Invert production

In the original work (72), the authors stated that heating of 42 with excess sodium iodide did not result in further exchange. The extensive studies of Stevens and co-workers (96, 97) on the displacement reactions of compounds much related to 40, indicate that the C-4 sulfonate group can indeed be displaced by various nucleophiles. In fact compound 42 and its C-4 epimer (43) (d-threo) have been subjected to displacement reactions with benzoate (38), acetate and azide (98) ions to give the corresponding C-4 inverted products. 

Alkylations of the germyllithium derived from germane R-5 were found to proceed with retention or inversion depending upon the nature of the alkyl halide employed (Scheme 5)9. Iodides gave rise to inverted products, whereas the corresponding chlorides or bromides yielded products with retention of configuration at Ge. 

In the example shown, there is slightly more of the inverted product in the reaction mixture, though the effect is not especially large. In other recorded examples, up to about 80% of the product might be the inverted form. It follows that the Sn2 process is accompanied by complete inversion, whereas an SnI process will involve racemization or partial inversion. 

In both cases, failure to yield inverted products exclusively is most probably due to a steric situation in which the steroid aglycon attacks the initially formed carbonium ion from the side of the plane of the ring that is opposite to the 5-methyl group, to give the o-d anomer as the major product. 

Molecular mechanics modeling (13) of hydroxide attack on the chiral trans benzyl derivative 6 indicated that steric control during transition state formation is a principal factor in the reduced amount of inverted product formed (15) compared to that for the cis isomer... 

Partial retention of configuration is attributed to anionic intermediates which slowly invert and thus are protonated with partially retained configuration. In the inversion case the anion is inverting more rapidly and is protonated from the side not shielded by the electrode thus yielding inverted product 492 ... 

The reaction H + 03 shows a very highly inverted product vibrational distribution peaking at the highest accessible level v = 9 for OH from H + 03 and v = 13 for OD from D + 03). Thus, almost all the available energy ( 93%) appears in the newly formed bond leaving only 7% to be partitioned between product translation and internal excitation of the 02 product. There is presently no experimental information regarding this partitioning. 

Shorter reaction times (2-5 hr) result in slightly decreased yields (65-75%) of inverted product. Lower yields (73-75%) were realized by the checkers when stirring at 40°C was omitted. 

Carpenter noted that the motion associated with the reaction coordinate of 33 is inversion at both carbon atoms that break their bond to nitrogen. The reaction dynamics model for the reaction is that passage over 33 will have energy in the reaction coordinate mode that will directly lead toward the inverted product 32x. Once momentnm has been placed into this inversion mode, it will continue unless a barrier is met. Carpenter pictures the mechanism as in Scheme 8.9. Molecules that cross 33 to form intermediate 34 are primarily directed onward to 32x. Only a small portion will remain in the shallow well and get turned toward 32n. 

Thermolysis of dialkoxyselenuranes 126 a and b was found to give oxiranes 127 a and b stereo specifically in high yield, although a small amount (2%) of an inverted product was obtained from 126b [64] (Eq. 30). 

Finally, the carboxylate anion acts as a nucleophile to displace tri-phenylphosphine oxide and give the inverted product. 

The Mitsunobu protocol has also been investigated in the stereocontrolled synthesis of glycosyl esters (O Scheme 78g) [431]. Complete stereochemical inversion at C-1 of the starting sugar is observed when the esterification is conducted with anomerically pure glycosyl hemiacetals. By corollary, complementary ratios of inverted products are formed when an anomeric mixture of sugars is esterifled. The stereochemical outcome of the esterification is not affected... 

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