[Hydroxy(tosyloxy)iodo]benzene Mediated α-Azidation of Ketones

Abstract: Reaction of various ketones with [hydroxy(tosyloxy)iodo]benzene (HTIB) followed by treatment of the α-tosyloxy ketones thus generated in situ with NaN 3 offers a one-pot procedure for the synthesis of α-azido ketones. The HTIB used in this conversion may also be generated in situ by using iodosobenzene in combination with p -toluene-sulphonic acid. Keywords: Hypervalent iodine, α-azido ketones, [hydroxy(tosyloxy)iodo]benzene, iodosobenzene. Introduction The application of organohypervalent iodine reagents is a fertile and attractive field in organic synthesis [1]. Of the various hypervalent iodine reagents, iodobenzene diacetate (IBD) [2] and [hydroxy(tosyloxy)iodo]benzene (HTIB) (Koser’s reagent) [3] have been found to be more versatile than other reagents such as iodosobenzene (IOB), etc. The relatively lesser utility of IOB is due to its polymeric nature [4], which makes it insoluble in common solvents. To overcome such difficulties, combination reagents were developed. For example, the utility of IOB is greatly enhanced when it is combined with acids [5], bases [6] or salts [7]. These reactions are thought to proceed via generation


Introduction
The application of organohypervalent iodine reagents is a fertile and attractive field in organic synthesis [1].Of the various hypervalent iodine reagents, iodobenzene diacetate (IBD) [2] and [hydroxy(tosyloxy)iodo]benzene (HTIB) (Koser's reagent) [3] have been found to be more versatile than other reagents such as iodosobenzene (IOB), etc.The relatively lesser utility of IOB is due to its polymeric nature [4], which makes it insoluble in common solvents.To overcome such difficulties, combination reagents were developed.For example, the utility of IOB is greatly enhanced when it is combined with acids [5], bases [6] or salts [7].These reactions are thought to proceed via generation in situ of the I(III) species 4 (Scheme 1).Continuing our investigations on the use of I(III) reagents, we now report a one pot α-azidation of ketones using HTIB or the combination reagent [(PhIO) n + p-TsOH] [8] and NaN 3.

Results and Discussion
Based on previous reports on the use of [hydroxy(tosyloxy)iodo]benzene (HTIB) [9] in one-pot syntheses of α-functionalized ketones, we first attempted the azidation of 1a using HTIB.Accordingly, acetophenone (1a) was oxidized with one equivalent of HTIB in acetonitrile and subsequently the α-tosyloxy ketone 2a generated in situ was treated with sodium azide.The reaction resulted in the formation of the corresponding α-azido acetophenone 3a in 80% yield (Method A, Scheme 2).In order to study the scope of this approach, various ketones 1b-1g were subjected to α−azidation using one equivalent of HTIB and NaN 3 to afford the corresponding α−azido ketones 3b-3g in yields ranging from 69% to 81% (Table 1).
In another important development, we established that it is possible to use a combination of iodosobenzene and p-toluenesulphonic acid [(PhIO)n + p-TsOH] in place of HTIB.This combination reagent generates HTIB in situ, which then reacts with ketones 1 to give the intermediary α-tosyloxy ketones 2 (Method B).
It is evident from the results summarized in Table 1 that Method A and Method B work equally well, although Method B is more convenient than Method A as the former avoids the preparation of HTIB.It is to be mentioned that the reported preparation of HTIB consists of two steps starting from iodosobenzene [10,11] (Scheme 3).

Conclusions
In summary, the present study offers a better alternative to the existing methods for the synthesis of α-azido ketones, which are valuable intermediates for various transformations [12] and are generally prepared by the reaction of α-halo ketones [12] or α-nosyloxy ketones [13] with sodium azide.
Similarly, other α-azido ketones 3b-3g were prepared from the corresponding ketones 1b-1g in good yields (Table 1).The identities of the products were confirmed by comparison of their melting points and spectral data with those reported in literature.

Method B. Using (PhIO) n + p-TsOH/ NaN 3 :
To iodosobenzene (2.20 g, 10 mmol) in acetonitrile (20 mL) was added p-toluenesulphonic acid (1.72 g, 10 mmol), the mixture was stirred at room temperature for 5 min.To the resulting suspension, acetophenone (1a, 1.20 g, 10 mmol) was added and the mixture was refluxed for 2 h.After cooling to room temperature sodium azide (1.30 g, 2.0 mmol) was added and stirred for 2 h.Usual work up (as given in Method A) gave 1.24 g of 3a.Compounds 3b-3g were similarly prepared in good yields from the corresponding ketones 1b-1g (Table 1).

Table 1 .
α-Azido ketones 2 prepared according to Scheme 2 a Yields of isolated pure product based on the amount of ketones 1 used.