Reactions of organoboranes with carbanions bearing three potential leaving groups: unusual processes, products and mechanisms

Accepted Manuscript

Reactions of organoboranes with carbanions bearing three potential leaving groups:

unusual processes, products and mechanisms

Basil A. Saleh, Keith Smith, Mark C. Elliott, D.Heulyn Jones, Benson M. Kariuki,

Gamal A. El Hiti

PII:

S0040-4020(16)30899-7

10.1016/j.tet.2016.09.005

TET 28076

DOI:

Reference:

To appear in: Tetrahedron

Received Date: 22 July 2016

Revised Date: 1 September 2016

Accepted Date: 5 September 2016

Please cite this article as: Saleh BA, Smith K, Elliott MC, Jones DH, Kariuki BM, El Hiti GA, Reactions of

organoboranes with carbanions bearing three potential leaving groups: unusual processes, products and

mechanisms, Tetrahedron (2016), doi: 10.1016/j.tet.2016.09.005.

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Reactions of organoboranes with carbanions

bearing three potential leaving groups:

Unusual processes, products and

mechanisms

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Basil A. Saleh,^a,bKeith Smith,^a,*Mark C. Elliott,^a,*D. Heulyn Jones,^aBenson M. Kariuki^aand Gamal A. El Hiti^c

^aSchool of Chemistry, Cardiff University, Main Building, Park Place, Cardiff, CF10 3AT, UK

^bDepartment of Chemistry, College of Science, University of Basrah, Basrah, Iraq

^cCornea Research Chair, Department of Optometry, College of Applied Medical Science, King Saud University, P. O. Box 10219, Riyadh 11443, Saudi

Arabia

1

ACCEPTED MANUSCRIPT

Tetrahedron

journal homepage: www.elsevier.com

Reactions of organoboranes with carbanions bearing three potential leaving groups:

unusual processes, products and mechanisms

Basil A. Saleh^a,b, Keith Smith^a,*, Mark C. Elliott^a,*, D. Heulyn Jones^a, Benson M. Kariuki^aand Gamal A. El

Hiti^c

^aSchool of Chemistry, Cardiff University, Main Building, Park Place, Cardiff, CF10 3AT, UK

^bDepartment of Chemistry, College of Science, University of Basrah, Basrah, Iraq

^cCornea Research Chair, Department of Optometry, College of Applied Medical Science, King Saud University, P. O. Box 10219, Riyadh 11443, Saudi Arabia

ARTICLE INFO

ABSTRACT

Article history:

Received

Received in revised form

Accepted

Known reagents that transfer three alkyl groups of a trialkylborane intramolecularly to a single

carbon atom lack features to influence stereochemistry. We have investigated four reagents of

type LiCCl₂X, where X might be amenable to variation. All behaved differently. With X = OR

(R = cyclohexyl, menthyl), the reagent decomposed, leading to only low yields of triple

migration products. With X = S(O)Ph, a single migration occurred, followed by isomerisation to

boron enolate-like species that hydrolysed to α-chloroalkyl phenyl sulfoxides or reacted with

aldehydes to aldol-like products. With X = SO₂Ph, the major product was the corresponding α,α-

dichloroalkyl phenyl sulfone, apparently formed through a redox reaction. With X =

S(O)(NMe)Ph, products of three intramolecular alkyl migrations were obtained with unhindered

trialkylboranes. Attempts have been made to gain understanding of the sulfoxide process by

investigating proportions of aldol-like products, using X-ray crystallography and ab initio

calculations.

Available online

Keywords:

Keyword_1 Trialkylborane

Keyword_2 Sulfoximine

Keyword_3 Rearrangement

Keyword_4 Sulfoxide

Keyword_5 Sulfone

.

1. Introduction

R¹

R³

R²

B

+

CCl₂OMe

MeOCl₂B

C

R³

R²

Rearrangement reactions of organoboron species provide

many well-established synthetic methods, several of which have

no counterparts outside of organoboron chemistry. For example,

several types of reaction, including carbonylation,¹cyanidation²

and the DCME (dichloromethyl methyl ether) reaction (Scheme

1),³allow transfer of all three alkyl groups from a trialkylborane

H₂O₂

NaOH

R¹

HO

C

R³

R²

to

a single carbon atom to generate tertiary-alkylboron

Scheme 1. Formation of tertiary alcohols by reaction of a

compounds, which can be oxidised to tertiary alcohols. Under

different conditions the carbonylation reaction can be controlled

to allow synthesis of products from just one or two alkyl group

migrations,⁴and cyanidation can also be controlled to give

products of two alkyl migrations,⁵but the DCME reaction

proceeds so readily to give three migrations that it cannot be

stopped at an intermediate stage except by using alternative

substrates possessing fewer alkyl groups.

trialkylborane with the anion of DCME

In principle, variants of the DCME reaction could have

enormous synthetic potential, for example if one or more of the

three leaving groups on carbon could be changed to render it less

readily displaced (so that the reaction could be intercepted before

all three groups had migrated) or incorporate a chiral moiety

(leading to the possibility of asymmetric induction). However,

only a few attempts at variation have been reported. Anions

derived from haloforms behave in much the same manner as the

anion from DCME, although the yields are somewhat poorer.⁶

The reactions of trialkylboranes with the anion derived from

tris(phenylthio)methane result in two spontaneous alkyl group

migrations, allowing synthesis of ketones following oxidation,

but the third migration can be induced by addition of mercuric

chloride to the mixture.⁷

2

Tetrahedron

In the present study we have undertaken reactions of

appropriate alkoxydichloromethane that might react in the

ACCEPTED MANUSCRIPT

organoboranes with anions derived from an alternative

alkoxydichloromethane, dichloromethyl sulfoxide,

desired manner, in view of the disappointing results with 1 we

a

decided to look instead at alternative types of reagents.

dichloromethyl sulfone and a dichloromethyl sulfoximine. The

behaviour of each anion type turned out to be quite different from

the others, revealing some new reaction types and indicating

some novel reaction mechanisms.

Reaction

with

(dichloromethylsulfinyl)benzene

(6):

Compound 6 offers interesting possibilities as a reagent because

of its chirality, resulting from the presence of a stereogenic sulfur

atom. It was prepared by chlorination of methyl phenyl sulfoxide

according to a literature procedure¹⁴and was obtained as a

colourless oil in 73% yield after column chromatography. We

presumed that the two chloride groups would be more readily

displaced than the sulfoxide group but hoped that the third group

might be susceptible to displacement under appropriate

conditions.¹⁵

2. Results and Discussion

Reaction with dichloro(menthyloxy)methane (1): The

simplest analogues of DCME, which might nevertheless offer

interesting new possibilities in reactions with trialkylboranes,

would involve replacing the methoxy group of DCME by an

alternative alkoxy group. We decided to investigate the reactions

of dichloro(menthyloxy)methane (1), the anion of which (2)

might complex to an unsymmetrical trialkylborane (i.e. one

bearing three different alkyl groups) to give two different

diastereoisomeric complexes (3 and 4), the stabilities of which

would not be identical and the rearrangements of which might

differ in terms of which diastereotopic chlorine would be

displaced first and/or which alkyl groups were located

appropriately to displace particular leaving groups (Fig. 1).⁸In

principle, this could lead to the production of a significant excess

of one enantiomer of the final tertiary alcohol over the other.

Therefore, we decided to look at the reaction of the anion with

such an unsymmetrical trialkylborane, and in order that the three

alkyl groups should have significantly different characteristics

and the tertiary alcohol product could be readily monitored by

A solution of trioctylborane was prepared by hydroboration of

1-octene with borane dimethyl sulfide complex in THF. This was

then added at –78 °C to a solution of anion 7, prepared by

deprotonation of 6 (1 equiv.) using lithium diisopropylamide

(LDA, 1.1 equiv.). The solution was stirred at –78 °C for 1 h then

the cooling bath was removed and the mixture stirred for a

further 1 h before oxidation of the organoboron product with

alkaline hydrogen peroxide. Work-up and separation of the

products by column chromatography gave the products expected

from two alkyl group migrations (dioctyl ketone, 8, Scheme 2)

and three alkyl group migrations (trioctylmethanol, 9), but in low

isolated yields, 3% and 1%, respectively; GC yields were 6% and

3% respectively. The major product (57% yield) was a

diastereoisomeric mixture of 1-chlorononyl phenyl sulfoxides

(10a), evidently formed via a single alkyl group migration

followed by hydrolysis of the organoboron intermediate rather

than oxidation. The rest of the material was octanol, resulting

from the oxidation of residual octylboron moieties. All of the

products contained small quantities of the 2-octyl isomers

because of the formation of about 6% of 2-octyl groups during

the hydroboration step.

HPLC,

we

selected

cyclopentyl(2-(4-

methoxyphenyl)ethyl)thexylborane (5) as the substrate.

CHCl₂

CCl₂

O

To our knowledge there are no known reactions of substituted

sulfoxides with organoboron compounds similar to that resulting

in the formation of compound 10a. Reactions of

dimethylsulfoxonium ylides with trialkylboranes are known, but

in those reactions dimethyl sulfoxide serves as a leaving group.¹⁶

Reactions of α-chlorosulfoxides with alkyllithium reagents in the

presence of alkylboronate esters result in thiophilic addition of

the alkyllithium to the sulfoxide followed by elimination of

sulfoxide with formation of an α-chloroalkyllithium species,

which then goes on to bring about homologation of the boronate

ester.¹⁷However, the formation of 10a appears to be more akin in

nature to the formation of homologated carbonyl compounds by

reactions of trialkylboranes with diazocarbonyl compounds¹⁸or

with anions derived from α-bromocarbonyl and related

compounds.¹⁹In those reactions the isolable boron intermediates

are boron enolates.²⁰Similar base-induced reactions occur with

α-bromosulfonyl compounds.²¹We assume the present reaction is

similar and that the boron-containing product of the reaction with

a generalised trialkylborane is 12, formed by rearrangement of

the initially formed intermediate 11 (Scheme 3).

1

2

MeO

R^A

Cl Cl

B

R^A

R^B

O

B

O

B

R^B

R^C

3

4

5

Fig. 1. Structures 1-5

The first task was to prepare 1. A literature procedure⁹was

used to prepare the formate ester of (–)-menthol, the purity of

which was confirmed by comparison of its reported H NMR

1

data⁹and its reported optical rotation¹⁰with those of the isolated

product. Several different methods^{11,12 ,13}were tried in order to

convert the menthyl formate into 1. In all cases there were

problems with formation of menthyl chloride as a significant by-

product, but a reasonably pure sample of 1 could be obtained by

use of a mixture of PCl₅and POCl₃to introduce the chlorines,

then removal of the POCl₃under reduced pressure and extraction

of the product into hexane, leaving the PCl₅as a residue.

Unfortunately, when this product was subjected to a standard

DCME-like reaction with 5, no tertiary alcohol was formed. Even

with the less hindered tri-n-octylborane and tricyclopentylborane

only very low yields of tertiary alcohols were obtained (5% and

4%,

respectively)

and

similarly

generated

cyclohexyloxydichloromethane also did not provide encouraging

results. Although we did not rule out the possibility of finding an

3

presumably because of the lower electrophilicity of the boron

reagent.

ACCEPTED MANUSCRIPT

Li

O

S

O

S

LDA

Ph

CHCl₂

Ph

CCl₂

Table 1. Preparation of 1-chloroalkyl sulfoxides (10)

according to Scheme 3

6

7

Product

R

Yield (%)^b

Diastereoisomer

ratio^a

i, Oct₃B

ii, H₂O₂,

NaOH

10a

10a^d

10b

10c

10d^e

10e

10f

Oct^c

61

40

92

88

40

0

84:16

82:18

78:22

84:16

81:19

–

Oct^d

O

S

Et

OH

Oct

O

Oct

+

Bu

Oct

Ph

Oct

e

Cl

10a, 57%

PhCH₂CH₂

8, 3%

9, 1%

Cyclopentyl

Ph

Scheme 2. Initial reaction of the anion derived from 6 with

trioctylborane

0

–

^aDetermined from the¹H NMR spectrum of the crude product prior to

purification.

O

S

R

B

R

R₃B

Li

O

S

Ph

R

^bIsolated yield for the mixture of diastereoisomers.

Cl

Ph

CCl₂

Cl

^cOnly around 82% of the R₃B molecules would be (1-Oct)₃B because the

7

hydroboration gives ca. 6% of 2-octyl groups.

^d9-Oct-9-BBN was used in this case.

BR₂

R

^eOnly around 40-50% of the R₃B molecules would be (PhCH₂CH₂)₃B

because the hydroboration gives ca. 20% of 1-phenylethyl groups.

O

S

O

S

O

S

H₂O

R

Ph

Cl

BR₂

Cl

In order to address point 2 we have compared the chemical

shifts of the protons adjacent to Cl for the two diastereoisomers

of 10a with those reported for 1-chloroethyl phenyl sulfoxide

(PhS(O)CHClCH₃, 10g, R = Me) prepared by methylation of 7.

For 10a the signals for the two isomers were at δ 4.46 (minor

isomer, 22%) and 4.36 (major isomer, 78%) ppm. For 10g, the

situation is more confused; reported values are 4.70 (major

isomer, 60%) and 4.50 (minor isomer, 40%) ppm in one report,²³

but the other way round, in unspecified proportions and lower

yield, in another.²⁴Clearly, the selectivity is low for this reaction,

but somewhat better for the new reaction. Because of the

contradictory data in the literature, we have repeated the

literature reaction giving the higher yield and confirm that it

gives the two diastereoisomers in around 60:40 proportions, with

the predominant diastereoisomer being the one that is the minor

one in the novel organoborane reaction.

Cl

10

12

11

Scheme 3. Possible mechanism for the formation of 10

Compounds of type similar to 10a have been prepared by

alkylation of anions derived from aryl chloromethyl sulfoxides

with alkyl halides²²and are useful synthetic intermediates.

Several interesting questions therefore arise.

1. Can a wider range of organic groups be introduced using

the route of Scheme 3 than is possible by nucleophilic

substitution reactions of organic halides?

2. How do the proportions of diastereoisomers formed

according to Scheme 3 compare with those formed by

alkylation of the anions derived from chloromethyl

sulfoxides? Is the predominant isomer the same one?

Point 3 was addressed by carrying out reactions of 7 with

triethylborane up to the point where intermediate 12 would be

formed and then adding alternative electrophiles (D₂O, Ph₂I⁺TfO^-

, substituted benzaldehydes) before work-up. Use of D₂O gave

the expected deuterio analogue of 10b, while diphenyliodonium

triflate did not react. The most interesting reactions involved the

substituted benzaldehydes (Scheme 4).

3. Could the intermediates of type 12 provide other useful

products by reaction with other electrophiles?

We have conducted some experiments to help answer such

questions.

To address point 1, we optimised the reaction conditions,

including replacing the oxidation step by a simple hydrolysis step

with aqueous ammonium chloride solution, and then we carried

O

BEt₂

R

Et

B

O

S

LDA

Et₃B

O

S

out reactions with

triethylborane,

a

range of organoboranes, including

Ar

H

Ph

Cl

S

O

Et

tributylborane, tricyclopentylborane,

Ph

CHCl₂

Ar

triphenylborane, the trialkylborane mixture formed by

hydroboration of styrene, and 9-octyl-9-borabicyclo[3.3.1]nonane

(9-Oct-9-BBN). The pure tri-prim-alkylboranes gave good yields

of compounds 10, but the yields from the impure cases (formed

by hydroboration of 1-octene and styrene) were much lower,

presumably because of lower proportions of tri-prim-

alkylboranes present in the mixtures, while tricyclopentylborane

and triphenylborane gave no comparable products (Table 1).

9-Oct-9-BBN gave 40% of 10a. From these results it would seem

that only relatively unhindered organoboranes take part in the

reaction, presumably because the initial complexation of the

anion with more hindered organoboranes is impeded. Also, no

reaction took place with pinacol butylboronate, in this case

Et

Cl

6

12 (R = Et)

13

O

S

OH

Ar

Ph

Cl

Et

14

Scheme 4. Reactions of 6 with Et₃B and then benzaldehydes

4

Tetrahedron

All six substituted benzaldehydes tested gave aldol-like

derived from 14a(iv). By a process of elimination, therefore, the

ACCEPTED MANUSCRIPT

products 14 as mixtures of diastereoisomers, in combined yields

of 45–58% (isolated, following column chromatography),

sometimes along with small quantities of an impurity (15). In

principle, four diastereomers of 14 are possible and in several

examples all four were formed. If the transition state were to be a

tight cyclohexane-like structure 13, similar to that involved in

reactions of boron enolates with aldehydes, then one might have

expected the Ph and Ar groups to be pseudo-equatorial, leading

to a SR or RS relationship for the configurations of the S atom

and the carbon atom bearing the hydroxyl group, with the

configuration of the double bond in 12 determining the

configuration of the chlorine-bearing carbon atom in 14.

However, the pseudo-tetrahedral arrangement of groups around

the sulfur atom in 12, compared to the trigonal arrangement of

groups around the corresponding carbon atom in boron enolates,

would obviously have a significant effect. The presence of at

least three diastereoisomers in all of the present cases and all four

in some suggests that the stereo-control is much less than for the

related aldol reactions of boron enolates.²⁵

structure of diastereoisomer 14a(ii) must be as shown in Fig. 2.

Having conclusively established the identities of the four

diastereoisomers of 14a, we assigned the structures of the

diastereoisomers of the other products of type 14 by reference to

their NMR spectra, particularly noting the chemical shift of the

CHOH proton and its coupling constant to the OH proton. Table

2 shows the yields of the different diastereoisomers for the

various products 14.

Table 2. Yields of diastereoisomers of compounds 14 formed

according to Scheme 4

Compound

Yield of specific diastereoisomer (%)^aTotal

product yield

(%)^b

(i)

(ii)

(iii)

(iv)

14a

14b

14c

14d

14e

23

18

10

22

2.5

–

14

17

14

11

18

17

10

20

9

57.5

52

–

45

4

48

Nevertheless, it was of interest to identify which

diastereoisomers were predominant, so the reaction with

benzaldehyde (giving product 14a) was investigated more

closely. The structures of one enantiomer of each of the four

possible diastereoisomers (all of which were inevitably racemic)

are given in Fig. 2. The crude product 14a was separated by

chromatography (silica; 3% ethyl acetate/chloroform).

8

50

^aAmount of pure material isolated after chromatography or calculated by

proportion of each component in a fraction after chromatography.

^bBy addition of yields of individual diastereoisomers; yields of crude product

prior to chromatography were greater.

Assuming a chair transition state in which the phenyl group of

the sulfoxide and the aryl group of the aldehyde are pseudo-

equatorial, stereoisomers (iii) and (iv) might have been expected

to predominate. Instead, three diastereoisomers were formed in

broadly comparable yields (9-23%), while the other

diastereoisomer (ii) was invariably formed in low yield (0-8%). It

was not immediately clear why one isomer was formed in so

much lower yield than the others, so these aspects were probed

computationally.

O

OH

O

OH

(R)

(S)

S

(R)

Ph

Ar

Ph

_(R)Ar

(R)

Cl Et

Et Cl

14(i)

14(ii)

O

S

OH

Ar

O

OH

O

OH

Calculations were carried out using Spartan 10 at the

B3LYP/6-31G(d) level of theory. Initially the geometry of the

sulfoxide enolate was investigated. Two local minima were

identified, corresponding to the structures shown in Fig. 3. In

both cases, the phenyl ring can be considered to be either pseudo

E or pseudo Z to the Et group, although there is significant

deviation from planarity, with a Et-C-S-Ph dihedral angle of 163°

for 12E and 39° for 12Z. The isomer designated 12E is

calculated to be 5.3 kJmol^-1more stable than 12Z.

(S)

S

(R)

(S)

Ph

Ar

(R)

(S)

Ph

Ar

(R)

Cl Cl

Et Cl

Cl Et

15

14(iii)

14(iv)

(a, Ar = Ph; b, Ar = 3-MeOC₆H₄; c, Ar = 4-MeOC₆H₄;

d, Ar = 4-BrC₆H₄; e, Ar = 4-FC₆H₄)

Fig. 2. Structures of the diastereoisomers of 14 and the impurity 15

formed alongside them

BEt₂

O

BEt₂

O

Ph

The first isomer eluted from the column (23% yield) was a

solid with relative stereochemistry, as confirmed by X-ray

crystallography, of RRR/SSS, confirming it as 14a(i). The second

isomer to elute (referred to as 14a(ii), 2.5% yield) was

contaminated with a single diastereoisomer of 15a (2.5% yield),

formed by direct reaction of anion 7 with benzaldehyde. This was

Et

S

Cl

S

Ph

Cl

Et

12E

-1465.61044 H

12Z

-1465.60844 H

Fig. 3. Calculated structures (B3LYP/6-31G(d)) and energies of major

and minor isomers of intermediate 12 (R = Et)

confirmed by independent synthesis of

a

mixture of

diastereoisomers of 15a by deprotonation of 6 with LDA

followed by addition of benzaldehyde. The sample of 14a(ii) was

contaminated with the less polar of the two isomers of 15a,

although the stereochemistry of this compound was not

determined. The third and fourth isomers (14a(iii) and 14a(iv),

total yield 32%; ca. 18% of one and 14% of the other isomer) co-

eluted, so they were converted into their 4-nitrobenzoates by

reaction with 4-nitrobenzoyl chloride in the presence of

triethylamine. The 4-nitrobenzoate esters were separated by

column chromatography and the individual isomers were then

characterised by X-ray crystallography, confirming the least

polar one to be derived from 14a(iii) and the more polar one to be

After extensive conformational analysis based on

cyclohexane-like structure 13, four transition states were located

at the B3LYP/6-31G(d) level of theory and the relative energies

are summarised in Table 3 and the corresponding structures are

depicted in Fig. 4. The transition states TS3 and TS4, leading to

14a(iii) and 14a(iv) respectively, resemble twisted chairs in

which both phenyl rings are pseudo-equatorial. Transition state

TS2, leading to 14a(ii), also resembles a twisted chair in which

the aldehyde phenyl is now pseudo-axial. This would explain

why this transition state is considerably higher in energy. In

5

contrast, transition state TS1, leading to 14a(i) resembles a

twisted boat which now permits both phenyl rings to be pseudo-

equatorial, despite the 1,3-anti arrangement of oxygen atoms in

the product. Therefore, the calculations correctly predict the

minor stereoisomer, and the relatively small difference in energy

between the three lowest energy transition states means it would

be difficult to predict which will be the major isomer with any

level of confidence.

cooled to –78 °C and lithium bis(trimethylsilyl)amide

ACCEPTED MANUSCRIPT

(LiHMDS), which has previously been used for the

deprotonation of 16,²⁷was added dropwise. The solution was

stirred for 30 minutes at –78 °C and 90 minutes at room

temperature and then worked up. The only product isolated

following column chromatography was 17 (Scheme 5), in 46%

yield for R = Et and 44% yield for R = n-Bu. The structure of 17a

was confirmed by X-ray crystallography.

The formation of compound 17 formally involves replacement

of hydride by the alkyl group of the trialkylborane and is

therefore an oxidation product; some other component of the

reaction mixture must have been reduced. It is probably

significant that the yield of 17 was in each case less than 50%,

consistent with half of the original 16 having been reduced. At

this stage it is not clear what process might be occurring or even

whether the reaction is ionic or radical in nature, but it is an

interesting reaction worthy of further investigation in the future.

Table 3. Relative B3LYP/6-31G(d) Free Energies of TS1,

TS2, TS3 and TS4 Transition States

Transition

State

Diastereoisomer

G° (a.u.)

∆E (KJ/mol)

TS1

TS2

TS3

TS4

14a(i) (RRR)

14a(ii) (RSR)

14a(iii) (RRS)

14a(iv) (RSS)

–1811.05655

–1811.03936

–1811.05909

–1811.05351

6.7

51.8

0 (lowest)

14.7

O

S

O

i, R₃B, THF

R

S

CHCl₂

ii, LiHMDS

iii, NH₄Cl

Cl Cl

16

17

(a, R = Et, 46%; b, R = n-Bu, 44%)

Scheme 5. Reactions of the anion of 16 with trialkylboranes

Reaction with N-methyl-S-(dichloromethyl)-S-

phenylsulfoximine (18): The final reagent investigated was

compound 18, which was prepared by chlorination of

N,S-dimethyl-S-phenylsulfoximine with t-butyl hypochlorite

according to a known procedure.²⁸In the first experiment, an

equimolar mixture of 18 and trioctylborane in THF at –78 °C was

treated with LDA and the mixture allowed to warm up to room

temperature and stirred for 1 hour before oxidation with alkaline

hydrogen peroxide. Work up and gas chromatographic analysis

revealed the presence of octanol (corresponding to 37% of

original octyl groups), the product of two alkyl group migrations

(dioctyl ketone, 13% yield) and that of three alkyl group

migrations (trioctylmethanol, 39% yield). A few reactions were

conducted to try to optimise production of the triple migration

product. Use of dichloromethane as co-solvent, a 20% excess of

18 and an overnight reaction period gave a GC calculated yield of

81% of the tertiary alcohol 19 along with 11% of ketone 20 and

octanol corresponding to 12% of original octyl groups (all figures

inclusive of 2-octyl isomers). These conditions (except without

any THF present in the cases of the mixed trialkylboranes) were

adopted as standard and the procedure (Scheme 6) was applied to

a range of organoboranes that were either purchased or generated

in situ as described in the experimental section. The purpose of

these experiments was to establish the limitations of the reaction

and to determine whether the formation of the tertiary alcohol

products (19) resulted from sequential intramolecular transfers of

alkyl groups from boron to carbon. The results are given in Table

4.

TS1

TS2

TS3

TS4

Fig. 4: Calculated B3LYP/6-31G(d) TS1 TS2, TS3 and TS4 Transition

States

Compound 16 was prepared Reaction with dichloromethyl 4-

tolyl sulfone (16): Although reactions of trialkylboranes with the

anion 7 derived from (dichloromethylsulfinyl)benzene (6) had

provided some interesting new reaction types, displacement of

the sulfinyl group had not proved useful and the goal of

generating a tert-alkylboron compound in good yield had not

been realised. Therefore, it was decided to investigate the

reaction of the anion derived from compound 16, which contains,

instead of a sulfinyl group, a sulfonyl group, which should be a

better leaving group. It was recognised that this reagent would

not benefit from the possibility of asymmetric induction offered

by 6, and also that there was precedent in the case of a

monobromo-substituted sulfone for a reaction that resulted in

replacement of the Br by an alkyl group from the organoborane

in exactly the same way as seen with 6 (see above), but it was felt

nevertheless to be worthy of investigation. In the event, the major

product was of a completely different kind.

As can be seen from Table 4, all of the reactions involving tri-

prim-alkylboranes, sec-alkyl-di-prim-alkylboranes and phenyldi-

prim-alkylboranes gave significant yields of the triple migration

product. The modest yield from the reaction of triethylborane is

primarily due to loss of product through evaporation and/or

dissolution in water during the work-up procedure. The low yield

in the case of 2-phenyl-2-hexanol reflects the poor synthesis of

the mixed trialkylborane, which contained a substantial amount

of phenyldibutylborane. However, additional experiments

conducted with more hindered organoboranes such as

Compound 16 was prepared in 40% yield by a known route

from sodium 4-toluenesulfinate, KOH and chloroform.²⁶It was

mixed with a trialkylborane (Et₃B or Bu₃B), the mixture was

6

Tetrahedron

ACCEPTED MANUSCRIPT

dioctylthexylborane,

butyldicyclohexylborane,

like intermediate that can also be trapped with aldehydes to give

β-hydroxyalkyl sulfoxides. By contrast, a related sulfonyl-

substituted anion (X = 4-MeC₆H₄SO₂) reacts to give the product

of overall replacement of hydride by an alkyl group from the

trialkylborane. Finally, the anion derived from S-dichloromethyl-

N-methyl-S-phenylsulfoximine (X = PhSO(NMe)) reacts to give

the product of displacement of all three leaving groups by alkyl

groups from the trialkylborane, leading to tertiary alcohols on

oxidation. These results illustrate several different pathways,

some with unprecedented mechanistic implications.

tricyclohexylborane and triphenylborane did not give the

expected tert-alcohol products. The fact that the less hindered

mixed trialkylboranes gave rise to the corresponding tertiary

alcohols verified that the reactions involve three intramolecular

organic group transfers, and this opens the way potentially to a

process involving asymmetric induction if an appropriate

enantiomerically enriched sulfoximine is used. This will be

explored in future work.

4. Experimental section

OH

R¹R³

Triethylborane and tributylborane were purchased as 1M

solutions in THF and used directly. Other simple trialkylboranes

and 9-alkyl-9-BBN were made by reaction of borane dimethyl

sulfide or 9-BBN with the corresponding alkene according to

R²

19

i, R¹R²R³B

NMe

O

S

+

CHCl₂

well

established

procedures.²⁹

Other

unsymmetrical

ii, LDA

O

iii, H₂O₂, NaOH

trialkylboranes were prepared in situ by sequential additions of

Et₃SiH and an alkene in the presence of BuLi to BCl₃or PhBCl₂

according to a literature method.³⁰The organoboranes prepared

by the latter approach were generally mixtures of different

trialkylboranes. NMR signal assignments are based on expected

chemical shifts and coupling patterns and have not been

18

R¹R²

20

Scheme 6. Reactions of anions of 18 with organoboranes

Table 4. Products formed in reactions according to Scheme 6

1

rigorously confirmed. As far as possible, first order H NMR

(ratio R¹R²R³B:18:LDA = 1:1.2:1.2)

coupling patterns are reported, even though some second order

effects might complicate the appearance of the signals.

Alkyl groups of R¹R²R³B

Yields of products (%)^a

R¹

R²

R³

19

20

–

4.1. Formation and reaction of dichloro(menthyloxy)methane (1)

Et

47^b

Two oven dried 100 mL round bottomed flasks (one equipped

with a magnetic stirrer bar and septum – capped stopcock, and

the other with a septum) joined by a sintered glass tube were

assembled hot and cooled under a stream of N₂. The flask with

the stirrer bar was transferred to a N₂glove-bag, PCl₅(1.5 g, 7.2

mmol) and POCl₃(2.0 mL, excess) were added, the flask was

removed from the glove-bag, reconnected to the sinter tube and

immersed in an ice bath, and 1-menthyl formate (1.0 g, 5.4

mmol) was added drop-wise with vigorous stirring. The mixture

was stirred at 0 °C for a further 6 h. Excess POCl₃was removed

under reduced pressure, dry hexane (25 mL) was introduced, and

the solution was filtered through the sinter into the second flask.

The hexane solution was transferred via cannula to a 50 mL flask

already under N₂, and the hexane was evaporated under a fast N₂

stream to give the impure crude title compound (1) as an air-

sensitive oil (80% conversion determined by ¹H NMR

spectroscopy); ¹H (400 MHz; CDCl₃) δ 7.10 (1H, s, CHCl₂), 3.70

(1H, app dt, J = 10.6, 4.1 Hz, CHO), 0.65 – 2.30 (18H, m, CH,

CH₂, CH₃); ¹³C (101 MHz; CDCl₃) δ 97.7, 81.1, 47.4, 40.2, 33.6,

31.1, 24.8, 22.6, 21.9, 20.8 and 15.7; unable to get further data

due to the compound’s instability. The crude product was

dissolved in anhydrous THF (10 mL) and transferred drop-wise

via cannula to a solution of trioctylborane (5 mmol) in THF (15

mL) at 0 °C, to which a freshly prepared solution of lithium

triethylcarboxide (15 mmol) in dry THF (10 mL) was added

dropwise over 15 min. The cooling bath was removed, and the

mixture was stirred for a further 1 h. A solution of ethylene

glycol (0.90 mL, 16 mmol) in dry THF (5 mL) was added drop-

wise, and the solution stirred overnight at room temperature. The

flask was then immersed in an ice bath, and NaOH (1.20 g) in

distilled water (5 mL) added drop-wise. Once the initial reaction

subsided, a solution of hydrogen peroxide in water (30% by

weight, 4.0 mL) and ethanol (5 mL) were added. The mixture

was heated to 45-50 °C for a further 1 h, with additional ethanol

added as needed to dissolve any boron salts that precipitated. The

aqueous layer was saturated with K₂CO₃, and an aliquot from the

Bu

81

13

11^c

–

Oct

Bu^d

Bu^e

Me^f

Oct

Bu^d

Bu^e

Bu^f

Oct

81(75)^c

(73)

(68)

(51)

(30)^g

c-Hex^d

c-Pent^d

Ph^e

–

Ph^f

–

^aBy GC estimation; figures in parentheses are of materials isolated by

chromatography.

^bA significant proportion of the product mixture may have been lost by

evaporation during work-up.

^cAll compounds contained 2-octyl isomers as a result of the preparation of

trioctylborane by hydroboration of 1-octene.

^dThe trialkylborane was prepared in situ from BCl₃, by sequential additions

of an alkene, Et₃SiH and n-BuLi.

^eThe trialkylborane was prepared in situ from PhBCl₂and 2 equiv. of n-BuLi.

^fThe trialkylborane was prepared in situ from PhBCl₂then sequential

addition of 1 equiv. of n-BuLi and 1-equiv. of MeLi; the product contained

both PhBBuMe and PhBBu₂.

^gPhC(OH)Bu₂(30% yield) was also isolated.

3. Conclusion

Four different kinds of anionic reagents of the type Cl₂XC^-

have been generated from the corresponding Cl₂CHX compounds

and reacted in situ with trialkylboranes. Each of the four reagent

types behaved differently. Alkoxydichloromethyl carbanions (i.e.

X = OR, where R is menthyl or cyclohexyl) appear to decompose

more quickly than they react with organoboranes, in contrast to

the case of X = OMe, where the reagent undergoes a very useful

reaction with organoboranes. This suggests that steric inhibition

of complexation of the anion to the organoborane is an issue.

Dichloro(phenylsulfinyl)methyl anion (X = SOPh) reacts to give

the product of replacement of one of the chlorine atoms by an

alkyl group from the organoborane, probably via a boron enolate-

7

4.5. 1-Chlorononyl Phenyl Sulfoxide (10a)

organic layer showed a 5% yield of tri-n-octylmethanol by GC

analysis.

ACCEPTED MANUSCRIPT

According to the general procedure, followed by flash column

chromatography (4:1 petroleum ether/diethyl ether), the reaction

of trioctylborane with the anion from 6 gave 10a (88 mg, 61%)

as a colourless oil as a 84:16 mixture of diastereoisomers; ν_max.

(neat) 3063, 2955, 2924, 2854, 1464, 1444 and 1051 cm^-1; ¹H

NMR (400 MHz; CDCl₃) δ 7.80 – 7.70 (2H of major isomer, m,

aromatic CH), 7.69 – 7.63 (2H of minor isomer, m, aromatic

CH), 7.60 – 7.49 (3H of both isomers, m, aromatic CH), 4.53 (1H

of minor isomer, dd, J = 9.5, 4.0 Hz, CHCl), 4.40 (1H of major

isomer, dd, J = 9.8, 3.0 Hz, CHCl), 2.32 – 2.15 (1H of minor

isomer, m, one of CH₂), 2.24 (1H of major isomer, dddd, J =

14.3, 9.4, 5.8, 3.0 Hz, one of CH₂), 1.93 (1H of major isomer,

app. dtd, J = 14.3, 9.8, 4.5 Hz, one of CH₂), 1.83 – 1.05 (12H of

major isomer and 13H of minor isomer, m, CH₂protons) and

0.87 (3H of both isomers, app. t, J = 6.9 Hz, CH₃); ¹³C NMR (101

MHz; CDCl₃) (major isomer): δ 141.3 (quat C), 132.2 (CH),

129.1 (CH), 126.0 (CH), 77.4 (CH), 31.9 (CH₂), 31.3 (CH₂), 29.4

(CH₂), 29.3 (CH₂), 29.0 (CH₂), 25.6 (CH₂), 22.8 (CH₂) and 14.2

(CH₃). Identifiable chemical shifts for the minor isomer: δ 131.9

(CH), 129.0 (CH), 125.8 (CH), 76.7 CH), 31.9 (CH₂), 31.2

(CH₂), 29.2 (CH₂), 28.9 (CH₂) and 26.3 (CH₂); EI-MS m/z (%)

286 (M⁺, ³⁵Cl, l5%), 234 (20), 125 (100), 78 (100); HRMS:

Found: M⁺, 286.1159. C₁₅H₂₃³⁵ClOS requires 286.1158.

4.2. Preparation of Dichloromethyl Phenyl Sulfoxide (6)¹⁴

N-Chlorosuccinimide (1.95 g, 14.62 mmol, 2.05 equiv.) was

added to a solution of methyl phenyl sulfoxide (1.00 g, 7.13

mmol) in THF (15 mL) at 0 °C. The solution was stirred at 0 °C

overnight and filtered. The solvent was removed in vacuo and the

residue purified by flash column chromatography (4:1 petroleum

ether/diethyl ether) to afford the title compound (1.084 g, 73%)

as a colourless oil, R_f= 0.26 (4:1 petroleum ether/diethyl ether);

¹H NMR (400 MHz; CDCl₃) δ 7.86 – 7.74 (2H, m, aromatic CH),

7.68 – 7.51 (3H, m, aromatic CH) and 6.17 (1H, s, CH); ¹³C

NMR (101 MHz; CDCl₃) δ 138.1, 133.2, 129.1, 126.7 and 83.1.

4.3. Reaction of Dichloromethyl Phenyl Sulfoxide (6) with

Trioctylborane

Borane (100 µL, 10.0 M in dimethyl sulfide, 1.0 mmol, 1

equiv.) and THF (5 mL) were added to a septum-capped 25 mL

flask containing a stirrer bar. The flask was immersed in an

ice-bath and 1-octene (0.47 mL, 3.0 mmol, 3 equiv.) was added

dropwise. The cooling bath was removed and the solution was

left to stir at room temperature for 1 h. The solution was mixed

with a solution of dichloromethyl phenyl sulfoxide (6) (209 mg,

1.0 mmol, 1 equiv.) in THF (5 mL) and cooled to –78 °C. LDA

(1.1 mmol in 2.0 mL of THF, 1.1 equiv.) was added dropwise

and the solution was stirred for 1 h at the same temperature. The

cooling bath was removed, and the reaction stirred for a further 1

h. The solution was cooled to 0 °C and oxidised with aq. NaOH

(3.0 M, 5 mL) followed by aq. H₂O₂(30%, 3 mL). After the

initial reaction subsided, the mixture was gently warmed (40 °C)

and stirred overnight. The aqueous layer was saturated with NaCl

and tetradecane (221.9 mg) was added. A sample from the

organic layer was subjected to GC analysis. The results were: 1-

octanol (55% of original octyl groups), dioctyl ketone (8) (6%

yield) and trioctylmethanol (9) (3% yield).

4.6. 1-Chlorononyl Phenyl Sulfoxide (10a) by Reaction with

n-Octyl-9-BBN

The n-octyl-9-BBN was prepared first. 9-BBN dimer (61 mg,

0.25 mmol) was placed in a 5 mL round bottom flask and flushed

with nitrogen for 10 minutes. THF (2 mL) was added and the

solution was cooled to 0°C. 1-Octene (79 mL, 0.5 mmol) was

added dropwise and the solution was allowed to warm to r.t. and

stirred for 2 h.

The general procedure was used for the reaction of 9-octyl-9-

BBN, which was added to the sulfoxide anion. Working up and

purifying the crude product afforded 10a (57 mg, 40%, 82:18

mixture of diastereoisomers).

The organic layer was separated, and the aqueous layer was

extracted with dichloromethane (3 × 10 mL). The organic layers

were combined, dried over magnesium sulfate and filtered. The

volatile solvents were evaporated under reduced pressure and the

crude product was purified by column chromatography on silica

gel (5% EtOAc/petroleum ether) to yield 10a (163 mg, 57%), 1-

octanol (188 mg, 48% of original octyl groups), dioctyl ketone

(8) (8 mg, 3% yield) and trioctylmethanol (9) (5 mg, 1% yield).

4.7. 1-Chloropropyl Phenyl Sulfoxide (10b)

According to the general procedure, followed by flash column

chromatography (4:1 petroleum ether/diethyl ether), the reaction

of triethylborane with 6 gave 10b (92 mg, 92%) as a colourless

oil as a 78:22 mixture of diastereoisomers; ν_max.(neat) 3061,

1

2974, 2937, 2877, 1444, 1084 and 1049 cm^-1; H NMR (400

4.4. General Procedure for Synthesis of 1-Chloroalkyl Phenyl

MHz; CDCl₃) δ 7.78 – 7.69 (2H of major isomer, m, aromatic

CH), 7.68 – 7.62 (2H of minor isomer, m, aromatic CH), 7.58 –

7.46 (3H of both isomers, m, aromatic CH), 4.46 (1H of minor

isomer, dd, J = 9.7, 4.1 Hz, CHCl), 4.36 (1H of major isomer dd,

J = 9.0, 3.1 Hz, CHCl), 2.23 (1H of each isomer, app. dqd, J =

14.6, 7.3, 3.1 Hz, one of CH₂), 1.96 (1H of major isomer, ddq, J

= 14.6, 9.0, 7.3 Hz, one of CH₂), 1.59 (1H of minor isomer, ddq,

J = 14.4, 9.7, 7.3 Hz, one of CH₂), 1.10 (3H of major isomer, t, J

= 7.3 Hz, CH₃) and 1.06 (3H of minor isomer, t, J = 7.3 Hz,

CH₃); ¹³C NMR (101 MHz; CDCl₃) (major isomer): δ 141.2 (quat

C), 132.2 (CH), 129.1 (CH), 126.0 (CH), 78.6 (CH), 24.9 (CH₂)

and 10.0 (CH₃); (minor isomer): δ 139.3 (quat C), 132.0 (CH),

128.9 (CH), 125.6 (CH), 78.2 (CH), 24.8 (CH₂) and 11.0 (CH₃);

MS (APCl⁺) m/z 205 (MH⁺, ³⁷Cl, 10%), 203 (MH⁺, ³⁵Cl, 30), 244

(30), 150 (100) and 109 (62); HRMS: Found MH⁺, 203.0292.

C₉H₁₂³⁵ClOS requires 203.0297.

Sulfoxides (10)

n-BuLi (0.38 mL, 1.6 M in hexane, 0.60 mmol, 1.2 equiv.)

was added dropwise to

a cooled (–78 °C) solution of

diisopropylamine (91 µL, 0.65 mmol, 1.3 equiv.) in dry THF (5

mL). The solution was warmed to 0 °C over a period of 20 min.

The solution was cooled again to –78 °C. To this solution was

added dichloromethyl phenyl sulfoxide (6) (105 mg, 0.50 mmol,

1.0 equiv.) and the mixture was stirred for 10 min.

Trialkylborane (0.50 mmol, 1.0 equiv.) in THF (5 mL) was added

and the mixture was stirred for 1 h, then the reaction was

quenched by addition of saturated ammonium chloride solution

(5 mL) before being warmed to room temperature. The organic

layer was separated, the aqueous layer was extracted with

dichloromethane (3 x 10 mL) and the organic layers were

combined and dried over magnesium sulfate. The solvents were

evaporated under reduced pressure. The crude product was

purified by flash column chromatography on silica gel (the eluent

is indicated in each case) to afford the corresponding sulfoxide

(10).

4.8. 1-Chloropentyl Phenyl Sulfoxide (10c)

According to the general procedure, followed by flash column

chromatography (30% diethyl ether/petroleum ether), the reaction

8

Tetrahedron

4.11. Reaction of Dichloromethyl Phenyl Sulfoxide (6) with

of tributylborane with 6 gave 10c (101 mg, 88%) as a

ACCEPTED MANUSCRIPT

Triethylborane and Aromatic Aldehydes – General Procedure

colourless oil as a 84:16 mixture of diastereoisomers; ν_max.(neat)

3057, 2957, 2931, 2862, 1444, 1084 and 1049 cm^-1; H NMR

1

To a cooled (–78 °C) solution of diisopropylamine (183 µL,

1.3 mmol, 1.3 equiv.) in dry THF (5 mL), n-BuLi (0.75 mL, 1.6

M in hexane, 1.2 mmol, 1.2 equiv.) was added dropwise. The

solution was warmed to 0 °C over a period of 20 min. then

cooled to –78 °C. A solution of 6 (209 mg, 1.0 mmol, 1.0 equiv.)

in THF (3 mL) was added and the mixture was stirred for 10 min.

Triethylborane (1.0 mL, 1.0 M in THF, 1.0 mmol, 1.0 equiv.)

was added and stirring was continued for 1 h. The appropriate

aromatic aldehyde (1.0 mmol) was added and the mixture was

stirred for a further 1 h. The mixture was allowed to warm to 0

°C over a period of 20 min and quenched by addition of sat. aq.

ammonium chloride solution (10 mL). The organic layer was

separated and the aqueous layer was extracted with

dichloromethane (3 × 15 mL); the organic layers were combined

and dried over magnesium sulfate. The solvents were evaporated

under reduced pressure and the crude material obtained was

subjected to silica-gel column chromatography (eluted with a

suitable ratio of ethyl acetate/chloroform) to afford the four pure

diastereoisomers of the product (except for methoxy substituted

products, where only three diastereoisomers were formed).

(400 MHz; CDCl₃) δ 7.82 – 7.49 (5H of both isomers, m,

aromatic CH), 4.53 (1H of minor isomer, dd, J = 9.5, 4.1 Hz,

CHCl), 4.40 (1H of major isomer, dd, J = 9.8, 3.0 Hz, CHCl),

2.31 – 2.21 (1H of minor isomer, m, one of CH₂), 2.26 (1H of

major isomer, dddd, J = 14.3, 8.6, 5.6, 3.0 Hz, one of CH₂), 1.94

(1H of major isomer, app. dtd, J = 14.3, 9.9, 4.6 Hz, one of CH₂),

1.78 – 1.22 (4H of major isomer and 5H of minor isomer, m) and

0.90 (3H of both isomers, app. t, J = 7.2 Hz, CH₃); ¹³C NMR

(101 MHz; CDCl₃) (major isomer): δ 141.3 (quat C), 132.2 (CH),

129.1 (CH), 126.0 (CH), 77.4 (CH), 31.1 (CH₂), 27.7 (CH₂), 22.2

(CH₂) and 13.9 (CH₃). Identifiable chemical shifts for the minor

isomer: δ 129.0 (CH), 126.8 (CH), 125.8 (CH), 30.9 (CH₂), 28.4

(CH₂) and 22.1 (CH₂); MS (APCl⁺) m/z 233 (MH⁺, ³⁷Cl, 10%),

231 (MH⁺, ³⁵Cl, 33%), 272 (40), 150 (100); HRMS: Found MH⁺,

231.0619. C₁₁H₁₆³⁵ClOS requires 231.0610.

4.9. 1-Chloro-3-phenylpropyl Phenyl Sulfoxide (10d)

According to the general procedure, followed by flash column

chromatography (4:1 petroleum ether/diethyl ether), the reaction

of tris(2-phenylethyl)borane (impure material from reaction of

styrene with borane dimethyl sulfide) with 6 gave 10d (56 mg,

40%) as a colourless oil as a 81:19 mixture of diastereoisomers;

ν_max.(neat) 3061, 3026, 2955, 2930, 2856, 1444, 1085 and 1049

cm^-1; ¹H NMR (400 MHz; CDCl₃) δ 7.67 – 7.58 (2H of the major

isomer, m, aromatic CH), 7.59 – 7.54 (2H of minor isomer, m,

aromatic CH), 7.53 – 7.38 (3H of both isomers, m, aromatic CH),

7.27 – 7.04 (5H of both isomers, m, aromatic CH), 4.40 (1H of

minor isomer, dd, J = 10.3, 3.7 Hz, CHCl), 4.30 (1H of major

isomer, dd, J = 10.2, 2.8 Hz, CHCl), 2.95 (1H of major isomer,

ddd, J = 13.9, 9.0, 4.7 Hz, one of CH₂), 2.90 (1H of minor

isomer, ddd, J = 13.7, 8.3, 5.1 Hz, one of CH₂), 2.71 (1H of each

isomer, app. dt, J = 13.9, 8.2 Hz, one of CH₂), 2.47 (1H of each

isomer, app. dddd, J = 14.3, 9.0, 7.8, 2.8 Hz, one of CH₂), 2.15

(1H of major isomer, dddd, J = 14.3, 10.2, 8.8, 4.7 Hz, one of

CH₂) and 1.84 (1H of minor isomer, dddd, J = 14.2, 10.3, 8.2, 5.2

Hz, one of CH₂); ¹³C NMR (126 MHz; CDCl₃) (major isomer):

δ 141.0 (quat C), 139.5 (quat C), 132.3 (CH), 129.2 (CH), 128.8

(CH), 128.6 (CH), 126.6 (CH), 125.9 (CH), 76.4 (CH), 32.8

(CH₂) and 31.8 (CH₂). (minor isomer): δ (quaternary C were not

clear), 132.0 (CH), 129.0 (CH), 128.8 (CH), 128.7 (CH), 126.7

(CH), 125.8 (CH), 75.3 (CH), 32.5 (CH₂) and 32.0 (CH₂); MS

(EI) m/z 278 (M⁺, ³⁵Cl, 5%), 91 (90); HRMS: Found M⁺,

278.0533. C₁₅H₁₅³⁵ClOS requires 278.0532.

4.12. Compound 14a

The general procedure was followed. The reaction of

triethylborane and benzaldehyde (102 µL, 1.0 mmol) with 6,

followed by flash column chromatography (3% ethyl

acetate/chloroform) gave three fractions; the first fraction

contained 14a(i) (72 mg, 23%) as a colourless solid; the second

fraction contained a mixture of 14a(ii) and 15a (16 mg, 5% of the

mixture, 1:1 ratio) as a colourless oil; the third fraction contained

diastereoisomers 14a(iii) and 14a(iv) (100 mg, 32%, 45:55 ratio)

as a colourless oil.

Data for 14a(i): Colourless solid (72 mg, 23%), m.p. 181 –

182 °C; ν_m₁_ax.(neat) 3201, 3065, 2968, 2937, 2879, 1442 and

1031 cm^-1; H NMR (400 MHz; CDCl₃) δ 7.98 – 7.94 (2H, m,

aromatic CH), 7.71 – 7.60 (3H, m, aromatic CH), 7.28 (5H, app.

s), 5.66 (1H, app. s, OH), 4.96 (1H, app. s, CHOH), 3.00 (1H, dq,

J = 15.3, 7.2 Hz, one of CH₂), 2.01 (1H, dq, J = 15.3, 7.4 Hz, one

of CH₂) and 1.30 (3H, app. t, J = 7.3 Hz, CH₃); ¹³C NMR (101

MHz, CDCl₃) δ 137.3 (quat C), 136.3 (quat C), 132.8 (CH),

129.0 (CH), 128.8 (CH), 128.5 (CH), 128.1 (CH), 127.7 (CH),

83.7 (quat C), 78.6 (CH), 23.3 (CH₂) and 8.0 (CH₃); MS (ES^–)

m/z (%), 347 ((M+Cl)^–, ³⁷Cl₂, 13%), 345 ((M+Cl)^–, ³⁷Cl³⁵Cl,

67%), 343 ((M+Cl)^–, ³⁵Cl₂, 100%), 313 (74), 255 (65), 223 (82);

HRMS: Found (M+Cl)^–, 343.0317. C₁₆H₁₇³⁵Cl₂O₂S requires

343.0326.

4.10. Deuteration of the Sulfoxide Enolate (d-10b)

The above general procedure was followed, but the reaction

was quenched with D₂O (5 mL) and then worked up as for 10a to

yield two diastereomers of d-10b (93 mg, 93%, approx. 73:27

ratio) as a colourless oil; ¹H NMR (400 MHz; CDCl₃) δ 7.79 –

7.70 (2H of major isomer, m, aromatic CH), 7.69 – 7.62 (2H of

minor isomer, m, aromatic CH), 7.59 – 7.47 (3H of both isomers,

m, aromatic CH), 2.29 (1H of minor isomer, app. dq, J = 14.6,

7.3 Hz, one of CH₂), 2.28 (1H of major isomer, app. dq, J = 14.7,

7.3 Hz, one of CH₂), 2.01 (1H of major isomer, app. dq, J = 14.6,

7.3 Hz, one of CH₂), 1.56 (1H of minor isomer, app. dq, J = 14.6,

7.3 Hz, one of CH₂), 1.15 (3H of major isomer, app. t, J = 7.3 Hz,

Selected crystallographic data: C₁₆H₁₇ClO₂S, FW = 308.80,

T = 296(2) K, λ = 1.54184 Å, Triclinic, P-1, a = 11.2998(3) Å, b

= 11.4679(3) Å, c = 12.4272(3) Å, α= 96.840(2)°, β= 92.254(2)°,

γ = 104.801(2)°, V = 1541.78(7) Å³, Z = 4, ρ_calc.= 1.330 Mg/m³,

crystal size = 0.322 x 0.272 x 0.190 mm³, µ = 3.442 mm^-1,

reflections collected = 25725, Independent reflections = 6107,

R_int= 0.0223, parameters = 365, R₁= 0.0332, wR₂= 0.0847 for

I>2σ(I) and R₁= 0.0396, wR₂= 0.0888 for all data. CCDC

1451735 contains the supplementary crystallographic data for

this structure. These data can be obtained free of charge from The

Cambridge

Crystallographic

Data

Centre

via

CH₃) and 1.12 (3H of minor isomer, app. t, J = 7.3 Hz, CH₃); ¹³

C

www.ccdc.cam.ac.uk/structures

NMR (101 MHz; CDCl₃) (major isomer): δ 141.3 (quat C), 132.2

(CH), 129.1 (CH), 126.0 (CH), 78.3 (1:1:1 t, J = 25.1 Hz, CD),

24.8 (CH₂) and 10.0 (CH₃); (minor isomer): δ 139.4 (quat C),

131.9 (CH), 129.0 (CH), 125.7 (CH), (CD signal not clear), 24.8

(CH₂) and 11.0 (CH₃).

9

(2H, d, J = 9.0 Hz, aromatic CH), 8.22 (2H, d, J = 9.0 Hz,

ACCEPTED MANUSCRIPT

aromatic CH), 7.78 – 7.68 (4H, m, aromatic CH), 7.54 – 7.46

(3H, m, aromatic CH), 7.44 – 7.38 (3H, m, aromatic CH), 6.55

(1H, s, CHO), 2.30 – 2.12 (2H, m, CH₂) and 1.13 (3H, app. t, J =

7.5 Hz, CH₃); ¹³C NMR (101 MHz; CDCl₃) δ 162.6 (quat C),

151.0 (quat C), 138.2 (quat C), 134.8 (quat C), 134.3 (quat C),

132.4 (CH), 131.1 (CH), 129.6 (CH), 129.1 (CH), 128.8 (CH),

128.4 (CH), 127.5 (CH), 123.9 (CH), 88.6 (quat C), 77.6 (CH),

27.5 (CH₂) and 9.8 (CH₃); MS (APCl⁺) m/z (%) 523

((M+Na+CH₃CN)⁺, ³⁷Cl, 25%), 521 ((M+Na+CH₃CN)⁺, ³⁵Cl,

100%), 482 ((M+Na)⁺, ³⁵Cl, 17%), 480 ((M+Na)⁺, ³⁵Cl, 58%);

HRMS: Found (M+Na)⁺, 480.0657. C₂₃H₂₀³⁵ClNaO₅S requires

480.0648.

Data for mixture of 14a(ii) and 15a: Colourless oil (16 mg,

5%, ca. 1:1 mixture of 14a(ii) and 15a); ν_max.(neat) 3348, 3061,

1

3005, 2931, 2883, 1610, 1444 and 1047 cm^-1; H NMR (400

Selected crystallographic data: C₂₃H₂₀ClNO₅S, FW

457.91, T = 150(2) K λ = 1.54184, Triclinic, P-1, a = 7.3284(2)

Å, b = 12.4907(3) Å, c = 12.9031(4) Å, α= 110.993(2)°, β=

102.930(2)°, γ = 95.432(2)°, V = 1054.73(5) Å³, Z = 2, ρ_calc.

1.442 Mg/m³, crystal size = 0.261 x 0.235 x 0.155 mm³, µ =

2.841 mm^-1, reflections collected

16433, Independent

=

MHz; CDCl₃) δ 7.88 – 7.83 (2H of 15a, m, aromatic CH), 7.77 –

7.72 (2H of 14a(ii), m, aromatic CH), 7.68 - 7.36 (8H of each

compound, m, aromatic CH), 5.50 (1H of 15a, d, J = 2.7 Hz,

CHOH), 5.20 (1H of 14a(ii), d, J = 8.7 Hz, CHOH), 4.92 (1H of

14a(ii), d, J = 8.7 Hz, OH), 4.15 (1H of 15a, d, J = 2.7 Hz, OH),

2.39 (1H of 14a(ii) dq, J = 14.7, 7.2 Hz, one of CH₂), 1.28 (1H of

14a(ii), dq, J = 14.7, 7.1 Hz, one of CH₂) and 1.07 (3H of 14a(ii),

app. t, J = 7.2 Hz); MS (APCl⁺) m/z (%) 374 ((M+Na+CH₃CN)⁺,

³⁷Cl, 40%), 372 ((M+Na+CH₃CN)⁺, ³⁵Cl, 100%), 333 ((M+Na)⁺,

³⁷Cl, 11%), 331 ((M+Na)⁺, ³⁵Cl, 53%), 228 (13) HRMS: Found

(M+Na)⁺, 331.0519. C₁₆H₁₇³⁵ClNaO₂S requires 331.0535.

,

=

reflections = 4150, R_int= 0.0187, parameters = 281, R₁= 0.0303,

wR₂= 0.0819 for I>2σ(I) and R₁=0.0311, wR₂= 0.0824 for all

data.

CCDC

1451736

contains

the

supplementary

crystallographic data for this structure. These data can be

obtained free of charge from The Cambridge Crystallographic

Data Centre via www.ccdc.cam.ac.uk/structures

Data for mixture of 14a(iii) and 14a(iv): Colourless oil (100

mg, 32%, 45:55 mixture of diastereoisomers); ν_max.(neat) 3338,

1

3065, 2939, 2879, 1442 and 1020 cm^-1; H NMR (400 MHz;

CDCl₃) δ 7.88 – 7.84 (2H of 14a(iii), m, aromatic CH), 7.84 –

7.80 (2H of 14a(iv), m, aromatic CH), 7.65 – 7.32 (8H of each

isomer, m, aromatic CH), 5.33 (1H of 14a(iv), d, J = 4.0 Hz,

CHOH), 5.18 (1H of 14a(iii), d, J = 3.3 Hz, CHOH), 3.61 (1H of

14a(iii), d, J = 3.3 Hz, OH), 3.20 (1H of 14a(iv), d, J = 4.0 Hz,

OH), 2.23 – 2.12 (2H of 14a(iii), m, CH₂), 1.88 (1H of 14a(iv),

dq, J = 15.0, 7.4 Hz, one of CH₂), 1.50 (1H of 14a(iv), dq, J =

15.0, 7.3 Hz, one of CH₂), 0.95 (3H of 14a(iv), app. t, J = 7.4 Hz,

CH₃) and 0.84 (3H of 14a(iii), app. t, J = 7.5 Hz, CH₃); ¹³C NMR

(101 MHz; CDCl₃) δ 138.8 (quat C), 138.5 (quat C), 138.0 (quat

C), 137.8 (quat C), 132.5 (CH), 132.3 (CH), 129.0 (CH), 128.9

(CH), 128.9 (CH), 128.8 (CH), 128.7 (CH), 128.4 (CH), 128.3

(CH), 128.0 (CH), 127.4 (CH), 127.2 (CH), 93.6 (quat C), 89.5

(quat C), 78.1 (CH), 75.2 (CH), 27.7 (CH₂), 24.7 (CH₂), 10.1

(CH₃) and 9.3 (CH₃); MS (ES⁺) m/z (%) 374 ((M+Na+CH₃CN)⁺,

³⁷Cl, 13%), 372 ((M+Na+CH₃CN)⁺, ³⁵Cl, 42%), 333 ((M+Na)⁺,

³⁷Cl, 37%), 331 ((M+Na)⁺, ³⁵Cl, 100%), 254 (20); HRMS: Found

(M+Na)⁺, 331.0550. C₁₆H₁₇³⁵ClNaO₂S requires 331.0536.

4-Nitrobenzoate of 14a(iv): R_f= 0.19 (1% EtOAc/CHCl₃), 40

mg (29%) colourless solid, m.p. 127 – 129 °C; ν_max.(neat) 3053,

4.13. Synthesis of 4-Nitrobenzoate Derivatives of Compounds

14a(iii) and 14a(iv)

1

2978, 2922, 2854, 1732, 1608, 1442 and 1049 cm^-1; H NMR

(400 MHz; CDCl₃) δ 8.08 (2H, d, J = 9.0 Hz, aromatic CH), 7.79

(2H, dd, J = 8.4, 1.1 Hz, aromatic CH), 7.68 (2H, d, J = 9.0 Hz,

aromatic CH), 7.49 - 7.45 (2H, m, aromatic CH), 7.35 – 7.31

(3H, m, aromatic CH), 7.16 (2H, app. t, J = 7.9 Hz, aromatic

CH), 6.89 (1H, tt, J = 7.4, 1.1 Hz, aromatic CH), 6.44 (1H, s,

CHO), 2.19 (1H, dq, J = 15.2, 7.0 Hz, one of CH₂), 1.42 (1H, dq,

J =15.2, 7.3 Hz, one of CH₂) and 1.23 (3H, app. t, J = 7.2 Hz,

CH₃); ¹³C NMR (101 MHz; CDCl₃) δ 162.0 (quat C), 150.5 (quat

C), 138.7 (quat C), 135.4 (quat C), 134.5 (quat C), 131.2 (CH),

130.6 (CH), 129.5 (CH), 128.8 (CH), 128.7 (CH), 128.4 (CH),

126.6 (CH), 123.1 (CH), 88.8 (quat C), 72.1 (CH), 30.0 (CH₂)

and 8.4 (CH₃); MS (APCl⁺) m/z 523 ((M+Na+CH₃CN)⁺, ³⁷Cl,

10%), 521 ((M+Na+CH₃CN)⁺, ³⁵Cl, 26%), 482 ((M+Na)⁺, ³⁷Cl,

27%), 480 ((M+Na)⁺, ³⁵Cl, 100%); HRMS: Found (M+Na)⁺,

480.0627. C₂₃H₂₀³⁵ClNaO₅S requires 480.0648.

The mixture of two diastereoisomers 14a(iii) and 14a(iv) (94

mg, 0.3 mmol) was dissolved in THF (10 mL). Triethylamine (93

µL, 0.66 mmol, 2.2 equiv.) was added, followed by 4-

dimethylaminopyridine (10 mg, catalytic amount) and

4-nitrobenzoyl chloride (112 mg, 2 equiv.). The solution was

warmed up to room temperature and stirred for 24 h. The reaction

was then quenched with sat. sodium bicarbonate. The organic

layer was separated and the aqueous layer was extracted with

chloroform (2 × 10 mL) and dried over magnesium sulfate. The

solvents were removed to yield

a

mixture of two

diastereoisomeric 4-nitrobenzoates (110 mg, 80%). The two

diastereomers were separated by flash column chromatography

on silica gel (1% EtOAc/CHCl₃).

4-Nitrobenzoate of 14a(iii): R_f= 0.21 (1% EtOAc/CHCl₃), 60

mg (43%), colourless solid, m.p. 133 – 134 °C; ν_max.(neat) 1728,

1523, 1074 and 1047 cm^-1; ¹H NMR (400 MHz; CDCl₃) δ 8.31

10

Tetrahedron

CCEPTED MANUSCRIPT

Selected crystallographic data: C₂₃H₂₀ClNO₅S, FW =

(101 MHz; CDCl₃) δ 159.1 (quat C), 138.9 (quat C), 136.3 (quat

A

457.91, T = 293(2) K

,

λ = 1.54184, Triclinic, P-1, a = 6.4998(2)

C), 132.8 (CH), 129.0 (CH), 128.6 (CH), 128.1 (CH), 121.3

(CH), 114.6 (CH), 113.7 (CH), 83.7 (quat C), 78.5 (CH), 55.4

(CH₃), 23.4 (CH₂) and 8.0 (CH₃); MS (APCl⁺) m/z (%) 341

(MH⁺, ³⁷Cl, 35), 339 (MH⁺, ³⁵Cl, 100), 186 (20), 136 (17);

HRMS: Found MH⁺, 339.0819. C₁₇H₂₀³⁵ClO₃S requires

339.0822.

Å, b = 7.7680(3) Å, c = 22.2674(8) Å, α= 91.378(3)°, β=

93.748(3)°, γ = 108.174(3)°, V = 1064.75(7) Å³, Z = 2, ρ_calc.

1.428 Mg/m³, crystal size = 0.457 x 0.135 x 0.065 mm³, µ =

2.815 mm^-1, reflections collected

16565, Independent

=

reflections = 4198, R_int= 0.0475, parameters =282, R₁= 0.0728,

wR₂= 0.2281 for I>2σ(I) and R₁=0.0810, wR₂= 0.2311 for all

Data for 14b(iii): Colourless oil (56 mg, 17%); ν_max.(neat)

data.

CCDC

1451737

contains

the

supplementary

1

3296, 3061, 2997, 2957, 2835, 1600, 1442 and 1020 cm^-1; H

crystallographic data for this structure. These data can be

obtained free of charge from The Cambridge Crystallographic

Data Centre via www.ccdc.cam.ac.uk/structures

NMR (400 MHz; CDCl₃) δ 7.85 (2H, dd, J = 8.2, 1.4 Hz,

aromatic CH), 7.60 – 7.49 (3H, m, aromatic, CH), 7.28 (1H, t, J

= 7.9 Hz, aromatic CH), 7.16 - 7.09 (2H, m, aromatic CH), 6.89

(1H, ddd, J = 8.2, 2.5, 0.7 Hz, aromatic CH), 5.13 (1H, s,

CHOH), 3.81 (3H, s, OCH₃), 3.52 (1H, br., OH), 2.11 (2H, app.

q, J = 7.5 Hz, CH₂) and 0.86 (3H, app. t, J = 7.5 Hz, CH₃); ¹³C

NMR (101 MHz; CDCl₃) δ 159.3 (quat C), 139.4 (quat C), 138.5

(quat C), 132.3 (CH), 129.0 (CH), 128.8 (CH), 127.5 (CH), 121.0

(CH), 114.4 (CH), 114.3 (CH), 89.5 (quat C), 77.9 (CH), 55.4

(CH₃), 24.9 (CH₂) and 10.1 (CH₃); MS (APCl⁺) m/z (%) 363

((M+Na)⁺, ³⁷Cl, 13%), 361 ((M+Na)⁺, ³⁵Cl, 36%), 341 (MH⁺,

³⁷Cl, 20%), 339 (MH⁺, ³⁵Cl, 56%), 195 (25), 154 (60); HRMS:

Found: 361.0636. C₁₇H₁₉³⁵ClNaO₃S requires 361.0641.

Data for 14b(iv): Colourless oil (56 mg, 17%); ν_max.(neat)

1

3356, 3061, 2937, 2883, 2837, 1599, 1442 and 1037 cm^-1; H

NMR (400 MHz; CDCl₃) δ 7.83 (2H, dd, J = 8.1, 1.5 Hz,

aromatic CH), 7.62 – 7.52 (3H, m, aromatic CH), 7.25 (1H, t, J =

7.9 Hz, aromatic CH), 7.06 – 7.00 (2H, m, aromatic CH), 6.88

(1H, ddd, J = 8.3, 2.6, 0.9 Hz, aromatic CH), 5.31 (1H, d, J = 3.9

Hz, CHOH), 3.80 (3H, s, OCH₃), 3.14 (1H, d, J = 3.9 Hz, OH),

1.91 (1H, dq, J = 15.0, 7.4 Hz, one of CH₂), 1.51 (1H, dq, J =

15.0, 7.4 Hz, one of CH₂) and 0.98 (3H, app. t, J = 7.4 Hz, CH₃);

¹³C NMR (101 MHz; CDCl₃) δ 159.6 (quat C), 139.5 (quat C),

138.8 (quat C), 132.5 (CH), 129.4 (CH), 128.9 (CH), 127.2 (CH),

120.7 (CH), 114.7 (CH), 113.7 (CH), 93.4 (quat C), 74.8 (CH),

55.4 (CH₃), 27.9 (CH₂) and 9.3 (CH₃); MS (ES⁺) m/z (%) 404

((M+Na+CH₃CN)⁺, ³⁷Cl, 35%), 402 ((M+Na+CH₃CN)⁺, ³⁵Cl,

100%), 363 ((M+Na)⁺, ³⁷Cl, 33%), 361 ((M+Na)⁺, ³⁵Cl, 75%),

341 (MH⁺, ³⁷Cl, 12%), 339 (MH⁺, ³⁵Cl, 32%), 258 (15), 177 (15);

HRMS: Found MH⁺, 339.0822. C₁₇H₂₀³⁵ClO₃S requires

339.0822.

4.14. Reduction of the 4-Nitrobenzoate Derivative of 14a(iii)

The 4-nitrobenzoate derivative of 14a(iii) (27 mg, 0.05 mmol)

was dissolved in CHCl₃(1 mL) and added dropwise with

swirling to a solution of sodium borohydride (10 mg) in a

mixture of ethanol and CHCl₃(5 mL). The solution was swirled

for 15 minutes further. Ice-cold water (5 mL) and 2M HCl (3

mL) were added. The mixture was extracted with chloroform (3

× 5 mL) and the chloroform extract was dried over magnesium

sulfate. After removal of the solvents, the crude product was

purified by flash column chromatography to yield 14a(iii) (10

mg, 67%) as a colourless oil. While this compound was not

analytically pure, it was sufficiently pure to allow the peaks for

compound 14a(iii) in the original mixture of 14a(iii) and 14a(iv)

to be identified.

4.16. Compound 14c

The general procedure for reaction of triethylborane and

4-methoxybenzaldehyde (121 µL, 1.0 mmol) with 6, followed by

flash column chromatography (3% ethyl acetate/chloroform),

gave three fractions; the first contained diastereoisomer 14c(i)

(60 mg, 18%) as a colourless solid; the second contained

diastereoisomer 14c(iii) (42 mg, 12%) as a colourless oil; the

third contained a mixture of 14c(iii) and 14c(iv) (52 mg, 15%,

1:2 ratio) as a colourless oil.

4.15. Compounds 14b

The general method, involving the reaction of triethylborane

and 3-methoxybenzaldehyde (121 µL, 1.0 mmol) with 6 followed

by flash column chromatography (3% ethyl acetate/chloroform),

gave three fractions; the first contained diastereoisomer 14b(i)

(60 mg, 18%) as a colourless solid; the second contained

diastereoisomer 14b(iii) (56 mg, 17%) as a colourless oil; the

third contained diastereoisomer 14b(iv) (56 mg, 17%) as a

colourless oil.

Data for 14c(i): Colourless solid (60 mg, 18%), m.p. 136 –

138 °C; ν_max.(neat) 3327, 3060, 2972, 2935, 2835, 1610, 1442

1

and 1030 cm^-1; H NMR (400 MHz; CDCl₃) δ 7.95 (2H, dd, J =

8.0, 1.5 Hz, aromatic CH), 7.69 – 7.60 (3H, m, aromatic CH),

7.20 (2H, d, J = 8.8, Hz, aromatic CH), 6.80 (2H, d, J = 8.8,

aromatic CH), 5.61 (1H, s, OH), 4.91 (1H, s, CHOH), 3.77 (3H,

s, OCH₃), 2.97 (1H, dq, J = 15.4, 7.2 Hz, one of CH₂), 2.00 (1H,

dq, J = 15.4, 7.4 Hz, one of CH₂) and 1.29 (3H, app. t, J = 7.3

Hz, CH₃); ¹³C NMR (101 MHz; CDCl₃) δ 159.7 (quat C), 136.4

(quat C), 132.7 (CH), 129.9 (CH), 129.4 (quat C), 129.0 (CH),

128.1 (CH), 113.1 (CH), 84.0 (quat C), 78.3 (CH), 55.3 (CH₃),

23.2 (CH₂) and 8.0 (CH₃); MS (ES⁺) m/z (%) 404

((M+Na+CH₃CN)⁺, ³⁷Cl, 30%), 402 ((M+Na+CH₃CN)⁺, ³⁵Cl,

100%), 363 ((M+Na)⁺, ³⁷Cl, 16%), 361 ((M+Na)⁺, ³⁵Cl, 50%),

Data for 14b(i): Colourless solid (60 mg, 18%), m.p. 177 –

1

178 °C; ν_max.(neat) 3242, 2978, 2872 and 1041 cm^-1; H NMR

(400 MHz; CDCl₃) δ 7.95 (2H, dd, J = 8.1, 1.5 Hz, aromatic CH),

7.70 – 7.60 (3H, m, aromatic CH), 7.18 (1H, t, J = 8.1 Hz,

aromatic CH), 6.88 – 6.79 (3H, m, aromatic CH), 5.66 (1H, s,

OH), 4.93 (1H, s, CHOH), 3.77 (3H, s, OCH₃), 2.98 (dq, J =

15.5, 7.2 Hz, 1H, one of CH₂), 2.03 (dq, J = 15.5, 7.4 Hz, 1H,

one of CH₂) and 1.30 (3H, app. t, J = 7.3 Hz, CH₃); ¹³C NMR

11

254 (70), 185 (35); HRMS: Found (M+Na)⁺, 361.0641.

C₁₇H₁₉³⁵ClNaO₃S, requires 361.0641.

m/z (%) 425 ((M+Cl)^–, ⁸¹Br³⁵Cl³⁷Cl and ⁷⁹Br³⁷Cl₂combined,

ACCEPTED MANUSCRIPT

49%), 423 ((M+Cl)^–, ⁸¹Br³⁵Cl₂and ⁷⁹Br³⁷Cl³⁵Cl combined,

100%), 421 ((M+Cl)^–, ⁷⁹Br³⁵Cl₂, 66%), 197 (27); HRMS: Found

(M+Cl)^–, 420.9439. C₁₆H₁₆⁷⁹Br³⁵Cl₂O₂S requires 420.9431.

Data for 14c(iii): Slightly impure colourless oil (42 mg,

12%); ν_max.(neat) 3311, 3063, 2997, 2931, 2837, 1608, 1442 and

1

1030 cm^-1; H NMR (400 MHz; CDCl₃) δ 7.87 – 7.83 (2H, m,

Data for mixture of 14d(ii) and 15d: Colourless oil (30 mg,

8%, 1:1 ratio); ν_max.(neat) 3344, 3065, 2974, 2939, 2881, 1591,

1444, 1074 and 1010 cm^-1; ¹H NMR (400 MHz; CDCl₃) δ 7.87 –

7.46 (9H of each compound, m, aromatic CH), 5.49 (1H of 15d,

d, J = 2.5 Hz, CHOH), 5.15 (1H of 14d(ii), d, J = 8.8 Hz,

CHOH), 5.03 (1H of 14d(ii), d, J = 8.8 Hz, OH), 4.32 (1H of 15d

, d, J = 2.5 Hz, OH), 2.39 (1H of 14d(ii), dq, J = 14.6, 7.2 Hz,

one of CH₂), 1.31 – 1.20 (1H of 14d(ii), m, one of CH₂) and 1.08

(3H of 14d(ii), app. t, J = 7.2 Hz, CH₃); ¹³C NMR (126 MHz,

CDCl₃) chemical shifts for both compounds: δ 137.3 (quat C),

137.3 (quat C), 136.6 (quat C), 134.7 (quat C), 133.6 (CH), 132.6

(CH), 131.4 (CH), 131.2 (CH), 130.8 (CH), 130.7 (CH), 129.1

(CH), 128.8 (CH), 128.2 (CH), 127.2 (CH), 122.9 (quat C), 121.6

(quat C), 93.8 (quat), 85.7 (quat C), 79.8 (CH), 77.6 (CH), 25.5

(CH₂) and 8.0 (CH₃); MS (ES) m/z (%) 425 ((M+Cl)^–,

⁸¹Br³⁵Cl³⁷Cl and ⁷⁹Br³⁷Cl₂combined, 49%), 423 ((M+Cl)^–,

⁸¹Br³⁵Cl₂and ⁷⁹Br³⁷Cl³⁵Cl combined, 100%), 421 ((M+Cl),

⁷⁹Br³⁵Cl₂, 68%), 200 (16), 198 (30); HRMS: Found (M+Cl)^–,

420.9430. C₁₆H₁₆⁷⁹Br³⁵Cl₂O₂S requires 420.9431.

aromatic, CH), 7.59 – 7.50 (3H, m, aromatic CH), 7.48 (2H, d, J

= 8.8 Hz, aromatic CH), 6.90 (2H, d, J =8.8 Hz, aromatic CH),

5.17 (1H, s, CHOH), 3.82 (3H, s, OCH₃), 3.40 (1H, br., OH),

2.22 – 2.11 (2H, m, CH₂) and 0.84 (3H, app. t, J = 7.5 Hz, CH₃);

¹³C NMR (101 MHz; CDCl₃) δ 160.0 (quat C), 138.5 (quat C),

132.2 (CH), 129.9 (CH), 129.8 (quat C), 128.8 (CH), 127.4 (CH),

113.4 (CH), 89.7 (quat C), 77.7 (CH), 55.4 (CH₃), 24.7 (CH₂) and

10.1 (CH₃); MS (APCl⁺) m/z (%) 339 (MH⁺, ³⁵Cl, 3%), 156

(100), 120 (63); HRMS: Found MH⁺, 339.0826. C₁₇H₂₀³⁵ClO₃S

requires 339.0822.

Data for mixture of diastereoisomers 14c(iii) and 14c(iv):

Colourless oil. (52 mg, 15%, isomers 14c(iii) and 14c(iv) in a 1:2

ratio); ν_max.(neat) 3267, 3063, 2970, 2841, 1606, 1440 and 1030

cm^-1; ¹H NMR (400 MHz; CDCl₃) δ 7.85 (2H of 14c(iii), dd, J =

8.2, 1.5 Hz, aromatic CH), 7.81 (2H of 14c(iv), dd, J = 8.1, 1.6

Hz, aromatic CH), 7.60 – 7.50 (3H of both isomers, m, aromatic

CH), 7.48 (2H of 14c(iii), d, J = 8.8 Hz, aromatic CH), 7.39 (2H

of 14c(iv), d, J = 8.7 Hz, aromatic CH), 6.92 – 6.84 (2H of both

isomers, m, aromatic CH), 5.28 (1H of 14c(iv), s, CHOH), 5.13

(1H of 14c(iii), s, CHOH), 3.81 (3H of 14c(iii), s, OCH₃), 3.80

(3H of 14c(iv), s, OCH₃), 3.52 (1H of 14c(iii), s, OH), 3.23 (1H

of 14c(iv), s, OH), 2.16 (2H of 14c(iii), app. q, J = 7.5 Hz, CH₂),

1.86 (1H of 14c(iv), dq, J = 15.0, 7.4 Hz, one of CH₂), 1.51 (1H

of 14c(iv), dq, J = 15.0, 7.3 Hz, one of CH₂), 0.95 (3H of 14c(iv),

app. t, J = 7.4 Hz, CH₃) and 0.86 (3H of 14c(iii), app. t, J = 7.5

Hz, CH₃); ¹³C NMR (101 MHz, CDCl₃) isomer 14c(iii): δ 159.9

(quat C), 138.5 (quat C), 132.2 (CH), 130.2 (quat C), 129.9 (CH),

128.7 (CH), 127.4 (CH), 113.4 (CH), 89.9 (quat C), 77.6 (CH),

55.4 (CH₃), 24.8 (CH₂) and 10.1 (CH₃); isomer 14c(iv): δ 160.1

(quat C), 138.8 (quat C), 132.4 (CH), 130.2 (quat C), 129.5 (CH),

128.9 (CH), 127.2 (CH), 113.8 (CH), 93.8 (quat C), 75.0 (CH),

55.4 (CH₃), 27.6 (CH₂) and 9.3 (CH₃). Peaks for the OMe and

one of the aromatic quaternary carbon atoms were not resolved

for the two isomers; MS (APCl⁺) m/z (%) 363 ((M+Na)⁺, ³⁷Cl,

35%), 361 ((M+Na)⁺, ³⁵Cl, 100%), 194 (100), 125 (100), 77

(100); HRMS: Found (M+Na)⁺, 361.0641. C₁₇H₁₉³⁵ClNaO₃S

requires 361.0641.

Data for mixture of 14d(iii) and 14d(iv): Colourless oil (130

mg, 34%, 40:60 ratio); ν_max.(neat) 3306, 3065, 2941, 2883, 1591,

1442 and 1030 cm^-1; H NMR (400 MHz; CDCl₃) δ 7.81 (2H of

1

14d(iii), dd, J = 8.3, 1.3 Hz, aromatic CH), 7.77 (2H of 14d(iv),

dd, J = 8.2, 1.4 Hz, aromatic CH), 7.63 – 7.43 (5H of each

isomer, m, aromatic CH), 7.40 (2H of 14d(iii), d, J = 8.5 Hz,

aromatic CH), 7.33 (2H of 14d(iv), d, J = 8.4 Hz, aromatic CH),

5.28 (1H of 14d(iv), d, J = 3.6 Hz, CHOH), 5.08 (1H of 14d(iii),

d, J = 3.3 Hz, CHOH), 4.09 (1H of 14d(iii), d, J = 3.3 Hz, OH),

3.47 (1H of 14d(iv), d, J = 3.6 Hz, OH), 2.11 (2H of 14d(iii),

app. q, J = 7.5 Hz, CH₂), 1.81 (1H of 14d(iv), dq, J = 15.1, 7.4

Hz, one of CH₂), 1.48 (1H of 14d(iv), dq, J = 15.1, 7.3 Hz, one of

CH₂), 0.96 (3H of 14d(iv), app. t, J = 7.4 Hz, CH₃) and 0.82 (3H

of 14d(iii), app. t, J = 7.5 Hz, CH₃); ¹³C NMR (101 MHz; CDCl₃)

chemical shifts for both isomers: δ 138.4 (quat C), 138.1 (quat

C), 137.0 (quat C), 137.0 (quat C), 132.6 (CH), 132.3 (CH),

131.5 (CH), 131.1 (CH), 130.4 (CH), 130.0 (CH), 129.0 (CH),

128.8 (CH), 127.4 (CH), 127.2 (CH), 123.1 (quat C), 122.9 (quat

C), 93.0 (quat C), 89.4 (quat C), 77.3 (CH), 74.7 (CH), 27.8

(CH₂), 24.8 (CH₂), 10.0 (CH₃) and 9.3 (CH₃); MS (ES^–) m/z (%)

425 ((M+Cl)^–, ⁸¹Br³⁵Cl³⁷Cl and ⁷⁹Br³⁷Cl₂combined, 13%), 423

((M+Cl)^–, ⁸¹Br³⁵Cl₂and ⁷⁹Br³⁷Cl³⁵Cl combined, 46%), 421

((M+Cl)^–, ⁷⁹Br ³⁵Cl₂, 26%), 299 (100), 255 (62); HRMS: Found

(M+Cl)^–, 420.9423. C₁₆H₁₆⁷⁹Br³⁵Cl₂O₂S requires 420.9431.

4.17. Compound 14d

The general procedure for the reaction of triethylborane and

4-bromobenzaldehyde (185 mg, 1.0 mmol) with 6, followed by

flash column chromatography (1% ethyl acetate/chloroform),

gave three fractions; the first contained diastereoisomer 14d(i)

(40 mg, 10%) as a colourless solid; the second contained a

mixture of 14d(ii) and 15d (30 mg, 8% of the mixture, 1:1 ratio)

as a colourless oil; the third fraction contained diastereoisomers

14d(iii) and 14d(iv) (130 mg, 34%, 40:60 ratio) as a colourless

oil.

4.18. Compound 14e

The general procedure for reaction of triethylborane and

4-fluorobenzaldehyde (108 µL, 1.0 mmol) with 6, followed by

flash column chromatography (5% ethyl acetate/chloroform),

gave three fractions; the first contained diastereoisomer 14e(i)

(70 mg, 22%) as a colourless solid; the second contained a

mixture of compounds 14e(ii) and 15e (56 mg, 17%, 1:1 ratio) as

a colourless oil; the third contained diastereoisomers 14e(iii) and

14e(iv) (64 mg, 20%, 54:46 ratio) as a colourless oil.

Data for 14d(i): Colourless solid (40 mg, 10%), m.p. 156 –

158 °C; ν_max.(neat) 3225, 3062, 2982, 2924, 2858, 1610, 1442

1

and 1030 cm^-1; H NMR (400 MHz; CDCl₃) δ 7.95 (2H, dd, J =

8.0, 1.4 Hz, aromatic CH), 7.73 – 7.60 (3H, m, aromatic CH),

7.40 (2H, d, J = 8.5 Hz, aromatic CH), 7.16 (2H, d, J = 8.5 Hz,

aromatic CH), 5.75 (1H, s, OH), 4.93 (1H, s, CHOH), 2.98 (1H,

dq, J = 15.4, 7.2 Hz, one of CH₂), 1.92 (1H, dq, J = 15.4, 7.4 Hz,

one of CH₂) and 1.29 (3H, app. t, J = 7.3 Hz, CH₃); ¹³C NMR

(101 MHz; CDCl₃) δ 136.3 (quat C), 136.1 (quat C), 132.9 (CH),

130.9 (CH), 130.4 (CH), 129.1 (CH), 128.0 (CH), 122.7 (quat C),

83.1 (quat C), 78.1 (CH), 23.2 (CH₂) and 7.9 (CH₃); MS (ES^–)

Data for 14e(i): Colourless solid (70 mg, 22%), m.p. 102 –

104 °C; ν_max.(neat) 3321, 3065, 2972, 2924, 2852, 1602, 1442

1

and 1053 cm^-1; H NMR (400 MHz; CDCl₃) δ 7.95 (2H,dd, J =

8.1, 1.5 Hz,), 7.71 – 7.61 (3H, m, aromatic CH), 7.29 - 7.22 (2H,

m, aromatic CH), 7.00 – 6.93 (2H, m, aromatic CH), 5.73 (1H, s,

exchanged with D₂O, OH), 4.94 (1H, s, CHOH), 2.99 (1H, dq, J

= 15.5, 7.2 Hz, one of CH₂), 1.95 (1H, dq, J = 15.5, 7.3 Hz, one

12

Tetrahedron

CCEPTED MANUSCRIPT

of CH₂) and 1.30 (3H, app. t, J = 7.3 Hz, CH₃); ¹³C NMR (101

mL) and the extract was dried over magnesium sulfate. The

A

MHz; CDCl₃) δ 162.8 (d, J = 247 Hz, quat C), 136.2 (quat C),

133.0 (d, J = 3 Hz, quat C), 132.9 (CH), 130.4 (d, J = 8 Hz, CH),

129.1 (CH), 128.0 (CH), 114.7 (d, J = 22 Hz, CH), 83.4 (quat C),

78.1 (CH), 23.2 (CH₂) and 7.9 (CH₃); MS (APCl⁺) m/z (%) 392

((M+Na+CH₃CN)⁺, ³⁷Cl, 33%), 390 (M+Na+CH₃CN)⁺, ³⁵Cl,

100%), 329 (MH⁺, ³⁷Cl, 8%), 327 (MH⁺, ³⁵Cl, 23%), 165 (78),

150 (93); HRMS: Found MH⁺, 327.0632. C₁₆H₁₇³⁵ClFO₂S

requires 327.0622.

solvents were removed to afford the diastereoisomers of 15a (126

mg, 80%) as a colourless solid. The diastereoisomers were

separated by flash column chromatography (4% EtOAc/CHCl₃).

Data for the first diastereoisomer: Colourless solid (75 mg,

48%), m.p. 186 – 188 °C; R_f= 0.25 (4% EtOAc/CHCl₃); ν_max.

(neat) 3342, 3061, 3011, 1444, 1080 and 1051 cm^-1; H NMR

1

(400 MHz; CDCl₃) δ 7.89 – 7.81 (2H, m, aromatic CH), 7.69 –

7.60 (3H, m, aromatic CH), 7.57 (2H, app. t, J = 7.6, aromatic

CH), 7.44 – 7.39 (3H, m, aromatic CH), 5.49 (1H, d, J = 2.5 Hz,

CHOH) and 4.14 (1H, d, J = 2.5 Hz, OH); ¹³C NMR (101 MHz;

CDCl₃) δ 137.4, 135.6, 133.4, 129.6, 129.1, 128.7, 128.2 (broad),

102.1 and 80.2; MS (APCl⁺) m/z (%) 382 ((M+Na+CH₃CN)⁺,

³⁷Cl₂, 1%), 380 ((M+Na+CH₃CN)⁺, ³⁵Cl³⁷Cl, 9%), 378

((M+Na+CH₃CN)⁺, ³⁵Cl₂, 12%), 319 (MH⁺, ³⁷Cl₂, 3%), 317

(MH⁺, ³⁷Cl³⁵Cl, 20%), 315 (MH⁺, ³⁵Cl₂, 29%), 198 (100), 157

(23); HRMS: Found MH⁺, 315.0004. C₁₄H₁₃³⁵Cl₂O₂S requires

315.0013.

Data for mixture of 14e(ii) and 15e: Colourless oil (56 mg,

17%, 1:1 ratio); ν_max.(neat) 3346, 3061, 3005, 2941, 1604, 1444

and 1047 cm^-1; ¹H NMR (400 MHz; CDCl₃) δ 7.84 (2H of either

14e(ii) or 15e, dd, J = 8.4, 1.2 Hz, aromatic CH), 7.74 (2H of

either 14e(ii) or 15e, dd, J = 8.1, 1.4 Hz, aromatic CH), 7.68 –

7.52 (5H of each compound, m, aromatic CH), 7.14 – 7.06 (2H of

each compound, m, aromatic CH), 5.51 (1H of 15e, d, J = 2.5 Hz,

CHOH), 5.18 (1H of 14e(ii), d, J = 8.6 Hz, CHOH), 5.00 (1H of

14e(ii), d, J = 8.6 Hz, OH), 4.30 (1H of 15e , d, J = 2.5 Hz, OH),

2.36 (1H of 14e(ii), dq, J = 14.6, 7.2 Hz, one of CH₂), 1.26 (1H

of 14e(ii), dq, J = 14.6, 7.1 Hz, one of CH₂) and 1.07 (3H of

14e(ii), app. t, J = 7.2 Hz, CH₃); ¹³C NMR (101 MHz; CDCl₃)

chemical shifts for both compounds: δ 163.5 (d, J = 249 Hz, quat

C), 162.4 (d, J = 254 Hz, quat C), 137.2 (quat C), 136.8 (quat C),

133.5 (CH), 133.3 (d, J = 3 Hz, quat C), 132.5 (CH), 131.5 (d, J

= 3 Hz, quat C), 131.0 (d, J = 8 Hz, CH), 130.71 (d, J = 8 Hz,

CH), 129.1 (CH), 128.7 (CH), 128.1 (CH), 127.2 (CH), 115.2 (d,

J = 22 Hz, CH), 115.0 (d, J = 22 Hz, CH), 86.0 (quat C), 83.6

(quat C), 79.6 (CH), 77.4 (CH), 25.5 (CH₂) and 8.1 (CH₃); MS

(APCl⁺) m/z (%) 392 (M+Na+CH₃CN)⁺, ³⁷Cl, 33%), 390

((M+Na+CH₃CN)⁺, ³⁵Cl, 100%), 329 (MH⁺, ³⁷Cl, 8%), 327

(MH⁺, ³⁵Cl, 37%), 349 (35), 390 (100), 261 (25); HRMS: Found

MH⁺, 327.0638. C₁₆H₁₇³⁵ClFO₂S requires 327.0622.

Data for the second diastereoisomer: Colourless solid (66

mg, 32%), m.p 193 – 194 °C; R_f= 0.22 (4% EtOAc/CHCl₃); ν_max.

(neat) 3244, 1442 and 1043 cm^-1; H NMR (400 MHz; CDCl₃)

1

δ 7.95 – 7.83 (2H, m, aromatic CH), 7.63 (1H, app. tt, J = 7.3,

1.4 Hz, aromatic CH), 7.60 – 7.53 (4H, m, aromatic CH), 7.45 –

7.33 (3H, m, aromatic CH), 5.48 (1H, d, J = 5.3 Hz, CHOH) and

4.08 (1H, d, J = 5.3 Hz, OH); ¹³C NMR (101 MHz; CDCl₃)

δ 137.5, 136.1, 133.1, 129.3, 129.2, 128.6, 128.3, 128.0, 102.3

and 76.5; MS (APCl⁺) m/z (%) 382 ((M+Na+CH₃CN)⁺, ³⁷Cl₂,

5%),

380

((M+Na+CH₃CN)⁺, ³⁵Cl³⁷Cl,

20%),

378

((M+Na+CH₃CN)⁺, ³⁵Cl₂, 31%), 319 (MH⁺, ³⁷Cl₂, 4%), 317

(MH⁺, ³⁵Cl³⁷Cl, 17%), 315 (MH⁺, ³⁵Cl₂, 24%), 198 (100), 157

(29); HRMS: Found MH⁺, 315.0016. C₁₄H₁₃³⁵Cl₂O₂S requires

315.0013.

Data for mixture of 14e(iii) and 14e(iv): Colourless oil (64

mg, 20%, 54:46 ratio); ν_max.(neat) 3323, 3065, 2984, 2941, 2885,

4.20. Synthesis of Dichloromethyl 4-Tolyl Sulfone (16)²⁶

1

1602, 1442 and 1030 cm^-1; H NMR (400 MHz; CDCl₃) δ 7.84

4-Toluenesulfinic acid sodium salt dihydrate (8.5 g, 40 mmol)

was placed in a 100 mL flask, followed by chloroform (12 mL,

150 mmol), potassium hydroxide (2.8 g, 50 mmol) and water (40

mL). The mixture was stirred and heated to reflux for 12 h. The

mixture was then extracted with dichloromethane (3 × 20 mL)

and the organic extracts were combined and dried over

magnesium sulfate. The solvents were removed to give the

essentially pure title compound (3.81 g, 40%) as a colourless

(2H of 14e(iii), dd, J = 8.2, 1.4 Hz, aromatic CH), 7.80 (2H of

14e(iv), dd, J = 8.1,1.5 Hz, aromatic CH), 7.63 – 7.43 (5H of

both isomers, m, aromatic CH), 7.08 – 7.00 (2H of both isomers,

m, aromatic CH), 5.36 (1H of 14e(iv), d, J = 3.5 Hz, CHOH),

5.21 (1H of 14e(iii), d, J = 3.2 Hz, CHOH), 3.80 (1H of 14e(iii),

d, J = 3.2 Hz, OH), 3.37 (1H of 14e(iv), d, J = 3.5 Hz, OH), 2.21

– 2.05 (2H of 14e(iii), m, CH₂), 1.83 (1H of 14e(iv), dq, J = 15.1,

7.4 Hz, one of CH₂), 1.50 (1H of 14e(iv), dq, J = 15.1, 7.3 Hz,

one of CH₂), 0.96 (3H of 14e(iv), app. t, J = 7.4 Hz, CH₃) and

0.80 (3H of 14e(iii), app. t, J = 7.5 Hz, CH₃); ¹³C NMR (101

MHz, CDCl₃) δ 163.1 (quat C, d, J = 248 Hz), 163.0 (quat C, d, J

= 248 Hz), 138.6 (quat C), 138.2 (quat C), 133.9 (quat C, d, J = 3

Hz), 133.6 (quat C, d, J = 3 Hz), 132.6 (CH), 132.4 (CH), 130.5

(CH, d, J = 8 Hz), 130.1 (CH, d, J = 8 Hz), 129.0 (CH), 128.8

(CH), 127.4 (CH), 127.2 (CH), 115.4 (CH, d, J = 22 Hz), 114.9

(CH, d, J = 21 Hz), 93.2 (quat C), 89.2 (quat C), 77.4 (CH), 74.7

(CH), 27.9 (CH₂), 24.4 (CH₂), 10.0 (CH₃) and 9.3 (CH₃); MS

(APCl⁺) m/z (%) 392 ((M+Na+CH₃CN)⁺, ³⁷Cl, 33%), 390

((M+Na+CH₃CN)⁺, ³⁵Cl, 100%), 351 ((M+Na)⁺, ³⁷Cl, 20%), 349

((M+Na)⁺, ³⁵Cl, 55%); HRMS: Found (M+Na)⁺, 349.0435.

C₁₆H₁₇³⁵ClFNaO₂S requires 349.0441.

1

solid, m.p. 89 – 90 °C (lit.²⁶89.5 – 90 °C); H NMR (400 MHz;

CDCl₃) δ 7.91 (2H, d, J = 8.0 Hz, aromatic CH), 7.43 (2H, d, J =

8.0 Hz, aromatic CH), 6.23 (1H, s, CHCl₂) and 2.50 (3H, s, CH₃);

¹³C NMR (101 MHz; CDCl₃) δ 147.2, 131.4, 130.1, 129.0, 80.0

and 22.0.

4.21. General Procedure for the Reaction of Dichloromethyl 4-

Tolyl Sulfone (16) with Trialkylboranes

Dichloromethyl 4-tolyl sulfone (16) (120 mg, 0.50 mmol) was

dissolved in THF (5 mL) and the trialkylborane (0.50 mmol) in

THF (0.5 – 5 mL)³¹was added. The mixture was cooled to –78

°C and lithium bis(trimethylsilyl)amide (LiHMDS) (0.60 mL, 1.0

M in THF, 0.60 mmol) was added dropwise. The solution was

stirred for 30 min at –78 °C and 90 min at room temperature. The

solution was then quenched with sat. ammonium chloride (5

mL). The organic layer was separated and the aqueous layer was

extracted with chloroform (3 × 10 mL). The solution was dried

over magnesium sulfate. After the removal of volatile solvents

under vacuum, the crude product was further purified by silica

column chromatography (5% diethyl ether/petroleum ether) to

give the product with yield and data as below.

4.19. Synthesis of 2,2-Dichloro-1-phenyl-2-(phenylsulfinyl)-1-

ethanol (15a)

LDA (0.6 mmol) was prepared freshly in THF (5 mL) and

cooled in a dry-ice bath. A solution of dichloromethyl phenyl

sulfoxide (6) (105 mg, 0.5 mmol) in THF (1 mL) was added.

After the solution was stirred for 10 minutes, benzaldehyde (51

µL, 0.5 mmol) was added and the solution stirred for 30 minutes

further. The solution was extracted into 1:1 ether-toluene (3 × 20

13

O

NH

NMe

1-((1,1-Dichloropropyl)sulfonyl)-4-methylbenzene (17a):

Colourless solid (62 mg, 46%), m.p. 52 – 54 °C; R_f= 0.28 (5%

O

ACCEPTED MANUSCRIPT

S

diethyl ether/petroleum ether); ν_max.(NaCl film) 3069, 2986,

2943, 2883, 1595, 1455, 1334, 1156 and 1076 cm^-1; H NMR

1

74%

80%

(400 MHz; CDCl₃) δ 7.96 (2H, d, J = 8.0 Hz, aromatic CH), 7.40

(2H, d, J = 8.0 Hz, aromatic CH), 2.54 (2H, q, J = 7.2 Hz, CH₂),

2.49 (3H, s, CH₃) and 1.32 (3H, t, J = 7.2 Hz, CH₃); ¹³C NMR

(126 MHz; CDCl₃) δ 146.6 (quat C), 132.5 (CH), 129.6 (CH),

129.2 (quat C), 102.0 (quat C), 33.6 (CH₂), 22.0 (CH₃) and 8.8

(CH₃); MS (APCl+) m/z (%) 288 ((M+NH₄)⁺, ³⁷Cl₂, 15%), 286

((M+NH₄)⁺, ³⁷Cl³⁵Cl, 68%), 284 ((M+NH₄)⁺, ³⁵Cl₂, 100%), 250

(8), 214 (13), 119 (100); HRMS: Found (M+NH₄)⁺, 284.0272.

C₁₀H₁₆³⁵Cl₂NO₂S requires 284.0273.

NMe

O

S

+

CH₂Cl

CHCl₂

64%

25%

4.23. Synthesis of S-Methyl-S-phenylsulfoximine³²

Selected crystallographic data: C₁₀H₁₂Cl₂O₂S, FW = 267.1,

T = 296(2) K, λ = 1.54184, Monoclinic, P21/n, a = 10.8436(3) Å,

b = 17.6380(3) Å, c = 13.1040(3) Å, α= 90°, β = 102.560(2)°, γ =

90°, V = 2446.29(10) Å³, Z = 8, ρ_calc.= 1.451 Mg/m³, crystal size

= 0.885 x 0.146 x 0.056 mm³, µ = 6.202 mm^-1, reflections

collected = 20117, independent reflections = 4902, R_int= 0.0289,

parameters = 275, R₁= 0.0339, wR₂= 0.0920 for I>2σ(I) and R₁

=0.0418, wR₂= 0.0994 for all data. CCDC 1451738 contains the

supplementary crystallographic data for this structure. These data

can be obtained free of charge from The Cambridge

Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures

Methyl phenyl sulfoxide (0.7 g, 5 mmol) was dissolved in

chloroform (10 mL). Sodium azide (360 mg, 5.5 mmol) was

added and the flask was immersed in an ice-bath. Sulfuric acid

(1.25 mL) was added dropwise. The mixture was then warmed to

45 °C and left to stir overnight. Ice-water (10 mL) was added and

the organic layer was separated. The aqueous layer was extracted

with chloroform (10 mL). The aqueous layer was made slightly

alkaline (pH ≈ 8.0) with 20% NaOH and extracted into

chloroform (3 × 20 mL). The combined extracts were dried over

magnesium sulfate and filtered. After removal of the solvent

under reduced pressure, the title compound (0.571 g, 74%) was

obtained as a pale yellow oil; ¹H NMR (400 MHz; CDCl₃)

δ 8.02 − 7.98 (2H, m, aromatic CH), 7.61 (1H, app. tt, J = 7.3,

1.3 Hz, aromatic CH), 7.54 (2H, app. broad t, J = 7.4 Hz,

aromatic CH), 3.09 (3H, s, CH₃) and 2.46 (1H, broad s, NH); ¹³

C

NMR (101 MHz; CDCl₃) δ 143.6, 133.2, 129.4, 127.8 and 46.3.

4.24. Synthesis of N,S-Dimethyl-S-phenylsulfoximine³³

A mixture of S-methyl-S-phenylsulfoximine (0.531 g, 3.42

mmol) and formaldehyde (8 mL, 37% in water) in 90% formic

acid (30 mL) was heated at 100 °C for 48 h. Sulfuric acid (21

mL, 2.0 M) was added and the resulting solution was extracted

with chloroform (3 × 20 mL). The organic layer was dried over

magnesium sulfate and the solvent was removed to leave the title

1

compound (0.462 g, 80%) as a colourless oil; H NMR (400

1-((1,1-Dichloropentyl)sulfonyl)-4-methylbenzene

Colourless solid (65 mg, 44%), m.p. 65 – 67 °C; R_f= 0.3 (5%

(17b):

MHz; CDCl₃) δ 7.88 (2H, d, J = 7.0 Hz, aromatic CH), 7.64 –

7.51 (3H, m, aromatic CH), 3.06 (3H, s, CH₃) and 2.62 (3H, s,

CH₃); ¹³C NMR (101 MHz; CDCl₃) δ 138.7, 133.1, 129.7, 128.9,

45.1 and 29.7.

diethyl ether/petroleum ether); ν_max.(neat) 3068, 2960, 2937,

1

2874, 1595, 1336, 1155 and 1084 cm^-1; H NMR (400 MHz;

CDCl₃) δ 7.96 (2H, d, J = 8.0 Hz, aromatic CH), 7.40 (2H, d, J =

8.0 Hz, aromatic CH), 2.52 – 2.46 (2H, m, CH₂), 2.49 (3H, s,

CH₃), 1.80 – 1.71 (2H, m, CH₂), 1.44 (2H, app. quintet, J = 7.4

Hz, CH₂) and 0.96 (3H, t, J = 7.4 Hz, CH₃); ¹³C NMR (101 MHz;

CDCl₃) δ 146.5 (quat C), 132.4 (CH), 129.5 (CH), 128.9 (quat

C), 100.9 (quat C), 39.1 (CH₂), 26.4 (CH₂), 22.1 (CH₂), 21.9

(CH₃) and 13.9 (CH₃); MS (APCl⁺) m/z (%) 316 ((M+NH₄)⁺,

³⁷Cl₂, 15%), 314 ((M+NH₄)⁺, ³⁷Cl³⁵Cl, 64%), 312 ((M+NH₄)⁺,

³⁵Cl₂, 100%), 280 (70), 119 (100); HRMS: Found (M+NH₄)⁺,

312.0583. C₁₂H₂₀³⁵Cl₂NO₂S requires M, 312.0592.

4.25. Chlorination of N,S-Dimethyl-S-phenylsulfoximine²⁸

A solution of N,S-dimethyl-S-phenylsulfoximine (169 mg, 1.0

mmol) in dichloromethane (10 mL) was placed in a 25 mL flask,

followed by addition of potassium carbonate (207 mg, 1.5

mmol). The flask was wrapped in aluminium foil and immersed

in an ice-bath. t-Butyl hypochlorite³⁴(0.23 mL, 2 mmol) was

added dropwise by syringe. The cooling bath was removed and

the mixture was stirred for 1 h, then heated to reflux for 2 h, after

which it was filtered. The solvents were removed from the filtrate

under reduced pressure to give the crude product. After column

chromatography on silica gel (20% diethyl ether/petroleum

ether), two products were separated (mono and dichloromethyl

products).

4.22. Synthesis of N-Methyl-S-(dichloromethyl)-S-

phenylsulfoximine (18)

N-Methyl-S-(chloromethyl)-S-phenylsulfoximine:

Colourless oil (131 mg, 64%); R_f: 0.2 (5:1, petroleum

1

ether/diethyl ether); H NMR (400 MHz; CDCl₃) δ 7.98 – 7.92

(2H, m, aromatic CH), 7.66 (1H, app. tt, J = 7.4, 1.2 Hz, aromatic

CH), 7.57 (2H, app. broad t, J = 7.5, aromatic CH), 4.66 (1H, d, J

= 12.3 Hz, one of CH₂), 4.54 (1H, d, J = 12.3 Hz, one of CH₂)

14

Tetrahedron

and 2.85 (3H, s, CH₃); ¹³C NMR (101 MHz; CDCl₃) δ 135.1,

stirring overnight with NaOH (3.0 M, 3 mL) and aq. H₂O₂(30%,

ACCEPTED MANUSCRIPT

133.9, 130.0, 129.4, 57.7 and 29.6.

3 mL). The organic layer was separated, the aqueous layer was

saturated with NaCl and extracted with dichloromethane (3 x 10

mL), and the organic layers were combined, dried (MgSO₄) and

filtered. Evaporation under reduced pressure left a crude product

that was purified by column chromatography (silica gel, 5%

EtOAc/petroleum ether). GC yields were based on the crude

product by reference to an added internal standard (tetradecane).

N-Methyl-S-(dichloromethyl)-S-phenylsulfoximine

(18):

Colourless solid (59 mg, 25%), m.p. 33 – 35 °C; R_f: 0.3 (5:1,

petroleum ether/diethyl ether); ¹H NMR (400 MHz; CDCl₃)

δ 8.08 – 8.04 (2H, m, aromatic CH), 7.70 (1H, app. tt, J = 7.5,

1.2 Hz, aromatic CH), 7.58 (2H, app. t, J = 7.7 Hz), 6.34 (1H, s,

CH) and 3.09 (3H, s, CH₃); ¹³C NMR (101 MHz; CDCl₃) δ 134.4

(CH), 132.9 (quat C), 130.7 (CH), 129.1 (CH), 80.8 (CH) and

29.9 (CH₃); MS (ES⁺) m/z (%) 242 (MH⁺, ³⁷Cl₂, 7%), 240 (MH⁺,

³⁷Cl³⁵Cl, 32%), 238 (MH⁺, ³⁵Cl₂, 38%); HRMS: Found MH⁺,

237.9851. C₈H₁₀³⁵Cl₂NOS requires 237.9860.

5-Butylnonan-5-ol:³⁵A pure sample of the title compound for

use in determining a GC response factor was obtained from

1

reaction of n-BuLi with 5-nonanone. Colourless oil; H NMR

(400 MHz; CDCl₃) δ 1.48 – 1.18 (18H, m, all CH₂groups), 1.07

(1H, broad s, OH) and 0.84 (9H, t, J = 6.6 Hz, CH₃); ¹³C NMR

(101 MHz; CDCl₃) δ 74.7, 39.1, 25.8, 23.5 and 14.3. Use of the

response factor thus obtained revealed a GC yield of 81% in the

reaction of tributylborane with compound 18.

4.26. General Procedure for the Reaction of Compound 18 with

Trialkylboranes

4.26.1. Preparation of trialkylboranes

9-Octylheptadecan-9-ol:^2aColourless oil (81% GC yield; 75%

1

All trialkylboranes were prepared in situ and used directly.

Trioctylborane and tricyclopentylborane were prepared by

hydroboration of 1-octene and cyclopentene, respectively, by a

well-established method,²⁹according to the following procedure.

To borane dimethyl sulfide complex (50 µL, 10.0 M, 0.50 mmol)

in THF (2 mL) in a septum-capped 50 mL round bottom flask

immersed in an ice bath was added 1-octene (0.24 mL, 1.50

mmol) or cyclopentene (132 µL, 1.50 mmol) dropwise. The

cooling bath was removed and the mixture was left to stir at room

temperature for 1 h to provide the solution used in the reaction.

isolated yield); H NMR (400 MHz; CDCl₃) δ 1.50 – 1.03 (43H,

m, all CH₂and OH), and 0.88 (9H, t, J = 6.9 Hz, CH₃); ¹³C NMR

(126 MHz; CDCl₃) δ 74.6, 39.5, 32.0, 30.4, 29.7, 29.5, 23.6, 22.8

and 14.2.

5-Cyclohexylnonan-5-ol: Colourless oil (83 mg, 73%); ν_max.

1

(neat) 3477, 2955, 2928, 2854 and 1450 cm^-1; H NMR (400

MHz; CDCl₃) δ 1.84 – 1.66 (5H, m), 1.54 – 0.97 (19H, m) and

0.91 (6H, t, J = 7.0 Hz, CH₃); ¹³C NMR (101 MHz; CDCl₃)

δ 75.9 (quat C), 45.2 (CH), 36.2 (CH₂), 27.1 (CH₂), 26.9 (CH₂),

26.8 (CH₂), 25.6 (CH₂), 23.6 (CH₂) and 14.3 (CH₃); MS (EI-MS)

m/z (%): molecular ion not seen; 208 (M⁺– H₂O, 17%), 151 (38),

109 (72), 69 (94); HRMS: Found (M⁺– H₂O), 208.2196. C₁₅H₂₈

requires M, 208.2191.

Dibutylcyclohexylborane and dibutylcyclopentylborane were

prepared by adaptation of a method of Soundarajan and

Matteson,³⁰followed by addition of n-BuLi, according to the

following procedure. To a mixture of BCl₃(0.50 mL, 1.0 M in

hexane, 0.5 mmol) and cyclohexene (51 µL, 0.5 mmol) or

cyclopentene (44 µL, 0.5 mmol) in hexane (2 mL) at -78 °C was

added Et₃SiH (80 µL, 0.5 mmol) dropwise and the mixture was

stirred for 15 min. The cooling bath was removed and the

mixture was stirred for 30 min and then re-cooled to -78 °C. n-

BuLi (0.63 mL, 1.6 M in hexane, 1.0 mmol) was added dropwise,

then the cooling bath was removed and the mixture was allowed

to stir for 1 h to provide the solution used in the reaction.

5-Cyclopentylnonan-5-ol: Colourless oil (72 mg, 68%); ν_max.

1

(neat) 3485, 2953, 2931, 2864 and 1456 cm^-1; H NMR (400

MHz; CDCl₃) δ 2.08 – 1.82 (1H, m, CH), 1.68 – 1.17 (20H, m,

all CH₂), 1.02 (1H, br, OH) and 0.91 (6H, t, J = 7.1 Hz, CH₃); ¹³

C

NMR (101 MHz; CDCl₃) δ 75.3 (quat C), 47.6 (CH), 37.5 (CH₂),

26.2 (CH₂), 26.0 (CH₂), 25.8 (CH₂), 23.6 (CH₂) and 14.3 (CH₃);

MS (EI-MS) m/z (%): molecular ion not seen; 194 (M⁺– H₂O,

28%), 137 (35), 95 (76); HRMS: Found (M⁺– H₂O), 194.2035.

C₁₄H₂₆requires M, 194.2035.

Dibutylphenylborane was prepared as follows. To a solution

of PhBCl₂(65 µL, 0.5 mmol) in dichloromethane (2 mL) at -78

°C was added n-BuLi (0.63 mL, 1.6 M in hexane, 1.0 mmol)

dropwise. The cooling bath was removed and the mixture was

allowed to stir for 1 h to provide the solution used in the reaction.

5-Phenylnonan-5-ol:³⁶Colourless oil (56 mg, 51%); ν_max.

1

(neat) 3419, 2957, 2931, 2860, 1458 and 1078 cm^-1; H NMR

(400 MHz; CDCl₃) δ 7.43 – 7.29 (4H, m, o- and m-CH), 7.22

(1H, tt, J = 7.0, 1.5 Hz, p-CH), 1.88 – 1.69 (5H, m), 1.33 – 1.13

(6H, m), 1.10 – 0.95 (2H, m) and 0.84 (6H, t, J = 7.0 Hz, CH₃);

¹³C NMR (101 MHz; CDCl₃) δ 146.6 (quat C), 128.1 (CH), 126.3

(CH), 125.4 (CH), 77.1 (quat C), 42.9 (CH₂), 25.7 (CH₂), 23.2

(CH₂) and 14.2 (CH₃); MS (EI-MS) m/z (%): molecular ion not

seen; 203 (M⁺– OH, 35%), 160 (33), 138 (55), 115 (64); HRMS:

Found (M⁺– OH), 203.1800. C₁₅H₂₃requires M, 203.1800.

Butylmethylphenylborane was prepared as follows. To a

solution of PhBCl₂(65 µL, 0.5 mmol) in dichloromethane (5 mL)

at -78 °C was added n-BuLi (0.31 mL, 1.6 M in hexane, 0.5

mmol), followed by MeLi (0.31 mL, 1.6 M in hexane, 0.5 mmol).

The cooling bath was removed and the mixture was allowed to

stir for 1 h to provide the solution used in the reaction. It was

recognised that this procedure was not likely to provide the pure

mixed trialkylborane, and indeed a substantial amount of

dibutylphenylborane was present in the solution, but it could

serve to establish whether the reaction would work in this case.

1

2-Phenylhexan-2-ol:³⁷Colourless oil (27 mg, 30%); H NMR

(400 MHz; CDCl₃) δ 7.47 – 7.43 (2H, m, aromatic CH), 7.38 –

7.32 (2H, m, aromatic CH), 7.25 (1H, tt, J = 7.3, 1.3 Hz, p-CH),

1.90 (1H, s, OH), 1.87 – 1.75 (2H, m, CH₂), 1.57 (3H, s, CH₃),

1.32 – 1.20 (3H, m, CH₂and one of CH₂), 1.19 – 1.08 (1H, m,

one of CH₂) and 0.86 (3H, t, J = 7.1 Hz, CH₃); ¹³C NMR (101

MHz; CDCl₃) δ 148.2 (quat C), 128.2 (CH), 126.5 (CH), 124.9

(CH), 74.8 (quat C), 44.0 (CH₂), 30.2 (CH₃), 26.2 (CH₂), 23.1

(CH₂) and 14.1 (CH₃).

4.26.2. Reactions of trialkylboranes with 18

LDA was prepared by dropwise addition of n-BuLi (0.38 mL,

1.6 M in hexane, 0.61 mmol, 1.2 equiv.) to a cooled (–78 °C)

solution of diisopropylamine (91 µL, 0.65 mmol, 1.3 equiv.) in

dry THF (2 mL). The solution was allowed to warm to 0 °C over

20 min, then added dropwise to a solution of 18 (119 mg, 0.50

mmol) and a trialkylborane (0.50 mmol) in THF and/or

dichloromethane (5 mL) at –78 °C. The solution was stirred for 1

h at –78 °C and overnight at room temperature, then oxidised by

Acknowledgments

BAS thanks the Iraqi Government for a studentship. DHJ

thanks the EPSRC and Cardiff University for a studentship. GEH

15

2013, 19, 16342–16356; (f) Hoyt, A. L.; Blakemore, P. R.

extends his appreciation to the Deanship of Scientific Research at

King Saud University for its funding for his research through the

research group project RGP-239.

ACCEPTED MANUSCRIPT

Tetrahedron Lett. 2014, 56, 2980–2982.

18. Hooz, J.; Gunn, D. M. J. Am. Chem. Soc. 1969, 91, 6195–6196

and references cited therein.

19. See, for example: (a) Brown, H. C.; Rogić, M. M.; Rathke, M. W.

J. Am. Chem. Soc. 1968, 90, 6218–6219; (b) Brown, H. C.; Rogić,

M. M.; Rathke, M. W.; Kabalka, G. W. J. Am. Chem. Soc. 1969,

91, 2150–2152.

20. Pasto, D. J.; Wojtkowski, P. W. Tetrahedron Lett. 1970, 11, 215–

218.

21. Truce, W. E.; Mura, L. A.; Smith, P. J.; Young, F. J. Org. Chem.

1974, 39, 1449–1450.

22. Satoh, T.; Oohara, T.; Ueda, Y.; Yamakawa, K. J. Org. Chem.

1989, 54, 3130–3136.

23. Moore, K. M.; Wemple, J. J. Org. Chem. 1978, 43, 2713–2714.

24. Mutterer, V.; Arnau, E. G.; Karlberg, A.-T.; Lepoittevin, J.-P.

Chem. Res. Toxicol. 2000, 13, 1028–1036.

25. Evans, D. A.; Vogel, E.; Nelson, J. V. J. Am. Chem. Soc, 1979,

101, 6120–6123.

26. Middelbos, W.; Strating, J.; Zwanenburg, B. Tetrahedron Lett.

1971, 12, 351–352.

27. Ni, C.; Zhang, L.; Hu, J. J. Org. Chem. 2008, 73, 5699–5713.

28. Johnson, C. R.; Corkins, H. G. J. Org. Chem. 1978, 43, 4136–

4140.

29. Pelter, A.; Smith, K; Brown, H. C. Borane Reagents, Academic

Press, London, 1988.

30. Soundararajan, R.; Matteson, D. S. Organometallics 1995, 14,

4157–4166.

31. Triethylborane and tributylborane were purchased as 1M solutions

in THF, so that 0.50 mL of the solution was used. Other boranes

were synthesised, and used as 0.1M solutions.

32. Johnson, C. R.; Haake, M.; Schroeck, C. W. J. Am. Chem. Soc.

1970, 92, 6594–6598.

5. References

1. Brown, H. C.; Rathke, M. W. J. Am. Chem. Soc. 1967, 89, 2737–

2738.

2. (a) Pelter, A.; Hutchings, M. G.; Rowe, K.; Smith, K. J. Chem.

Soc., Perkin Trans. 1 1975, 138–142; (b) Pelter, A.; Hutchings, M.

G.; Smith, K. J. Chem. Soc. D: Chem. Commun. 1971, 1048–

1048.

3. Brown, H. C.; Carlson, B. A. J. Org. Chem. 1973, 38, 2422–2424;

Brown, H. C.; Katz, J. J.; Carlson, B. A. J. Org. Chem. 1973, 38,

3968–3970.

4. Brown, H. C. Acc. Chem. Res. 1969, 2, 65–72.

5. (a) Pelter, A.; Smith, K.; Hutchings, M. G.; Rowe, K. J. Chem.

Soc., Perkin Trans. 1 1975, 129–138; (b) Pelter, A.; Hutchings, M.

G.; Smith, K. J. Chem. Soc. D: Chem. Commun. 1970, 1529–

1530; 1971, 1048–1050.

6. Brown, H. C.; Carlson, B. A.; Prager, R. H. J. Am. Chem. Soc.

1971, 93, 2070–2071.

7. Pelter, A.; Rao, J. M. J. Organomet. Chem. 1985, 285, 65–69.

8. For a discussion of the various factors that influence organoboron

rearrangements, see: Aggarwal, V. K.; Fang, G. Y.; Ginesta, X.;

Howells, D. M.; Zaja, M. Pure. Appl. Chem. 2006, 78, 215–229.

9. Hill, D. R.; Hsiao, C.-N.; Kurukulasuriya, R.; Wittenberger, S. J.

Org. Lett. 2002, 4, 111–113.

10. Ruoliene, J.; Adomenas, P.; Surutkaitis, R. A.; Denis, G. I.

Zhurnal Organicheskoi Khimii 1984, 20, 1305-1310.

11. (a) Gross, H.; Rieche, A.; Höft, E. Chem. Ber. 1961, 94, 544–550;

(b) Gross, H.; Rieche, A.; Höft, E.; Beyer, E. Org. Synth. Coll.

1973, 5, 365–367.

33. Johnson, C. R.; Schroeck, C. W.; Shanklin, J. R. J. Am. Chem.

Soc. 1973, 95, 7424–7431.

12. Bognaŕ, R.; Farkas, I.; Menyhárt, M.; Gross, H.; Paulsen, H. Carb.

Res. 1968, 6, 404–413.

34. Mintz, M. J.; Walling, C. Org. Synth. Coll. 1973, 5, 184–187.

35. Runge, M. B.; Mwangi, M. T.; Miller II, A. L.; Perring, M.;

Bowden, N. B. Angew. Chem. Int. Ed. 2008, 47, 935–939.

36. Miyoshi, N.; Matsuo, T.; Wada, M. Eur. J. Org. Chem. 2005,

4253–4255.

13. Dabee, A; Gauthier, P; Senet, J.-P. US Patent 5672770, 1997.

14. Miyagawa, T.; Satoh, T. Tetrahedron Lett. 2007, 48, 4849–4853.

15. For an example of use of a sulfoxide as a leaving group, induced

by reaction with N-chlorosuccinimide, see: Casey, M.; Manage, A.

C.; Murphy, P. J. Tetrahedron Lett. 1992, 33, 965–968.

16. See: Busch, B. B.; Paz, M. M.; Shea, K. J.; Staiger, C. L.;

Stoddard, J. M.; Walker, J. R.; Zhou, X.-Z.; Zhu, H. J. Am. Chem.

Soc. 2002, 124, 3636–3646 and references cited therein.

17. (a) Blakemore, P. R.; Marsden, S. P.; Vater, H. W. Org. Lett.

2006, 8, 773–776; (b) Blakemore, P. R.; Burge, M. S. J. Am.

Chem. Soc., 2007, 129, 3068–3069; (c) Emerson, C. R.; Zakharov,

L. N.; Blakemore, P. R. Org. Lett. 2011, 13, 1318–1321; (d) Sun,

X.; Blakemore, P. R. Org. Lett. 2013, 15, 4500–4503; (e)

Emerson, C. R.; Zakharov, L. N.; Blakemore, P. R. Chem.-Eur. J.

37. Syrgiannis, Z.; Gebhardt, B.; Dotzer, C.; Hauke, F.; Graupner, R.;

Hirsch, A. Angew. Chem. Int. Ed. 2010, 49, 3322–3325.

Supplementary Material

Computational details, atomic coordinates for calculated

structures. Copies of ¹H and ¹³C NMR spectra.

Article Doi

Reactions of organoboranes with carbanions bearing three potential leaving groups: unusual processes, products and mechanisms

DOI: 10.1016/j.tet.2016.09.005

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