Alkylation of phosphinite/phosphonite-boranes via temporary protection of the P-H bond

SYNTHESIS

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2020, 52, 2410–2426

paper

2410

de

K. Modzelewski, S. Sowa

Paper

Synthesis

Alkylation of Phosphinite/Phosphonite-Boranes via Temporary

Protection of the P–H Bond

Kamil Modzelewski

in situ deprotection and P-alkylation

Sylwia Sowa*

0

0-

0

2-3

4

9

4-1

1

7

0

BH₃

P

BH₃

P

BH₃

P

NaH/EX

OH

R¹

Department of Organic Chemistry, Faculty of Chemistry,

Institute of Chemical Sciences, Marie Curie-Sklodowska

University in Lublin, 33 Gliniana St., Lublin 20-614, Poland

sylwia.sowa@poczta.umcs.lublin.pl

Ph

EtO

i-PrO

E

R²O

O

–

O

–

up to 85% yield

up to 83% yield

protected P–H bond

BH₃

P

BH₃

NaH/EX in DMF

P

OH

Ph

L-MenthylO

Ph

L-MenthylO

up to 91% yield

Ph

L-MenthylO

E

O

–

O

–

up to 98% yield

in situ deprotection and diastereoselective P-alkylation

Received: 04.01.2020

Accepted after revision: 06.04.2020

Published online: 22.06.2020

More recently, Montchamp’s group applied an acetal

protection–cleavage approach to a wide range of syntheses

and transformations of H-phosphinates⁷and has also devel-

oped parallel chemistry using borane analogues.⁸

DOI: 10.1055/s-0040-1707104; Art ID: ss-2020-z0007-op

Abstract A new alkylation protocol for the synthesis of tertiary

phosphonite/phosphinite-boranes is developed. P-Alkylation products

are obtained exclusively in moderate to very good yields from easily ac-

cessible (1-hydroxy-1-methylethyl)/(1-hydroxy-1-cyclohexyl) phos-

phonite/phosphinite-boranes upon reaction with a variety of electro-

philes under mild conditions. The methodology opens up new synthetic

routes for organophosphorus chemistry and offers access to valuable

alkyl phosphonite/phosphinite-boranes. In contrast to previously re-

ported oxidative removal–substitution sequences for the preparation of

optically active phosphinite-boranes, our protocol provides a one-step

procedure that occurs without loss of stereochemical information at

phosphorus. This new approach provides a rather advantageous proto-

col when compared to direct alkylation methods (which may undergo

P-epimerization) and occurs in a stereoselective manner even at 0 °C.

On the other hand, and even earlier, Kharasch observed

that -hydroxyalkylphosphonates under basic conditions

(10% NaOH solution) underwent a retro-addition reaction

enabling recovery of aldehydes.⁹On the basis of this investi-

gation, Baylis developed conditions for an analogous depro-

tection method for 1-hydroxy-1-methylethylphospho-

nates/phosphinates

and

1-hydroxy-1-methylethyl-H-

phosphinates.¹⁰Later, a similar process of deformylation of

-hydroxymethylphosphine-boranes in the presence of

KOH or under thermal conditions was described by Imamoto

in 2000.¹¹

In the same paper, an even more important approach

based on oxidative degradation of a hydroxymethyl moiety

was presented.¹¹The decarboxylation of (R)-(adaman-

tyl)hydroxymethyl(methyl)phosphine-borane using RuCl₃/

K₂S₂O₈/KOH enabled access to the corresponding secondary

phosphine-borane with excellent enantioselectivity and

high yield. Later, a further precedent for the use of this pro-

cedure was reported by Buono where oxidative removal of

the hydroxymethyl group in the case of adamantyl (hy-

droxymethyl)phenylphophinous acid-borane was effected

with good yield and diastereoselectivity.¹²

An equally significant impact on the field of oxidative

degradation processes was reported in a methodology in-

troduced in 2012 by Montchamp’s group.¹³They described

another useful reagent, (hydroxymethyl)-H-phosphinic

acid (prepared from H₃PO₂and paraformaldehyde), the hy-

droxymethyl moiety of which could be oxidatively un-

masked to provide the corresponding H-phosphinate. In

contrast to Imamotos’s decarboxylation process, this proto-

col features a Kim–Corey removal of the hydroxymethyl

group proceeding via decarbonylation. This method

Key words alkylation, chemoselectivity, protecting group, in situ

deprotection, phosphinite-boranes, phosphonite-boranes, diastereo-

selectivity

During the last 40 years, methods based on the tempo-

rary protection of P–H bonds have slowly been developed

into a powerful synthetic strategy for the preparation of or-

ganophosphorus compounds.¹First, Gallagher²and others³

introduced the ‘Ciba-Geigy reagents’ (in which one P–H

bond of hypophosphorous acid is masked temporarily), and

these were extensively explored for the syntheses of many

phosphonic and phosphinic acid derivatives,⁴some of them

for biological purposes.^3c,4dLater, Hall employed these com-

pounds in an elegant preparation of non-symmetrical sec-

ondary phosphine oxides.⁵An interesting example of the

deprotection of Ciba-Geigy reagents was presented by

Baylis, who proved that removal of a ketal protecting group

could be achieved using TMSCl in chloroform, in contrast to

acetals which were not reactive under the same condi-

tions.⁶

Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

2411

K. Modzelewski, S. Sowa

Paper

Synthesis

allowed a large-scale preparation of diastereomerically

pure L-menthyl (hydroxymethyl)-H-phosphinate [a chiral

equivalent of an alkyl phosphinate, ROP(O)H₂],¹⁴which was

shown to be a versatile intermediate for the synthesis of P-

stereogenic compounds.¹⁵

for the functionalization of -hydroxyphosphine-boranes.²⁸

Buono²⁹has developed an enantioselective alkylation

methodology that uses P-stereogenic -hydroxyalkyl-

phosphine-boranes as precursors for

a synthetically

demanding class of optically active secondary phosphine-

The above examples suggest that temporary masking of

a P–H group can solve problems of chemoselectivity during

transformations of hypophosphites and other organophos-

phorus compounds. A further advantage is that the protect-

ing moiety can be re-introduced in a later step. An alterna-

tive strategy is to use masked species and cleave them in

situ under reaction conditions that allow the typical reac-

tivity of P–H-type compounds to be expressed. In 1977,

Whitham and Postle reported the unexpected formation of

1,2-bis(diphenylphosphinoyl)ethane after treatment of di-

phenyl(hydroxymethyl)phosphine oxide with n-BuLi and

Br₂.¹⁶Subsequently, Cristau observed the same retro-

formylation process as a step in the reaction of diphenyl-

boranes³⁰(Scheme 1, C).

Imamoto 2000¹¹

BH₃

P

BH₃

P

KOH (3 equiv.)

OH

A

PhMe, 80 °C, 5 h

Ad

Me

Ad

Me

H

11%, 93% ee

99% ee

Kann 2012²⁴

BH₃

P

BH₃

NaH, KI, EtBr

DMF, rt, 5 h

+

OEt

OH

P

B

R

Me

Et

Me

19–28%

Me

R = t-Bu, Ph

major product

(racemic)

Buono 2016²⁹

BH₃

P

BH₃

P

1. NaH, 2. RX

(hydroxymethyl)phosphine

oxide

with

diphenyl-

OH

t-Bu

Ph

C

R

t-Bu

Ph

THF, 0 °C to rt

24 h

(vinyl)phosphine oxide, also leading to the formation of

Me

1,2-bis(diphenylphosphinoyl)ethane.¹⁷

30–87%, up to 99% ee

er 95:5, dr = 1:1

Later, in situ deprotection became an intentional syn-

thetic tactic enabling generation of the desired P anions or

radicals, which could be smoothly and immediately reacted

under the utilized reaction conditions. For example, Yuan

showed that 1,1-diethoxyalkylphosphinates could be con-

verted into phosphonates or phosphonamides in one-pot

reactions that proceed through the H-phosphinate.¹⁸

During the last few years, a number of organophospho-

rus compounds possessing the hydroxyalkyl moiety have

been used more extensively. -Hydroxyalkylphosphonates

have been employed for palladium-¹⁹and rhodium-

catalyzed²⁰phosphonation of C(sp²)–H bonds. Meanwhile,

Hayashi and co-workers have also presented a palladium-

catalyzed P–C coupling reaction using (hydroxymethyl)di-

phenylphosphine sulfide as a Ph₂P(S)H equivalent.²¹Re-

cently, Chen performed a P–C bond cleavage and radical

alkynylation of -hydroxyalkyl/phosphonic/phosphinic

acid derivatives and -hydroxyalkylphosphine oxides.²²

In early studies, the reverse additions to carbonyl com-

pounds of -hydroxyphosphine-boranes were observed by

Imamoto¹¹and others²³under thermal, basic and oxidative

(as mentioned before) conditions, and all of these cases

were found to be compatible with the formation of the ex-

pected products featuring P–H bonds (Scheme 1, A). Kann

and co-workers were the first to employ such reactivity as

part of an in situ P-alkylation process, through the reaction

of tertiary -hydroxyphosphine-boranes with an electro-

phile in the presence of a base (Scheme 1, B).²⁴

Buono 2019³¹

1. NaH

2. NIS

3. RNH₂

BH₃

P

R

P

OH

D

THF, 0 °C to rt

1 h

t-Bu

Ph

t-Bu

Ph

N

H

Me

er 95:5, dr = 1:1

40–81%, up to 88% ee

Scheme 1 Reported examples using an -hydroxyalkyl group as a

masking group in the P-alkylation of phosphine-boranes

In 2019 the same group used an analogous synthetic

route to allow the synthesis of enantiomerically pure

aminophosphine-boranes that involved the umpolung of an

in situ generated P-anion (Scheme 1, D).³¹

Herein, we present our results concerning the alkylation

of phosphinite-boranes and phosphonite-boranes; these

are readily available via a recently reported chemoselective

reduction of the P=O bond in -hydroxyphosphonates and

-hydroxyphosphinates.^12,28b,d,32To the best of our knowl-

edge, there are only a few precedents for the direct alkyla-

tion of (RO)₂P(BH₃)H⁸and (RO)RP(BH₃)H,^12,33presumably

because of the poor availability of these species. Our meth-

od provides a promising pathway for overcoming this prob-

lem.

We began our study with the synthesis of a series of

-hydroxyphosphonite-boranes 5a,b and -hydroxyphos-

phinite-boranes 6a,b. These are accessible through an

Abramov reaction of compounds 1 and 2 with acetone or

cyclohexanone leading to the corresponding phosphonates

3a,b and phosphinates 4a,b in moderate yields (see the

Supporting Information). A subsequent chemoselective re-

duction of the P=O bond in presence of ester bonds in 3 and

4 afforded phosphonite/phosphinite-boranes 5 and 6 in

good yields (Scheme 2).³²Unfortunately, the yields achieved

on gram scale for 5a,b were lower than those reported

Pioneered by Köster²⁵and continued by Keglevich²⁶and

others,²⁷the employment of borane complexes as reducing

agents for P=O bonds has opened new synthetic routes to

phosphine-boranes. In the same way, the synthetic access

to -hydroxyphosphine-boranes has been improved recent-

ly, which enhances the potential of retro-addition reactions

2412

K. Modzelewski, S. Sowa

Paper

Synthesis

We used sodium hydride as the base for the initial test

O

P

reactions because it has been used regularly in earlier de-

carbonylative eliminations.^24,30,31When compound 5a was

treated with an equimolar amount of NaH, even after 16

hours, it appeared that the starting material was not fully

consumed in typical solvents (Et₂O, PhMe, THF) (Table 1,

entries 1, 3 and 5). In Et₂O and PhMe, we observed the for-

mation of an inseparable mixture of 8 (with a shift of 94.24

ppm in the ³¹P NMR spectrum) and the H-phosphonite-bo-

rane 9 (with a shift of 121.8 ppm) rather than the expected

product 7a or its O-alkylation product (Table 1, entries 1

and 3). However, products 8 and 9 are both derived from

the desired P-anion: acid 8 is presumably formed through

its oxidation, whilst 9 is its protonation product. In THF, 5a

underwent partial deprotection–alkylation but the desired

phosphonite-borane 7a was obtained in only 10% yield (iso-

lated) along with 8 and 9 (not isolated). Nonetheless, these

preliminary results suggested that compound 5a was a po-

tentially good precursor of the P-anion, and that the P–C

bond in -hydroxyphosphonite-borane 5a may be far more

labile than has been found for other phosphine-boranes.²¹

Using 1.5 equivalents of base in PhMe, Et₂O and THF led to

complete conversion of 5a and shifted the selectivity of the

reaction towards the formation of 7a (Table 1, entries 2, 4

and 6). It should be noted, however, that the desired

R¹O

H

1, 3, 5: R¹= i-Pr, R²= i-PrO

2, 4, 6: R¹= Et, R²= Ph

a: R³= R⁴= Me

R²

1,2

O

b: R³–R⁴= –(CH₂)₅–

R³

R⁴

BH₃

O

P

R³

R⁴

BH₃·THF (10 equiv)

THF, 60 °C, 24 h

R³

R⁴

P

R¹O

R²

OH

3a 74%

3b 37%

4a 64%

4b 38%

5a 50%

5b 53%

6a 67%

6b 69%

Scheme 2 Synthesis of -hydroxyphosphonite/phosphinite-boranes

previously³²due to the instability of these compounds

during extraction. Still, our two-step procedure provides

precursors 5 and 6 that can be stored at –20 °C for long pe-

riods of time. To develop the most selective conditions for

the alkylation reaction, an optimization study was under-

taken. Compound 5a was used as the model starting mate-

rial with benzyl chloride as the electrophile (Table 1).

Table 1 Optimization of the Conditions for the Reaction of 5a with Base and Benzyl Chloride

BH₃

P

BH₃

P

BH₃

P

1. NaH

2. PhCH₂Cl (1.2 equiv)

BH₃

P

and/or

Ph

i-PrO

OH

Me

i-PrO

OH

H

conditions

Me

5a

7a

8

9

Yield (%)^a,b

Entry

Base (equiv)

Conditions

7a

8

9

1^c

2

NaH (1.0)

NaH (1.5)

NaH (1.0)

NaH (1.5)

NaH (1.0)

NaH (1.5)

NaH (1.0)

NaH (1.5)

DIPEA (1.5)

DBU (1.0)

Et₂O, 0 °C to 25 °C, 16 h

PhMe, 0 °C to 25 °C, 16 h

THF, 0 °C to 25 °C, 16 h

DMF, 0 °C to 25 °C, 40 min

MeCN, 25 °C, 4 h

–

0 (44)

0 (11)

0 (15)

0 (49)

0 (11)

–

15 (25)

–

0 (62)

0 (36)

–

3^c

4

40 (51)

10 (25)

58 (90)

28 (60)

38 (60)

37 (64)

72 (90)

–

5^c

6

0 (60)

–

7

0 (20)

0 (30)

0 (34)

–

0 (15)

trace

–

8

9^d

10^e

11

12

–

THF, 25 °C, 24 h

–

^aYields of isolated products.

^bNumbers in parentheses indicate yields according to ³¹P NMR spectroscopy.

^cStarting material 1a was still present in the reaction mixture.

^dPure NaH (95%) was used.

^eThe base was added after addition of the electrophile

2413

K. Modzelewski, S. Sowa

Paper

Synthesis

compound 7a was the major product only in THF and could

only be isolated in moderate yield (58%) (Table 1, entry 6).

Given these results, and the earlier work of Kann et al.

showing the beneficial effect of DMF on the P-alkylation of

phosphidoboranes that are transiently generated from hy-

droxymethylphosphine-boranes (Scheme 1, B),²⁴we were

led to screen this solvent. When the reaction was carried

out in DMF, total conversion of the starting material was

observed after 40 minutes, even when a stoichiometric

amount of base was used, and subsequent reaction with the

electrophile led predominantly to 7a (Table 1, entry 7).

Increasing the amount of base to 1.5 equivalents result-

ed in a higher yield of the P-alkylation product (38%) (Table

1, entry 8), although byproducts 8 and 9 were still ob-

served. Even using dry NaH did not limit the formation of 8

(Table 1, entry 9). After a number of further unsuccessful at-

tempts to prevent the partial oxidation of the in situ gener-

ated anion, we reversed our standard procedure and added

the base after the addition of the electrophile. This provided

the product in 72% yield without the formation of signifi-

cant amounts of acid 8 (Table 1, entry 10). Unfortunately, in

both protocols, purification of the crude reaction mixture

was accompanied with partial loss of 7a that was even

more severe when extraction was involved (Table 1, entries

6 and 10). It should be noted that reactions carried out with

organic bases such as DBU or DIPEA⁷did not give any prod-

uct, and in these cases the starting material was recovered

unchanged (Table 1, entries 11 and 12). Subsequent studies

therefore employed the conditions used for entries 6 and

10, in THF and DMF respectively. These appear to be the

most appropriate solvents for the transformation.

Once optimization had been completed, we decided to

check the reactivity of 5a towards other electrophiles using

both sets of conditions (Table 2) (see Table 1, entry 6 for

conditions A and entry 10 for conditions B). The use of a

more hindered benzyl halide (Table 2, entry 2) showed no

influence upon the reaction selectivity in DMF and provid-

ed 7c in 83% yield. When 5a was treated with MeI according

to conditions B, the main observed reaction product was 7b

that was isolated in 53% yield (Table 2, entry 8). The same

excellent chemoselectivity was observed when the reaction

was carried out in DMF (Table 2, entry 3). However, in this

Table 2 Reactivity of Compounds 5a,b under Optimized Reaction Conditions

BH₃

P

BH₃

P

BH₃

P

BH₃

P

BH₃

P

BH₃

P

Me

A or B

and/or

Ph

and/or

OH

i-PrO

OH

i-PrO

E

O

Ph

OH

2

R¹

R

Ph

5a R¹= R²= Me

5b R¹–R²= –(CH₂)₅–

7a–c

8

10

11

12

A: EX (1.2 equiv), NaH (1.5 equiv), DMF, 0 °C, 3 min, then 0–25 °C, 40 min

B: EX (1.2 equiv), NaH (1.5 equiv), THF, 0 °C, 3 min, then 0–25 °C, 16 h

Entry

Reactant

EX

PhCH₂Cl

Conditions

Product

Yield (%)^a,b

1

5a

A

7a

7b

7c

72 (90)

83 (90)

0 (100)

2

2-MeC₆H₄CH₂Cl

MeI

3^c

4

PhCHO

10

8

54 (70)

0 (30)

5

6

5b

PhCH₂Cl

PhCHO

A

7a

85 (93)

10

8

49 (59)

0 (41)

7

5a

PhCH₂Cl

MeI

B

7a

7c

58 (90)

53 (90)

8

9^d

PhCHO

10

12

16

31

10

5b

PhCH₂Cl

PhCHO

B

7a

8

37 (59)

0 (41)

11^c

11

10

61

33

^aYields of isolated products.

^bNumbers in parentheses indicate the yields according to ³¹P NMR spectroscopy.

^cEX (1.5 equiv) was used.

^dYields according to ¹H NMR spectroscopy. Compounds 10 and 12 were isolated as a mixture.The major isomer (7%) was separated from a mixture of 10 and 12.

Compound 12 was obtained as mixture of geometric isomers (ratio = 1:0.81). The stereochemistry of the geometric isomers of 12 was not defined. The appear-

ance of the C=CH group in the ¹H NMR spectra of both diastereoisomers is very similar and did not give clear insight in the stereochemistry of the structure of

geometric isomers.

2414

K. Modzelewski, S. Sowa

Paper

Synthesis

BH₃

P

BH₃

P

BH₃

P

BH₃

P

NaH

PhCHO

NaH

O

P

OH

Na

i-PrO

OH

i-PrO

Ph

O

path A

–

Me

Ph

Me

5a

11

10

phospho-Fries rearrangement

NaH

aldol reaction

PhCHO

BH₃

P

BH₃

O

OH

Ph

O

P

O

i-PrO

O

Ph

i-PrO

E1cB

Ph

Me

Ph

Me

path B

12 (cis + trans)

O

Michael addition

phospho-Fries rearrangement

Ph

Scheme 3 Proposed mechanism of the formation of products 10 and 12

case, because 7b is volatile, the product was completely lost

during removal of the solvent. Attempted alkylation of the

more hindered phosphonite-borane 5b with benzyl chlo-

ride was achieved successfully in DMF with the same selec-

tivity as for 5a (85% yield of 7a) (Table 2, entry 5). However,

when the solvent was changed to THF, compound 7a was

obtained as a mixture with 8, of which 7a was isolated in

only 37% yield (Table 2, entry 10). Finally, we wanted to

check the addition of an in situ generated P-anion to a car-

bonyl group. Unexpectedly, the outcome of the reaction

with benzaldehyde appeared to depend on both the reac-

tion conditions and the structure of the ketone leaving from

5 (Table 2, entries 4, 6, 9 and 11). When compound 5a was

subjected to reaction with a base and subsequently with

benzaldehyde in THF, a mixture of 10 and 12 was obtained

Next, we investigated the structurally similar -hy-

droxyphosphinite-boranes 6 possessing a single ester group

at phosphorus. Initially, we decided to check both protocols

to choose the most appropriate set of conditions for the re-

action of 6a (Table 3). Compound 6a proved to be more

prone to unmasking and in situ alkylation with benzyl chlo-

ride than 5a, and it reacted well in the presence of a stoi-

chiometric amount of base (Table 3, entries 1 and 3). The

use of 1.5 equivalents of sodium hydride lowered the reac-

tion selectivity in both THF and DMF (Table 3, entries 2 and

4). Thus, the best chemoselectivity towards P-alkylation

was observed when a 1:1 ratio of 6a/NaH was used, with

the reaction of benzyl chloride with 6a leading exclusively

to 13a, which was isolated in 76% yield (Table 3, entry 1).

1

(16% and 31%, respectively, according to the H NMR spec-

Table 3 Optimization of the Ratio of 6a/NaH in the Reaction of 6a

with Benzyl Chloride

trum) (Table 2, entry 9). Compound 10 results from the ex-

pected P-anion addition to the carbonyl group and a subse-

quent phospho-Fries rearrangement (Scheme 3, path A).³⁴

Formation of product 12 (as a mixture of cis/trans isomers)

was unexpected (Scheme 3, path B); it seems that 4-phen-

ylbut-3-en-2-one was formed in an initial aldol condensa-

tion of acetone with benzaldehyde, and this Michael accep-

tor then reacted with the P-anion to form an adduct that

also underwent phospho-Fries rearrangement³⁴to give the

two isomers of the phosphorus ester 12 (Scheme 3, path B).

Subjecting 5a to the same reaction under conditions A led

predominantly to 10 (in a mixture with 8), which was iso-

lated in 54% yield (Table 2, entry 4). An analogous reaction

sequence from 5b revealed similar selectivity and provided

10 (49%) in a mixture with 8 (not isolated) (Table 2, entry

6). Surprisingly, when 5b was treated with benzaldehyde

under conditions B, the selectivity changed dramatically. In

this case the major species observed in the crude NMR

spectrum was the desired product 11 (~90%) along with

traces of ester 10 (Table 2, entry 11). However, an aqueous

work-up promoted the transformation of product 11 into

10, so that 11 and 10 were finally isolated in respective

yields of 61% and 33%.

1. NaH

2. PhCH₂Cl (1.2 equiv)

BH₃

P

BH₃

P

Ph

OH

Me

Ph

EtO

Ph

EtO

A or B

Me

6a

13a

A: DMF, 0 °C, 3 min, then 0 to 25 °C, 40 min

B: THF, 0 °C, 3 min, then 0 to 25 °C, 16 h

Entry

NaH (equiv)

Conditions

Yield of 13a (%)^a,b

1

2

3

4

1.0

1.5

1.0

1.5

A

B

76 (100)

44 (48)

59 (72)

48 (52)

^aYield of isolated product.

^bNumbers in parentheses indicate the yields according to ³¹P NMR spec-

troscopy.

The data collected in Table 4 indicates that most alkyl

halides are highly reactive in the alkylation of P-anions that

are formed in situ from 6a under the optimized conditions.

In most cases, conversion is high, and moderate to high

yields of 13a–f were obtained (Table 4, entries 1–9). Inter-

2415

K. Modzelewski, S. Sowa

Paper

Synthesis

estingly, when 2,4′-dichlorobenzophenone was used as the

electrophile with 6a, two products, 13g and 14, were isolat-

ed in yields of 24% and 64%, respectively. Once again, the

formation of 14 (Table 4, entry 10) can be attributed to a

phospho-Fries rearrangement³⁴analogous to those ob-

served in the case of 5a and benzaldehyde (see Table 2, en-

tries 4, 6, 9 and 11). We also checked the reactivity of inac-

tivated electrophiles in the P-alkylation reaction. When

i-PrBr was used in the reaction with 6a, the selectivity of

the reaction decreased, although complete conversion of 6a

was achieved and the expected product 13d was isolated in

a modest yield (Table 4, entry 6). In sharp contrast to i-PrBr,

subjecting i-PrOTs to the reaction with 6a resulted in a

complex mixture (Table 4, entry 7). In this case, product

13d was formed in poor conversion (12%) according to the

³¹P NMR spectrum of the crude reaction mixture.

Subsequently, we increased the steric crowding around

the  carbon of the nucleophile precursor to investigate any

potential effect upon the reaction outcome. It was found

that the cleavage of cyclohexanone from 6b and subsequent

alkylation with benzyl chloride was as efficient as the cor-

responding acetone elimination from 6a; thus, phosphinite-

borane 13a was obtained in 70% yield (Table 4, entry 13).

However, when i-PrI was chosen as the electrophile, the

starting material was not fully consumed and the product

13d was isolated in a much lower 44% yield (Table 4, entry

14). Furthermore, the reaction of 6a with benzaldehyde un-

der these conditions showed lower selectivity (Table 4, en-

try 11) than was observed with 5a and 5b (see Table 2, en-

tries 4, 6, 9 and 11). The only product detected was 15; this

again must be assumed to arise from the Michael addition

of the P-anion to in situ generated 4-phenylbut-3-en-2-one

(from the aldol condensation of acetone and benzaldehyde)

Table 4 Scope of the P-Alkylation of Compounds 6a,b

BH₃

P

BH₃

P

BH₃

P

BH₃

P

BH₃

P

1. NaH (1.0 equiv)

2. EX (1.2 equiv)

Ph

and/or

Ph

EtO

OH

OEt

Ph

EtO

Ph

EtO

Ph

EtO

Ph

EtO

E

O

P

A or B

2

R¹

R

Ph

15

O

BH₃

Cl

6a R¹= R²= Me

6b R¹–R²= –(CH₂)₅–

13a–g

14

16

A: DMF, 0 °C, 3 min, then 0 to 25 °C, 40 min

B: THF, 0 °C, 3 min, then 0 to 25 °C, 16 h

Entry

Reactant

EX

Conditions

A

Product

Yield (%)^a,b

1

2

6a

6b

6a

PhCH₂Cl

13a

13b

13c

13d

13e

13f

13g

15

76 (100)

62 (100)

83 (100)

63 (100)

55 (90)

43 (82)

0 (12)

2-MeC₆H₄CH₂Cl

MeI

A

B

3

4^c

i-PrI

5

i-PrI

6

i-PrBr

7^d

i-PrOTs

8^d

CH₂=CHCH₂Br

MeOCH₂Cl

ClCH₂C(O)C₆H₄Cl-p

PhCHO

79 (90)

65 (100)

24

9^c

10^e

11^f

12

13

14^c,d

15^g

16

7 (10)

ethylene oxide

PhCH₂Cl

16

13

13a

13d

15

70 (100)

44 (85)

30 (33)

26

i-PrI

PhCHO

ethylene oxide

16

^aYield of isolated product.

^bNumbers in parentheses indicate the yields according to ³¹P NMR spectroscopy.

^cEX (1.5 equiv) was used.

^dStarting material 6a was still present in the reaction mixture.

^eCompound 13g was obtained in a mixture with 14 (isolated in 64% yield).

^fCompound 15 was obtained and isolated as a mixture of diastereoisomers (dr = 1:0.53 according to the ¹H NMR spectrum).

^gCompound 15 was obtained and isolated as a mixture of diastereoisomers (dr = 1:0.48 according to the ¹H NMR spectrum).

2416

K. Modzelewski, S. Sowa

Paper

Synthesis

BH₃

P

BH₃

P

BH₃

P

BH₃

P

BH₃

P

Ph

–

Na

BH₃

Ph

EtO

O

R

Ph

NaH,

EtO

6a

P

Ph

EtO

P

R

OEt

Ph

EtO

OH

Me

Ph

EtO

Ph

P

O

EtO

BH₃

Me

BH₃

16

P

6a

R

Ph

O

Scheme 4 A plausible mechanism for the formation 16 via a -hydroxyphosphinite-borane; R = C(Me)₂OH

and was isolated in 7% yield. The use of conditions B in-

creased the yield of 15 to 30% (Table 4, entry 15). Attempted

reaction of 6a with ethylene oxide failed to afford the ex-

pected -hydroxyethyl-substituted product. Instead, we ob-

served the formation of 16 which was isolated in 13%

(when using DMF as the solvent) and 26% (using THF) yields

(Table 4, entries 12 and 16). We propose that compound 16

is formed according to the mechanism depicted in Scheme

4. First, the in situ formed P-anion undergoes reaction with

ethylene oxide to give the corresponding alkoxide anion,

subsequent reaction of which with another molecule of 6a

leads transiently to a diphosphorus-containing intermedi-

ate. This reacts with a further P-anion to afford the isolated

product 16.

P-Stereogenic phosphinates were obtained from (R_P)-17,

which had been prepared in 45% yield (dr = 97:3) according

to the procedure reported by Mislow³⁵and Han³⁶(Scheme

5, step a) (see the Supporting Information). (R_P)-17 then re-

acted with acetone and with cyclohexanone (Scheme 5,

step b) to afford the -hydroxyphosphinates (S_P)-18a and

(S_P)-18b, respectively, in good yields and with excellent ste-

reoselectivity.^32b

Reduction of (S_P)-18a and (S_P)-18b (Scheme 5, step c)

with 5 equivalents of BH₃·SMe₂at 50 °C for 16–18 hours

proceeded with complete chemoselectivity and led to the

complete conversion of the starting material in both cases.

The expected phosphinite-boranes (R_P)-19a and (R_P)-19b

were isolated as single diastereoisomers (determined on

the basis of ³¹P NMR spectroscopy) in 76% and 70% isolated

yields, respectively. Their configurations were estimated on

the basis of previous reports which described the reduction

with BH₃complexes as a stereoinvertive process.^12,28b,d,32

Having in hand P-stereogenic -hydroxyphosphinite-

boranes (R_P)-19a and (R_P)-19b, we turned our attention to

address the important question of diastereoselectivity in

the P-alkylation process (Table 5). Diastereoselective trans-

formations of these molecules would provide a valuable al-

ternative to literature methods, which involve either direct

alkylation³³or oxidation–substitution¹²approaches. De-

spite the fact that compounds of type 19 are achieved in a

three-step synthesis (Scheme 5), their advantage is that

they can be stored at –20 °C for prolonged periods without

loss of stereochemical information, and this makes them

good precursors for other key P-stereogenic compounds.

It was reassuring to find that 19a provided product 20a

in a completely chemo- and diastereoselective fashion

within 40 minutes at 0 °C after treatment with benzyl chlo-

ride (Table 5, entry 1). For comparison, an analogous syn-

thesis was attempted in THF over 16 hours. In the presence

of one equivalent of base, it was found that the selectivity of

the P-alkylation reaction was dramatically lower, and a

mixture containing 19a and 20a (isolated in 43% yield)

along with two other undetermined products was obtained

(Table 5, entry 2). Increasing the quantity of NaH to 1.5

equivalents in the same solvent allowed the chemoselectiv-

ity to be shifted towards 20a, but it was still obtained as a

mixture of diastereoisomers in a 1:0.28 ratio and in 98%

yield (Table 5, entry 3). These results appear to confirm that

the reactions carried out in DMF provide the most appro-

priate conditions for obtaining products 20 diastereoselec-

tively.

PhPCl₂

a

O

P

O

P

R¹

R²

R¹

R²

L-MenthylO

Ph

H

L-MenthylO

b

Ph

OH

(R_P)-17 45%

(dr = 97:3)

(S_P)-18a (1 diastereomer) 78%

(S_P)-18b (1 diastereomer) 53%

a: R¹= R²= Me

b: R¹–R²= –(CH₂)₅–

BH₃·SMe₂(5 equiv)

c

THF, 50 °C, 16–18 h

BH₃

P

R¹

R²

Ph

L-MenthylO

OH

(R_P)-19a (1 diastereomer) 76%

(R_P)-19b (1 diastereomer) 70%

When methyl iodide was used as the electrophile in re-

actions with 19a under the optimized conditions, the con-

version of the starting material was lower and product 20c

was isolated in a modest 63% yield (Table 5, entry 4). How-

ever, nearly quantitative formation of 20c (83% isolated

Scheme 5 Synthesis of -hydroxyphosphonite/phosphinite-boranes

2417

K. Modzelewski, S. Sowa

Paper

Synthesis

Table 5 Diastereoselective P-Alkylation of Compounds 19a,b

BH₃

P

BH₃

P

NaH/EX

P

OH

R²

and/or

Ph

L-MenthylO

Ph

L-MenthylO

E

Ph

H

DMF, 0 °C, 3 min

DMF, 0 °C, time

R¹

L-MenthylO

19a R¹= R²= Me

19b R¹–R²= –(CH₂)₅–

21

20a,c–f

Entry

Reactant

NaH (equiv)/EX (equiv)

Time

40 min

Product

Yield (%)^a,b

1

2^c

3^c

4^d

5^d

6^d

7

(R_P)-19a

NaH (1.0)/PhCH₂Cl (1.2)

NaH (1.5)/PhCH₂Cl (1.2)

NaH (1.0)/MeI (1.2)

(S_P)-20a

20a

98 (100)

43 (45)

16 h

98 (100, dr = 1:0.28)

63 (70)

40 min

2 h

(S_P)-20c

(S_P)-20d

(S_P)-20e

NaH (1.0)/MeI (2.0)

83 (93)

NaH (1.0)/i-PrI (1.5)

68 (70)

NaH (1.05)/i-PrI (2.5)

80 (100)

45 (77)

8^d

9

NaH (1.05)/i-PrBr (2.5)

NaH (1.05)/i-PrOTs (2.5)

NaH (1.05)/CH₂=CHCH₂Br (1.5)

NaH (1.0)/MeOCH₂Cl (1.2)

2 h

0 (10)

10^d

2 h

80 (90)

11^d,e,f

40 min

(R_P)-20f

21

20 (30)

11 (15)

12^d,g

13

(R_P)-19a

(R_P)-19b

NaH (1.05)/MeOCH₂Cl (2.5)

NaH (1.0)/PhCH₂Cl (1.2)

NaH (1.05)/MeI (2.5)

2 h

40 min

1 h

(R_P)-20f

(S_P)-20a

(S_P)-20c

(S_P)-20d

(S_P)-20e

44 (57)

85 (100)

91 (98)

66 (71)

66 (75)

14^d

15^d

16^d

NaH (1.05)/i-PrI (2.5)

2 h

NaH (1.05)/CH₂=CHCH₂Br (2.5)

2 h

^aYield of isolated product.

^bNumbers in parentheses indicate the yields according to ³¹P NMR spectroscopy.

^cReaction was carried out in THF.

^dStarting material was still present in the reaction mixture.

^eCompounds 20e and 21 were isolated as a mixture.

^fYield according to ¹H NMR spectroscopy.

^gTraces of 21 were observed in the crude reaction mixture but not isolated.

yield) was achieved upon treatment of 19a with 2 equivalents

of MeI (Table 5, entry 5). Difficulties in effecting full conver-

sion of the starting material were also observed with other

electrophiles. The use of a secondary alkyl iodide (i-PrI) in

the reaction with 20a led to only 70% of the product in the

crude reaction mixture (according to ³¹P NMR spectrosco-

py), from which the desired product 20d was isolated as a

single diastereoisomer in 68% yield (Table 5, entry 6). To ob-

tain complete conversion of 19a in the reaction with iso-

propyl iodide, we increased the amount of base and electro-

phile; this allowed us to prepare 20d as the sole product in

80% isolated yield (Table 5, entry 7). In turn, when i-PrBr

was used as the electrophile in the reaction with 19a under

the same conditions, the conversion of the starting material

was not complete and the product 20d was isolated in 45%

yield (Table 5, entry 8). The worst performance of com-

pound 19a in an alkylation was observed with i-PrOTs. In

this reaction 10% of 20d was observed in the ³¹P NMR spec-

trum of the crude reaction mixture (Table 5, entry 9). An

analogous reaction of 19a with allyl bromide afforded 20e

in 80% yield in the presence of 1.5 equivalents of the elec-

trophile (Table 5, entry 10). Poor performance in the alkyla-

tion of 19a was evident in the reaction with MeOCH₂Cl

(MOMCl). In this case, our standard conditions gave a mix-

ture containing unreacted compound 19a along with prod-

ucts 20f and 21, isolated as a mixture that provided 20% and

11% yields, respectively (according to the ¹H NMR spec-

trum) (Table 5, entry 11). Unfortunately, even under im-

proved conditions, compound 19a provided 20f in only 44%

yield (Table 5, entry 12). However, compound 19b showed

good selectivity in the in situ alkylation process; prior addi-

tion of benzyl chloride along with one equivalent of the

base allowed the desired product 20a to be isolated in 85%

yield (Table 5, entry 13). Reactions of 19b with other elec-

trophiles were also performed under the modified condi-

tions (Table 5, entries 14–16). In the reaction of 19b with

MeI, the starting material was nearly fully consumed after 1

hour and product 20c was obtained in a very high 91% yield

(Table 5, entry 14). Unlike 19a, treatment of 19b with

isopropyl iodide or allyl bromide led to only a 71–75%

2418

K. Modzelewski, S. Sowa

Paper

Synthesis

conversion of the starting material after 2 hours, and both

20d and 20e were obtained in moderate yields (Table 5, en-

tries 15 and 16). These results suggest that the basic cleav-

age of cyclohexanone from 19b is slower than that of ace-

tone from 19a (Table 5, entries 6 and 15). It appears also

that overall ketone cleavage reflects the reactivity of the

electrophile used in the P-alkylation reaction.

a base has also been demonstrated. The configurational sta-

bility of P-stereogenic -hydroxyphosphinite-boranes

under the described reaction conditions makes them useful

precursors that can be converted into key P-stereogenic

species with high stereospecificity.

It is noteworthy that all the products of the reactions

carried out in DMF were obtained as single diastereoiso-

mers, both observed in the crude reaction mixtures and

isolated as the sole diastereoisomers (determined on basis

of ³¹P NMR spectroscopy).

According to the literature, direct alkylation of

Ph(MenthylO)P(BH₃)H at phosphorus proceeds with reten-

tion of configuration, with the P-anion being responsible for

the attack at the electrophile.^33aIt is also important to note

that removal of the hydroxymethyl group under oxidative

conditions from a P-stereogenic adamantyl (hydroxymethyl)-

phenylphophinous acid-borane had no influence on the

configuration at the phosphorus atom.¹²

All reactions were performed under an argon atmosphere using

Schlenk techniques. Anhydrous solvents were used, and glassware

was heated under vacuum prior use. All chemicals were used as re-

ceived unless noted otherwise. Solvents for chromatography and

crystallization were distilled once before use and the solvents for ex-

traction were used as received. THF, Et₂O and toluene were distilled

from sodium/benzophenone ketyl under argon. Caution! All reac-

tions and column chromatography must be carried out in an efficient

fume hood because of the irritating odor accompanying the isolation

process. Thin-layer chromatography (TLC) was performed with Merck

precoated silica gel plates and samples were visualized under UV light

or with KMnO₄solution or iodine. The reaction products were puri-

fied by column chromatography over Fluka silica gel (60–240 mesh),

Merck basic Al₂O₃(70–230 mesh) or Merck neutral Al₂O₃(70–230

mesh).

Overall, it appears reasonable to expect that a P-anion is

generated slowly during our protocols and that it is gradu-

ally alkylated with the electrophile. This is supported by the

presence of starting material in some cases after quenching

the reaction mixture. The dramatic differences in the reac-

tion times in THF and DMF might be explained by their sol-

vating properties. Less polar THF slowed the P-alkylation

process, which in turn resulted in longer reaction times.

This presumably allows side reactions to take place (e.g.,

protonation, oxidation). DMF is more polar than THF, which

leads to an increased rate of the alkylation process, even

with more bulky electrophiles (e.g., i-PrI).

In sharp contrast to the partial or complete racemiza-

tion of -hydroxyphosphine-boranes in DMF,^24,30(R_P)-19a

and (R_P)-19b exhibited enhanced configurational stability

of the in situ generated P-anion. This is consistent with ear-

lier observations from the Imamoto group; these showed

that this type of anion, generated via direct deprotonation

of Ph(MenthylO)P(BH₃)H in the presence of an excess of

base, is stable in THF at 0 °C and undergoes diastereoselec-

tive alkylation with MeI.^33aIt seems possible that the bulky

menthoxy substituent is responsible for the enhanced sta-

bility of these species.

Melting points were determined on a Büchi Melting Point M-560 ap-

paratus in a capillary tube and are uncorrected. Optical rotations

were measured on a Perkin Elmer 341LC polarimeter using a 1 mL cell

with a 10 mm path length and are reported as follows: []_D²⁵(c: g/100

mL, in solvent). IR spectra were recorded as solids or thin films on a

Thermo Scientific Nicolet iS50 FT-IR ATR fitted with a diamond prism

(4000–400 cm^–1window); only the strongest/structurally most im-

portant peaks (cm^–1) are listed. ¹H NMR, ¹¹B NMR, ¹³C NMR and ³¹P

NMR spectra were recorded on a Bruker Avance 500 spectrometer at

ambient temperature in CDCl₃unless otherwise noted. Chemical

shifts () are reported in ppm from tetramethylsilane with the solvent

as an internal standard (CDCl₃: 7.27 ppm for ¹H and 77 ppm for ¹³C).

Mass spectra were recorded on a Shimadzu GC-MS QP2010S mass

spectrometer in electron ionization (EI) mode. HPLC-HRMS was per-

formed on a Shimadzu HRMS ESI-IT-TOF instrument using a reverse-

phase stationary phase with water/MeCN (65:35) as eluent, electro-

spray ionization (ESI), and an IT-TOF detector. Elemental analyses

were recorded on a PERKIN ELMER CHN 2400.

Alkylation of -Hydroxyphosphinite-Boranes and -Hydroxy-

phosphonite-Boranes in THF; General Procedure B

To a Schlenk tube (25 mL) equipped with a magnetic stir bar and an

argon inlet was added -hydroxyphosphonite-borane 5 (0.25 mmol)

or -hydroxyphosphinite-borane 6 (0.25 mmol) in anhydrous de-

gassed THF (2 mL) and the resulting mixture was cooled to 0 °C using

an ice bath. NaH (15 mg, 0.375 mmol, 60% in mineral oil or 10 mg,

0.25 mmol, 60% in mineral oil) was added and the mixture was stirred

at the same temperature for 3 min. The electrophile (0.3 mmol) was

then added and the ice bath was removed. The reaction mixture was

stirred at room temperature for 16 h and then quenched by addition

of saturated NH₄Cl solution (1 mL) and extracted with CHCl₃(5 × 5

mL). The combined organic phases were dried over Na₂SO₄, filtered

and evaporated under reduced pressure. The residue was purified by

short (5 cm) column chromatography on neutral Al₂O₃using hex-

ane/EtOAc (40:1 v/v) or n-pentane/EtOAc (100:1 v/v) as the eluent.

In summary, we have presented an efficient method for

the in situ P-alkylation of -hydroxyphosphinite/phosphonite-

boranes in which the P–H bond is temporarily protected as

a hydroxyalkyl derivative. Two protocols for the synthesis of

alkyl phosphinite/phosphonite-boranes using a range of

electrophiles have been presented. A straightforward and

new diastereoselective approach allowing the alkylation of

P-stereogenic -hydroxyphosphinite-boranes under mild

conditions via a retro-Abramov reaction in the presence of

2419

K. Modzelewski, S. Sowa

Paper

Synthesis

Benzylphosphonous Acid-Borane Diisopropyl Ester (7a) (Table 2,

entry 7), General Procedure B

IR (ATR, thin film): 2980, 2394, 1685, 1141, 972, 784 cm^–1

.

¹H NMR (500 MHz, CDCl₃):  = 7.27–7.30 (m, 2 H), 7.20–7.23 (m, 3 H),

4.96–5.00 (m, 1 H), 4.70–4.77 (m, 2 H), 3.45 (d, J_P–H= 7.25 Hz, 2 H),

2.01–2.03 (m, 3 H), 1.35 (d, J_P–H= 5.99 Hz, 6 H), 1.29 (d, J_P–H= 6.31 Hz,

6 H), 0.25–0.85 (br m, 3 H).

¹³C NMR (125 MHz, CDCl₃):  = 144.8 (d, ²J_P–C= 7.3 Hz, C), 140.3 (s, C),

128.4 (d, J_P–C= 6.4 Hz, CH), 126.0 (s, CH), 113.9 (d, J_P–C= 6.4 Hz, CH),

72.2 (d, ²J_P–C= 3.6 Hz, CHO), 31.8 (s, CH₂), 23.9 (d, ³J_P–C= 3.6 Hz, CH₃),

23.8 (d, ³J_P–C= 4.5 Hz, CH₃), 21.2 (s, CH₃).

-Hydroxyphosphonite-borane 5a (0.056 g, 0.25 mmol) reacted with

PhCH₂Cl (0.3 mmol, 34.5 L) and NaH (15 mg, 0.375 mmol, 60% in

mineral oil) according to general procedure B to afford 7a (0.0368 g,

0.145 mmol, 58%) as a colorless oil.

R_f= 0.36 (hexane/EtOAc, 40:1).

IR (ATR, thin film): 2978, 2929, 2484, 1104, 974, 696 cm^–1

¹H NMR (500 MHz, CDCl₃):  = 7.23–7.30 (m, 5 H), 4.51–4.60 (m, 2 H),

.

³¹P NMR (202 MHz, CDCl₃):  = 109.26 (br m).

3.11 (d, J_P–H= 11.82 Hz, 2 H), 1.28 (d, J_H–H= 6.15 Hz, 6 H), 1.13 (d, J_H–H

=

6.15 Hz, 6 H), 0.15–0.82 (br m, 3 H).

Anal. Calcd for C₁₆H₂₈BO₃P: C, 61.96; H, 9.10. Found: C, 62.23; H, 9.32.

¹³C NMR (125 MHz, CDCl₃):  = 131.4 (d, J_P–C= 3.6 Hz, C), 130.4 (d,

³J_P–C= 5.5 Hz, CH), 128.4 (d, ¹J_P–C= 83.6 Hz, C), 128.1 (d, ⁴J_P–C= 2.7 Hz,

CH), 126.7 (d, ⁵J_P–C= 2.7 Hz, CH), 72.3 (d, ²J_P–C= 3.6 Hz, CHO), 39.5 (d,

¹J_P–C= 55.4 Hz, CH₂), 24.1 (d, ³J_P–C= 2.7 Hz, CH₃), 23.8 (d, ³J_P–C= 4.5 Hz,

CH₃).

2

12 (Minor Isomer) (Table 2, entry 9), General Procedure B

Isolated together with the major diastereoisomer and 10. Yield estab-

lished for both forms of 12–31% according to 1H NMR. 17% of 12 ma-

jor and 14% of 12 minor. R_f= 0.68 (hexane/EtOAc, 6:1).

³¹P NMR (202 MHz, CDCl₃):  = 139.44 (br m).⁸

¹¹B NMR (160 MHz, CDCl₃):  = –42.71 (br m).⁸

MS (EI, 70 eV): m/z (%) = 254 (1) [M]⁺, 240 (10) [M – BH₃]⁺, 149 (37),

139 (14), 121 (10), 107 (100), 92 (35), 91 (64), 65 (54).

HRMS (ESI): m/z [2 M – H]⁺calcd for C₂₆H₄₇B₂O₄P₂: 507.3125; found:

¹H NMR (500 MHz, CDCl₃):  = 7.30–7.36 (m, 2 H), 7.20–7.23 (m, 3 H),

5.40–5.50 (m, 1 H), 4.46–4.77 (m, 2 H), 3.37 (d, J_P–H= 8.04 Hz, 2 H),

2.00 (br s, 3 H), 1.36 (d, J_P–H= 5.83 Hz, 6 H), 1.33 (d, J_P–H= 6.31 Hz, 6 H),

0.25–0.85 (br m, 3 H).

¹³C NMR (125 MHz, CDCl₃):  = 145.8 (d, ²J_P–C= 7.3 Hz, C), 140.1 (s, C),

128.4 (d, J_P–C= 10.0 Hz, CH), 126.1 (s, CH), 114.1 (d, J_P–C= 5.5 Hz, CH),

72.1 (d, ²J_P–C= 3.6 Hz, CHO), 32.9 (s, CH₂), 23.79 (d, ³J_P–C= 2.7 Hz, CH₃),

23.76 (d, ³J_P–C= 3.6 Hz, CH₃), 16.7 (d, J_P–C= 2.7 Hz, CH₃).

507.3134.

Anal. Calcd for C₁₃H₂₄BO₂P: C, 61.44; H, 9.52. Found: C, 61.33; H, 9.42.

³¹P NMR (202 MHz, CDCl₃):  = 109.38 (br m).

Methylphosphonous Acid-Borane Diisopropyl Ester (7c) (Table 2,

entry 8), General Procedure B

Phosphorous Acid-Borane Diisopropyl Benzyl Ester (10) (Table 2,

entry 9), General Procedure B

¹H NMR (500 MHz, CDCl₃):  = 7.37–7.39 (m, 4 H), 7.32–7.38 (m, 1 H),

5.02 (d, J_P–H= 7.41 Hz, 2 H), 4.63–4.71 (m, 2 H), 1.31 (d, J_H–H= 6.31 Hz,

6 H), 1.30 (d, J_H–H= 6.15 Hz, 6 H), 0.22–0.95 (br m, 3 H).

-Hydroxyphosphonite-borane 5a (0.056 g, 0.25 mmol) reacted with

MeI (0.3 mmol, 18.7 L) and NaH (15 mg, 0.375 mmol, 60% in mineral

oil) according to general procedure B to afford 7c (0.0236 g, 0.133

mmol, 53%) as a colorless oil.

R_f= 0.47 (n-pentane/EtOAc, 100:1).

3

¹³C NMR (125 MHz, CDCl₃):  = 136.3 (d, J_P–C= 6.4 Hz, C), 128.5 (d,

IR (ATR, thin film): 2955, 2917, 2848, 1462, 1091, 608 cm^–1

.

J_P–C= 7.3 Hz, CH), 128.3 (d, J_P–C= 10.0 Hz, CH), 127.6 (s, CH), 125.5 (s,

CH), 71.7 (d, ²J_P–C= 2.7 Hz, CHO), 67.4 (d, ²J_P–C= 2.7 Hz, CH₂O), 23.82 (d,

³J_P–C= 3.6 Hz, CH₃), 23.79 (d, ³J_P–C= 2.7 Hz, CH₃).

³¹P NMR (202 MHz, CDCl₃):  = 111.80 (br m).

¹¹B NMR (160 MHz, CDCl₃):  = –43.67 (br m).

¹H NMR (500 MHz, CDCl₃):  = 4.57–4.67 (m, 2 H), 1.47 (d, J_P–H= 8.51

Hz, 3 H), 1.30 (d, J_P–H= 5.99 Hz, 6 H), 1.29 (d, J_P–H= 5.99 Hz, 6 H), 0.23–

0.83 (br m, 3 H).

2

¹³C NMR (125 MHz, CDCl₃):  = 71.6 (d, J_P–C= 3.6 Hz, CHO), 24.11 (d,

³J_P–C= 3.6 Hz, CH₃), 24.08 (d, ³J_P–C= 3.6 Hz, CH₃), 17.3 (d, ¹J_P–C= 59.0 Hz,

CH₃).

1-Hydroxy-1-phenylmethylphosphonousAcid-BoraneDiisopropyl

Ester (11) (Table 2, entry 11), General Procedure B

³¹P NMR (202 MHz, CDCl₃):  = 140.71 (br m).⁸

¹¹B NMR (160 MHz, CDCl₃):  = –45.28 (br m).⁸

MS (EI, 70 eV): m/z (%) = 164 (28) [M – BH₃]⁺, 94 (11), 93 (11), 91 (12),

-Hydroxyphosphonite-borane 5b (0.066 g, 0.25 mmol) reacted with

PhCHO (0.375 mmol, 38.1 L) and NaH (15 mg, 0.375 mmol, 60% in

mineral oil) according to general procedure B to afford 11 (0.041 g,

0.153 mmol, 61%) as a colorless oil.

81 (10), 80 (100).

Anal. Calcd for C₇H₂₀BO₂P: C, 47.23; H, 11.32. Found: C, 47.43; H,

11.45.

R_f= 0.38 (hexane/EtOAc, 10:1).

IR (ATR, thin film): 3377, 2978, 2929, 2391, 1374, 974, 715 cm^–1

.

¹H NMR (500 MHz, CDCl₃):  = 7.40–7.44 (m, 2 H), 7.30–7.39 (m, 3 H),

4.89 (d, J_P–H= 3.15 Hz, 1 H), 4.54–4.64 (m, 2 H), 2.61 (br s, 1 H), 1.30 (d,

J_H–H= 6.31 Hz, 3 H), 1.29 (d, J_H–H= 6.15 Hz, 3 H), 1.21 (d, J_H–H= 6.15 Hz,

3 H), 1.11 (d, J_H–H= 6.15 Hz, 3 H), 0.14–0.87 (br m, 3 H).

Phosphorous Acid-Borane Diisopropyl (3-Phenyl-1-methyl-prop-

1-enyl) Ester (12) (Table 2, entry 9), General Procedure B

-Hydroxyphosphonite-borane 5a (0.056 g, 0.25 mmol) reacted with

PhCHO (0.3 mmol, 30.5 L) and NaH (15 mg, 0.375 mmol, 60% in min-

eral oil) according to general procedure B to afford 12 (as a mixture of

isomers, ratio = 1:0.81) and phosphorous acid-borane diisopropyl

benzyl ester (10) as a mixture in 31% and 16% yield, respectively (ac-

cording to the ¹H NMR spectrum).

5

¹³C NMR (125 MHz, CDCl₃):  = 135.2 (s, C), 128.2 (d, J_P–C= 2.7 Hz,

3

4

CH), 127.9 (d, J_P–C= 2.7 Hz, CH), 127.6 (d, J_P–C= 4.5 Hz, CH), 74.6 (d,

¹J_P–C= 67.2 Hz, CHO), 72.4 (d, ²J_P–C= 4.5 Hz, CHO), 72.4 (d, ²J_P–C= 5.5 Hz,

CHO), 24.1 (br s, 2 × CH₃), 23.8 (d, J_P–C= 4.5 Hz, CH₃), 23.6 (d, J_P–C

4.5 Hz, CH₃).

3

=

12 (Major Isomer) (Table 2, entry 9), General Procedure B

³¹P NMR (202 MHz, CDCl₃):  = 134.61 (br m).⁸

¹¹B NMR (160 MHz, CDCl₃):  = –44.78 (br m).⁸

Yield: 5.4 mg, 0.0175 mmol (7%); colorless oil; R_f= 0.69 (hexane/EtOAc,

6:1).

2420

K. Modzelewski, S. Sowa

Paper

Synthesis

MS (EI, 70 eV): m/z (%) = 214 (1) [M – BH₃– C₃H₇]⁺, 172 (1) [M – BH₃–

C₆H₁₄]⁺, 155 (3), 149 (8), 108 (18), 107 (100), 106 (22), 105 (34), 91

(14).

³¹P NMR (202 MHz, CDCl₃):  = 115.65 (br m, major), 113.89 (br m,

minor).

¹¹B NMR (160 MHz, CDCl₃):  = –42.93 (br m).

Anal. Calcd for C₁₃H₂₄BO₃P: C, 57.81; H, 8.96. Found: C, 57.63; H, 8.86.

Anal. Calcd for C₁₈H₂₄BO₂P: C, 68.81; H, 7.70. Found: C, 68.73; H, 7.86.

Benzyl(phenyl)phosphinous Acid-Borane Ethyl Ester (13a) (Table

3, entry 3), General Procedure B

1,2-Bis(ethoxyphenylboranatophosphinyl)ethane (16) (Table 4,

entry 16), General Procedure B

-Hydroxyphosphinite-borane 6a (0.057 g, 0.25 mmol) reacted with

PhCH₂Cl (0.3 mmol, 34.5 L) and NaH (10 mg, 0.25 mmol, 60% in min-

eral oil) according to general procedure B to afford 13a (0.038 g, 0.148

mmol, 59%) as a colorless oil.

-Hydroxyphosphinite-borane 6a (0.057 g, 0.25 mmol) reacted with

ethylene oxide (103.4 L, 0.3 mmol, 2.5–3.3 M in THF) and NaH (10

mg, 0.25 mmol, 60% in mineral oil) according to general procedure B

to afford 16 (0.0254 g, 0.065 mmol, 26%) as a waxy solid.

R_f= 0.53 (hexane/EtOAc, 20:1).

IR (ATR, thin film): 2925, 2379, 1064, 1037, 772, 699 cm^–1

¹H NMR (500 MHz, CDCl₃):  = 7.58–7.62 (m, 2 H), 7.50–7.53 (m, 1 H),

7.39–7.41 (m, 2 H), 7.20–7.24 (m, 3 H), 6.98–7.03 (m, 2 H), 3.95–4.05

R_f= 0.33 (hexane/EtOAc, 10:1).

.

¹H NMR (500 MHz, CDCl₃):  = 7.67–7.76 (m, 4 H), 7.52–7.57 (m, 2 H),

7.43–7.53 (m, 4 H), 3.93–4.02 (m, 2 H), 3.77–3.87 (m, 2 H), 1.96–2.15

(m, 4 H), 1.26 (t, J_H–H= 7.25 Hz, 3 H), 1.24 (t, J_H–H= 7.25 Hz, 3 H), 0.3–

1.04 (br m, 6 H).

(m, 1 H), 3.83–3.91 (m, 1 H), 3.31 (d, J_P–H= 10.09 Hz, 2 H), 1.27 (t, J_H–H

=

6.94 Hz, 3 H), 0.46–1.10 (br m, 3 H).

¹³C NMR (125 MHz, CDCl₃):  = 132.3 (s, CH), 130.8–131.0 (m, CH),

128.8–129.9 (m, CH), 63.7 (s, CH₂O), 23.6 (dd, J = 8.6 Hz, J = 43.1 Hz,

CH₂), 16.6 (d, J_P–C= 3.7 Hz, CH₃), 16.5 (d, J_P–C= 3.1 Hz, CH₃).

³¹P NMR (202 MHz, CDCl₃):  = 114.05 (br m).

¹¹B NMR (160 MHz, CDCl₃):  = –44.78 (br m).

¹³C NMR (125 MHz, CDCl₃):  = 131.8 (d, J_P–C= 2.7 Hz, CH), 131.3 (d,

²J_P–C= 6.4 Hz, C), 131.2 (d, ¹J_P–C= 55.4 Hz, C), 130.9 (d, ²J_P–C= 10.9 Hz,

CH), 130.1 (d, ³J_P–C= 4.5 Hz, CH), 128.3 (d, ³J_P–C= 10.0 Hz, CH), 128.0 (d,

4

5

2

⁴J_P–C= 2.7 Hz, CH), 126.8 (d, J_P–C= 2.7 Hz, CH), 63.8 (d, J_P–C= 2.7 Hz,

CH₂O), 39.4 (d, ¹J_P–C= 40.0 Hz, CH₂), 16.6 (d, ³J_P–C= 6.3 Hz, CH₃).

Anal. Calcd for C₁₈H₃₀B₂O₂P₂: C, 59.72; H, 8.35. Found: C, 59.88; H,

8.55.

³¹P NMR (202 MHz, CDCl₃):  = 110.30 (br m).

¹¹B NMR (160 MHz, CDCl₃):  = –45.28 (br m).

MS (EI, 70 eV): m/z (%) = 258 (M)⁺(1), 244 (M – BH₃)⁺(25), 154 (10),

153 (100), 141 (11), 125 (88), 109 (34), 91 (56).

Reversed Alkylation of -Hydroxyphosphinite-Boranes and -Hy-

droxyphosphonite-Boranes in DMF; General Procedure A

HRMS (ESI): m/z [2 M – H] calcd for C₃₀H₃₉B₂O₂P₂: 515.2600; found:

515.2617.

To a Schlenk tube (25 mL) equipped with a magnetic stir bar and an

argon inlet were added anhydrous degassed DMF (2 mL), -hydroxy-

phosphonite-borane 5 (0.25 mmol) or -hydroxyphosphinite-borane

6 (0.25 mmol) and the electrophile (0.3 mmol). The resulting mixture

was cooled to 0 °C using an ice bath and then NaH (15 mg, 0.375

mmol, 60% in mineral oil or 10 mg, 0.25 mmol, 60% in mineral oil)

was added and the mixture was stirred at the same temperature for 3

min. The ice bath was removed and the reaction mixture was

quenched by the addition of anhydrous NH₄Cl (~300 mg), filtered and

evaporated under reduced pressure. The residue was purified by short

(5–10 cm) column chromatography on neutral Al₂O₃using hex-

ane/EtOAc (40:1 v/v) or hexane/EtOAc (10:1 v/v) as the eluent.

Anal. Calcd for C₁₅H₂₀BOP: C, 69.80; H, 7.81. Found: C, 69.63; H, 7.72.

3-Oxo-1-phenylbutyl(phenyl)phosphinous Acid-Borane Ethyl

Ester (15) (Table 4, entry 15), General Procedure B

-Hydroxyphosphinite-borane 6a (0.057 g, 0.25 mmol) reacted with

PhCHO (0.3 mmol, 30.5 L) and NaH (10 mg, 0.25 mmol, 60% in min-

eral oil) according to general procedure B to afford 15 (0.024 g, 0.075

mmol, 30%) isolated as a mixture of two diastereoisomers (dr =

1:0.48).

¹H NMR (500 MHz, CDCl₃):  (mixture of diastereoisomers) = 7.47–

7.53 (m, 2 H), 7.42–7.47 (m, 4 H), 7.33–7.39 (m, 4 H), 7.19–7.22 (m, 2

H), 7.10–7.13 (m, 4 H), 7.06–7.11 (m, 2 H), 6.92–6.95 (m, 2 H), 4.02–

4.10 (m, 1 H), 3.84–3.92 (m, 4 H), 3.77–3.82 (m, 1 H), 3.17–3.21 (m, 2

H), 3.12–3.16 (m, 1 H), 2.97–3.03 (m, 1 H), 2.10 (s, 3 H), 2.03 (s, 3 H),

1.29 (t, J_H–H= 7.25 Hz, 3 H), 1.18 (t, J_H–H= 7.25 Hz, 3 H), 0.42–0.95 (br

m, 6 H).

Benzylphosphonous Acid-Borane Diisopropyl Ester (7a) (Table 2,

entry 1), General Procedure A

-Hydroxyphosphonite-borane 5a (0.056 g, 0.25 mmol) reacted with

PhCH₂Cl (0.3 mmol, 34.5 L) and NaH (15 mg, 0.375 mmol, 60% in

mineral oil) according to general procedure B to afford 7a (0.046 g,

0.18 mmol, 72%) as a colorless oil.

¹³C NMR (125 MHz, CDCl₃):  (mixture of diastereoisomers) = 205.1

3

(d, J_P–C= 11.8 Hz, C=O, major), 204.7 (d, J_P–C= 12.7 Hz, C=O, minor),

2-Methylbenzylphosphonous Acid-Borane Diisopropyl Ester (7b)

(Table 2, entry 2), General Procedure A

135.2 (d, ²J_P–C= 5.5 Hz, C, minor), 134.4 (s, C, major), 131.95 (d, J_P–C

3.6 Hz, C, minor), 131.93 (d, J_P–C= 2.7 Hz, C, major), 131.25 (d, J_P–C

=

2

-Hydroxyphosphonite-borane 5a (0.056 g, 0.25 mmol) reacted with

2-MeC₆H₄CH₂Cl (0.3 mmol, 39 L) and NaH (15 mg, 0.375 mmol, 60%

in mineral oil) according to general procedure B to afford 7b (0.056 g,

0.208 mmol, 83%) as a colorless oil.

10.5 Hz, CH, major), 131.24 (d, ²J_P–C= 10.5 Hz, CH, minor), 130.5 (d,

¹J_P–C= 55.4 Hz, C, minor), 130.0 (d, ¹J_P–C= 53.6 Hz, C, major), 129.6 (d,

J_P–C= 3.6 Hz, CH, minor), 129.5 (d, J_P–C= 4.5 Hz, CH, major), 128.3 (d,

³J_P–C= 10.5 Hz, CH, minor), 128.2 (d, ³J_P–C= 10.0 Hz, CH, major), 128.0

(d, J_P–C= 1.8 Hz, CH, minor), 127.9 (d, J_P–C= 2.7 Hz, CH, major), 127.3

(d, J_P–C= 2.7 Hz, CH, minor), 127.2 (d, J_P–C= 2.7 Hz, CH, major), 64.2 (d,

²J_P–C= 3.6 Hz, OCH₂, minor), 64.0 (d, ²J_P–C= 3.6 Hz, OCH₂, major), 43.2

R_f= 0.48 (hexane/EtOAc, 20:1).

IR (ATR, thin film): 2978, 2385, 1386, 1064, 1002, 886, 772 cm^–1

.

¹H NMR (500 MHz, CDCl₃):  = 7.23–7.26 (m, 1 H), 7.13–7.18 (m, 3 H),

4.54–4.63 (m, 2 H), 3.15 (d, J_P–H= 12.30 Hz, 2 H), 2.38 (s, 3 H), 1.29 (d,

J_H–H= 6.15 Hz, 6 H), 1.13 (d, J_H–H= 6.15 Hz, 6 H), 0.14–0.84 (br m, 3 H).

1

3

(d, J_P–C= 41.8 Hz, major/minor), 42.7 (d, J_P–C= 3.6 Hz, CH₂, major),

3

42.3 (d, J_P–C= 4.5 Hz, CH₂, minor), 30.5 (s, CH₃, major), 30.3 (s, CH₃,

minor), 16.7 (d, ³J_P–C= 6.4 Hz, CH₃, major), 16.4 (d, ³J_P–C= 6.4 Hz, CH₃,

minor).

2421

K. Modzelewski, S. Sowa

Paper

Synthesis

¹³C NMR (125 MHz, CDCl₃):  = 137.3 (d, ²J_P–C= 5.5 Hz, C), 131.3 (d, J_P–C

=

R_f= 0.57 (hexane/EtOAc, 20:1).

IR (ATR, thin film): 2978, 2383, 1036, 711 cm^–1

¹H NMR (500 MHz, CDCl₃):  = 7.49–7.61 (m, 3 H), 7.37–7.45 (m, 2 H),

7.02–7.15 (m, 3 H), 6.94–6.99 (m, 1 H), 3.93–4.03 (m, 1 H), 3.80–3.87

(m, 1 H), 3.33 (d, J_P–H= 10.09 Hz, 2 H), 2.08 (s, 3 H), 1.25 (t, J_H–H= 6.94

Hz, 3 H), 0.47–1.10 (br m, 3 H).

3

4.5 Hz, CH), 130.1 (d, J_P–C= 2.7 Hz, CH), 129.9 (d, J_P–C= 3.6 Hz, C),

.

2

126.9 (d, J_P–C= 3.6 Hz, CH), 125.5 (d, J_P–C= 2.7 Hz, CH), 72.3 (d, J_P–C

=

3.6 Hz, CHO), 36.4 (d, ¹J_P–C= 55.4 Hz, CH₂), 24.2 (d, ³J_P–C= 2.7 Hz, CH₃),

23.7 (d, ³J_P–C= 4.5 Hz, CH₃), 20.3 (s, CH₃).

³¹P NMR (202 MHz, CDCl₃):  = 140.71 (br m).

¹¹B NMR (160 MHz, CDCl₃):  = –42.55 (br m).

¹³C NMR (125 MHz, CDCl₃):  = 131.8 (d, J_P–C= 2.7 Hz, CH), 131.3 (d,

4

MS (EI, 70 eV): m/z (%) = 254 (3) [M – BH₃]⁺, 153 (12) [M – BH₃

–

²J_P–C= 6.4 Hz, C), 131.2 (d, ¹J_P–C= 55.4 Hz, C), 130.9 (d, ²J_P–C= 10.9 Hz,

CH), 130.1 (d, ³J_P–C= 4.5 Hz, CH), 128.3 (d, ³J_P–C= 10.0 Hz, CH), 128.0 (d,

C₃H₇]⁺, 149 (25), 135 (7), 107 (100), 106 (34), 105 (65), 103 (18), 91

(13).

5

2

⁴J_P–C= 2.7 Hz, CH), 126.8 (d, J_P–C= 2.7 Hz, CH), 63.8 (d, J_P–C= 2.7 Hz,

CH₂O), 39.4 (d, ¹J_P–C= 40.0 Hz, CH₂), 16.6 (d, ³J_P–C= 6.3 Hz, CH₃).

Anal. Calcd for C₁₄H₂₆BO₂P: C, 62.71, H, 9.77. Found: C, 62.98; H, 9.99.

³¹P NMR (202 MHz, CDCl₃):  = 110.98 (br m).

¹¹B NMR (160 MHz, CDCl₃):  = –41.12 (br m).

MS (EI, 70 eV): m/z (%) = 259 (6), 258 (32) [M – BH₃]⁺, 153 (100), 125

Methylphosphonous Acid-Borane Diisopropyl Ester (7c) (Table 2,

entry 3), General Procedure A

-Hydroxyphosphonite-borane 5a (0.056 g, 0.25 mmol) reacted with

MeI (0.3 mmol, 18.7 L) and NaH (15 mg, 0.375 mmol, 60% in mineral

oil) according to general procedure A to afford 7c (100%, according to

the ³¹P NMR spectrum).

(93), 109 (34), 105 (41), 104 (8), 103 (11).

HRMS (ESI): m/z [2 M – H]⁺calcd for C₃₂H₄₃B₂O₂P₂: 543.2940; found:

543.2925.

Anal. Calcd for C₁₆H₂₂BOP: C, 70.62; H, 8.15. Found: C, 70.88; H, 8.33.

Phosphorous Acid-Borane Diisopropyl Benzyl Ester (10) (Table 2,

entry 4), General Procedure A

Methyl(phenyl)phosphinous Acid-Borane Ethyl Ester (13c) (Table

4, entry 3), General Procedure A

-Hydroxyphosphonite-borane 5a (0.056 g, 0.25 mmol) reacted with

PhCHO (0.3 mmol, 30.5 L) and NaH (15 mg, 0.375 mmol, 60% in min-

eral oil) according to general procedure A to afford 10 (0.365 g, 0.135

mmol, 54%) as a yellowish oil.

-Hydroxyphosphinite-borane 6a (0.057 g, 0.25 mmol) reacted with

MeI (0.3 mmol, 18.7 L) and NaH (10 mg, 0.25 mmol, 60% in mineral

oil) according to general procedure A to afford 13c (0.038 g, 0.208

mmol, 83%) as a colorless oil.

R_f= 0.68 (hexane/EtOAc, 6:1).

R_f= 0.37 (hexane/EtOAc, 20:1).

IR (ATR, thin film): 2980, 2390, 1375, 975, 784 cm^–1

.

IR (ATR, thin film): 2980, 2925, 2378, 1437, 1032, 742 cm^–1

.

MS (EI, 70 eV): m/z (%) = 214 (2) [M – BH₃– C₃H₇]⁺, 173 (4) [M – BH₃–

¹H NMR (500 MHz, CDCl₃):  = 7.78–7.82 (m, 2 H), 7.52–7.57 (m, 1 H),

7.48–7.51 (m, 2 H), 3.95–4.03 (m, 1 H), 3.76–3.84 (m, 1 H), 1.70 (d,

J_P-H= 9.46 Hz, 3 H), 1.26 (t, J_H-H= 6.94 Hz, 3 H), 0.48–1.13 (br m, 3 H).

C₆H₁₄]⁺, 172 (6) [M – BH₃– C₆H₁₄]⁺, 123 (13), 91 (100), 77 (8), 65 (26).

Anal. Calcd for C₁₃H₂₄BO₃P: C, 57.81; H, 8.96. Found: C, 57.90; H, 8.99.

¹³C NMR (125 MHz, CDCl₃):  = 132.6 (d, J_P-C= 56.3 Hz, C), 131.9 (d,

1

Benzylphosphonous Acid-Borane Diisopropyl Ester (7a) (Table 2,

entry 5), General Procedure A

⁴J_P-C= 2.7 Hz, CH), 130.5 (d, ²J_P-C= 11.8 Hz, CH), 128.7 (d, ³J_P-C= 10.0 Hz,

CH), 63.1 (d, ²J_P-C= 2.7 Hz, CH₂O), 16.7 (d, ¹J_P-C= 47.3 Hz, CH₃), 16.6 (d,

³J_P-C= 6.4 Hz, CH₃).

-Hydroxyphosphonite-borane 5b (0.066 g, 0.25 mmol) reacted with

PhCH₂Cl (0.3 mmol, 34.5 L) and NaH (15 mg, 0.375 mmol, 60% in

mineral oil) according to general procedure A to afford 7a (0.054 g,

0.213 mmol, 85%) as a colorless oil.

³¹P NMR (202 MHz, CDCl₃):  = 108.11 (br m).

¹¹B NMR (160 MHz, CDCl₃):  = –41.29 (br m).

MS (EI, 70 eV): m/z (%) = 168 (36), [M - BH₃]⁺, 141 (13), 140 (27), 139

(100), 125 (62), 124 (14), 121 (14).

HRMS (ESI): m/z [2(M – BH₃+O) + Na]⁺calcd for C₁₈H₂₆O₄P₂: 391.1199;

Phosphorous Acid-Borane Diisopropyl Benzyl Ester (10) (Table 2,

entry 6), General Procedure A

-Hydroxyphosphonite-borane 5b (0.066 g, 0.25 mmol) reacted with

PhCHO (0.3 mmol, 30.5 L) and NaH (15 mg, 0.375 mmol, 60% in min-

eral oil) according to general procedure A to afford 10 (0.033 g, 0.123

mmol, 49%) as a yellowish oil.

found: 391.1192.

Anal. Calcd for C₉H₁₆BOP: C, 59.39; H, 8.86. Found: C, 58.99; H, 8.47.

Isopropyl(phenyl)phosphinous Acid-Borane Ethyl Ester (13d)

(Table 4, entry 4), General Procedure A

Benzyl(phenyl)phosphinous Acid-Borane Ethyl Ester (13a) (Table

4, entry 1), General Procedure A

-Hydroxyphosphinite-borane 6a (0.057 g, 0.25 mmol) reacted with

i-PrI (0.375 mmol, 37.5 L) and NaH (10 mg, 0.25 mmol, 60% in min-

eral oil) according to general procedure A to afford 13d (0.033 g, 0.158

mmol, 63%) as a colorless oil.

-Hydroxyphosphinite-borane 6a (0.057 g, 0.25 mmol) reacted with

PhCH₂Cl (0.3 mmol, 34.5 L) and NaH (10 mg, 0.25 mmol, 60% in min-

eral oil) according to general procedure A to afford 13a (0.049 g, 0.19

mmol, 76%) as a colorless oil.

R_f= 0.49 (hexane/EtOAc, 20:1).

IR (ATR, thin film): 2976, 2929, 2378, 1437, 1023, 732, 694 cm^–1

.

¹H NMR (500 MHz, CDCl₃):  = 7.71–7.76 (m, 2 H), 7.46–7.56 (m, 3 H),

4.00–4.10 (m, 1 H), 3.82–3.89 (m, 1 H), 2.07–2.17 (m, 1 H), 1.29 (t,

J_H–H= 7.25 Hz, 3 H), 1.16 (dd, J_H–H= 7.25 Hz, J_P–H= 15.76 Hz, 3 H), 1.01

(dd, J_H–H= 6.94 Hz, J_P–H= 16.39 Hz, 3 H), 0.35–0.95 (br m, 3 H).

2-Methylbenzyl(phenyl)phosphinous Acid-Borane Ethyl Ester

(13b) (Table 4, entry 2), General Procedure A

-Hydroxyphosphinite-borane 6a (0.057 g, 0.25 mmol) reacted with 2-

MeC₆H₄CH₂Cl (0.3 mmol, 39 L) and NaH (10 mg, 0.25 mmol, 60% in min-

eral oil) according to general procedure B to afford 13b (0.0422 g, 0.155

mmol, 62%) as a colorless oil.

2422

K. Modzelewski, S. Sowa

Paper

Synthesis

4

¹³C NMR (125 MHz, CDCl₃):  = 131.6 (d, J_P–C= 2.7 Hz, CH), 131.2 (d,

MS (EI, 70 eV): m/z (%) = 198 (17) [M – BH₃]⁺, 168 (23), 153 (77), 141

(7), 140 (5), 125 (100), 124 (20), 21 (11), 109 (42), 108 (5), 107 (10),

104 (8), 91 (16).

HRMS (ESI): m/z [2 M – H]⁺calcd for C₂₀H₃₅B₂O₄P₂: 423.2187; found:

423.2186.

²J_P–C= 10.0 Hz, CH), 131.0 (d, J_P–C= 49.1 Hz, C), 128.4 (d, J_P–C= 10.0

Hz, CH), 63.5 (d, ²J_P–C= 3.6 Hz, CH₂O), 29.3 (d, ¹J_P–C= 45.4 Hz, CH), 16.6

(d, ³J_P–C= 6.4 Hz, CH₃), 15.7 (s, CH₃), 15.3 (d, ²J_P–C= 1.8 Hz, CH₃).

³¹P NMR (202 MHz, CDCl₃):  = 119.19 (br m).

¹¹B NMR (160 MHz, CDCl₃):  = –43.51 (br m).

1

3

Anal. Calcd for C₁₀H₁₈BO₂P: C, 56.65; H, 8.56. Found: C, 56.61; H, 8.86.

MS (EI, 70 eV): m/z (%) = 210 (5) [M]⁺197 (11), 196 (91) [M – BH₃]⁺,

167 (13), 154 (25), 153 (74), 152 (15), 151 (11), 126 (18), 125 (100),

110 (10), 109 (71), 108 (13), 107 (14), 105 (14), 104 (21).

Phenylphosphonous Acid-Borane Ethyl [1-(4-Chlorophenyl)vinyl]

Ester (14) and 1-(4-Chlorophenyl)-2-[ethoxy(phenyl)boranato-

phosphinyl]-1-ethanone (13g) (Table 4, entry 10), General Proce-

dure A

Anal. Calcd for C₁₁H₂₀BOP: C, 62.90; H, 9.60. Found: C, 63.21; H, 9.98.

-Hydroxyphosphinite-borane 6a (0.057 g, 0.25 mmol) reacted with

ClCH₂C(O)C₆H₄Cl-p (0.3 mmol, 56.7 mg) and NaH (10 mg, 0.25 mmol,

60% in mineral oil) according to general procedure A to afford com-

pounds 14 and 13g.

Allyl(phenyl)phosphinous Acid-Borane Ethyl Ester (13e) (Table 4,

entry 8), General Procedure A

-Hydroxyphosphinite-borane 6a (0.057 g, 0.25 mmol) reacted with

allyl bromide (0.3 mmol, 26 L) and NaH (10 mg, 0.25 mmol, 60% in

mineral oil) according to general procedure A to afford 13e (0.041 g,

0.198 mmol, 79%) as a colorless oil.

Compound 14

Yield: 0.051 g, 0.16 mmol (64%); colorless oil; R_f= 0.63 (hexane/EtOAc,

6:1).

R_f= 0.41 (hexane/EtOAc, 20:1).

IR (ATR, thin film): 2961, 2925, 2378, 1260, 1017, 798 cm^–1

.

IR (ATR, thin film): 3212, 2981, 2389, 1489, 1262, 1263, 1096, 988

¹H NMR (500 MHz, CDCl₃):  = 7.73–7.77 (m, 2 H), 7.44–7.57 (m, 3 H),

5.64–5.75 (m, 1 H), 5.01–5.15 (m, 2 H), 4.00–4.10 (m, 1 H), 3.86–3.94

(m, 1 H), 2.72–2.84 (m, 2 H), 1.29 (t, J_H–H= 6.94 Hz, 3 H), 0.48–1.47 (br

m, 3 H).

cm^–1

.

¹H NMR (500 MHz, CDCl₃):  = 7.83–7.88 (m, 2 H), 7.55–7.60 (m, 1 H),

7.47–7.51 (m, 2 H), 7.44–7.48 (m, 2 H), 7.28–7.32 (m, 2 H), 5.21 (dd,

J_H–H= 2.05 Hz, J_P–H= 2.99 Hz, 1 H), 4.98 (dd, J_H–H= 2.36 Hz, J_P–H= 2.86

Hz, 1 H), 4.23–4.31 (m, 1 H), 4.09–4.17 (m, 1 H), 1.39 (t, J_H–H= 7.05 Hz,

3 H), 0.51–1.13 (br m, 3 H).

4

¹³C NMR (125 MHz, CDCl₃):  = 131.9 (d, J_P–C= 1.8 Hz, CH), 131.3 (d,

2

3

¹J_P–C= 55.4 Hz, C), 130.9 (d, J_P–C= 11.0 Hz, CH), 128.5 (d, J_P–C= 10.0

Hz, CH), 127.3 (d, ²J_P–C= 6.4 Hz, CH), 120.3 (d, ³J_P–C= 11.0 Hz, CH₂), 63.7

(d, ²J_P–C= 2.7 Hz, CH₂O), 37.0 (d, ¹J_P–C= 42.7 Hz, CH₂), 16.6 (d, ³J_P–C= 6.4

Hz, CH₃).

¹³C NMR (125 MHz, CDCl₃):  = 152.6 (d, ²J_P–C= 10.0 Hz, C), 134.9 (s, C),

133.3 (d, ³J_P–C= 3.6 Hz, C), 132.7 (d, ⁴J_P–C= 2.7 Hz, CH), 130.7 (d, ²J_P–C

=

12.7 Hz, CH), 130.4 (d, ¹J_P–C= 65.4 Hz, C), 128.6 (d, ³J_P–C= 11.0 Hz, CH),

³¹P NMR (202 MHz, CDCl₃):  = 110.30 (br m).

¹¹B NMR (160 MHz, CDCl₃):  = –41.43 (br m).

128.6 (s, CH), 126.6 (s, CH), 99.0 (d, ³J_P–C= 5.4 Hz, CH₂), 64.6 (d, ²J_P–C

4.5 Hz, CH₂O), 16.3 (d, ³J_P–C= 5.5 Hz, CH₃).

=

³¹P NMR (202 MHz, CDCl₃):  = 131.34 (br m).

¹¹B NMR (160 MHz, CDCl₃):  = –41.21 (br m).

MS (EI, 70 eV): m/z (%) = 308 (7), 307 (12), 306 [M – BH₃]⁺, 277 (12),

170 (19), 153 (19), 143 (9), 142 (30), 141 (94), 139 (40), 138 (11), 137

(69), 136 (11), 126 (8), 125 (86), 124 (10).

MS (EI, 70 eV): m/z (%) = 194 [M –BH₃]⁺, 193 (5), 154 (9), 153 (96), 141

(9), 126 (7), 125 (100), 109 (41).

HRMS (ESI): m/z [2 M – H]⁺calcd for C₂₂H₃₅B₂O₂P₂: 415.2287; found:

415.2297.

Anal. Calcd for C₁₁H₁₈BOP: C, 63.50; H, 8.72. Found: C, 63.61; H, 8.98.

HRMS (ESI): m/z [M – BH₃+ O + Na]⁺calcd for C₁₆H₁₆ClO₃PNa:

Methoxymethyl(phenyl)phosphinous Acid-Borane Ethyl Ester

(13f) (Table 4, entry 9), General Procedure A

345.0418; found: 345.0420.

Anal. Calcd for C₁₆H₁₉BClO₂P: C, 59.95; H, 5.97. Found: C, 59.99; H,

6.12.

-Hydroxyphosphinite-borane 6a (0.057 g, 0.25 mmol) reacted with

MOMCl (0.375 mmol, 28 L) and NaH (10 mg, 0.25 mmol, 60% in min-

eral oil) according to general procedure A to afford 13f (0.034 g, 0.163

mmol, 65%) as a colorless oil.

Compound 13g

Yield: 0.0192 g, 0.06 mmol (24%); colorless oil; R_f= 0.45 (hexane/EtOAc,

6:1).

R_f= 0.32 (hexane/EtOAc, 20:1).

IR (ATR, thin film): 2957, 2922, 2853, 1258, 1105, 1026, 774 cm^–1

¹H NMR (500 MHz, CDCl₃):  = 7.81–7.86 (m, 2 H), 7.54–7.59 (m, 1 H),

7.52–7.58 (m, 2 H), 4.06–4.13 (m, 1 H), 3.96–4.02 (m, 1 H), 3.91–4.03

(m, 2 H), 3.44 (s, 3 H), 1.32 (t, J_H–H= 6.94 Hz, 3 H), 0.44–1.09 (br m, 3

H).

.

IR (ATR, thin film): 3060, 2979, 2928, 2384, 1676, 1578, 1268, 1027,

997, 771 cm^–1

.

¹H NMR (500 MHz, CDCl₃):  = 7.77–7.80 (m, 2 H), 7.71–7.76 (m, 2 H),

7.52–7.56 (m, 1 H), 7.43–7.49 (m, 2 H), 7.37–7.40 (m, 2 H), 4.02–4.10

(m, 1 H), 3.89–3.99 (m, 1 H), 3.79–3.82 (m, 1 H), 3.63–3.70 (m, 1 H),

1.25 (t, J_H–H= 6.94 Hz, 3 H), 0.49–1.15 (br m, 3 H).

4

¹³C NMR (125 MHz, CDCl₃):  = 132.3 (d, J_P–C= 1.8 Hz, CH), 131.4 (d,

1

3

²J_P–C= 11.0 Hz, CH), 129.5 (d, J_P–C= 58.1 Hz, C), 128.5 (d, J_P–C= 10.0

¹³C NMR (125 MHz, CDCl₃):  = 191.3 (d, ²J_P–C= 4.5 Hz, C), 140.1 (s, C),

1

2

135.3 (s, C), 132.4 (d, ⁴J_P–C= 2.7 Hz, CH), 130.8 (d, ²J_P–C= 11.8 Hz, CH),

Hz, CH), 72.4 (d, J_P–C= 53.6 Hz, CH₂O), 64.0 (d, J_P–C= 2.7 Hz, CH₂O),

61.8 (d, ³J_P–C= 8.2 Hz, OCH₃), 16.7 (d, ³J_P–C= 6.4 Hz, CH₃).

130.6 (d, ¹J_P–C= 58.1 Hz, C), 130.3 (s, CH), 128.8 (s, CH), 128.7 (d, ³J_P–C

=

10.8 Hz, CH), 64.4 (d, ²J_P–C= 2.7 Hz, CH), 42.6 (d, ¹J_P–C= 31.8 Hz, CH₂),

16.5 (d, ³J_P–C= 6.4 Hz, CH₃).

³¹P NMR (202 MHz, CDCl₃):  = 107.65 (br m).

¹¹B NMR (160 MHz, CDCl₃):  = –42.19 (br m).

³¹P NMR (202 MHz, CDCl₃):  = 108.42 (br m).

2423

K. Modzelewski, S. Sowa

Paper

Synthesis

¹¹B NMR (160 MHz, CDCl₃):  = –40.28 (br m).

The residue was purified by short (5–10 cm) column chromatography

on neutral Al₂O₃using hexane/EtOAc (40:1 v/v) or hexane/EtOAc

(20:1 v/v) as the eluent.

MS (EI, 70 eV): m/z (%) = 308 (6), 307 (12) [M – BH₃]⁺, 279 (12), 170

(19), 153 (19), 142 (60), 141 (94), 139 (38), 138 (11), 137 (69), 126 (8),

125 (86), 124 (9), 111 (30), 109 (21), 107 (21).

(S_P)-Benzyl(phenyl)phosphinous Acid-Borane L-Menthyl Ester

[(S_P)-20a] (Table 5, entry 1), General Procedure C

HRMS (ESI): m/z [M + Na]⁺calcd for C₁₆H₁₉BClO₂PNa: 343.0794;

found: 343.0789.

(R_P)-19a (0.05 g, 0.149 mmol) reacted with PhCH₂Cl (0.179 mmol,

20.6 L) and NaH (6 mg, 0.149 mmol, 60% in mineral oil) according to

general procedure C to afford (S_P)-20a (0.054 g, 0.146 mmol, 98%) as a

colorless oil.

Anal. Calcd for C₁₆H₁₉BClO₂P: C, 59.95; H, 5.97. Found: C, 60.11; H,

6.05.

3-Oxo-1-phenylbutyl(phenyl)phosphinous Acid-Borane Ethyl Es-

ter (15) (Table 4, entry 11), General Procedure A

[]_D²⁵–110.5 (c 1.02, CHCl₃); R_f= 0.66 (hexane/EtOAc, 20:1).

IR (ATR, thin film): 2979, 2862, 2382, 1436, 997, 693 cm^–1

.

-Hydroxyphosphinite-borane 6a (0.057 g, 0.25 mmol) reacted with

PhCHO (0.3 mmol, 30.5 L) and NaH (10 mg, 0.25 mmol, 60% in min-

eral oil) according to general procedure A to afford 15 (0.006 g, 0.018

mmol, 7%, dr = 1:0.53).

¹H NMR (500 MHz, CDCl₃):  = 7.63–7.69 (m, 2 H), 7.47–7.51 (m, 1 H),

7.37–7.42 (m, 2 H), 7.18–7.23 (m, 3 H), 7.00–7.05 (m, 2 H), 4.01–4.09

(m, 1 H), 3.26–3.36 (m, 2 H), 1.92–1.98 (m, 1 H), 1.71–1.79 (m, 1 H),

1.57–1.67 (m, 2 H), 1.35–1.42 (m, 1 H), 1.25–1.34 (m, 2 H), 0.95–1.04

(m, 1 H), 0.88 (d, J_P–H= 6.62 Hz, 3 H), 0.78–0.94 (m 1 H), 0.76 (d, J_P–H

7.25 Hz, 3 H), 0.55–1.22 (br m, 3 H), 0.42 (d, J_P–H= 6.94 Hz, 3 H).

=

1,2-Bis(ethoxyphenylboranatophosphinyl)ethane (16) (Table 4,

entry 12), General Procedure A

¹³C NMR (125 MHz, CDCl₃):  = 131.8 (d, ¹J_P–C= 60.9 Hz, C), 131.75 (d,

²J_P–C= 6.4 Hz, C), 131.7 (d, ⁴J_P–C= 1.8 Hz, CH), 131.0 (d, ²J_P–C= 10.9 Hz,

CH), 130.3 (d, ³J_P–C= 4.5 Hz, CH), 128.1 (d, ³J_P–C= 10.0 Hz, CH), 127.9 (d,

-Hydroxyphosphinite-borane 6a (0.057 g, 0.25 mmol) reacted with

ethylene oxide (103.4 L, 0.3 mmol, 2.5–3.3 M in THF) and NaH (10

mg, 0.25 mmol, 60% in mineral oil) according to general procedure A

to afford 16 (0.0127 g, 0.033 mmol, 13%) as a waxy solid.

5

2

⁴J_P–C= 2.7 Hz, CH), 126.7 (d, J_P–C= 3.6 Hz, CH), 80.4 (d, J_P–C= 3.6 Hz,

1

CHO), 48.7 (d, J_P–C= 5.5 Hz, CH), 43.7 (s, CH₂), 40.8 (d, J_P–C= 39.9 Hz,

R_f= 0.33 (hexane/EtOAc, 10:1).

CH₂), 34.0 (s, CH₂), 31.4 (s, CH), 25.4 (s, CH), 22.6 (s, CH₂), 22.1 (s, CH₃),

20.9 (s, CH₃), 15.1 (s, CH₃).

³¹P NMR (202 MHz, CDCl₃):  = 107.76 (br m).

¹¹B NMR (160 MHz, CDCl₃):  = –41.16 (br m).

MS (EI, 70 eV): m/z (%) = 218 (9), 217 (67) [M – BH₃– C₁₀H₁₉]⁺, 216

(42), 215 (10), 126 (7), 125 (100), 123 (15), 121 (10), 96 (13), 95 (66).

Isopropyl(phenyl)phosphinous Acid-Borane Ethyl Ester (13d)

(Table 4, entry 6), General Procedure A

-Hydroxyphosphinite-borane 6a (0.057 g, 0.25 mmol) reacted with

i-PrBr (0.3 mmol, 28.2 L) and NaH (10 mg, 0.25 mmol, 60% in miner-

al oil) according to general procedure A to afford 13d (0.023 g, 0.108

mmol, 43%).

Anal. Calcd for C₂₃H₃₄BOP: C, 75.01; H, 9.30. Found: C, 75.22; H, 9.40.

Benzyl(phenyl)phosphinous Acid-Borane Ethyl Ester (13a) (Table

4, entry 13), General Procedure A

(S_P)-Methyl(phenyl)phosphinous Acid-Borane L-Menthyl Ester

[(S_P)-20c] (Table 5, entry 5), General Procedure C^33a

-Hydroxyphosphinite-borane 6b (0.067 g, 0.25 mmol) reacted with

PhCH₂Cl (0.3 mmol, 34.5 L) and NaH (10 mg, 0.25 mmol, 60% in min-

eral oil) according to general procedure A to afford 13a (0.045 g, 0.175

mmol, 70%).

(R_P)-19a (0.05 g, 0.149 mmol) reacted with MeI (0.298 mmol, 18.6 L)

and NaH (6 mg, 0.149 mmol, 60% in mineral oil) according to general

procedure C to afford (S_P)-20c (0.036 g, 0.124 mmol, 83%) as a color-

less oil.

[]_D²⁵–121.1 (c 0.52, CHCl₃); R_f= 0.67 (hexane/EtOAc, 20:1).

IR (ATR, thin film): 2951, 2932, 2869, 2374, 1438, 986, 749 cm^–1

Isopropyl(phenyl)phosphinous Acid-Borane Ethyl Ester (13d)

(Table 4, entry 14), General Procedure A

.

¹H NMR (500 MHz, CDCl₃):  = 7.81–7.85 (m, 2 H), 7.51–7.55 (m, 1 H),

7.45–7.50 (m, 2 H), 3.39–4.02 (m, 1 H), 2.22–2.26 (m, 1 H), 1.71–1.79

(m, 1 H), 1.73 (d, J_P–H= 9.14 Hz, 3 H), 1.57–1.67 (m, 2 H), 1.42–1.49 (m,

1 H), 1.23–1.29 (m, 2 H), 1.06–1.13 (m, 1 H), 0.79–0.97 (m 1 H), 0.93

(d, J_P–H= 6.62 Hz, 3 H), 0.77 (d, J_P–H= 6.94 Hz, 3 H), 0.54–1.20 (br m, 3

H), 0.41 (d, J_P–H= 6.94 Hz, 3 H).

-Hydroxyphosphinite-borane 6b (0.067 g, 0.25 mmol) reacted with

i-PrI (0.375 mmol, 37.5 L) and NaH (10 mg, 0.25 mmol, 60% in min-

eral oil) according to general procedure A to afford 13d (0.035 g, 0.11

mmol, 44%).

Stereoselective Alkylation of -Hydroxy Phosphite-Boranes 19a,b;

General Procedure C (Table 5)

1

¹³C NMR (125 MHz, CDCl₃):  = 133.0 (d, J_P–C= 61.7 Hz, C), 131.8 (d,

2

3

⁴J_P–C= 1.8 Hz, CH), 130.6 (d, J_P–C= 10.9 Hz, CH), 128.4 (d, J_P–C= 10.0

Hz, CH), 79.3 (d, ²J_P–C= 3.6 Hz, CHO), 48.8 (d, J_P–C= 5.5 Hz, CH), 43.6 (s,

CH₂), 34.1 (s, CH₂), 31.4 (s, CH), 25.4 (s, CH₃), 22.7 (s, CH₂), 22.1 (s,

CH₃), 20.9 (s, CH₃), 17.8 (d, ¹J_P–C= 46.3 Hz, CH₃), 15.2 (s, CH₃).

To a Schlenk tube (25 mL) equipped with a magnetic stir bar and an

argon inlet was added (R_P)-19a (0.05 g, 0.149 mmol) or (R_P)-19b

(0.056 g, 0.149 mmol) in anhydrous DMF (1.5 mL) and the resulting

mixture was cooled to 0 °C using an ice bath. NaH (6 mg, 0.149 mmol,

60% in mineral oil or 6.3 mg, 0.156 mmol, 60% in mineral oil) was

added and the mixture was stirred at the same temperature for 3 min.

The electrophile (0.179 mmol or 0.373 mmol) was then added and

the mixture was stirred at the same temperature for 40 min or 1–2 h.

The reaction mixture was quenched by the addition of anhydrous

NH₄Cl (~300 mg), filtered and evaporated under reduced pressure.

³¹P NMR (202 MHz, CDCl₃):  = 106.17 (br m).

¹¹B NMR (160 MHz, CDCl₃):  = –39.70 (br m).

MS (EI, 70 eV): m/z (%) = 156 (C₆H₂₀O) (7), 142 (6), 141 (80), 140 (M –

BH₃– C₁₀H₁₉) (100), 139 (25), 138 (25), 125 (45), 123 (26), 96 (18), 95

(97).

Anal. Calcd for C₁₇H₃₀BOP: C, 69.88; H, 10.35. Found: C, 69.93; H,

10.22.

2424

K. Modzelewski, S. Sowa

Paper

Synthesis

(S_P)-Isopropyl(phenyl)phosphinous Acid-Borane L-Menthyl Ester

[(S_P)-20d] (Table 5, entry 7), General Procedure C

(R_P)-Methoxymethyl(phenyl)phosphinous Acid-Borane L-Menthyl

Ester [(R_P)-20f] (Table 5, entry 12), General Procedure C

(R_P)-19a (0.05 g, 0.149 mmol) reacted with i-PrI (0.373 mmol, 37.3

L) and NaH (6.3 mg, 0.156 mmol, 60% in mineral oil) according to

general procedure C to afford (S_P)-20d (0.038 g, 0.119 mmol, 80%) as a

colorless oil.

(R_P)-19a (0.05 g, 0.149 mmol) reacted with MOMCl (0.373 mmol, 27.8

L) and NaH (6.3 mg, 0.156 mmol, 60% in mineral oil) according to

general procedure C to afford (R_P)-20f (0.021 g, 0.066 mmol, 44%) as a

colorless oil.

[]_D²⁵–137.9 (c 1.25, CHCl₃); R_f= 0.69 (hexane/EtOAc, 10:1).

[]_D²⁵–105 (c 0.71, CHCl₃); R_f= 0.52 (hexane/EtOAc, 10:1).

IR (ATR, thin film): 2958, 2934, 2864, 2385, 1453, 1110, 978, 794 cm^–1

.

IR (ATR, thin film): 2954, 2626, 2868, 2378, 1437, 1111, 1009, 984,

694 cm^–1

.

¹H NMR (500 MHz, CDCl₃):  = 7.77–7.82 (m, 2 H), 7.49–7.53 (m, 1 H),

7.42–7.47 (m, 2 H), 3.99–4.06 (m, 1 H), 2.25–2.29 (m, 1 H), 2.18–2.29

(m, 1 H), 1.67–1.74 (m, 1 H), 1.56–1.67 (m, 2 H), 1.40–1.49 (m, 1 H),

1.25–1.39 (m, 2 H), 1.21 (dd, J_H–H= 6.94 Hz, J_H–H= 16.08 Hz, 3 H), 1.05–

1.12 (m, 1 H), 0.94 (dd, J_H–H= 7.25 Hz, J_H–H= 16.71 Hz, 3 H), 0.93 (d,

J_H–H= 6.62 Hz, 3 H), 0.78–0.99 (m, 1 H), 0.75 (d, J_H–H= 7.25 Hz, 3 H),

0.42–1.00 (br m, 3 H), 0.31 (d, J_H–H= 6.94 Hz, 3 H).

¹H NMR (500 MHz, CDCl₃):  = 7.73–7.88 (m, 2 H), 7.52–7.56 (m, 1 H),

7.46–7.50 (m, 2 H), 4.06–4.15 (m, 1 H), 3.89–3.98 (m, 2 H), 3.43 (s, 3

H), 2.22–2.28 (m, 1 H), 1.80–1.87 (m, 1 H), 1.59–1.69 (m, 2 H), 1.44–

1.52 (m, 1 H), 1.32–1.40 (m, 1 H), 1.12–1.19 (m, 1 H), 0.83–1.00 (m, 2

H), 0.95 (d, J_H–H= 6.62 Hz, 3 H), 0.80 (d, J_H–H= 6.94 Hz, 3 H), 0.51 (d,

J_H–H= 6.94 Hz, 3 H), 0.47–1.18 (br m, 3 H).

4

¹³C NMR (125 MHz, CDCl₃):  = 131.6 (d, J_P–C= 2.7 Hz, C), 131.5 (d,

¹³C NMR (125 MHz, CDCl₃):  = 132.0 (d, J_P–C= 1.8 Hz, CH), 131.4 (d,

²J_P–C= 10.9 Hz, CH), 131.3 (d, ¹J_P–C= 56.3 Hz, CH), 130.6 (d, ³J_P–C= 10.0

²J_P–C= 10.0 Hz, CH), 130.1 (d, J_P–C= 63.8 Hz, C), 128.4 (d, J_P–C= 10.0

Hz, CH), 80.2 (d, ²J_P–C= 3.6 Hz, CHO), 70.3 (d, ¹J_P–C= 52.7 Hz, CH₂), 61.8

(d, ³J_P–C= 8.2 Hz, OCH₃), 48.7 (d, J_P–C= 4.4 Hz, CH), 43.4 (s, CH₂), 34.1 (s,

CH₂), 31.5 (s, CH), 25.5 (s, CH), 22.7 (s, CH₂), 22.2 (s, CH₃), 20.9 (s, CH₃),

15.3 (s, CH₃).

1

2

Hz, CH), 79.5 (d, ²J_P–C= 4.5 Hz, CHO), 48.8 (d, J_P–C= 5.5 Hz, CH), 43.6 (s,

1

CH₂), 34.1 (s, CH₂), 31.4 (s, CH), 29.6 (d, J_P–C= 46.3 Hz, CH), 25.4 (s,

CH₃), 22.6 (s, CH₂), 22.1 (s, CH₃), 20.9 (s, CH₃), 16.1 (s, CH₃), 15.6 (d,

²J_P–C= 2.7 Hz, CH₃), 15.0 (s, CH₃).

³¹P NMR (202 MHz, CDCl₃):  = 117.14 (br m).

¹¹B NMR (160 MHz, CDCl₃):  = –39.70 (br m).

³¹P NMR (202 MHz, CDCl₃):  = 104.62 (br m).

¹¹B NMR (160 MHz, CDCl₃):  = –41.75 (br m).

MS (EI, 70 eV): m/z (%) = 170 (10), 169 (100), 168 (82) [M – BH₃

₁₀H₁₂]⁺, 138 (12), 126 (54), 125 (68), 109 (21), 96 (10), 95 (48).

–

MS (EI, 70 eV): m/z (%) = 172 (11), 171 (74) [M – BH₃– C₁₀H₁₉]⁺, 141

(12), 140 (100), 138 (12), 134 (25), 125 (52), 121 (21), 95 (49).

C

HRMS (ESI): m/z [(M – BH₃+ O) + Na]⁺calcd for C₁₉H₃₁O₂PNa:

345.1954; found: 345.1953.

Anal. Calcd for C₁₈H₃₂BO₂P: C, 67.09; H, 10.01. Found: C, 67.15; H,

10.18.

Anal. Calcd for C₁₉H₃₄BOP: C, 71.26; H, 10.70. Found: C, 71.56; H,

10.80.

L-Menthoxy(phenyl)phosphine-Borane (21) (Table 5, entry 11),

General Procedure C³³

(R_P)-19a (0.05 g, 0.149 mmol) reacted with MOMCl (0.179 mmol, 17.9

L) and NaH (6 mg, 0.149 mmol, 60% in mineral oil) according to gen-

eral procedure C to afford an inseparable mixture of (R_P)-20f (20%)

and 21 (11%) (yields determined from the ¹H NMR spectrum).

(S_P)-Allyl(phenyl)phosphinous Acid-Borane L-Menthyl Ester

[(S_P)-20e] (Table 5, entry 10), General Procedure C

(R_P)-19a (0.05 g, 0.149 mmol) reacted with allyl bromide (0.224

mmol, 19.3 L) and NaH (6.3 mg, 0.156 mmol, 60% in mineral oil) ac-

cording to general procedure C to afford (S_P)-20e (0.038 g, 0.119

mmol, 80%) as a colorless oil.

R_f= 0.45 (hexane/EtOAc, 10:1).

¹H NMR (500 MHz, CDCl₃):  = 7.78–7.83 (m, 2 H), 7.55–7.62 (m, 2 H),

7.51–7.55 (m, 1 H), 7.14 (dq, J_P–H= 340.68 Hz, J_H-H= 5.67 Hz, 1 H),

3.99–4.06 (m, 1 H), 2.03–2.10 (m, 1 H), 1.91–1.99 (m, 1 H), 1.59–1.66

(m, 2 H), 1.41–1.51 (m, 1 H), 1.31–1.40 (m, 1 H), 1.05–1.12 (m, 1 H),

0.83–1.00 (m, 2 H), 0.92 (d, J_H–H= 6.62 Hz, 3 H), 0.85 (d, J_H–H= 7.09 Hz,

3 H), 0.71 (d, J_H–H= 6.94 Hz, 3 H), 0.50–1.15 (br m, 3 H).

[]_D²⁵–105 (c 1.215, CHCl₃); R_f= 0.67 (hexane/EtOAc, 6:1).

IR (ATR, thin film): 2926, 2866, 2379, 1437, 984, 772 cm^–1

.

¹H NMR (500 MHz, CDCl₃):  = 7.77–7.82 (m, 2 H), 7.50–7.54 (m, 1 H),

7.44–7.48 (m, 2 H), 5.62–5.74 (m, 1 H), 5.00–5.12 (m, 2 H), 4.01–4.10

(m, 1 H), 2.75–2.87 (m, 2 H), 2.20–2.27 (m, 1 H), 1.72–1.79 (m, 1 H),

1.57–1.67 (m, 2 H), 1.42–1.51 (m, 1 H), 1.26–1.35 (m, 1 H), 1.06–1.13

(m, 1 H), 0.82–0.97 (m, 2 H), 0.94 (d, J_H–H= 6.31 Hz, 3 H), 0.77 (d, J_H–H

6.94 Hz, 3 H), 0.51–1.13 (br m, 3 H), 0.44 (d, J_H–H= 6.94 Hz, 3 H).

4

¹³C NMR (125 MHz, CDCl₃):  = 132.6 (d, J_P–C= 1.8 Hz, CH), 132.0 (d,

²J_P–C= 9.1 Hz, CH), 129.0 (d, ¹J_P–C= 66.3 Hz, C), 128.8 (d, ²J_P–C= 10.0 Hz,

=

2

CH), 80.3 (d, J_P–C= 6.4 Hz, CHO), 48.7 (d, J_P–C= 5.5 Hz, CH), 42.0 (d,

J_P–C= 1.8 Hz, CH₂), 34.0 (s, CH₂), 31.4 (s, CH), 25.5 (s, CH), 22.9 (s, CH₂),

22.0 (s, CH₃), 20.9 (s, CH₃), 15.8 (s, CH₃).

³¹P NMR (202 MHz, CDCl₃):  = 93.17 (br m).

MS (EI, 70 eV): m/z (%) = 126 (100) [M – BH₃– C₁₀H₁₉]⁺, 125 (52), 123

(13), 109 (33), 95 (12), 83 (31), 81 (21).

4

¹³C NMR (125 MHz, CDCl₃):  = 131.7 (d, J_P–C= 2.7 Hz, CH), 131.6 (d,

2

3

¹J_P–C= 60.9 Hz, C), 131.0 (d, J_P–C= 10.0 Hz, CH), 128.3 (d, J_P–C= 10.0

Hz, CH), 127.8 (d, ²J_P–C= 6.4 Hz, CH), 120.1 (d, ³J_P–C= 10.9 Hz, CH₂), 79.8

(d, ²J_P–C= 3.6 Hz, CHO), 48.8 (d, J_P–C= 5.5 Hz, CH), 43.7 (s, CH₂), 38.1 (d,

¹J_P–C= 41.8 Hz, CH₂), 34.1 (s, CH), 34.5 (s, CH), 25.5 (s, CH), 22.7 (s,

CH₂), 22.2 (s, CH₃), 20.9 (s, CH₃), 15.2 (s, CH₃).

³¹P NMR (202 MHz, CDCl₃):  = 107.82 (br m).

¹¹B NMR (160 MHz, CDCl₃):  = –41.16 (br m).

(S_P)-Isopropyl(phenyl)phosphinous Acid-Borane L-Menthyl Ester

[(S_P)-20d] (Table 5, entry 8), General Procedure C

(R_P)-19a (0.05 g, 0.149 mmol) reacted with i-PrBr (0.373 mmol, 34.9

L) and NaH (6.3 mg, 0.156 mmol, 60% in mineral oil) according to

general procedure C to afford (S_P)-20d (0.021 g, 0.061 mmol, 45%).

MS (EI, 70 eV): m/z (%) = 168 (6), 167 (52), 166 (33) [M – BH₃

₁₀H₁₉]⁺, 139 (12), 126 (6), 125 (100), 123 (12), 95 (49).

–

C

Anal. Calcd for C₁₉H₃₂BOP: C, 71.71; H, 10.14.; Found: C, 71.80; H,

10.26.

2425

K. Modzelewski, S. Sowa

Paper

Synthesis

(S_P)-Benzyl(phenyl)phosphinous Acid-Borane L-Menthyl Ester

[(S_P)-20a] (Table 5, entry 13), General Procedure C

2008, 51, 4315. (d) Fougère, C.; Guénin, E.; Hardouin, J.;

Lecouvey, M. Eur. J. Org. Chem. 2009, 6048. (e) Yao, Q.; Yuan, C.

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(h) Kinbara, A.; Ito, M.; Abe, T.; Yamagishi, T. Tetrahedron 2015,

71, 7614.

(R_P)-19b (0.056 g, 0.149 mmol) reacted with PhCH₂Cl (0.179 mmol,

20.6 L) and NaH (6 mg, 0.149 mmol, 60% in mineral oil) according to

general procedure C to afford (S_P)-20a (0.047 g, 0.127 mmol, 85%).

(S_P)-Methyl(phenyl)phosphinous Acid-Borane L-Menthyl Ester

[(S_P)-20c] (Table 5, entry 14), General Procedure C^33a

(R_P)-19b (0.056 g, 0.149 mmol) reacted with MeI (0.373 mmol, 23.2

L) and NaH (6.3 mg, 0.156 mmol, 60% in mineral oil) according to

general procedure C to afford (S_P)-20c (0.039 g, 0.136 mmol, 91%).

(5) Hall, P. G.; Riebli, P. Synlett 1999, 1633.

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(b) Coudray, L.; Kantrowitz, E. R.; Montchamp, J.-L. Bioorg. Med.

Chem. Lett. 2009, 19, 900. (c) Coudray, L.; Pennebaker, A. F.;

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dron 2008, 64, 9181.

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4185.

(S_P)-Isopropyl(phenyl)phosphinous Acid-Borane L-Menthyl Ester

[(S_P)-20d] (Table 5, entry 15), General Procedure C

(R_P)-19b (0.056 g, 0.149 mmol) reacted with i-PrI (0.373 mmol, 37.3

L) and NaH (6.3 mg, 0.156 mmol, 60% in mineral oil) according to

general procedure C to afford (S_P)-20d (0.031 g, 0.098 mmol, 66%).

(S_P)-Allyl(phenyl)phosphinous Acid-Borane L-Menthyl Ester

[(S_P)-20e] (Table 5, entry 16), General Procedure C

(R_P)-19b (0.056 g, 0.149 mmol) reacted with allyl bromide (0.373

mmol, 32.3 L) and NaH (6.3 mg, 0.156 mmol, 60% in mineral oil) ac-

cording to general procedure C to afford (S_P)-20e (0.031 g, 0.098

mmol, 66%).

(12) Gatineau, D.; Nguyen, D. H.; Herault, D.; Vanthuyne, N.; Leclaire,

J.; Giordano, L.; Buono, G. J. Org. Chem. 2015, 80, 4132.

(13) Berger, O.; Gavara, L.; Montchamp, J.-L. Org. Lett. 2012, 14, 3405.

(14) Berger, O.; Montchamp, J.-L. Angew. Chem. Int. Ed. 2013, 52,

11377; Angew. Chem. 2013, 125, 11587.

(15) (a) Berger, O.; Montchamp, J.-L. Chem. Eur. J. 2014, 20, 12385.

(b) Berger, O.; Montchamp, J.-L. Org. Biomol. Chem. 2016, 14,

7552.

Acknowledgment

Sylwia Sowa thanks Prof. Marek Stankevič for support and fruitful

conversations during the preparation of this manuscript. The authors

wish to thank Dr. Duncan Carmichael for kindly reading the manu-

script.

(16) Postle, S. R.; Whitham, G. H. J. Chem. Soc., Perkin Trans. 1 1977,

2084.

Supporting Information

(17) Cristau, H. J.; Virieux, D. Tetrahedron Lett. 1999, 40, 703.

(18) Yao, Q.; Yuan, C. J. Org. Chem. 2012, 77, 10985.

(19) Min, M.; Kang, D.; Jung, S.; Hong, S. Adv. Synth. Catal. 2016, 358,

1296.

Supporting information for this article is available online at

https://doi.org/10.1055/s-0040-1707104.

S

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orit

n

gInformati

o

n

S

u

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orti

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n

(20) Li, C.; Yano, T.; Ishida, N.; Murakami, M. Angew. Chem. Int. Ed.

2013, 52, 9801; Angew. Chem. 2013, 125, 9983.

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Article Doi

Alkylation of phosphinite/phosphonite-boranes via temporary protection of the P-H bond

DOI: 10.1055/s-0040-1707104

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Full text of DOI:10.1055/s-0040-1707104

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