 0.32]. After dilution with diethyl ether (200 mL) the reaction

mixture was worked up according to the procedure of Mihai-

lovic.^[27]The resulting suspension was filtered and the residue

washed thoroughly with diethyl ether. The filtrate was dried over

Na₂SO₄, filtered and the solvent removed in vacuo. The product

was purified by flash chromatography (silica gel, PE/EE, 8:2).

(d, J_7a,7b= 10.3 Hz, 1 H, 7-H_a), 1.91–1.97 (m, 1 H, 5-H), 2.01–2.20 Recrystallization from hexane/ethyl acetate gave 16·BH₃(11.1 g,

(m, 3 H, 1-H, 4-H), 2.29–2.38 (m, 1 H, 7-H_b), 3.04 (ddd, J_2,P

=

94%) as colorless plates. M.p. 122–123°C. [α]²_D¹= –63.4 (c = 1.47,

CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 0.50–1.50 (br. s, 3 H,

BH₃), 1.02 (s, 3 H, 8-H), 1.08 (s, 1 H, OH, H/D), 1.18 (s, 3 H, 9-

H), 1.23 (m, 1 H, 7-H_a), 1.85–1.92 (m, 1 H, 5-H), 1.98 (dddd, J_4a,4b

= 14.0, J = 3.1, J = 3.1, J = 3.1 Hz, 1 H, 4-H_a), 2.06–2.19 (m, 1

H, 4-H_b), 2.20–2.30 (m, 2 H, 1-H, 7-H_b), 2.48–2.78 (m, 3 H, 2-H,

CHP, CH₂O), 3.34 (t, J = 10.3 Hz, 1 H, CH₂O), 7.35–7.54 (m, 6

H, Ph-H_m,p), 7.67–7.74 (m, 2 H, Ph-H_o), 7.84–7.90 (m, 2 H, Ph-

H_o). ¹³C NMR (CDCl₃, 75 MHz): δ = 23.03 (q, C-8), 25.44 (d, J_C,P

20.6, J = 6.6, J = 2.6 Hz, 1 H, 2-H), 4.18–4.35 (m, 1 H, CHP),

4.80, 4.94 (2bs, 2 H, NH₂, H/D), 7.30–7.44 (m, 3 H, Ph-H_m,p), 7.48–

7.55 (m, 3 H, Ph-H_m,p), 7.76–7.85 (m, 2 H, Ph-H_o), 7.94–8.02 (m,

2 H, Ph-H_o). ¹³C NMR (CDCl₃): δ = 21.31 (dd, J_C,P= 36.8 Hz,

CHP), 21.76 (q, C-8), 27.11 (qd, J_C,P= 1.2 Hz, C-9), 27.53 (td,

J_C,P= 3.4 Hz, C-4), 29.58 (t, C-7), 39.00 (s, C-6), 40.28 (dd, J_C,P

= 4.5 Hz, C-5), 45.68 (dd, J_C,P= 5.6 Hz, C-1), 46.08 (dd, J_C,P

4.5 Hz, C-2), 127.89 (dd, J_C,P= 9.6 Hz, Ph-C_m), 128.30 (d, J_C,P

=

53.0 Hz, Ph-C_i), 128.49 (d, J_C,P= 54.2 Hz, Ph-C_i), 128.59 (dd, J_C,P= 32.8 Hz, CHP), 27.06 (q, J_C,P= 1.7 Hz, C-9), 28.82 (t, J_C,P

= 9.6 Hz, Ph-C_m), 130.94 (dd, J_C,P= 2.3 Hz, Ph-C_p), 131.07 (dd, 1.7 Hz, C-4), 29.20 (t, C-7), 38.95 (s, C-6), 40.44 (d, J_C,P= 4.0 Hz,

J_C,P= 2.3 Hz, Ph-C_p), 132.70 (dd, J_C,P= 8.4 Hz, Ph-C_o), 133.32 C-5), 41.24 (d, J_C,P= 6.2 Hz, C-1), 44.18 (d, J_C,P= 2.8 Hz, C-2),

=

(dd, J_C,P= 8.5 Hz, Ph-C_o), 175.00 (d, J_C,P= 2.8 Hz, C=O). ³¹P

NMR (CDCl₃): δ = +26.3. ¹¹B NMR (CDCl₃): δ = –42.3. HR-

MS (FAB+) C₂₂H₂₈BNOP (M⁺+ H – H₂) calcd. 365.2069; found

365.2002.

65.66 (t, J_C,P= 1.7 Hz, CH₂O), 127.64 (s, J_C,P= 54.2 Hz, Ph-C_i),

128.50 (d, J = 9.6 Hz, Ph-C_m), 128.66 (d, J = 9.6 Hz, Ph-C_m),

129.74 (d, J = 51.4 Hz, Ph-C_i), 131.17 (d, J_C,P= 2.3 Hz, Ph-C_p),

131.26 (d, J_C,P= 2.3 Hz, Ph-C_p), 132.50 (d, J_C,P= 7.9 Hz, Ph-C_o),

133.10 (d, J_C,P= 7.9 Hz, Ph-C_o). ³¹P NMR (CDCl₃): δ = +27.0.

¹¹B NMR (CDCl₃): δ = –40.9. C₂₂H₃₀BOP (352.30): calcd. C 75.00,

H 8.60, P 8.79; found C 74.94, H 8.89, P 8.86.

(–)-(1S,2R,3S)-3-(Boranatodiphenylphosphanyl)-N,6,6-trimethylbi-

cyclo[3.1.1]heptane-2-carboxamide (15·BH₃): Methylamine hydro-

chloride (150 mg, 2.22 mmol) and DCC (355 mg, 1.72 mmol) were

added to a cooled (–60°C) solution of 10·BH₃(600 mg, 1.64 mmol)

(–)-(1S,2R,3S)-[3-Diphenylphosphanyl-6,6-dimethylbicyclo[3.1.1]-

and DMAP (210 mg, 1.72 mmol) in anhydrous CH₂Cl₂(5 mL). hept-2-yl]methanaminium 4-Methylbenzenesulfonate (17): A solu-

The mixture was allowed to slowly warm to room temperature and

further stirred for 2 days [TLC: PE/ethyl acetate/iPrOH, 90:3:3,

R_f(10·BH₃) = 0.47, R_f(15·BH₃) = 0.41]. The resultant suspension

was filtered through celite (eluent: CH₂Cl₂) and the filtrate was

washed with 1 n HCl, sat. hydrogencarbonate solution, water and

brine. The organic layer was dried over Na₂SO₄, filtered and the

solvent removed under reduced pressure. The residue was purified

by flash chromatography (silica gel, PE/ethyl acetate/iPrOH, 90:3:3)

to give 15·BH₃(570 mg, 92%) as amorphous powder. M.p. 167–

169°C. [α]²_D²= –55.6 (c = 1.16, CHCl₃). ¹H NMR (300 MHz,

tion of 11 (6.90 g, 207 mmol) in diethyl ether (80 mL) was added

dropwise within 1 h to a cooled (0°C), stirred suspension of LiAlH₄

(7.90 g, 208 mmol) in diethyl ether (130 mL). The mixture was then

allowed to reach room temperature and progress of the reaction

was monitored by TLC [PE/ethyl acetate, 9:1, R_f(11) = 0.31, R_f(17)

= ca. 0.0]. After 12 h diethyl ether (200 mL) was added and the

reaction mixture was worked up according to the procedure of Mi-

hailovic involving controlled precipitation of aluminum oxide.^[27]

This was filtered off and the residue was thoroughly washed with

diethyl ether. The filtrate was dried over Na₂SO₄and concentrated

CDCl₃): δ = 0.50–1.50 (br. s, 3 H, BH₃), 1.08 (s, 3 H, 8-H), 1.15 (s, in vacuo. The residue was dissolved in diethyl ether (20 mL). On

3 H, 9-H), 1.55 (d, J_7a,7b= 10.3 Hz, 1 H, 7-H_a), 1.88–1.97 (m, 1 5 mL of this solution a layer of a solution of p-toluenesulfonic acid

H, 5-H), 2.05–2.18 (m, 3 H, 1-H, 4-H), 2.29–2.35 (m, 1 H, 7-H_b), (950 mg, 5.00 mmol) in THF (10 mL) was placed, avoiding mixing

2.29 (d, J = 4.8 Hz, 3 H, NCH₃; after H/D exchange: s), 2.96 (ddd,

as far as possible. The product crystallized upon standing over a

J_2,P= 20.2, J = 7.0, J = 2.2 Hz, 1 H, 2-H), 4.12–4.35 (m, 1 H, period of several days. The crystals were washed with a small

CHP), 4.89 (bd, J = 4.8 Hz, 1 H, NH, H/D), 7.27–7.40 (m, 3 H, amount of cold (0°C) THF. A second crop was obtained from the

Ph-H_m,p), 7.47–7.52 (m, 3 H, Ph-H_m,p), 7.77–7.84 (m, 2 H, Ph-H_o), mother liquor to give an overall yield of 17 (1.33 g, 53%) as color-

7.91–7.99 (m, 2 H, Ph-H_o). ¹³C NMR (CDCl₃): δ = 21.72 (dd, J_C,P

less needles. M.p. 232–236°C (dec.). [α]²_D¹= –11.9 (c = 1.72,

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FULL PAPER

CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 0.81 (d, J_7a,7b= 9.6 Hz, (m, 1 H, Ar-H). ¹³C NMR (CDCl₃): δ = 21.91 (q, C-8), 23.15 (dd,

1 H, 7-H_a), 0.96 (s, 3 H, 8-H), 1.04 (s, 3 H, 9-H), 1.68–1.85 (m, 2 J_C,P= 32.3 Hz, C-3), 27.15 (q, C-9), 28.33 (dt, J_C,P= 3.4 Hz, C-

H, 4-H_a, 5-H), 2.11–2.31 (m, 4 H, 1-H, 4-H_b, 7-H_b, CHP), 2.32– 4), 29.37 (t, C-7), 39.09 (s, C-6), 40.54 (dd, J_C,P= 4.5 Hz, C-5),

2.49 (m, 1 H, CH₂N), 2.38 (s, 3 H, Ar-CH₃), 2.59–2.73 (m, 1 H,

CH₂N), 7.17–7.33 (m, 5 H, Ph-H, Ar-H), 7.34–7.42 (m, 3 H, Ph-

44.72 (dd, J_C,P= 5.7 Hz, C-1), 45.20 (dd, J_C,P= 4.3 Hz, C-2),

51.40 (q, COOCH₃), 126.16, 126.84, 127.04, 127.15, 127.38, 127.59,

127.81, 127.94, 129.65, 129.76, 130.33, 130.61, 130.64, 130.74,

130.77, 132.65, 132.76, 133.33, 133.43, 133.55, 140.86, 140.91,

148.56, 148.67 (Ar-C), 174.40 (s, COOCH₃). ³¹P NMR (CDCl₃): δ

= +30.2 [(R_P)-18·BH₃], –1.6 [(R_P)-18]. ¹¹B NMR (CDCl₃): δ = –42.

H), 7.56–7.66 (m, 4 H, Ph-H), 7.74 (d, J = 8.1 Hz, 2 H, Ar-H). ¹³

C

NMR (CDCl₃, 75 MHz): δ = 21.15 (q, Ar-CH₃), 22.17 (q, C-8),

26.35 (q, C-9), 28.15 (dd, J_C,P= 14.2 Hz, CHP), 29.67 (t, C-7),

31.27 (td, J_C,P= 13.0 Hz, C-4), 38.72 (d, J_C,P= 1.1 Hz, C-6), 40.9,

41.09 (2d, C-1, C-5), 42.93 (dd, J_C,P= 6.2 Hz, C-2), 43.16 (t,

C

₂₉H₃₄O₂BP (456.37): calcd. C 76.32, H 7.51, P 6.79; found C

CH₂N), 126.09 (d, Ar-C), 128.33 (dd, J_C,P= 6.8 Hz, Ph-C_m), 128.73 76.48, H 7.61, P 6.82.

(dd, J_C,P= 7.0 Hz, Ph-C_m), 128.79 (d, Ar-C), 129.01, 129.13 (2d,

tert-Butyl (1S,2R,3S)-3-[Boranatobiphenyl-2-yl(phenyl)phosphanyl]-

Ph-C_p), 133.04 (dd, J_C,P= 18.6 Hz, Ph-C_o), 134.36 (dd, J_C,P= 19.2

Hz, Ph-C_o), 135.68 (d, J_C,P= 15.8 Hz, Ph-C_i), 137.37 (d, J_C,P

6,6-dimethylbicyclo[3.1.1]heptane-2-carboxylate (19·BH₃): Ester 4b

(1.70 g, 7.66 mmol) and phosphane 8b (4.00 g, 15.26 mmol) were

reacted according to GP 1 (reaction time: 6 h). The crude product

was dissolved in THF and the solution cooled to –78°C, stirred

and dropwise treated with BH₃·THF (1 m in THF, 15.3 mL, 15.3

mmol). Stirring was continued for 15 h and residual borane hy-

=

17.5 Hz, Ph-C_i), 139.87, 141.68 (2s, Ar-C). ³¹P NMR (CDCl₃): δ =

+4.8 (17), δ = +43.5 (17-oxide). C₂₉H₃₆NO₃PS (509.69): calcd. C

68.33, H 7.13, N 2.75, P 6.08, S 6.29; found C 68.30, H 7.40, N

2.76, P 6.10, S 6.29.

Methyl (1S,2R,3S)-3-[Boranatobiphenyl-2-yl(phenyl)phosphanyl]- drolyzed by addition of water and then brine (50 mL). The mixture

6,6-dimethylbicyclo[3.1.1]heptane-2-carboxylate (18·BH₃): Ester 4a was extracted with THF (5×100 mL) and the combined organic

(1.50 g, 8.30 mmol) and phosphane 8b (4.30 g, 16.4 mmol) were layers were dried over Na₂SO₄, filtered and concentrated in vacuo.

reacted according to GP 1 (reaction time: 6 h). After filtration of

the reaction mixture through a pad of silica gel (PE/ethyl acetate,

70:1) and evaporation of the solvent, the crude product was dis-

solved in anhydrous THF (120 mL) and BH₃·THF (1 m in THF)

(16.4 mL, 16.4 mmol) was added at –78°C. After stirring overnight

residual borane was hydrolyzed by addition of water. Then brine

(100 mL) was added and the mixture was extracted with THF

The residue was dissolved in PE/ethyl acetate, 70:1 and the solution

filtered through silica gel. The crude product was dissolved in anhy-

drous THF (40 mL) and BH₃·THF (1 m in THF) (15.3 mL,

15.3 mmol) was added at –78°C. After stirring overnight residual

borane was hydrolyzed by addition of water. Upon addition of

brine (100 mL) the mixture was extracted with THF (5×100 mL),

and the organic layers dried over Na₂SO₄, filtered and concentrated

(5 × 100 mL). The combined organic layers were dried over in vacuo. The diastereomeric products were separated by flash

Na₂SO₄, filtered and the solvent was evaporated under reduced

pressure. The diastereomeric phosphanes were separated by flash

chromatography {silica gel, PE/THF, 50:1, R_f[(S_P)-18·BH₃] = 0.18,

R_f[(R_P)-18·BH₃] = 0.14}. Crystallization of these compounds was

achieved by adding a layer of hexane on to a concentrated solution

in THF/ethyl acetate. This gave (S_P)-18·BH₃(1.14 g, 30%) as color-

less hexagon-shaped crystals and (R_P)-18·BH₃(0.98 g, 25%) as col-

orless, rectangular crystals.

chromatography {600 g of silica gel, PE/ethyl acetate, 70:1, R_f[(S_P)-

19·BH₃] = 0.12, R_f[(R_P)-19·BH₃] = 0.09} to give (S_P)-19·BH₃

(1.98 g, 44%) and (R_P)-19·BH₃(1.52 g, 34%), both colorless pow-

ders.

(S_P)-19·BH₃: M.p. 155–157°C. [α]²_D⁰= –88.6 (c = 1.00, CHCl₃). ¹H

NMR (300 MHz, CDCl₃): δ = 0.5–1.7 (br. s, 3 H, BH₃), 0.99 (s, 3

H, 8-H), 1.16 [s, 9 H, C(CH₃)₃], 1.18 (s, 3 H, 9-H), 1.54 (d, J_7a,7b

= 10.3 Hz, 1 H, 7-H_a), 1.85 (m_c, 1 H, 5-H), 1.77–2.37 (m, 4 H, 1-

H, 4-H, 7-H_b), 3.30 (ddd, J = 21.1, J = 6.9, J = 2.2 Hz, 1 H, 2-H),

(S_P)-18·BH₃: M.p. 145–146°C. [α]²_D⁰= +93.4 (c = 0.99, CHCl₃). ¹H

NMR (300 MHz, CDCl₃): δ = 0.5–1.5 (br. s, 3 H, BH₃), 0.93 (s, 3 3.99 (ddt, J_P,H= 17.8, J_3,4= 11.4, J_2,3= 6.6 Hz, 1 H, 3-H), 6.93–

H, 8-H), 1.14 (s, 3 H, 9-H), 1.23 (d, J_7a,7b= 9.9 Hz, 1 H, 7-H_a),

7.05 (m, 5 H, Ar-H), 7.11–7.21 (m, 6 H, Ar-H), 7.35–7.42 (m, 2 H,

1.81 (m_c, 1 H, 5-H), 1.90–2.31 (m, 4 H, 1-H, 4-H, 7-H_b), 3.29 (s, 3 Ar-H), 8.14–8.26 (m, 1 H, Ar-H). ¹³C NMR (CDCl₃): δ = 22.14

H, OCH₃), 3.35 (ddd, J_P,H= 13.6, J = 6.3, J = 4.1 Hz, 1 H, 2-H), (q, C-8), 22.35 (dd, J_C,P= 34.5 Hz, C-3), 27.30 (q, C-9), 27.80 [q,

3.88 (m, 1 H, 3-H), 7.01–7.09, 7.11–7.18, 7.19–7.27 (3m, 11 H, Ar- C(CH₃)₃], 28.50 (t, C-4), 29.20 (t, C-7), 39.20 (s, C-6), 40.48 (dd,

H), 7.33–7.34 (m, 2 H, Ar-H), 8.11 (m_c, 1 H, Ar-H). ¹³C NMR

(CDCl₃): δ = 21.91 (q, C-8), 23.12 (dd, J_C,P= 34.5 Hz, C-3), 27.05

(dd, J_C,P= 1.1 Hz, C-9), 28.30 (t, C-4), 29.54 (t, C-7), 39.06 (s, C-

J_C,P= 3.5 Hz, C-5), 44.88 (dd, J_C,P= 5.6 Hz, C-1), 46.23 (dd, J =

5.1 Hz, C-2), 80.13 [s, C(CH₃)₃], 126.62, 126.66, 126.81, 127.22,

127.32, 127.41, 127.88, 128.01, 128.08, 129.10, 129.45, 129.48,

6), 40.49 (dd, J_C,P= 3.9 Hz, C-5), 44.54 (dd, J_C,P= 5.7 Hz, C-1), 130.59, 130.62, 131.99, 132.09, 132.47, 132.59, 135.57, 135.78,

45.57 (dd, J_C,P= 5.1 Hz, C-2) 51.56 (q, COOCH₃), 126.35, 126.66, 141.50, 141.54, 147.77 (Ar-C), 173.19 [d, J_C,P= 2.8 Hz, CO-

126.81, 126.84, 126.99, 127.14, 127.51, 127.88, 127.99, 128.12, OC(CH₃)₃]. ³¹P NMR (CDCl₃): δ = +32.0 [(S_P)-19·BH₃], δ –5.1

129.08, 129.73, 129.76, 130.53, 130.56, 132.07, 132.15, 132.71, [(S_P)-19]. ¹¹B NMR (CDCl₃): δ = –38. C₃₂H₄₀O₂BP (498.45): calcd.

132.82, 135.37, 135.58, 141.26, 141.30, 147.58, 147.59 (Ar-C), C 77.11, H 8.09, P 6.21; found C 76.97, H 8.21, P 6.24.

174.66 (d, J_C,P= 2.8 Hz, COOCH₃). ³¹P NMR (CDCl₃): δ = +32.1

(R_P)-19·BH₃: M.p. 59–60°C. [α]²_D⁰= –3.8 (c = 1.00, CHCl₃). ¹H

[(S_P)-18·BH₃], –5.2 [(S_P)-18]. ¹¹B NMR (CDCl₃): δ = +39.

NMR (300 MHz, CDCl₃): δ = 0.1–1.2 (br. s, 3 H, BH₃), 0.94 (s, 3

H, 8-H), 1.10 [s, 9 H, C(CH₃)₃], 1.16 (s, 3 H, 9-H), 1.76 (d, J_7a,7b

= 10.0 Hz, 1 H, 7-H_a), 1.88 (br. s, 1 H, 5-H), 1.29–2.33 (m, 4 H,

C₂₉H₃₄O₂BP (456.37): calcd. C 76.32, H 7.51, P 6.79; found C

76.14, H 7.50, P 6.79.

(R_P)-18·BH₃: M.p. 200–201°C. [α]²_D⁰= +39.7 (c = 0.99, CHCl₃). ¹H

1-H, 4-H, 7-H_b), 3.07 (m, 1 H, 2-H), 4.08 (m, 1 H, 3-H), 7.10 (m,

NMR (300 MHz, CDCl₃): δ = 0.4–1.4 (br. s, 3 H, BH₃), 0.96 (s, 3 1 H, Biph-H), 7.23–7.31 (m, 3 H, Ar-H), 7.31–7.41 (m, 2 H, Ar-

H, 8-H), 1.18 (s, 3 H, 9-H), 1.72 (d, J_7a,7b= 9.1 Hz, 1 H, 7-H_a),

1.92 (br. s, 1 H, 5-H), 2.07–2.30 (m, 4 H, 1-H, 4-H, 7-H_b), 3.25

(m_c, 1 H, 2-H), 3.20 (s, 3 H, OCH₃), 3.98 (m_c, 1-H, 3-H), 6.81 (br.

s, 2 H, Ar-H), 7.11–7.19 (m, 2 H, Ar-H), 7.23–7.34 (m, 2 H, Ar-

H), 7.46–7.63 (m, 5 H, Ar-H), 7.68–7.77 (m, 1 H, Ar-H), 7.93–8.01

(m, 1 H, Ar-H), 8.11–8.18 (m, 1 H, Ar-H). ¹³C NMR (CDCl₃): δ

= 21.92 (q, C-8), 22.91 (dd, J_C,P= 35.3 Hz, C-3), 27.20 (q, C-9),

27.74 [q, C(CH₃)₃], 28.50 (t, C-4), 29.06 (t, C-7), 39.10 (s, C-6),

H), 7.35–7.49 (m, 3 H, Ar-H), 7.53–7.62 (m, 3 H, Ar-H), 8.12–8.19 40.46 (dd, J_C,P= 4.5 Hz, C-5), 44.96 (dd, J_C,P= 4.6 Hz, C-1), 46.65

Eur. J. Org. Chem. 2005, 3246–3262

New Chiral Phosphane Ligands

FULL PAPER

(dd, J_C,P= 10.9 Hz, C-2), 80.08 [s, C(CH₃)₃], 121.67–148.95 (Ar- 1 H, 7-H_a), 1.15 (s, 3 H, 9-H), 1.21 (d, J = 9.0 Hz, 4-H_a), 1.58 (d,

C), 173.54 [d, J_C,P= 2.8 Hz, COOC(CH₃)₃]. ³¹P NMR (CDCl₃): δ

J = 10.0 Hz, PCH₃), 1.90–1.96 (m, 1 H, 5-H), 2.07–2.25 (m, 3 H,

= +29.1 [(R_P)-19·BH₃], δ –1.5 [(R_P)-19]. ¹¹B NMR (CDCl₃): δ = H-1, 4-H_b, 7-H_b), 2.79 (ddd, ³J_2,P= 21.1, J = 6.7, J = 2.3 Hz, 1 H,

–41. C₃₂H₄₀O₂BP (498.45): calcd. C 77.11, H 8.09, P 6.21; found

C 76.82, H 7.94, P 6.33.

2-H), 3.27–3.38 (m, 1 H, 3-H), 7.35–7.44 (m, 3 H, 3Ј-H, 4Ј-H),

7.72–7.78 (m, 2 H, 2Ј-H). ¹³C NMR (CDCl₃, 75 MHz): δ = 9.05

(dq, J = 38.6 Hz, C-1ЈЈ), 21.62 (q, C-8), 24.42 (dd, J = 34.9 Hz, C-

3), 26.65 (dq, J = 2.8 Hz, C-9), 27.14 (t, C-7), 27.66 [3q, CO-

OC(CH₃)₃], 29.28 (t, C-4), 38.89 (s, C-6), 40.20 (dd, J = 4.7 Hz, C-

5), 44.16 (dd, J = 4.7 Hz, C-1), 46.27 (dd, J = 2.8 Hz, C-2), 80.29

[s, COOC(CH₃)₃], 128.10 (ds, J = 51.8 Hz, C-1Ј), 128.28 (dd, J =

9.4 Hz, C-3Ј), 131.27 (dd, J = 2.8 Hz, C-4Ј), 132.83 (dd, J = 8.5

Hz, C-2Ј), 173.05 (ds, J = 2.4 Hz, COOtBu). ³¹P NMR (CDCl₃): δ

= +19.95 [(R_P)-21·BH₃], –12.07 [(R_P)-21]. ¹¹B NMR (CDCl₃): δ =

–40.33. C₂₁H₃₄BO₂P (360.24): calcd. C 70.01, H 9.51; found C

70.27, H 9.55.

tert-Butyl (1S,2R,3S)-6,6-Dimethyl-3-[boranato(1-naphthyl)phenyl-

phosphanyl]bicyclo[3.1.1]heptane-2-carboxylate (20·BH₃): Ester 4b

(0.47 g, 2.11 mmol) and phosphane 8c (1.00 g, 4.23 mmol) were

reacted according to GP 1 (reaction time: 7 h). The cold reaction

mixture was dropwise treated with BH₃·THF (1 m in THF, 5.00

mL, 5.00 mmol) and the mixture stirred overnight and allowed to

reach room temperature. Residual borane was hydrolyzed by ad-

dition of water. Upon addition of brine (30 mL) the mixture was

extracted five times with THF, the organic layers dried over

Na₂SO₄, filtered and concentrated in vacuo. The product was puri-

fied by flash chromatography [silica gel, PE/ethyl acetate, 30:1,

R_f(20·BH₃) = 0.12] to give 20·BH₃(0.70 g, 68%) as mixture of dia-

stereomers. Recrystallization from PE/ethyl acetate gave 0.23 g

(21%) of (S_P)-20·BH₃as colorless, cubic crystals. M.p. 147–149°C.

(–)-(1R,2S,3R)-6,6-Dimethyl-3-(R_P)-(boranatomethylphenylphos-

phanyl)bicyclo[3.1.1]heptane-2-carboxylic Acid (22·BH₃): A solution

of (R_P)-21·BH₃(250 mg, 0.691 mmol) in degassed trifluoroacetic

acid (1 mL) was stirred for 30 min at room temperature (CAU-

TION! Strong evolution of gas.). The solvent was removed and the

residue was dissolved in diethyl ether (10 mL). After addition of 2

m aqueous KOH (1 mL) the mixture was stirred for 30 min (evol-

1

[α]²_D⁰= –103.7 (c = 1.00, CHCl₃). H NMR (300 MHz, CDCl₃): δ

= 0.5–1.5 (br. s, 3 H, BH₃), 0.88 [s, 9 H, C(CH₃)₃], 0.98 (s, 3 H, 8-

H), 1.17 (s, 3 H, 9-H), 1.42 (m, 1 H, 7-H_a), 1.98 (m, 1 H, 5-H),

2.22 (m, 2 H, 1-H, 4-H_a), 2.45–2.62 (m, 2 H, 4-H_b, 7-H_b), 3.08 ution of gas). The reaction mixture was extracted thrice with di-

(ddd, J_P,H= 21.7, J_2,3= 6.6, J_1,2= 1.8 Hz, 2 H, 2-H), 4.35 (m, 1 ethyl ether. The combined organic layers were dried over Na₂SO₄,

H, 3-H), 7.33 (m, 1 H, Naph-H), 7.33–7.52 (m, 6 H, Naph-H), filtered and concentrated in vacuo. The crude product was dis-

7.73–7.79 (m, 3 H, Ar-H), 7.93 (d, J = 8.1 Hz, 1 H, Naph-H), 8.10

(d, J = 8.1 Hz, 1 H, Naph-H), 8.27 (dd, J = 13.4, J = 7.4 Hz, 1 H,

Naph-H). ¹³C NMR (CDCl₃): δ = 22.02 (q, C-8), 22.17 (dd, J_C,P

solved in THF, the solution cooled to –78°C and BH₃·THF (1 m

in THF) (2.0 mL, 2.0 mmol) was added. After stirring for 1 h 1 m

HCl (2 mL) was added at –78°C and the mixture was allowed to

= 34.4 Hz, C-3), 27.17 (q, C-9), 27.34 [q, C(CH₃)₃], 28.51 (dt, J_C,Pwarm to room temperature. It was then extracted with diethyl ether

= 1.1 Hz, C-4), 29.04 (t, C-7), 39.09 (s, C-6), 40.52 (dd, J_C,P= 3.4

Hz, C-5), 44.65 (dd, J_C,P= 7.4 Hz, C-1), 46.93 (dd, J_C,P= 5.0 Hz,

C-2), 79.95 [s, C(CH₃)₃], 124.48, 124.54, 124.65, 125.17, 125.91,

126.301, 127.05, 127.11, 128.71, 128.81, 128.84, 130.03, 130.66,

(4 × 5 mL) and the combined organic layers were dried over

Na₂SO₄and concentrated in vacuo. Flash chromatography (silica

gel, PE/ethyl acetate/iPrOH, 98:1:1) gave 22·BH₃(153 mg, 73%) as

colorless needles. M.p. 183–184°C. [α]²_D¹= –10.4 (c = 0.99, CHCl₃).

130.69, 130.75, 132.51, 132.62, 132.84, 132.88, 133.75, 133.80, ¹H NMR (500 MHz, CDCl₃): δ = 0.2–1.4 (br. s, 3 H, BH₃), 0.83

2

133.92, 134.01, 136.31, 136.47, (Ar-C), 172.38 [d, J_C,P= 3.0 Hz,

(s, 3 H, 8-H), 1.14 (d, J_7a,7b= 10.2 Hz, 1 H, 7-H_a), 1.15 (s, 3 H,

9-H), 1.59 (d, J = 9.9 Hz, PCH₃), 1.94–2.01 (m, 1 H, 5-H), 2.11–

COOC(CH₃)₃]. ³¹P NMR (CDCl₃): δ = +31.5 [(S_P)-20·BH₃], –4.9

[(S_P)-20]. ¹¹B NMR (CDCl₃): δ = –39. C₂₄H₃₄O₂BP (472.41): calcd. 2.25 (m, 3 H, 7-H_b, 4-H_a, 4-H_b), 2.31–2.40 (m, 1 H, 1-H), 2.92

3

C 76.27, H 8.11, P 6.56; found C 76.09, H 8.19, P 6.59.

(ddd, J_2,1= 2.5, J_2,3= 6.5, J_2,P= 20.2 Hz, 1 H, 2-H), 3.16–3.24

(m, 1 H, 3-H), 7.24–7.42 (m, 3 H, 3Ј-H, 4Ј-H), 7.70–7.74 (m, 2 H,

2Ј-H). ¹³C NMR (CDCl₃, 75 MHz): δ = 8.75 (dq, J = 39.5 Hz, C-

1ЈЈ), 21.39 (q, C-8), 24.61 (dd, J = 34.8 Hz, C-3), 26.78 (t, C-4),

26.79 (q, C-9), 29.23 (t, C-7), 38.86 (s, C-6), 40.02 (dd, J = 3.7 Hz,

C-5), 43.79 (dd, J = 3.7 Hz, C-1), 44.96 (dd, J = 1.8 Hz, C-2),

127.74 (ds, J = 51.8 Hz, C-1Ј), 128.32 (dd, J = 10.3 Hz, C-3Ј),

131.47 (dd, J = 1.9 Hz, C-4Ј), 132.64 (dd, J = 8.5 Hz, C-2Ј), 179.62

(ds, J = 2.8 Hz, COOH). ³¹P NMR (CDCl₃): δ = +21.35

(22·BH3); –15.44 (22). ¹¹B NMR (CDCl₃): δ = –41.9. HMS

(FAB+): C₁₇H₂₆BO₂P calcd. 304.1763, found 304.1764.

tert-Butyl (1S,2S,3-R,R_P)-6,6-Dimethyl-3-(boranatomethylphenyl-

phosphanyl)bicyclo[3.1.1]heptane-2-carboxylate [(R_P)-21·BH₃]: A

solution of methyldiphenylphosphane (3.38 g, 16.9 mmol) in THF

(20 mL) was treated with powdered lithium (239 mg, 34.7 mmol).

After stirring for 12 h at room temperature the mixture was filtered

and the filtrate treated with a solution of tert-butyl chloride (1.29 g,

15.3 mmol) in THF (7 mL). The solution of lithium methylphen-

ylphosphide obtained in this way was heated to reflux for 10 min

and was then directly used in the reaction with ester 4b (2.82 g,

12.7 mmol) in degassed THF (35 mL) according to GP 1 (reaction

time: 3 h). Conversion was monitored by TLC [PE/ethyl acetate/

iPrOH, 99:0.5:0.5, R_f(21) = 0.20, R_f(8d) = 0.14]. The reaction mix-

ture was cooled to –78 °C, BH₃·THF (1 m in THF, 60 mL, 60

mmol) was added and progress of the reaction monitored by TLC

Di-tert-butyl 3,3Ј-[Ethane-1,2-diylbis(boranatophenylphospanediyl)]-

bis[(1S,2R,3S)-6,6-dimethylbicyclo[3.1.1.]heptane-2-carboxylate]

(23). A. Preparation of 23a–c by Conjugate Addition/Epimerization:

Under nitrogen, five drops of aqueous Et₄NOH (40%) were added

[PE/ethyl acetate/iPrOH, 99:0.5:0.5, R_f[(R_P)-21·BH₃] = 0.37, to a solution of 8e (2.00 g, 8.12 mmol) in degassed acetonitrile (80

R_f[(S_P)-21·BH₃] = 0.27, R_f(PhMePH·BH₃) = 0.27]. After 1 h the mL). The mixture was stirred for 15 min at room temperature, then

mixture was allowed to warm to room temperature overnight and

excess borane was destroyed by addition of 1 n HCl (20 mL). The

reaction mixture was extracted with diethyl ether, the organic layer

dried over Na₂SO₄, filtered and the filtrate was concentrated in

vacuo. The product was purified by flash chromatography (silica

4b (3.61 g, 16.24 mmol) was added and stirring was continued for

36 h. Then the solvent was removed and the residue dissolved in

degassed toluene (50 mL). The solution was heated to reflux for

8 h, then cooled to –78°C and treated with BH₃·THF (1 m in THF)

(16.2 mL, 16.2 mmol). After stirring for 16 h excess of borane was

gel, PE/ethyl acetate/iPrOH, 99:0.5:0.5) to give (R_P)-21·BH₃(1.01 g, destroyed by addition of water. Brine (50 mL) was added and the

22%) as colorless needles. M.p. 129°C. [α]²_D⁰= +1.7 (c = 0.96,

CHCl₃). H NMR (500 MHz, CDCl₃): δ = 0.25–1.25 (br. s, 3 H, dried over Na₂SO₄and the solvent was removed in vacuo. The

mixture was extracted with THF. The combined organic layers were

1

BH₃), 0.84 (s, 3 H, 8-H), 1.12 [s, 9 H, COOC(CH₃)₃], 1.08–1.18 (m, product was purified by repeated flash chromatography {silica, pe-

Eur. J. Org. Chem. 2005, 3246–3262

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3259

G. Helmchen et al.

FULL PAPER

troleum ether/ethyl acetate, 30:1, R_f[(R_P,S_P)-23a·BH₃] = 0.09,

R_f[(S_P,S_P)-23b·BH₃] = 0.08, R_f[(R_P,R_P)-23c·BH₃] = 0.06} to give

(R_P,S_P)-23a·BH₃(1.17 g, 20 %), (S_P,S_P)-23b·BH₃(1.84 g, 32 %),

(R_P,R_P)-23c·BH₃(0.46 g, 8%) and a mixture of (R_P,S_P)-23a·BH₃

and (S_P,S_P)-23b·BH₃(0.42 g, 7%) as white colorless powders.

(CH₃)₃]. ³¹P NMR (CDCl₃): δ = +32.5 (23b·BH₃), +5.2 (23b). ¹¹B

NMR (CDCl₃): δ = –45. C₄₂H₆₆O₄P₂B₂(718.55): calcd. C 70.21,

H 9.26, P 8.62; found C 70.17, H 9.35, P 8.53.

(R_P,R_P)-23c·BH₃: M.p. 225°C (dec.). [α]²_D⁰= –17.2 (c = 0.50,

CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 0.3–1.0 (br. s, 6 H,

BH₃), 0.76 (s, 6 H, 8-H), 1.05 [s, 18 H, C(CH₃)₃], 1.08 (s, 6 H, 9-

H), 1.21 (d, J_7a,7b= 7.6 Hz, 2 H, 7-H_a), 1.69–1.74 (br. s, 2 H, 13-

H_a), 1.89 (br. s, 2 H, 5-H), 2.09–2.32 (m, 10 H, 1-H, 4-H, 7-H_b, 13-

H_b), 2.68 (ddd, J_P,H= 20.6, J_2,3= 6.4, J_1,2= 1.8 Hz, 2 H, 2-H),

3.25 (ddd, J_P,H= 23.9, J_3,4= 11.5, J_2,3= 6.0 Hz, 2 H, 3-H), 7.34

(t, J = 7.3 Hz, 4 H, H_m), 7.44 (t, J = 7.3 Hz, 2 H, H_p), 7.54 (br. s,

4 H, H_o). ¹³C NMR (CDCl₃): δ = 16.92 (dt, J_C,P= 35.5 Hz, C-13),

21.54 (q, C-8), 23.83 (dd, J_C,P= 34.5 Hz, C-3), 26.82 (t, C-4), 27.07

(q, C-9), 27.59 [q, C(CH₃)₃], 29.20 (t, C-7), 38.86 (s, C-6), 40.11 (d,

C-5), 44.17 (d, C-1), 46.12 (d, C-2), 80.28 [s, C(CH₃)₃], 125.27 (d,

J_C,P= 49.8 Hz, C_i), 128.32, 128.36 (2dd, J_C,P= 4.6, J_C,P= 4.0 Hz,

C_m), 131.66 (d, C_p), 133.59, 133.62 (2dd, J_C,P= 4.0, J_C,P= 3.3

Hz, C_o), 172.93 [s, COOC(CH₃)₃]. ³¹P NMR (CDCl₃): δ = +32.3

(23c·BH₃), +5.9 (23c). ¹¹B NMR (CDCl₃): δ = –45. C₄₂H₆₆O₄P₂B₂

(718.55): calcd. C 70.21, H 9.26, P 8.62; found C 70.15, H 9.38, P

8.52.

B. Selective Preparation of 23a by Conjugate Addition of Diphos-

phane 8e Catalyzed by NEt₄OH: In the same way as described

above, diphosphane 8e (0.50 g, 2.0 mmol) was treated with ester 4b

(910 mg, 4.01 mmol). The crude phosphanes were reacted with

BH₃·THF by stirring overnight, avoiding P-epimerization. After

work-up as described above, flash chromatography yielded (R_P,S_P)-

23a·BH₃(630 mg, 43%), (S_P,S_P)-23b·BH₃(70 mg, 5%) and (R_P,R_P)-

23c·BH₃(10 mg, 0.7%).

C. Selective Preparation of 23a by Conjugate Addition of the Dilithio

Derivative of 8e: A cold (–78°C) solution of 8e (0.50 g, 2.0 mmol)

in THF (20 mL) was treated with nBuLi (4.10 mmol, 1.6 m solution

in n-hexane). The mixture was then stirred at room temperature for

15 min, cooled to –78°C and then ester 4b (910 mg, 4.10 mmol)

was added. After 3 days, complexation with borane and work-up

according to GP 1 followed by flash chromatography as described

above gave of (R_P,S_P)-23a·BH₃(650 mg, 45%) and (S_P,S_P)-23b·BH₃

(50 mg, 3%).

Crystal Structure Determinations: Crystal data were recorded on a

AED II diffractometer for 10-O, and on a Enraf–Nonius

KappaCCD diffractometer for 12, on a Siemens/Stoe Syntex R3

diffractometer for (S_P)-19·BH₃and (S_P)-20·BH₃, and on a Bruker

Smart CCD diffractometer for (R_P)-21·BH₃and 23b·BH₃; Mo-Kα

radiation (μ = 0.71073 Å); temperature 150(2) K for 12, and 200(2)

K for (R_P)-21·BH₃and 23b·BH₃, otherwise room temperature; χ-

scans, absorption correction based on multi-scans for 12 and

23b·BH₃or else ψ-scans; the structures were solved by direct meth-

ods and refined against F²with a full-matrix least-squares algo-

rithm using the SHELXTL (5.10) software package, except for the

structure 12 which was solved using the direct methods program

SIR92 and refined against F with a full-matrix least-squares refine-

ments using CRYSTALS program suite; all non hydrogen atoms

were refined anisotropically, hydrogen atoms were treated by using

appropriate riding models, except of the cyclonutyl hydrogens in 12

and the hydrogen atoms of the BH₃in (S_P)-19·BH₃, (S_P)-20·BH₃,

(R_P)-21·BH₃and 23b·BH₃which were refined isotropically.

(R_P,S_P)-23a·BH₃: M.p. 254°C (dec.). [α]²_D¹= –10.0 (c = 1.01,

CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 0.2–0.9 (br. s, 6 H,

BH₃), 0.72, 1.06 (2d, J = 7.6 Hz, 2 H, 7-H_a, 7Ј-H_a), 0.74, 0.75 (2s,

6 H, 9-H, 9Ј-H), 1.05, 1.08 (2s, 6 H, 8-H, 8Ј-H), 1.07, 1.20 [2s, 18

H, C(CH₃)₃], [1.46–1.80 (6H), 1.81–1.93 (1H), 1.98–2.10 (2H),

2.11–2.19 (2H), 2.23–2.41 (3H), (5 m, 1-H, 4-H, 5-H, 7-H_b, 13-H,

1Ј-H, 4Ј-H, 5Ј-H, 7Ј-H_b, 13Ј-H)], 2.71 (ddd, J = 20.3, J = 6.5, J =

2.4 Hz, 1 H, 2Ј-H), 2.86 (ddd, J = 20.9, J = 6.7, J = 2.7 Hz, 1 H,

2-H), 3.19 (ddd, J = 22.4, J = 12.1, J = 6.0 Hz, 1 H, 3Ј-H), 3.36

(ddd, J = 23.2, J = 11.5, J = 6.0 Hz, 1 H, 3-H), 7.35–7.43(m, 3 H,

Ar-H), 7.44–7.53 (m, 3 H, Ar-H), 7.67, 7.80 (2t, J = 8.2 Hz, each

2 H, Ar-H). ¹³C NMR (CDCl₃): δ = 16.29, 17.09 (2dt, J_C,P= 33.9,

J_C,P= 32.2 Hz, PCH₂), 21.57, 21.61 (2q, C-8, C-8Ј), 23.97, 24.41

(2dd, J_C,P= 35.6, J_C,P= 33.9 Hz, C-3, C-3Ј), 26.79, 27.15 (2t, C-

4, C-4Ј), 27.00, 27.07 (2q, C-9, C-9Ј), 27.64, 27.76 [2q, C(CH₃)₃],

29.03, 29.09 (2t, C-7, C-7Ј), 38.85, 38.89 (2s, C-6, C-6Ј), 40.06,

40.09 (2d, C-5, C-5Ј), 43.96, 44.14 (2dd, J_C,P= 4.2, J_C,P= 3.4 Hz,

C-1, C-1Ј), 46.06, 46.07 (2d, C-2, C-2Ј), 80.40, 80.97 [2s, C(CH₃)₃],

125.00, 126.31 (2d, J_C,P= 48.3, J_C,P= 50.9 Hz, C_i, CЈ_i), 128.57,

129.01 (2dd, J_C,P= 9.3, J_C,P= 9.3 Hz, C_m, CЈ_m), 131.57, 131.74

(2d, C_p, CЈ_p), 132.89, 133.61 (2dd, J_C,P= 7.6, J_C,P= 7.6 Hz, C_o,

CЈ_o), 172.74, 173.39 [2s, COOC(CH₃)₃]. ³¹P NMR (CDCl₃): δ =

+32.5 (23a·BH₃); 6.7, 7.3 (each d, J_P,P= 16.2 Hz) (23a). ¹¹B NMR

(CDCl₃): δ = –47. C₄₂H₆₆O₄P₂B₂(718.55): calcd. C 70.21, H 9.26,

P 8.62; found C 69.99, H 9.25, P 8.53.

Crystal Data of 10-O: C₂₂H₂₅O₃P, M_r= 368.39, crystal dimension

0.40×0.60×0.70 mm³, orthorhombic, space group P2₁2₁2₁, a =

10.501(5) Å, b = 11.278(6) Å, c = 17.780(9) Å, V = 2105.7(18) Å³,

Z = 4, ρ_calcd.= 1.162 gcm^–3, F(000) = 784, μ = 0.147 mm^–1, T_min.

= 0.93, T_max.= 1.00, 3.0° Յ 2Θ Յ 52.5°, 3995 reflections measured,

3995 unique, 2528 observed [I Ͼ 2σ(I)], 240 parameters refined,

0.1(2) Flack parameter (absolute structure), final residual values

R(F) = 0.052, wR(F²) = 0.116 for observed reflections (mm³), or-

thorhombic, sp residual electron density –0.20 to 0.17 e·Å^–3.

(S_P,S_P)-23b: M.p. 234°C (dec.). [α]²_D⁰= –18.6 (c = 1.02, CHCl₃). ¹H

NMR (300 MHz, CDCl₃): δ = 0.2–1.0 (br. s, 6 H, BH₃), 0.71 (s, 6

H, 9-H), 1.09 (s, 6 H, 8-H), 1.34 (d, J_7a,7b= 10.2 Hz, 2 H, 7-H_a),

1.39 [s, 18 H, C(CH₃)₃], 1.48–1.62 (m, 4 H, 4-H_a, PCH₂), 1.64–1.76

(m, 4 H, 4-H_b, 5-H), 1.84 (m_c, 2 H, PCH₂), 2.17 (ddd, J_7a,7b= 10.3,

J_1,7b= 6.2, J_5,7b= 6.2 Hz, 2 H, 7-H_b), 2.38 (br. s, 2 H, 1-H), 3.00

(ddd, J_P,H= 20.2, J_2,3= 6.2, J_1,2= 2.7 Hz, 2 H, 2-H), 3.25 (ddd,

J_P,H= 23.9, J_3,4= 11.5, J_2,3= 6.0 Hz, 2 H, 3-H), 7.37 (t, J = 7.5

Hz, 4 H, Ar-H), 7.50 (m_c, 6 H, Ar-H). ¹³C NMR (CDCl₃): δ =

Crystal Data of 12: C₂₄H₃₀NOP, M_r= 379.48, crystal dimension

0.14×0.44×0.44 mm³, monoclinic, space group P2₁,

a =

11.1636(3) Å, b = 6.6031(2) Å, c = 14.4940(5) Å, V = 1056.44(6)

Å³, Z = 2, ρ_calcd.= 1.193 gcm^–3, F(000) = 408, μ = 0.143 mm^–1,

T_min.= 0.94, T_max.= 0.98, 5.0° Յ 2Θ Յ 27.5°, 11284 reflections

measured, 4547 unique, 3727 observed [I Ͼ 3σ(I)], 261 parameters

refined, Flack parameter (absolute structure) –0.03(8), final resid-

ual values R(F) = 0.0362, wR(F) = 0.0413 for observed reflections,

residual electron density –0.34 to 0.29 e·Å^–3.

17.45 (dt, J_C,P= 32.2 Hz, PCH₂), 21.49 (q, C-8), 23.81 (dd, J_C,P

=

35.6 Hz, C-3), 26.92 (q, C-9), 26.97 (t, C-4), 27.94 [q, C(CH₃)₃], Crystal Data of (S_P)-19·BH₃: C₃₂H₄₀BO₂P, M_r= 498.45, crystal

28.76 (t, C-7), 38.79 (s, C-6), 39.97 (d, C-5), 43.85 (d, C-1), 45.89

dimension 0.50×0.95×0.99 mm³, space group P2₁2₁2₁, a =

(d, C-2), 81.18 [s, C(CH₃)₃], 126.95 (d, J_C,P= 50.9 Hz, C_i), 128.69, 11.498(2) Å, b = 11.863(3) Å, c = 21.620(5) Å, V = 2949(1) Å³, Z

128.73 (2dd, J_C,P= 4.2, J_C,P= 5.1 Hz, C_m), 131.47 (d, C_p), 132.58,

132.61 (2dd, J_C,P= 4.2, J_C,P= 4.2 Hz, C_o), 173.84 [s, COOC-

= 4, ρ_calcd.= 1.12 gcm^–3, F(000) = 1072, μ = 0. 12 mm^–1, T_min.

0.85, T_max.= 1.00, 3.0° Յ 2Θ Յ 60°, 6158 reflections measured,

=

3260

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New Chiral Phosphane Ligands

FULL PAPER

1978, 100, 5491–5494; c) R. B. Kings, J. Bakos, C. D. Hoff, L.

Marko, J. Org. Chem. 1979, 44, 1729–1731; d) M. J. Burk, A.

Pizzano, J. A. Martín, L. M. Liable-Sands, A. L. Rheingold,

Organometallics 2000, 19, 250–260.

G. Elsner, in: Houben-Weyl, Methoden der Organischen Chemie

(Ed.: M. Regitz), vol. E1, p. 113, Georg Thieme, Stuttgart,

1982.

J. F. G. A. Jansen, B. L. Feringa, Tetrahedron: Asymmetry

1990, 1, 719–720.

The terms myrtenic acid for 6,6-dimethylbicyclo[3.1.1]hept-2-

ene-2-carboxylic acid and myrtanic acid for the hydrogenation

product are used in analogy to the well known term myrtenal.

6158 unique, 4553 observed [I Ͼ 2σ(I)], 336 parameters refined,

Flack parameter (absolute structure) 0.0(1), final residual values

R(F) = 0.059, wR(F²) = 0.131 for observed reflections, residual elec-

tron density –0.26 to 0.23 e·Å^–3.

[5]

Crystal Data of (S_P)-20·BH₃: C₃₀H₃₈BO₂P, M_r= 472.38, crystal

dimension 0.40×0.40×0.45 mm³, orthorhombic, space group

P2₁2₁2₁, a = 10.700(2) Å, b = 13.555(3) Å, c = 19.284(4) Å, V =

2797(1) Å³, Z = 4, ρ_calcd.= 1.12 gcm^–3, F(000) = 1016, μ =

0.12 mm^–1, T_min.= 0.93, T_max.= 1.00, 3.0° Յ 2Θ Յ 45°, 3172 reflec-

tions measured, 3172 unique, 2197 observed [I Ͼ 2σ(I)], 317

parameters refined, Flack parameter (absolute structure) –0.1(2),

final residual values R(F) = 0.067, wR(F²) = 0.117 for observed

reflections, residual electron density –0.20 to 0.18 e·Å^–3.

[6]

[7]

[8]

[9]

G. Knühl, P. Sennhenn, G. Helmchen, J. Chem. Soc. Chem.

Commun. 1995, 1845–1846.

a) T. Bunlaksananusorn, P. Knochel, J. Org. Chem. 2004, 69,

4595–4601; b) T. Bunlaksananusorn, K. Polborn, P. Knochel,

Angew. Chem. 2003, 115, 4071–4073; Angew. Chem. Int. Ed.

2003, 42, 3941–3943; c) T. Bunlaksananusorn, A. P. Luna, M.

Bonin, L. Micouin, P. Knochel, Synlett 2003, 14, 2240–2242;

d) T. Bunlaksananusorn, P. Knochel, Tetrahedron Lett. 2002,

43, 5817–5819.

A. D. Sadow, I. Haller, L. Fadini, A. Togni, J. Am. Chem. Soc.

2004, 126, 14704–14705.

a) S. Schleich, G. Helmchen, Eur. J. Org. Chem. 1999, 2515–

2521; b) E. J. Bergner, G. Helmchen, Eur. J. Org. Chem. 2000,

419–423.

a) Y. Okada, T. Minami, Y. Sasaki, Y. Umezu, M. Yamagushi,

Tetrahedron Lett. 1990, 31, 3905–3908; b) Y. Okada, T. Min-

ami, Y. Umezu, S. Nishikawa, R. Mori, Y. Nakayama, Tetrahe-

dron: Asymmetry 1991, 2, 667–682; c) T. Minami, Y. Okada, T.

Otaguro, S. Tawaraya, T. Furuichi, T. Okauchi, Tetrahedron:

Asymmetry 1995, 6, 2469–2474.

a) F. W. Semmler, K. Bartelt, Ber. Dtsch. Chem. Ges. 1907, 40,

1363–1377; b) F. W. Semmler, B. Zaar, Ber. Dtsch. Chem. Ges.

1911, 441, 815–819.

Crystal Data of (R_P)-21·BH₃: C₂₁H₃₄BO₂P, M_r= 360.26, crystal

dimension 0.48×0.24×0.14 mm³, polyhedron, space group P2₁, a

= 9.6722(1) Å, b = 9.6698(1) Å, c = 12.435(5) Å, V = 1094.18(16)

Å³, ρ_calcd.= 1.093 gcm^–3, μ = 0.136 mm^–1, T_min.= 0.76, T_max.

=

0.98, 3.4° Յ 2Θ Յ 54.8°, 11069 reflections measured, 4988 unique,

4376 observed [I Ͼ 2σ(I)], 276 parameters refined, Flack parameter

(absolute structure) 0.05(6), final residual values R(F) = 0.035,

wR(F²) = 0.081 for observed reflections, residual electron density

–0.19 to 0.23 e·Å^–3.

[10]

[11]

Crystal Data of 23b·BH₃: M_r

= 718.51, crystal dimension

0.10×0.37×0.38 mm³, monoclinic, space group P2₁, a = 10.653(2)

Å, b = 17.468(4) Å, c = 23.914(4) Å, β = 98.40(2) °, V = 4402(1)

Å³, Z = 4, ρ_calcd.= 1.08 gcm^–3, F(000) = 1560, μ = 0.14 mm^–1,

T_min.= 0.86, T_max.= 1.00, 3.0° Յ 2Θ Յ 51.2°, 20475 reflections

measured, 13652 unique [R(int) = 0.0235], 10817 observed [I Ͼ

2σ(I)], 957 parameters refined, Flack parameter (absolute struc-

ture) –0.02(6), final residual values R(F) = 0.048, wR(F²) = 0.096

for observed reflections, residual electron density –0.24 to 0.18

e·Å^–3.

[12]

[13]

[14]

[15]

[16]

R. Krishnamurti, H. G. Kuivila, J. Org. Chem. 1986, 51, 4947–

4953.

CCDC-147755 (for 10-O), -261244 (for 12), -147752 [for (S_P)-

19·BH₃], -147753 [for (S_P)-20·BH₃], -166021 [for (R_P)-21·BH₃]

and -147754 (for 23b·BH₃) contain the supplementary crystallo-

graphic data for this paper. These data can be obtained free of

charge from The Cambridge Crystallographic Data Centre via

www.ccdc.cam.ac.uk/data_request/cif.

E. J. Corey, N. W. Gilman, B. Ganem, J. Am. Chem. Soc. 1968,

90, 5616–5617.

M. Peer, J. C. deJong, M. Kiefer, T. Langer, H. Rieck, H.

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A. W. Dox, Org. Synth. Collect. Vol. I, 1942, Wiley, New York,

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D. A. Blinn, R. S. Button, V. Farazi, M. K. Neeb, C. L. Tabley,

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[17]

[18]

Acknowledgments

[19]

[20]

M. Peer, J. C. deJong, M. Kiefer, T. Langer, H. Rieck, H.

Schell, P. Sennhenn, J. Sprinz, H. Steinhagen, B. Wiese, G.

Helmchen, Tetrahedron 1996, 52, 7547–7583.

The borane adducts of the phosphanyl carboxylic acids were

deprotected by mixing 20 µmol of the phosphanyl borane un-

der nitrogen with 1 mL of diethylamine and stirring the mix-

ture for 15 min at 50–60°C.

This work was supported by the Deutsche Forschungsgemeinschaft

and the Fonds der Chemischen Industrie. We thank Dr. B. Nuber,

Dr. A. W. Cowley and Dr. F. Rominger for X-ray crystal structures,

ˇ

and Peter Soba for the preparation of 23a–c.

[21]

[22]

B. R. Kimpton, W. McFarlane, A. S. Muir, P. G. Patel, J. L.

Brookham, Polyhedron 1993, 12, 2525–2534.

G. Helmchen, B. Glatz, Ein präparativ einfaches System und

Säulen höchster Trennleistung zur präparativen Mitteldruck-

Flüssigkeitschromatographie, Stuttgart, 1979, unpublished ma-

nuscript, available upon request.

The enantiomeric excess of (–)-(1R)-myrtenal was typically

96% ee; determination by GC: Column Chrompac Permethyl-

β-CD (50 m×0.25 mm), oven temp.: 110°C, He (1 bar), injec-

tor temp.: 250°C, detector temp.: 250°C: t_R[(1S)-1] = 13.2 min,

t_R[(1R)-1] = 14.3 min.

For ³¹P NMR monitoring samples (0.3 mL) were quickly trans-

ferred into a cooled (–78°C) NMR tube, kept under nitrogen,

charged with dry, degassed methanol (0.1 mL).

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[2] a) H. Brunner, W. Zettlmeier, Handbook of Enantioselective Ca-

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[23]

[24]

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www.eurjoc.org

3261

G. Helmchen et al.

FULL PAPER

[25] In earlier experiment we used quenching with deoxygenated

Na₂SO₄·10H₂O. It is then necessary to remove solid material

by filtering before adding BH₃·THF.

[26] Should small amounts of the corresponding phosphane oxide

be formed could this to some extent be removed via crystalli-

zation, otherwise via column chromatography {silica gel, PE/

diethyl ether/DCM/iPrOH, 70:15:15:1, R_f(4b)

R_f(10·BH₃) = 0.25, R_f(10-oxide) = 0.14}.

=

0.63,

[27] V. M. Micovic, M. L. Mihailovic, J. Org. Chem. 1953, 18, 1190–

1200.

Received February 28, 2005

3262

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Article Doi

Syntheses of new chiral phosphane ligands by diastereoselective conjugate addition of phosphides to enantiomerically pure acceptor-substituted olefins from the chiral pool

DOI: 10.1002/ejoc.200500144

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